https://www.cyclopropenium.com/publications daily 0.75 2024-11-19 https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579550401822-CCHYX0IL2A256H5SGM5V/fulvene.gif Publications - Bandar, J. S.; Coscia, R. W.; Lambert, T. H. Tetrahedron 2011, 67, 4364-4370. Cleavage of fulvenes under mild conditions and interchange between electron-deficient fulvenes and their constituent cyclopentadienes and imines is demonstrated for the first time. A series of cyclopentadienes and imines are investigated to probe the dependence of fulvene equilibration on structure. The exchange of one fulvene for another is demonstrated in the first reported example of transfulvenation. Finally, the metathesis of two fulvenes to generate all four possible cross products is shown. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/266c132f-b390-4fb0-ae63-8fef390d2704/electrophoto_Chemrev.jpg Publications - Lamb, M. C.; Steiniger, K. A.; Trigoura, L. K.; Wu, J.; Kundu, G.; Huang, H.; Lambert, T. H. Chem. Rev. 2024, 124, 122264-12304. Electrocatalysis and photocatalysis have been the focus of extensive research efforts in organic synthesis in recent decades, and these powerful strategies have provided a wealth of new methods to construct complex molecules. Despite these intense efforts, only recently has there been a significant focus on the combined use of these two modalities. Nevertheless, the past five years have witnessed rapidly growing interest in the area of electrophotocatalysis. This hybrid strategy capitalizes on the enormous benefits of using photons as reagents while also employing an electric potential as a convenient and tunable source or sink of electrons. Research on this topic has led to a number of methods for C–H functionalization, reductive cross-coupling, and olefin addition among others. This field has also seen the use of a broad range of catalyst types, including both metal and organocatalysts. Of particular note has been work with open-shell photocatalysts, which tend to have comparatively large redox potentials. Electrochemistry provides a convenient means to generate such species, making electrophotocatalysis particularly amenable to this intriguing class of redox catalyst. This review surveys methods in the area of electrophotocatalysis as applied to organic synthesis, organized broadly into oxidative, reductive, and redox neutral transformations. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579614651949-QNTA34UGQ8VTZ518VTBA/TS+cyclopropenimines.gif Publications - Bandar, J. S.; Sauer, G. S.; Wulff, W. D.; Lambert, T. H.; Vetticatt, M. J. J. Am. Chem. Soc. 2014, 136, 10700-10707. Experimental 13C kinetic isotope effects have been used to interrogate the rate-limiting step of the Michael addition of glycinate imines to benzyl acrylate catalyzed by a chiral 2,3-bis(dicyclohexylamino) cyclopropenimine catalyst. The reaction is found to proceed via rate-limiting carbon–carbon bond formation. The origins of enantioselectivity and a key noncovalent CH···O interaction responsible for transition state organization are identified on the basis of density functional theory calculations and probed using experimental labeling studies. The resulting high-resolution experimental picture of the enantioselectivity-determining transition state is expected to guide new catalyst design and reaction development. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/9014496c-17ad-4149-913b-04d825e9e79c/cyclopropenium.jpg Publications - Wilson, R. M.; Lambert, T. H. Acc. Chem. Res. 2022, 55, 3057-3069. Cyclopropenium ions are the smallest class of aromatic compounds, satisfying Hückel’s rules of aromaticity with two π electrons within a three-membered ring. First prepared by Breslow in 1957, cyclopropenium ions have been found to possess extraordinary stability despite being both cationic and highly strained. In the 65 years since their first preparation, cyclopropenium ions have been the subject of innumerable studies concerning their synthesis, physical properties, and reactivity. However, prior to our work, the reactivity of these unique carbocations had not been exploited for reaction promotion or catalysis. Over the past 13 years, we have been exploring aromatic ions as unique and versatile building blocks for the development of catalysts for organic chemistry. A major portion of this work has been focused on leveraging the remarkable properties of the smallest of the aromatic ions─cyclopropeniums─as a design element in the invention of highly reactive catalysts. Indeed, because of its unique profile of hydrolytic stability, compact geometry, and relatively easy oxidizability, the cyclopropenium ring has proven to be a highly advantageous construction module for catalyst invention. In this Account, we describe some of our work using cyclopropenium ions as a key element in the design of novel catalysts. First, we discuss our early work aimed at promoting dehydrative reactions, starting with Appel-type chlorodehydrations of alcohols and carboxylic acids, cyclic ether formations, and Beckmann rearrangements and culminating in the realization of catalytic chlorodehydrations of alcohols and a catalytic Mitsunobu-type reaction. Next, we describe the development of cyclopropenimines as strong, neutral organic Brønsted bases and, in particular, the use of chiral cyclopropenimines for enantioselective Brønsted catalysis. We also describe the development of higher-order cyclopropenimine superbases. The use of tris(amino)cyclopropenium (TAC) ions as a novel class of phase-transfer catalysts is discussed for the reaction of epoxides with carbon dioxide. Next, we describe the formation of a cyclopropenone radical cation that has a portion of its spin density on the oxygen atom, leading to some peculiar metal ligand behavior. Finally, we discuss recent work that employs TAC electrophotocatalysts for oxidation reactions. The key intermediate for this chemistry is a TAC radical dication, which as an open-shell photocatalyst has remarkably strong excited-state oxidizing power. We describe the application of this strategy to transformations ranging from the oxidative functionalization of unactivated arenes to the regioselective derivatization of ethers, C–H aminations, vicinal C–H diaminations, and finally aryl olefin dioxygenations. Collectively, these catalytic platforms demonstrate the utility of charged aromatic rings, and cyclopropenium ions in particular, to enable unique advances in catalysis. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579376284263-8VSNFLGI6G4MN82QS7YP/daco.png Publications - Strater, Z. M.; Rauch, M.; Jockusch, S.; Griffith, A. K.; Lambert, T. H. Angew. Chem. Int. Ed. 2019, 58, 8049-8052. Single electron oxidation of 2,3‐diaminocyclopropenones is shown to give rise to stable diaminocyclopropenium oxyl (DACO) radical cations. Cyclic voltammetry reveals reversible oxidations in the range of +0.70–1.10 V (vs. SCE). Computational, EPR, and X‐ray analysis support the view that the oxidized species is best described as a cyclopropenium ion with spin density located on the heteroatom substituents, including 23.5 % on oxygen. The metal–ligand behavior of the DACO radical is also described. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579551070924-S093VV1H3N2TN7A2282A/Mannich.gif Publications - Bandar, J. S.; Lambert, T. H. J. Am. Chem. Soc. 2013, 135, 11799-11802. Cyclopropenimine 1 is shown to catalyze Mannich reactions between glycine imines and N-Boc-aldimines with high levels of enantio- and diastereocontrol. The reactivity of 1 is shown to be substantially greater than that of a widely used thiourea cinchona alkaloid-derived catalyst. A variety of aryl and aliphatic N-Boc-aldimines are effective substrates for this transformation. A preparative-scale reaction to deliver >90 mmol of product is shown using 1 mol % catalyst. The products of this transformation can be converted into several useful derivatives. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/f7695497-d53b-4e2e-b01c-3d81358cdcd9/PAG_HBD.jpeg Publications - Shankel, S. L.; Ma, Y.; Spivey, J. A.; Filien, L.; Lambert, T. H.; Fors, B. P. Eur. Polym. J. 2024, 207, 112814. Photoacid generators (PAGs) have facilitated a number of technology breakthroughs in the electronic, coating, and additive manufacturing industries. Traditionally, PAGs that contain weakly coordinating anions, such as PF6−, generate Brønsted superacids under UV irradiation for rapid cationic polymerizations. However, PAGs with strongly coordinating anions remain under-utilized as they form weak acids that are inefficient or even incapable of initiating polymerization. To expand the scope of potential counteranions in PAGs, we leveraged a thiophosphoramide hydrogen bond donor (HBD) to catalyze photoinitiated cationic polymerizations from diphenyliodonium PAGs. Through the formation of hydrogen bonds between the HBD and PAG counteranion, acceleration of the polymerization rate was observed for a range of non-coordinating and coordinating anions. The effect of the HBD on the polymerization kinetics was investigated by 1H − NMR titrations and geometry optimizations. Extending HBD catalysis beyond photopolymerizations, addition of HBD also enabled hydrochloric acid to initiate controlled reversible addition − fragmentation chain transfer (RAFT) polymerization under ambient conditions. With the versatility of HBD, there is potential to access initiation systems that were previously believed to be impractical for cationic polymerization. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/74c3cf99-e295-4120-9388-99e20e62a9be/aminooxygenation.jpg Publications - Huang, H.; Lambert, T. H. J. Am. Chem. Soc. 2022, 144, 18803-18809. A method for the regiodivergent aminooxygenation of aryl olefins under electrophotocatalytic conditions is described. The procedure employs a trisaminocyclopropenium (TAC) ion catalyst with visible light irradiation under a controlled electrochemical potential to convert aryl olefins to the corresponding oxazolines with high chemo- and diastereoselectivity. With the judicious choice between inexpensive and abundant reagents, namely water or urethane, either 2-amino-1-ol or 1-amino-2-ol derivatives could be prepared from the same substrate. This method is amenable to multigram synthesis of the oxazoline products with low catalyst loadings. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579617417877-WYLXKSJGNRKRDB7MLBFW/reductive+electrophoto.jpeg Publications - Kim, H.; Kim, H.; Lambert, T. H.; Lin, S. J. Am. Chem. Soc. 2020, 142, 2087-2092. We describe a new electrophotocatalytic strategy that harnesses the power of light and electricity to generate an excited radical anion with a reducing potential of −3.2 V vs SCE, which can be used to activate substrates with very high reduction potentials (Ered ≈ −1.9 to −2.9 V). The resultant aryl radicals can be engaged in various synthetically useful transformations to furnish arylboronate, arylstannane, and biaryl products. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1622554791987-6BPWJU8HB8U9QL08RTWY/acetoxyhydroxylation_TOC.jpg Publications - Huang, H.; Lambert, T. H. J. Am. Chem. Soc. 2021, 143, 7247-7252. A method for the acetoxyhydroxylation of olefins with syn stereoselectivity under electrophotocatalytic conditions is described. The procedure uses a trisaminocyclopropenium (TAC) ion catalyst with visible light irradiation under a controlled electrochemical potential to convert aryl olefins to the corresponding glycol monoesters with high chemo- and diastereoselectivity. This reaction can be performed in batch or in flow, enabling multigram synthesis of the monoester products. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579615412261-ENK8IF29RWC96DCVRKCM/transfection.jpg Publications - Brucks, S. D.; Freyer, J. L.; Lambert, T. H.; Campos, L. M. Polymers 2017, 9, 79-87. The realization of gene therapy relies on the development of delivery vectors with high efficiency and biocompatibility. With a multitude of structures accessible, the core challenge is precisely tuning vector structure to probe and optimize structure–property relationships. Employing a modular strategy, two pairs of cationic polymers based on the trisaminocyclopropenium (TAC) ion were synthesized where the substituents differ in the degree of alkyl chain branching. All TAC-based polymers exhibited higher transfection efficiencies than the untreated controls, with variable in vitro toxicities. Considering both cytotoxicity and transfection efficacy, an optimal nonviral vector was identified. Our studies highlight the importance of exercising precise control over polymer structure, both in terms of backbone identity and substituent nature, and the necessity of a robust, modular platform from which to study them. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579615106513-VZLKT26LLQRTAAMENK18/lactide+polymer.gif Publications - Stukenbroeker, T. S.; Bandar, J. S.; Zhang, X.; Lambert, T. H.; Waymouth, R. M. ACS Macro Lett. 2015, 4, 853-856. Cyclopropenimine superbases were employed to catalyze the ring-opening polymerization of lactide. Polymerization occurred readily in the presence and absence of alcohol initiators. Polymerizations in the absence of alcohol initiators revealed a competitive initiation mechanism involving deprotonation of lactide by the cyclopropenimine to generate an enolate. NMR and MALDI-TOF analysis of the poly(lactides) generated from cyclopropenimines in the absence of alcohol initiators showed acylated lactide and hydroxyl end groups. Model studies and comparative experiments with guanidine and phosphazene catalysts revealed the subtle influence of the nature of the superbase on competitive initiation processes. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579614563707-322HA29XE9KV6D0OT0OL/diaziridinium.gif Publications - Allen, J. M.; Lambert, T. H. Tetrahedron 2014, 70, 4111-4117. A diaziridinium ion has been synthesized in high yield and its structure unambiguously confirmed by X-ray crystal analysis. The predicted N-transfer reactivity with olefins of this species was not observed. Instead, upon heating, the diaziridinium ion underwent ring opening to produce a dihydrobenzodiazepene product in good yield, thus achieving a formal N-insertion of the starting dihydroisoquinoline substrate. This process has been demonstrated on 11 total substrates. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579382051343-QFB7MM0YXW3HUP83ECP5/tylophora.gif Publications - Ambrosini, L. A.; Cernak, T. A.; Lambert, T. H. Tetrahedron 2010, 66, 4882-4887. A rapid synthetic approach to the tylophora alkaloids antofine and 13aα-secoantofine is presented that makes use of a multicatalytic oxidative aminochlorocarbonylation/Friedel–Crafts reaction as the key step. This reaction, along with a one-pot, three-step telescoped process offers a three or four-pot sequence to access the title compounds in high overall yield. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579615283907-VCFMYILAHYC374ZWXSQY/macrostere.gif Publications - Mishiro, K.; Hu, F.; Paley, D. W.; Min, W.; Lambert, T. H. Eur. J. Org. Chem. 2016, 1655-1659. The “deltic guanidinium” ion is described here as a “macrostere” of the guanidinium ion. The use of the 2,4‐dimethoxybenzyl protecting group allows for the synthesis of the fully unsubstituted parent compound and a variety of derivatives bearing multiple N–H functions for the first time. Deltic urea, deltic thiourea, and deltic benzamidine are also synthesized. A comparison of the physical properties of guanidinium and deltic guanidinium ions is provided. The use of a deltic guanidinium dendrimer for cell transport is demonstrated. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579616083337-U3SOAWMQKBQPYY9N94YQ/metathesis+review.gif Publications - Lambert, T. H. Synlett 2019, 30, 1954-1965. Carbonyl-olefin metathesis is a potentially powerful yet underexplored reaction in organic synthesis. In recent years, however, this situation has begun to change, most notably with the introduction of several different catalytic technologies. The development of one of those new strategies, based on hydrazine catalysts and a novel [3+2] paradigm for double bond metathesis, is discussed herein. First, the stage is set with a description of some potential applications of carbonyl-olefin metathesis and a discussion of alternative strategies for this intriguing reaction. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/c0252881-1e12-4cea-8c1d-218c6de24f4c/Ullmann.jpg Publications - Stone, I. B.; Starr, R. L.; Hoffmann, N.; Wang, X.; Evans, A. M.; Nuckolls, C.; Lambert, T. H.; Steigerwald, M. L.; Berkelbach, T. C.; Roy, X.; Venkataraman, L. Chem. Sci. 2022, 13, 10798-10805. The electric fields created at solid–liquid interfaces are important in heterogeneous catalysis. Here we describe the Ullmann coupling of aryl iodides on rough gold surfaces, which we monitor in situ using the scanning tunneling microscope-based break junction (STM-BJ) and ex situ using mass spectrometry and fluorescence spectroscopy. We find that this Ullmann coupling reaction occurs only on rough gold surfaces in polar solvents, the latter of which implicates interfacial electric fields. These experimental observations are supported by density functional theory calculations that elucidate the roles of surface roughness and local electric fields on the reaction. More broadly, this touchstone study offers a facile method to access and probe in real time an increasingly prominent yet incompletely understood mode of catalysis. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579381631091-6CG7GZL6V3UQ7CNGJPPF/LG+potential.gif Publications - Fisher, E. L.; Lambert, T. H. Org. Lett. 2009, 11, 4108-4110. The facility with which a substituted cyclopentadienyl anion may function as a leaving group for palladium-catalyzed allylation reactions is demonstrated. Reaction of several allylcyclopentadienyl substrates is shown. Nucleophilic displacement of carbon with nitrogen is achieved in the deallylation of allylpenta-p-acetylphenylcyclopentadiene with N-methylbenzylamine. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579381523117-YMR6HLVV00IMY9MNOQH4/methylene+transfer.gif Publications - Hardee, D. J.; Lambert, T. H. J. Am. Chem. Soc. 2009, 131, 7536-7537. A new method for cyclopropanation involving intramolecular methylene transfer from an epoxide to an olefin has been developed. This La(OTf)3-catalyzed process proceeds with good efficiency and with high stereoselectivity. A range of examples illustrating substrate scope are given along with a mechanistic rationale. Also demonstrated is an asymmetric cyclopropane synthesis that combines enantioselective epoxidation with this methylene-transfer protocol. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579550894473-D8UVC156EYI1KCH1E6Q9/aminocyclopropeniums.gif Publications - Bandar, J. S.; Lambert, T. H. Synthesis 2013, 45, 2485-2498. This review covers the preparation, physical properties, and applications of cyclopropenium ions bearing one, two, or three amino substituents. It provides a description of the most reliable methods to access these unique structures as well as a discussion of the reactivity profiles of the common subtypes. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/faef0a2e-2559-4c43-a8fc-c36b0af350d7/cyclobutene.jpg Publications - Holl, M. G.; Lambert, T. H. ACS Catal. 2022, 12, 4813-4817. The ring-opening carbonyl-olefin metathesis of cyclobutenes to furnish gamma, delta-unsaturated aldehydes—formal Claisen rearrangement products—is reported. The bistrifluoroacetic acid salt of 2,3-diazabicyclo[2.2.2]octane promotes these reactions efficiently with a variety of cyclobutenes and aldehydes, including aliphatic, alpha, beta-unsaturated, aryl, and heteroaryl aldehydes. Catalytic reactions are also demonstrated. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579615526127-YCVWR4KL9H42X78MEA22/PCCP_synthesis.gif Publications - Gheewala, C. D.; Radtke, A. M.; Hui, J.; Hon, A. B.; Lambert, T. H. Org. Lett. 2017, 19, 4227-4230. Protocols for the synthesis of diverse pentacarboxycyclopentadienes are described. Starting from readily available pentacarbomethoxycyclopentadiene, transesterification offers single-step access to aliphatic ester derivatives, while treatment with amines produces mono- or diamides. For less nucleophilic alcohols, an alternative procedure involving the in situ generation and esterification of a putative cyclopentadiene pentaacid chloride has been developed. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1616768942576-W419YSF2X6KA60LQF9GZ/diamination+revised.jpg Publications - Shen, T.; Lambert, T. H. Science 2021, 371, 620-626. The conversion of unactivated carbon-hydrogen (C–H) bonds to carbon–nitrogen (C–N) bonds is a highly valued transformation. Existing strategies typically accomplish such reactions at only a single C–H site because the first derivatization diminishes the reactivity of surrounding C–H bonds. Here, we show that alkylated arenes can undergo vicinal C–H diamination reactions to form 1,2-diamine derivatives through an electrophotocatalytic strategy, using acetonitrile as both solvent and nitrogen source. The reaction is catalyzed by a trisaminocyclopropenium (TAC) ion, which undergoes anodic oxidation to furnish a stable radical dication while the cathodic reaction reduces protons to molecular hydrogen. Irradiation of the TAC radical dication (wavelength of maximum absorption of 450 to 550 nanometers) with a white-light compact fluorescent light generates a strongly oxidizing photoexcited intermediate. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1633707298778-19T04WXT0OKMOYLIGW5P/NiPCCP.jpg Publications - Steiniger, K. A.; Lambert, T. H. Org. Lett. 2021, 23, 8013-8017. The efficient and regioselective hydrosilylation of epoxides co-catalyzed by a pentacarboxycyclopentadienyl (PCCP) diamide nickel complex and Lewis acid is reported. This method allows for the reductive opening of terminal, monosubstituted epoxides to form unbranched, primary alcohols. A range of substrates including both terminal and non-terminal epoxides are shown to work, and a mechanistic rationale is provided. This work represents the first use of a PCCP derivative as a ligand for transition metal catalysis. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/4dd650a2-317c-48fd-985a-34b4d25e4c92/distonic.jpeg Publications - Steiniger, K. A.; Lambert, T. H. Science Adv. 2023, 9, eadg3026. The conversion of carbonyls to olefins is a transformation of great importance for complex molecule synthesis. Standard methods use stoichiometric reagents that have poor atom economy and require strongly basic conditions, which limit their functional group compatibility. An ideal solution would be to catalytically olefinate carbonyls under nonbasic conditions using simple and widely available alkenes, yet no such broadly applicable reaction is known. Here, we demonstrate a tandem electrochemical/electrophotocatalytic reaction to olefinate aldehydes and ketones with a broad range of unactivated alkenes. This method involves the oxidation-induced denitrogenation of cyclic diazenes to form 1,3-distonic radical cations that rearrange to yield the olefin products. This olefination reaction is enabled by an electrophotocatalyst that inhibits back-electron transfer to the radical cation intermediate, thus allowing for the selective formation of olefin products. The method is compatible with a wide range of aldehydes, ketones, and alkene partners. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/6f972990-0a37-40fd-be1a-9c2d45ac2af1/heteroarene+RCCOM.jpg Publications - Cho, E. K.; Quach, K. P.; Zhang, Y.; Sim, J. H.; Lambert, T. H. Chem. Sci. 2022, 13, 2418-2422. The use of hydrazine-catalyzed ring-closing carbonyl-olefin metathesis (RCCOM) to synthesize polycyclic heteroaromatic (PHA) compounds is described. In particular, substrates bearing Lewis basic functionalities such as pyridine rings and amines, which strongly inhibit acid catalyzed RCCOM reactions, are shown to be compatible with this reaction. Using 5 mol% catalyst loadings, a variety of PHA structures can be synthesized in from biaryl alkenyl aldehydes, which themselves are readily prepared by cross-coupling. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579381711380-XDSALB5XR1L3LD5KUM3M/chlorodehydration.gif Publications - Kelly, B. D.; Lambert, T. H. J. Am. Chem. Soc. 2009, 131, 13930-13931. A novel paradigm for the activation of alcohols toward nucleophilic displacement via formation of cyclopropenium ethers is described. The conversion of a range of alcohol substrates to the corresponding alkyl chlorides occurs rapidly upon treatment with 3,3-dichloro-1,2-diphenylcyclopropene. 1H NMR data support the intermediacy of a cyclopropenium intermediate, and the reaction is demonstrated to proceed primarily via the SN2 mechanism for 1-phenylethanol. A total of 12 examples of substrate scope are provided. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579617204443-AXH6OL47QS62UI3353J0/SnAr+electrophoto.png Publications - Huang, H.; Lambert, T. H. Angew. Chem. Int. Ed. 2020, 59, 658-662. The electrophotocatalytic SNAr reaction of unactivated aryl fluorides at ambient temperature without strong base is demonstrated. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579616614397-9ZHX2FXBNUZERCOBEI4Y/PCCP+cationic+polymer.gif Publications - Kottisch, V.; O’Leary, J. M.; Michaudel, Q.; Stache, E.; Lambert, T. H.; Fors, B. J. Am. Chem. Soc. 2019, 141, 10605-10609. Cationic polymerizations provide a valuable strategy for preparing macromolecules with excellent control but are inherently sensitive to impurities and commonly require rigorous reagent purification, low temperatures, and strictly anhydrous reaction conditions. By using pentacarbomethoxycyclopentadiene (PCCP) as the single-component initiating organic acid, we found that a diverse library of vinyl ethers can be controllably polymerized under ambient conditions. Additionally, excellent chain-end fidelity is maintained even without rigorous monomer purification. We hypothesize that a tight ion complex between the PCCP anion and the oxocarbenium ion chain end prevents chain-transfer events and enables a polymerization with living characteristics. Furthermore, terminating the polymerization with functional nucleophiles allows for chain-end functionalization in high yields. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579550483944-JRMGD7L8GZAHDNVABX2U/image-asset.gif Publications - Vanos, C. M.; Lambert, T. H. Angew. Chem. Int. Ed. 2011, 50, 12222-12226. 2,3‐Bis‐(p‐methoxyphenyl)cyclopropenone is a highly efficient catalyst for the chlorodehydration of 20 diverse alcohol substrates. With oxalyl chloride as catalytic activator, this nucleophilic substitution proceeded through cyclopropenium‐activated intermediates and resulted in complete stereochemical inversion in substrates with chiral centers. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/6a0c29ee-00c6-4bbe-b0b4-2cffca11ae7f/Split.jpg Publications - Ma, Y.; Drilling, R. J.; Recker, E. A.; Kim, J.-W.; Shankel, S. L.; Hu, J.; Easley, A. D.; Page, Z. A.; Lambert, T. H.; Fors, B. P. ACS Cent. Sci. 2024, ASAP. The synthesis of polymeric thermoset materials with spatially controlled physical properties using readily available resins is a grand challenge. To address this challenge, we developed a photoinitiated polymerization method that enables the spatial switching of radical and cationic polymerizations by controlling the dosage of monochromatic light. This method, which we call Switching Polymerizations by Light Titration (SPLiT), leverages the use of substoichiometric amounts of a photobuffer in combination with traditional photoacid generators. Upon exposure to a low dose of light, the photobuffer inhibits the cationic polymerization, while radical polymerization is initiated. With an increased light dosage, the buffer system saturates, leading to the formation of a strong acid that initiates a cationic polymerization of the dormant monomer. Applying this strategy, patterning is achieved by spatially varying light dosage via irradiation time or intensity allowing for simple construction of multimaterial thermosets. Importantly, by the addition of an inexpensive photobuffer, such as tetrabutylammonium chloride, commercially available resins can be implemented in grayscale vat photopolymerization 3D printing to prepare sophisticated multimodulus constructs. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1614953057692-HVZI60GKERYCASND3C8R/heteroarene.jpeg Publications - Huang, H.; Lambert, T. H. Angew. Chem. Int. Ed. 2021, 60, 11163-11167. The electrophotocatalytic heterofunctionalization of arenes is described. Using 2,3‐dichloro‐5,6‐dicyanoquinone (DDQ) under a mild electrochemical potential with visible light irradiation, arenes undergo oxidant‐free hydroxylation, alkoxylation, and amination with high chemoselectivity. In addition to batch reactions, an electrophotocatalytic recirculating flow process is demonstrated, enabling the conversion of benzene to phenol on a gram scale. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579381194160-MGZM4ZOEZG6PVP77AMYA/multicatalysisI.gif Publications - Cernak, T. A.; Lambert, T. H. J. Am. Chem. Soc. 2009, 131, 3124-3125. An oxidative carbonylation reaction that generates acid chloride functionality has been developed. Furthermore, this aminochlorocarbonylation reaction has been merged with a catalytic Friedel−Crafts acylation to produce a highly efficient tandem multicatalytic synthesis of pyrrolidinyl ketones. Significant variation of the aromatic nucleophile and substrate are shown. Two examples of incorporation of this method in triple-catalytic sequences are also demonstrated. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579615201801-EYA6C6S25RNO02Y42C64/CPacid.gif Publications - Gheewala, C. D.; Collins, B. E.; Lambert, T. H. Science 2016, 351 , 961-965. Chiral acid catalysts are useful for the synthesis of enantioenriched small molecules, but the standard catalysts require laborious and expensive preparations. Here, we describe a chiral Brønsted acid prepared in one step from naturally occurring (–)-menthol and readily available 1,2,3,4,5-pentacarbomethoxycyclopentadiene. Aromatic stabilization serves as a key contributing factor to the potent acidity of the resulting compound, which is shown to catalyze both Mukaiyama-Mannich and oxocarbenium aldol reactions with high efficiency and enantioselectivity. Catalyst loadings as low as 0.01 mole percent and preparative scalability (25 grams) are demonstrated. Alternative amide catalysts are also shown to be promising platforms. In addition to proton catalysis, a chiral anion pathway is demonstrated to be viable with this catalyst system. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/78c6a431-668d-4bf7-a45e-f1d3b1f7279e/MOF+amidation.jpg Publications - Ahmad, B. I. Z.; Jerozal, R. T.; Meng, S.; Lambert, T. H.; Milner, P. J. ChemRxiv: 10.26434/chemrxiv-2023-65k97 The synthesis of amides from amines and carboxylic acids is the most widely carried out reaction in medicinal chemistry. Yet, most amide couplings are still carried out using stoichiometric reagents, leading to significant waste; few synthetic catalysts for this transformation have been adopted industrially due to their limited scope and/or poor recyclability. The majority of catalytic approaches focus on a single activation mode, such as enhancing the electrophilicity of the carboxylic acid partner using a Lewis acid. In contrast, nature effortlessly forges and breaks amide bonds using precise arrays of Lewis/Brønsted acidic and basic functional groups. Drawing inspiration from these systems, herein we report a simple defect engineering strategy to co-localize Lewis acidic Zr sites with other catalytically active species within porous metal-organic frameworks (MOFs). Specifically, the combination of pyridine N-oxide and Zr open metal sites within the framework MOF-808 produces a heterogeneous catalyst that facilitates amide bond formation with broad functional group compatibility. We propose that the formation of a hydrogen-bonding network at the defect sites helps to lower the energy barrier for amide bond formation. The defective MOF-808 catalyst can be recycled at least five times without losing crystallinity or catalytic activity. This defect engineering strategy can be potentially generalized to produce libraries of catalytically active MOFs with different combinations of co-localized active sites, mimicking the complexity of enzyme active sites. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579618184260-7WTGD5ZX8J7X0MP33WSB/norbornene+ROCOM.png Publications - Jermaks, J.; Quach, P.; Seibel, Z. M.; Pomarole, J.; Lambert, T. H. Chem. Sci. 2020, 11, 7884-7895. Preprint: ChemRxiv, https://doi.org/10.26434/chemrxiv.11385774.v1 A computational and experimental study of the hydrazine-catalyzed ring-opening carbonyl-olefin metathesis of norbornenes is described. Detailed theoretical investigation of the energetic landscape for the full reaction pathway with six different hydrazines revealed several crucial aspects for the design of next-generation hydrazine catalysts. This study indicated that a [2.2.2]-bicyclic hydrazine should offer substantially increased reactivity versus the previously reported [2.2.1]-hydrazine due to a lowered activation barrier for the rate-determining cycloreversion step, a prediction which was verified experimentally. Optimized conditions for both cycloaddition and cycloreversion steps were identified, and a brief substrate scope study for each was conducted. A complication for catalysis was found to be the slow hydrolysis of the ring-opened hydrazonium intermediates, which were shown to suffer from a competitive and irreversible cycloaddition with a second equivalent of norbornene. This problem was overcome by the strategic incorporation of a bridgehead methyl group on the norbornene ring, leading to the first demonstrated catalytic carbonyl-olefin metathesis of norbornene rings. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579376861307-RSHOJDB8E76UMJ9263ZR/one_pot_pccp.gif Publications - Radtke, M. A.; Dudley, C. C.; O'Leary, J. M.; Lambert, T. H. Synthesis 2019, 51, 1135-1138. 1,2,3,4,5-Pentacarbomethoxycyclopentadiene (PCCP) is a strong organic acid and a precursor to useful organocatalysts, including chiral Brønsted acids and silicon-based Lewis acids. The synthetic route to PCCP, first reported in 1942, is inconvenient for a number of reasons. The two-step synthesis requires the purification of intermediates from intractable side-products, high reaction temperatures, and extensive labor (3 days). We have developed an improved procedure that delivers PCCP efficiently in 24 hours in one pot at ambient temperature and without isolation. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/18c28a03-75f4-4905-ba5b-90473b052efe/polyimide.jpg Publications - Ji, W.; Zhang, X.; Qu, H.; Xin, L.; Luedtke, A.; Huang, H.; Lambert, T. H.; Qu, D. Nano Energy 2022, 96, 107130. The integration of organic electrode materials (OEMs) with solid-state electrolytes (SSEs) is expected to build an all-solid-state battery (ASSB) with long-term sustainability, high safety, and high energy density. Despite this great promise, the cell-level energy density is still far from practically applicable, which stems from the ultrathick SSE layer and thin cathode layer used in a pellet-type ASSB design. Here, a cost-effective polyimide (PI) material was first exploited as an organic cathode for sulfide-based ASSBs. A capacity of ~190 mAh g−1 was delivered with almost no capacity decay over 300 cycles. Moreover, for the first time, a dry-film approach was introduced to manufacture a sheet-type Li−organic ASSB with an ultrathin SSE layer and a high-areal-loading PI cathode. Notably, PI is a perfect candidate for dry-film technology due to its high thermal stability and extraordinary chemical inertness toward sulfide SSEs. Remarkably, the free-standing SSE membrane was merely 46 µm thick, and an ultralow areal resistance of 3.3 Ω cm2 was achieved, more than tenfold lower than that of reported SSE pellets. One order of magnitude boost in the cell-level energy density was achieved. This work presents a significant leap in transferring organic ASSB technology from laboratory research to factory manufacturing. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579616907682-Y61JFK80JR6S2JD3KLVE/chromene+metathesis.gif Publications - Zhang, Y.; Jermaks, J.; MacMillan, S. N.; Lambert, T. H. ACS Catal. 2019, 9, 9259-9264. The catalytic ring-closing carbonyl-olefin metathesis (RCCOM) of O-allyl salicylaldehydes to form 2H-chromenes is described. The method utilizes a [2.2.1]-bicyclic hydrazine catalyst and operates via a [3 + 2]/retro-[3 + 2] metathesis manifold. The nature of the allyl substitution pattern was found to be crucial, with sterically demanding groups such as adamantylidene or diethylidene offering optimal outcomes. A survey of substrate scope is shown along with a discussion of mechanism supported by DFT calculations. Steric pressure arising from syn-pentane minimization of the diethylidene moiety is proposed to facilitate cycloreversion. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579615571595-PXG19P1J5WYFNZ905L17/arylsulfonic.gif Publications - Nacsa, E. D.; Lambert, T. H. Org. Chem. Front. 2018, 5, 64-69. The intramolecular cross-coupling of sulfonic acid derivatives occurs in the presence of tris(trimethylsilyl)silane (TTMSS) at room temperature and in air to form biaryl compounds. A photoredox-catalyzed procedure is also described. These protocols provide mild and convenient alternatives to standard tin-mediated reactions. Combined with the trivial preparation of the substrates from activated sulfonic acids and 2-halophenols or anilines, this work presents a useful means to employ sulfonic acid derivatives in cross-coupling transformations. A modified linker to realize high regioselectivity is also presented. Finally, a one-pot cross-coupling procedure is demonstrated. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579615766983-PMY4P180PCNOHZ80MA29/ionic_liquid.jpeg Publications - Griffin, P. J.; Freyer, J. L.; Han, N.; Yin, X.; Gheewala, C.; Lambert, T. H.; Campos, L. M.; Winey, K. I. Macromolecules 2018, 51, 1681-1687. Ion transport in polymerized ionic liquids (poly-ILs) occurs via a fundamentally different mechanism than in monomeric ionic liquids, and recently progress has been made toward understanding ion conduction in poly-ILs. To gain insight into the nature of ionic conductivity in ionic polymers, we investigate the physical properties of the trisaminocyclopropenium (TAC) ion, as it is an aromatic carbocation with unique structural and electronic properties. Herein, we characterize the thermal properties, local morphology, and dielectric response of a series of monomeric and polymeric TAC ionic liquids with different counterions. We have found that the extent of a “superionic” mechanism depends on the nature of the ion pair and can result in anomalously high conductivity at the calorimetric Tg. Our results suggest that the molecular volumes of the cationic and anionic species are important parameters that impact ion conductivity in polymerized ionic liquids. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580070760912-7U835AD2LYN2Z8CMN6PX/inverse_DA.jpg Publications - Gheewala, C.; Hirschi, J. S.; Lee, W.-H.; Paley, D. W.; Vetticatt, M. J.; Lambert, T. H. J. Am Chem. Soc. 2018, 140, 3523-3527. An enantioselective catalytic inverse-electron-demand Diels–Alder reaction of salicylaldehyde acetal-derived oxocarbenium ions and vinyl ethers to generate 2,4-dioxychromanes is described. Chiral pentacarboxycyclopentadiene (PCCP) acids are found to be effective for a variety of substrates. Computational and X-ray crystallographic analyses support the unique hypothesis that an anion with point-chirality-induced helical chirality dictates the absolute sense of stereochemistry in this reaction. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/46706749-db23-4d0a-976d-d1331e1fbbd8/sulfide+cathode.jpg Publications - Ji, W.; Zhang, X.; Zheng, D.; Huang, H.; Lambert, T. H.; Qu, D. Adv. Funct. Mater. 2022, 2202919. The combination of organic electrode materials and sulfide electrolytes is expected to enable the development of all-solid-state organic batteries featuring high energy density, safety, and sustainability. Here, thiuram hexasulfide is first reported as a low-cost and high-capacity cathode material for solid-state organic batteries based on sulfide electrolytes. Notably, a capacity of ≈600 mA h g−1 is delivered and the capacity retention is 80.8% after 500 cycles. An electrochemically reversible change of the cathode interface is revealed upon cycling. The full cell displays an oscillating stress change of up to 0.6 MPa during cycling, predominated by the anode side. The energy density is 1140 Wh kg−1 at the material level and 376 Wh kg−1 at the electrode level, which are among the best-reported organic cathodes to date. A high areal capacity of 10.4 mA h cm−2 is reached with a high mass loading cathode. A dry-film approach is further explored to manufacture sheet-type cells. The free-standing Li6PS5Cl film with a thickness of only 48 µm demonstrates an ultralow areal resistance of 3.9 Ω cm2, which significantly boosts the cell-level energy density and reduces the cell internal resistance. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/0e9cf668-fbe3-402c-b1f9-8556437429e2/electrophoto_perspective.jpg Publications - Huang, H.; Steiniger, K. A.; Lambert, T. H. J. Am. Chem. Soc. 2022, 144, 12567-12583. Visible-light photocatalysis and electrocatalysis are two powerful strategies for the promotion of chemical reactions that have received tremendous attention in recent years. In contrast, processes that combine these two modalities, an area termed electrophotocatalysis, have until recently remained quite rare. However, over the past several years a number of reports in this area have shown the potential of combining the power of light and electrical energy to realize new catalytic transformations. Electrophotocatalysis offers the ability to perform photoredox reactions without the need for large quantities of stoichiometric or superstoichiometric chemical oxidants or reductants by making use of an electrochemical potential as the electron source or sink. In addition, electrophotocatalysis is readily amenable to the generation of open-shell photocatalysts, which tend to have exceptionally strong redox potentials. In this way, potent yet selective redox reactions have been realized under relatively mild conditions. This Perspective highlights recent advances in the area of electrophotocatalysis and provides some possible avenues for future work in this growing area. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579615345044-3SPEFM001FKM96HG2BIP/ClickibILs.gif Publications - Freyer, J. L.; Brucks, S. D.; Gobieski, G. S.; Russell, S. T.; Yozwiak, C. E.; Sun, M.; Chen. Z.; Jiang, Y.; Bandar, J. S.; Stockwell, B. R.; Lambert, T. H.; Campos, L. M. Angew. Chem. Int. Ed. 2016, 55, 12382-12386. The potential applications of cationic poly(ionic liquids) range from medicine to energy storage, and the development of efficient synthetic strategies to target innovative cationic building blocks is an important goal. A post‐polymerization click reaction is reported that provides facile access to trisaminocyclopropenium (TAC) ion‐functionalized macromolecules of various architectures, which are the first class of polyelectrolytes that bear a formal charge on carbon. Quantitative conversions of polymers comprising pendant or main‐chain secondary amines were observed for an array of TAC derivatives in three hours using near equimolar quantities of cyclopropenium chlorides. The resulting TAC polymers are biocompatible and efficient transfection agents. This robust, efficient, and orthogonal click reaction of an ionic liquid, which we term ClickabIL, allows straightforward screening of polymeric TAC derivatives. This platform provides a modular route to synthesize and study various properties of novel TAC‐based polymers. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579381031012-T7QKBN5ZYC8OAIE9W4KC/4plus1.gif Publications - Coscia, R. W.; Lambert, T. H. J. Am. Chem. Soc. 2009, 131, 2496-2498. A formal [4 + 1] cycloaddition of 1,3-dienyl β-keto esters has been developed. This two step process involves Pd(II)-catalyzed intramolecular cyclopropanation to produce vinylcyclopropanes and a subsequent mild vinylcyclopropane−cyclopentene rearrangement promoted by MgI2. The cyclopropanation method notably requires the use of Mg(ClO4)2, presumably to facilitate keto−enol tautomerization, and is greatly improved by the use of copper(II) isobutyrate as co-oxidant. A range of substrates with various substitution patterns is demonstrated. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579550164330-6CNXVEZ3VJ8LA2G4ATDS/Beckmann.gif Publications - Vanos, C. M.; Lambert, T. H. Chem. Sci. 2010, 1, 705-708. The concept of cyclopropenium activation has been extended to include dehydrative rearrangements in the context of the Beckmann rearrangement. Geminal dichlorocyclopropenes are shown to rapidly and efficiently convert oximes to amides at room temperature, with reactivity that far surpasses other organic-based promoters. Twelve total examples are provided, including a complex steroidal substrate on preparative scale. Evidence is provided that suggests previously reported organocatalytic Beckmann rearrangements may in fact be self-propagating rather than catalytic. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/b1ca1909-2cab-4c09-aa8c-088223297d95/PCCPRAFT.jpg Publications - Shankel, S. L.; Lambert, T. H.; Fors, B. P. Polymer Chem. 2022, 13, 5974-5979. Cationic reversible addition–fragmentation chain transfer (RAFT) polymerizations have permitted the controlled polymerization of vinyl ethers and select styrenics with predictable molar masses and easily modified thiocarbonylthio chain ends. However, most cationic RAFT systems require inert reaction conditions with highly purified reagents and low temperatures. Our groups recently developed a living cationic polymerization that does not require these rigorous conditions by utilizing a strong organic acid (pentacarbomethoxycyclopentadiene (PCCP)) and a hydrogen bond donor. By combining our PCCP acid promoted polymerization with a chain transfer agent, we have designed a tolerant cationic RAFT system that can be performed neat, open to the air, and at room temperature. Additionally, this system allows us to utilize catalytic amounts of the PCCP acid to furnish polymers with chain end functionality that can be easily isolated and further manipulated to make functional materials. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579616844138-U0B5UJVDMG8W27T2JLL1/single+molecule+coupling.jpg Publications - Zang, Y.; Stone, I.; Inkpen, M. S.; Liu, Z.-F.; Ng, F.; Lambert, T. H.; Nuckolls, C.; Steigerwald, M. L.; Roy, X.; Venkataraman, L. Angew. Chem. Int. Ed. 2019, 58, 16008-16012. A single‐molecule method has been developed based on the scanning tunneling microscope (STM) to selectively couple a series of aniline derivatives and create azobenzenes. The Au‐catalyzed oxidative coupling is driven by the local electrochemical potential at the nanostructured Au STM tip. The products are detected in situ by measuring the conductance and molecular junction elongation and compared with analogous measurements of the expected azobenzene derivatives prepared ex situ. This single‐molecule approach is robust, and it can quickly and reproducibly create reactions for a variety of anilines. We further demonstrate the selective synthesis of geometric isomers and the assembly of complex molecular architectures by sequential coupling of complementary anilines, demonstrating unprecedented control over bond formation at the nanoscale. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579550326976-UU8NEJ0UU8FDQJGSAV8S/diol.gif Publications - Kelly, B. D.; Lambert, T. H. Org. Lett. 2011, 13, 740-743. The dehydrative cyclization of diols to cyclic ethers via cyclopropenium activation is described. Using 2,3-diphenylcyclopropene and methanesulfonic anhydride, a series of 1,4- and 1,5-diols are rapidly cyclized to furnish tetrahydrofurans and tetrahydropyrans in high yield. Eleven total substrates are shown, including a gram scale cyclization of a diterpene derivative. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1584622797282-PIW7XSN1HXPESW12WW6J/Na_battery.jpg Publications - Ji, W.; Huang, H.; Zhang, X.; Zheng, D.; Ding, T.; Lambert, T. H.; Qu, D. Nano Energy, 2020, https://doi.org/10.1016/j.nanoen.2020.104705 Overcharge abuse can trigger thermal runaway when a device is left unattended. Redox shuttles, as economic and efficient electrolyte additives, have been proven to provide reliable and reversible protection for state-of-art Li-ion batteries (LIBs) against overcharge. Here, a functional organic salt, trisaminocyclopropenium perchlorate (TAC•ClO4), is developed and employed as a redox shuttle for overcharge protection in a Na-ion battery system. This type of novel redox shuttle molecule is reported for the first time. As a unique ionic compound with the smallest aromatic ring structure, TAC•ClO4 exhibits distinctive attributes of fast diffusion, high solubility, and ultrahigh chemical / electrochemical stability in both redox states. With merely 0.1 M TAC•ClO4 in electrolyte, Na3V2(PO4)3 cathode can carry overcharge current even up to 10C or 400% SOC. Na3V2(PO4)3/hard carbon cells demonstrated strong anti-overcharging ability of 176 cycles at 0.5C rate and 54 cycles at 1C rate with 100% overcharge. Moreover, TAC•ClO4 addition has little impact on the electrochemical performance of Na-ion batteries, especially on the rate performance and the initial Columbic efficiency. Interestingly, a unique and reversible electrochromic behavior of TAC•ClO4 electrolyte can promptly provide the device an overcharge alarm under a designed potential to further enhance the safety level. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579551254790-8LAZVEXNL4X3L42924R3/catalytic+substitution.gif Publications - An, J.; Denton, R. M.; Lambert, T. H.; Nacsa, E. Org. Biomol. Chem. 2014, 12, 2993. Bimolecular nucleophilic substitution reactions of alcohols are fundamentally important transformations in organic chemistry yet, to date, they are relatively underdeveloped with respect to catalysis. This Article describes the emerging area of catalytic SN2 reactions with specific emphasis on the design and development of phosphorus(V) and cyclopropenone-based catalytic SN2 reactions of alcohols. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579617317830-1M1723FHKVWSN86PERLQ/ether+electrophoto.jpeg Publications - Huang, H.; Strater, Z. M.; Lambert, T. H. J. Am. Chem. Soc. 2020, 142, 1698-1703. The highly regioselective electrophotocatalytic C–H functionalization of ethers is described. These reactions are catalyzed by a trisaminocyclopropenium (TAC) ion at mild electrochemical potential with visible light irradiation. Ethers undergo oxidant-free coupling with isoquinolines, alkenes, alkynes, pyrazoles, and purines with typically high regioselectivity for the less-hindered α-position. The reaction is proposed to operate via hydrogen atom transfer (HAT) from the substrate to the photoexcited TAC radical dication, thus demonstrating a new reactivity mode for this electrophotocatalyst. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579550075205-IQ6P96EJUO7IMDUYZO8T/multicatalysis.gif Publications - Ambrosini, L. M.; Lambert, T. H. Chem. Cat. Chem. 2010, 2, 1373-1380. Heavy reliance on iterative synthetic strategies represents one of the most serious drawbacks of modern organic synthesis. There has been increasing interest of late in the development of processes that attempt to alleviate this dependence by achieving multiple transformations in a single vessel, thereby circumventing the need for intermittent isolation and purification. One such strategy is encompassed by the term multicatalysis, an approach wherein multiple catalytic reactions are executed in a single flask, either in tandem or sequentially. In this Minireview, some recent efforts in the field of multicatalysis, including our own work, are discussed. In addition, a case regarding the need for consistent terminology in this rapidly developing field is advanced. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1622555094212-P9XZXX2UD7RDGP5SOGJL/Ritter_TOC.jpg Publications - Shen, T.; Lambert, T. H. J. Am. Chem. Soc. 2021, 143, 8597-8602. A method for C−H bond amination via an electrophotocatalytic Ritter-type reaction is described. The reaction is catalyzed by a trisaminocyclopropenium (TAC) ion in an electrochemical cell under irradiation. These conditions convert benzylic C−H bonds to acetamides without the use of a stoichiometric chemical oxidant. A range of functionality is shown to be compatible with this transformation, and several complex substrates are demonstrated. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579615046181-VQ7QH9CW9I7QPB5859HF/higherorderbase.gif Publications - Nacsa, E. D.; Lambert, T. H. J. Am. Chem. Soc. 2015, 137, 10246-10253. The synthesis and characterization of six new classes of higher-order superbases, including five that incorporate cyclopropenimine functionality, has been achieved. We propose a nomenclature that designates these as the CG2, GC2, PC3, PC1, C3, and GP2 classes of superbases. The pKBH+ values were measured to be between 29.0 and 35.6 in acetonitrile. Linear correlations of ten superbase basicities vs that of their substituents demonstrated the insulating effect of the cyclopropenimine core. The molecular structures of several of these materials were obtained by single-crystal X-ray analysis, revealing interesting aspects of conformational bias and noncovalent organization. The types of superbasic cores and substituents were each reliably shown to affect selectivity for deprotonation over alkylation. Higher-order cyclopropenimine and guanidine superbase stability to hydrolysis was found to correlate to basicity. Finally, a GC2 base was found to catalyze conjugate additions of α-aryl ester pronucleophiles, representing the first report of a neutral Brønsted base to catalyze such reactions. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/804245d7-d566-4086-818b-c2af0178480c/cyclobuteneROMP.png Publications - Kellner-Rogers, J. S.; Hsu, J. H.; Keresztes, I.; Fors, B. P.; Lambert, T. H. Angew. Chem. Int. Ed. 2024, 63, e202413093. ChemRxiv. 10.26434/chemrxiv-2024-0qlff Materials formed by the ring-opening metathesis polymerization (ROMP) of cyclic olefins are highly valued for industrial and academic applications but are difficult to prepare free of metal contaminants. Here we describe a highly efficient metal-free ROMP of cyclobutenes using hydrazine catalysis. Reactions can be initiated via in situ condensation of a [2.2.2]-bicyclic hydrazine catalyst with an aliphatic or aromatic aldehyde initiator. The polymerizations show living characteristics, achieving excellent control over molecular weight, low dispersity values, and high chain-end fidelity. Additionally, the hydrazine can be used in substoichiometric amounts relative to the aldehyde chain-end while maintaining good control over molecular weight and low dispersity values, indicating that a highly efficient chain transfer mechanism is occurring. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1632489694901-2XZQM91NVBAC0LIOMCVO/single_molecule.jpg Publications - Stone, I.; Starr, R. L.; Zang, Y.; Nuckolls, C.; Steigerwald, M. L.; Lambert, T. H.; Roy, X.; Venkataraman, L. Nat. Rev. Chem. 2021, 5, 695-710. Chemical reactions that occur at nanostructured electrodes have garnered widespread interest because of their potential applications in fields including nanotechnology, green chemistry and fundamental physical organic chemistry. Much of our present understanding of these reactions comes from probes that interrogate ensembles of molecules undergoing various stages of the transformation concurrently. Exquisite control over single-molecule reactivity lets us construct new molecules and further our understanding of nanoscale chemical phenomena. We can study single molecules using instruments such as the scanning tunnelling microscope, which can additionally be part of a mechanically controlled break junction. These are unique tools that can offer a high level of detail. They probe the electronic conductance of individual molecules and catalyse chemical reactions by establishing environments with reactive metal sites on nanoscale electrodes. This Review describes how chemical reactions involving bond cleavage and formation can be triggered at nanoscale electrodes and studied one molecule at a time. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579615472837-SCPVLCSPR4C8GXNRDM2I/Raman.gif Publications - Hu, F.; Brucks, S. D.; Lambert, T. H.; Campos, L. M.; Min, W. Chem. Commun. 2017, 53, 6187-6190. A novel nanoparticle-based imaging strategy is introduced that couples biocompatible organic nanoparticles and stimulated Raman scattering (SRS) microscopy. Polymer nanoparticles with vibrational labels incorporated were readily prepared for multi-color SRS imaging with excellent photo-stability. The Raman-active polymer dots are nontoxic, rapidly enter various cell types, and are applied in multiplexed cell-type sorting. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579381362917-7KL13LKYTNN0XN37KB9S/multicatalysis+bismuth.gif Publications - Kelly, B. D.; Allen, J. M.; Tundel, R. E.; Lambert, T. H. Org. Lett. 2009, 11, 1381-1383. A multicatalytic synthesis of complex tetrahydrofurans has been developed involving a Bi(OTf)3-catalyzed nucleophilic addition/hydroalkoxylation sequence. Complex tetrahydrofuranyl products may be formed rapidly in high yield and with good diastereoselectivity. The demonstrated scope of hydroalkoxylation has also been expanded to include substrates bearing useful functional handles including carboxylate ester, olefin, nitrile, and nitro groups. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579615696500-40DISI86J08PEZQ14H79/liquid_crystal.jpeg Publications - Litterscheidt, J.; Judge, P.; Bühlmeyer, A.; Bader, K.; Bandar, J. S.; Lambert, T. H.; Laschat, S. Liquid Crystals 2018, 45, 1250-1258. The influence of the size of a single ionic head group on the mesomorphic properties of hexaalkoxytriphenylenes was investigated by synthesising three derivatives with increasing head group diameter. The derivatives were investigated with optical polarising microscopy (POM), differential scanning calorimetry (DSC) and X-ray scattering (WAXS, SAXS). For the derivative with the small trimethylammonium head group, an enantiotropic mesophase was found. The derivative with the bigger tetramethylguanidine head group only showed a monotropic phase and the derivative with the largest bisdiisopropylaminocyclopropenium head group displayed no liquid crystaline properties at all. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579382229787-IC9W23LMY4DX6FTMG2H2/chlorodehydrationII.gif Publications - Hardee, D. J.; Kovalchuke, L.; Lambert, T. H. J. Am. Chem. Soc. 2010, 132, 5002-5003. The first example of aromatic cation-activated nucleophilic acyl substitution has been achieved. The conversion of carboxylic acids to their corresponding acid chlorides occurs rapidly in the presence of 3,3-dichlorocyclopropenes via the intermediacy of cyclopropenium carboxylate complexes. The effect of cyclopropene substituents on the rate of conversion is examined. The addition of tertiary amine base is found to dramatically accelerate reaction, and conditions were developed for the preparation of acid sensitive acid chlorides. Preparative scale peptide couplings of two N-Boc amino acids were achieved with this method. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/8292c127-e653-4e4b-b587-20bd6d48d2ab/alkylhalideolefinmetathesis.jpeg Publications - Kellner-Rogers, J. S.; Wang, R.; Lambert, T. H. Org. Lett. 2024, 26, 1078-1082. ChemRxiv: 10.26434/chemrxiv-2023-v1rbg The first platform for oxidative alkyl halide-olefin metathesis is described. The procedure employs diazenes as catalysts, which effect cyclization of alkenyl alkyl halides to generate cyclic olefins and carbonyl products. The synthesis of phenanthrene, coumarin, and quinolone derivatives is demonstrated, as well as the potential to apply this strategy to other electrophiles. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1629124495747-14JX058G0H457LRAA181/pyroglutamate.jpg Publications - Seibel, Z. M.; Bandar, J. S.; Lambert, T. H. Beilstein J. Org. Chem. 2021, 17, 2077-2084. *Invited contribution for special issue on asymmetric organocatalysis A procedure for the enantioselective synthesis of a-substituted glutamates and pyroglutamates via cyclopropenimine-catalyzed Michael addition of amino ester imines is described. Enantioselectivities of up to 94% have been achieved, and a variety of functional groups were found to be compatible. The impact of catalyst structure and imine substitution is discussed. Compared to other methods, this protocol allows for broader and more enantioselective access to pyroglutamate derivatives. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1611083965645-62GSR5K4HIK50TSJP5P7/ange202013419-toc-0001-m.jpg Publications - Kottisch, V.; Jermaks, J.; Mak, J.-Y.; Woltornist, R. A.; Lambert, T. H.; Fors, B. P. Angew. Chem. Int. Ed. 2021, 60, 4535-4539. The synthesis of high‐molecular‐weight poly(vinyl ethers) under mild conditions is a significant challenge, since cationic polymerization reactions are highly sensitive to chain‐transfer and termination events. We identified a novel and highly effective hydrogen bond donor (HBD)–organic acid pair that can facilitate controlled cationic polymerization of vinyl ethers under ambient conditions with excellent monomer compatibility. Poly(vinyl ethers) of molar masses exceeding 50 kg mol−1 can be produced within 1 h without elaborate reagent purification. Modification of the HBD structure allowed tuning of the polymerization rate, while DFT calculations helped elucidate crucial intermolecular interactions between the HBD, organic acid, and polymer chain end. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/65244533-045f-40cc-9b2a-c861f4535add/cyclopropene+ROMP.jpg Publications - Quach, P.; Hsu, J. H.; Keresztes, I.; Fors, B. P.; Lambert, T. H. Angew. Chem. Int. Ed. 2022, 61 , e202203344. Preprint: 10.26434/chemrxiv-2022-q8n0b A new strategy for the ring–opening metathesis polymerization (ROMP) of cycloalkenes using hydrazonium initiators is described. The initiators, which are formed by the condensation of 2,3-diazabicyclo[2.2.2]octane and an aldehyde, polymerize cyclopropene monomers by a sequence of [3+2] cycloaddition and cycloreversion reactions. This process generates short chain polyolefins (Mn ≤ 9.4 kg/mol) with relatively low dispersities (Đ ≤ 1.4). The optimized conditions showed efficiency comparable to that achieved with Grubbs’ catalyst. A positive correlation between monomer to initiator ratio and degree of polymerization was revealed through NMR spectroscopy. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1629123962239-6MQSM9AN33X3IT00YTLE/carbonylolefin+met+chem+rev.jpeg Publications - Albright, H.; Davis, A. J.; Gomez-Lopez, J. L.; Vonesh, H. L.; Quach, P. K.; Lambert, T. H.; Schindler, C. S. Chem. Rev. 2021, 121, 9359-9406. This Review describes the development of strategies for carbonyl–olefin metathesis reactions relying on stepwise, stoichiometric, or catalytic approaches. A comprehensive overview of currently available methods is provided starting with Paternò–Büchi cycloadditions between carbonyls and alkenes, followed by fragmentation of the resulting oxetanes, metal alkylidene-mediated strategies, [3 + 2]-cycloaddition approaches with strained hydrazines as organocatalysts, Lewis acid-mediated and Lewis acid-catalyzed strategies relying on the formation of intermediate oxetanes, and protocols based on initial carbon–carbon bond formation between carbonyls and alkenes and subsequent Grob-fragmentations. The Review concludes with an overview of applications of these currently available methods for carbonyl–olefin metathesis in complex molecule synthesis. Over the past eight years, the field of carbonyl–olefin metathesis has grown significantly and expanded from stoichiometric reaction protocols to efficient catalytic strategies for ring-closing, ring-opening, and cross carbonyl–olefin metathesis. The aim of this Review is to capture the status quo of the field and is expected to contribute to further advancements in carbonyl–olefin metathesis in the coming years. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579550270346-5QPI7LDHDTOSVLL5HUGV/tropylium.gif Publications - Allen, J. M.; Lambert, T. H. J. Am. Chem. Soc. 2011, 133, 1260-1262. Tropylium ion mediated α-cyanation of amines is described. Even in the presence of KCN, tropylium ion is capable of oxidizing various amine substrates, and the resulting iminium ions undergo salt metathesis with cyanide ion to produce aminonitriles. The byproducts of this transformation are simply cycloheptatriene, a volatile hydrocarbon, and water-soluble potassium tetrafluoroborate. Thirteen total substrates are shown for the α-cyanation procedure, including a gram scale synthesis of 17β-cyanosparteine. In addition, a tropylium ion mediated oxidative aza-Cope rearrangement is demonstrated. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1596729249758-282AEG969U5P9AZAO92C/TAC+Li+battery+II.jpeg Publications - Ji, W.; Huang, H.; Zheng, D.; Zhang, X.; Ding, T.; Lambert, T. H.; Qu, D. Energy Stor. Mater. 2020, 32, 185-190. Safety concerns have severely impeded the practical application of high-energy-density lithium-based batteries. Dendrite growth and overcharging can lead to particularly catastrophic thermal failure. Here we report an organic cation, trisaminocyclopropenium (TAC), as a bi-functional electrolyte additive to suppress dendrite growth and offer reversible overcharge protection for metallic lithium-based batteries. During the Li plating process, TAC cations with aliphatic chains can form a positively charged electrostatic shield around Li protrusions, repelling the approaching Li+ and thereby attaining a more uniform plating. A two times longer cycle life of 300 h at 1 mA cm−2 is achieved in a Li|Li symmetric cell in comparison with the control. During the overcharging process, the redox-active TAC can repeatedly shuttle between two electrodes, maintaining the cell voltage within a safe value. A solid protection of 117 cycles (~1640 h) at 0.2 C with a 100% overcharge is achieved in a LiFePO4/Li4Ti5O12 cell. This study sheds fresh light on the ability of organic cations to build safer batteries. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/ff587328-ffc3-4653-bfe7-ed32a8d2dacd/Rickroll.jpg Publications - Bartholomew, A. K.; Stone, I. B.; Steigerwald, M. L.; Lambert, T. H.; Roy, X. J. Am. Chem. Soc. 2022, 144, 16773-16777. Direct conversion of solar energy to mechanical work promises higher efficiency than multistep processes, adding a key tool to the arsenal of energy solutions necessary for our global future. The ideal photomechanical material would convert sunlight into mechanical motion rapidly, without attrition, and proportionally to the stimulus. We describe crystals of a tetrahedral isocyanoazobenzene–copper complex that roll continuously when irradiated with broad spectrum white light, including sunlight. The rolling results from bending and straightening of the crystal due to blue light-driven isomerization of a highly twisted azobenzene ligand. These findings introduce geometrically constrained crystal packing as a strategy for manipulating the electronic properties of chromophores. Furthermore, the continuous, solar-driven motion of the crystals demonstrates direct conversion of solar energy to continuous physical motion using easily accessed molecular systems. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579615878119-KCE9IRU6PA2H459E2RPH/PCCP+silyl.jpg Publications - Radtke, M. A.; Lambert, T. H. Chem. Sci. 2018, 9, 6406–6410. The synthesis and characterization of silicon Lewis acid complexes that incorporate highly electron-deficient cyclopentadienes is reported. Several pentacarboxycyclopentadienyl and monocarboxytetracyanocyclopentadienyl complexes were prepared. A comparison of their reactivities for catalysis of the allylation of an electron-deficient benzaldehyde was established. The use of a monocarboxytetracyano silylium donor was shown to be effective for the allylation or arylation of a variety of electrophiles via an anion abstraction pathway. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579618372104-CON4WZT953SGSQY3TD9Z/benzocinnoline.gif Publications - Stone, I. B.; Jermaks, J.; MacMillan, S. N.; Lambert, T. H. Angew. Chem. Int. Ed. 2018, 57, 12494-12498. An organocatalytic oxidation platform that capitalizes on the capacity of hydrazines to undergo rapid autoxidation to diazenes is described. Commercially available benzo[c]cinnoline is shown to catalyze the oxidation of alkyl halides to aldehydes in a novel mechanistic paradigm involving nucleophilic attack, prototropic shift, and hydrolysis. The hydrolysis and reoxidation events occur readily with only adventitious oxygen and water. A survey of the scope of viable substrates is shown along with mechanistic and computational studies that give insight into this mode of catalysis. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579551143245-YL9C7KWQXAPHNSFLN2XR/Metathesis_calculations.gif Publications - Hong, X.; Liang, Y.; Griffith, A. K.; Lambert, T. H.; Houk, K. N. Chem. Sci. 2014, 5, 471-475. The mechanism of hydrazine-catalyzed carbonyl-olefin metathesis relying on a novel (3 + 2) strategy is studied by density functional theory (DFT) calculations. The origins of the special reactivity of cyclopropene in this transformation are revealed, and the reactivities of different alkenes in the (3 + 2) cycloadditions and cycloreversions are compared. It is found that the ease of distortion of reactants accelerates cycloadditions, and that the strain release is the controlling factor for cycloreversions. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579550569196-F7C0LK5I1DKKTFD7ZE0K/cyclopropenimine.gif Publications - Bandar, J. S.; Lambert, T. H. J. Am. Chem. Soc. 2012, 134, 5552-5555. Cyclopropenimines are shown to be a highly effective new class of enantioselective Brønsted base catalysts. A chiral 2,3-bis(dialkylamino)cyclopropenimine catalyzes the rapid Michael reaction of a glycine imine substrate with high levels of enantioselectivity. A preparative scale reaction to deliver 25 g of product is demonstrated, and a trivial large scale synthesis of the optimal catalyst is shown. In addition, the basicity of a 2,3-bis(dialkylamino)cyclopropenimine is measured for the first time and shown to be approximately equivalent to the P1-tBu phosphazene base. An X-ray crystal structure of the protonated catalyst is shown along with a proposed mechanistic and stereochemical rationale. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579614902840-RILR2ICR1Q3269DOFDW4/polyelectrolyte.gif Publications - Jiang, Y.; Freyer, J. L.; Cotanda, P.; Brucks, S. D.; Killops, K. L.; Bandar, J. S.; Torsitano, C.; Balsara, N. P.; Lambert, T. H.; Campos, L. M. Nature Commun. 2015, 6, 5950. Versatile polyelectrolytes with tunable physical properties have the potential to be transformative in applications such as energy storage, fuel cells and various electronic devices. Among the types of materials available for these applications, nanostructured cationic block copolyelectrolytes offer mechanical integrity and well-defined conducting paths for ionic transport. To date, most cationic polyelectrolytes bear charge formally localized on heteroatoms and lack broad modularity to tune their physical properties. To overcome these challenges, we describe herein the development of a new class of functional polyelectrolytes based on the aromatic cyclopropenium ion. We demonstrate the facile synthesis of a series of polymers and nanoparticles based on monomeric cyclopropenium building blocks incorporating various functional groups that affect physical properties. The materials exhibit high ionic conductivity and thermal stability due to the nature of the cationic moieties, thus rendering this class of new materials as an attractive alternative to develop ion-conducting membranes. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/3632381a-83ef-4711-b9b8-f0f1b7703dfa/sulfide+solid+state.jpg Publications - Ji, W.; Zhang, X.; Xin, L.; Luedtke, A.; Zheng, D.; Huang, H.; Lambert, T. H.; Qu, D. Energy Stor. Mater. 2022, 45, 680-686. All-solid-state batteries (ASSBs) have become increasingly attractive recently due to their better safety and prospective long-term stability compared with conventional liquid batteries. However, obtaining a sustainable cathode candidate to match the solid electrolyte with regards to operating potential, chemical compatibility, and mechanical property is still an open challenge. Herein, the chemical incompatibility of quinone-based active materials and sulfide-based electrolyte were unveiled for the first time through a heteroconjugate addition reaction mechanism. To develop a quinone cathode customized for sulfide-based ASSBs, poly-(anthraquinonyl sulfide)-graphene (PAQS-G) nanocomposite was reported. The stable polymer framework of PAQS can protect the quinone redox center by preventing nucleophilic attack from sulfide-based solid electrolytes. The graphene additives can ameliorate redox kinetics and improve active material utilization. The PAQS-G cathode exhibited a specific capacity of ∼178 mAh g−1 and a high material utilization of ∼79%. Excellent cycling stability was achieved with 94 % capacity after 200 cycles in lithium batteries and 95.5 % capacity after 300 cycles in sodium batteries at 0.1C rate, respectively. A promising potential for energy storage applications was demonstrated. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579616753834-1YWM6MJGAN63DMKQDV83/TAC+electrophoto.jpg Publications - Huang, H.; Strater, Z. M.; Rauch, M.; Shee, J.; Sisto, T. J.; Nuckolls, C.; Lambert, T. H. Angew. Chem. Int. Ed. 2019, 58, 13318-13322. Visible‐light photocatalysis and electrocatalysis are two powerful strategies for the promotion of chemical reactions. Here, these two modalities are combined in an electrophotocatalytic oxidation platform. This chemistry employs a trisaminocyclopropenium (TAC) ion catalyst, which is electrochemically oxidized to form a cyclopropenium radical dication intermediate. The radical dication undergoes photoexcitation with visible light to produce an excited‐state species with oxidizing power (3.33 V vs. SCE) sufficient to oxidize benzene and halogenated benzenes via single‐electron transfer (SET), resulting in C−H/N−H coupling with azoles. A rationale for the strongly oxidizing behavior of the photoexcited species is provided, while the stability of the catalyst is rationalized by a particular conformation of the cis‐2,6‐dimethylpiperidine moieties. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579614971473-HJXZJJP095D7GNEMMS3J/phasetransfer.gif Publications - Bandar, J. S.; Tanaset, A.; Lambert, T. H. Chem. Eur. J. 2015, 21 , 7365-7368. This work establishes the cyclopropenium ion as a viable platform for efficient phase‐transfer catalysis of a diverse range of organic transformations. The amenability of these catalysts to large‐scale synthesis and structural modification is demonstrated. Evaluation of the molecular structure of an optimal catalyst reveals some unique structural features of these systems. Finally, a discussion of electronic charge distribution underscores an important consideration for catalyst design. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579618048277-5IIVI63JSVK49D15EBQA/quinoline+RCCOM.png Publications - Zhang, Y.; Sim, J. H.; MacMillan, S. N.; Lambert, T. H. Org. Lett. 2020, 22, 6026-6030. Preprint: ChemRxiv, https://doi.org/10.26434/chemrxiv.11342477.v1 The synthesis of 1,2-dihydroquinolines by the hydrazine-catalysed ring-closing carbonyl-olefin metathesis (RCCOM) of N-prenylated 2-aminobenzaldehydes is reported. Substrates with a variety of substitution patterns are shown, and the compatibility of these conditions with a range of additives is demonstrated. With an acid-labile protecting group on the nitrogen atom, in situ deprotection and autoxidation furnishes quinolines. In comparison to related oxygen-containing substrates, the cycloaddition step of the catalytic cycle is shown to be slower, but the cycloreversion is found to be more facile. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1596728858741-PTJJJL8INPH14NMSXXON/TAC+Li+battery.jpeg Publications - Ji, W.; Huang, H.; Huang, X.; Zhang, X.; Zheng, D.; Ding, T.; Chen, J.; Lambert, T. H.; Qu, D. J. Mat. Chem. A 2020, 8, 17156-17162. Ni-rich layered cathode materials are at the forefront to be deployed in the high energy density Li-ion batteries for the automotive market. However, the intrinsic poor structural and interfacial stability during overcharging could trigger violent thermal failure, which severely limits their wide application. To protect the Ni-rich cathode from overcharging, we firstly report a redox-active cation, thioether-substituted diaminocyclopropenium, as an electrolyte additive to limit the cell voltage within the safe value during overcharging. The organic cation demonstrates a record-breaking electrochemical reversibility at ~4.55 V versus Li+/Li and solubility (0.5 M) in carbonate-based electrolyte. The protection capability of the additive was explored in two cell chemistries: a LiNi0.8Co0.15Al0.05O2/graphite cell and a LiNi0.8Co0.15Al0.05O2/silicon-graphene cell with an areal capacity of ~2.2 mAh cm-2 and ~3 mAh cm-2, respectively. With 0.2 M addition, the LiNi0.8Co0.15Al0.05O2/graphite cell survived 54 cycles at 0.2 C with 100% overcharge. Moreover, the cell can carry an utmost 4.4 mA cm-2 (2 C) with 100% overcharge and a maximum capacity of 7540% SOC at 0.2 C. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/c2704f86-bf70-436a-9a66-6b4b5b7fb155/Nature_oxygenations.png Publications - Shen, T.; Li, Y.-L.; Ye, K.-Y.; Lambert, T. H. Nature 2023, 614, 275-280. Oxygen-containing functional groups are nearly ubiquitous in complex small molecules. The installation of multiple C–O bonds by the concurrent oxygenation of contiguous C–H bonds in a selective fashion would be highly desirable but has largely been the purview of biosynthesis. Multiple, concurrent C–H bond oxygenation reactions by synthetic means presents a challenge, particularly because of the risk of overoxidation. Here we report the selective oxygenation of two or three contiguous C–H bonds by dehydrogenation and oxygenation, enabling the conversion of simple alkylarenes or trifluoroacetamides to their corresponding di- or triacetoxylates. The method achieves such transformations by the repeated operation of a potent oxidative catalyst, but under conditions that are sufficiently selective to avoid destructive overoxidation. These reactions are achieved using electrophotocatalysis, a process that harnesses the energy of both light and electricity to promote chemical reactions. Notably, the judicious choice of acid allows for the selective synthesis of either di- or trioxygenated products. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/302f6c1a-5331-4575-98d5-570793c176e8/pdhf.jpg Publications - Spring, S.; Hsu, J.; Sifri, R.; Yang, S.-M.; Cerione, C.; Lambert, T. H.; Ellison, C.; Fors, B. J. Am. Chem. Soc. 2022, 144, 15727-15734. Creation of strong and tough plastics from sustainable and biorenewable resources is a significant challenge in polymer science. This challenge is further complicated when attempting to make these materials using an economically viable process, which is often hindered by the production and availability of chemical feedstocks and the efficiency of the monomer synthesis. Herein, we report the synthesis and characterization of a strong thermoplastic made from 2,3-dihydrofuran (DHF), a monomer made in one step from 1,4-butanediol, a bioalcohol already produced on the plant scale. We developed a green, metal-free cationic polymerization to enable the production of poly(2,3-dihydrofuran) (PDHF) with molecular weights of up to 256 kg/mol at room temperature. Characterization of these polymers showed that PDHF possesses high tensile strength and toughness (70 and 14 MPa, respectively) comparable to commercial polycarbonate, high optical clarity, and good barrier properties to oxygen, carbon dioxide, and water. These properties make this material amenable to a variety of applications, from food packaging to high strength windows. Importantly, we have also developed a facile oxidative degradation process of PDHF, providing an end-of-life solution for PDHF materials. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/759d3a54-8214-49f0-b44e-4a53d16fb8eb/azadifunct.jpeg Publications - Kundu, G.; Lambert, T. H. J. Am. Chem. Soc. 2024, 146, 1794-1798. A method to functionalize two vicinal C–H bonds of saturated azaheterocycles is described. The procedure involves subjecting the substrate to a mixture of hydrochloric acid, acetic acid, and acetic anhydride in an undivided electrochemical cell at a constant current, resulting in stereoselective conversion to the corresponding α-acetoxy-β-chloro derivative. The α-position can be readily substituted with a range of other groups, including alkyl, aryl, allyl, alkynyl, alkoxy, or azido functionalities. Furthermore, we demonstrate that the β-chloro position can be engaged in Suzuki cross-coupling. This protocol thus enables the rapid diversification of simple five-, six-, and seven-membered saturated azaheterocycles at two adjacent positions. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579381837898-6NM4BSN59XKF1J7FRWH9/ketonylation.gif Publications - Ambrosini, L. A.; Cernak, T. A.; Lambert, T. H. Synthesis - Featured Article 2010, 870-881. The first oxidative formylation and oxidative ketonylation of alkenylamines and alkenyl alcohols is demonstrated. A range of substrates that participate in this process are provided. Oxidative formylation was found to proceed optimally with the use of triphenylsilane as the hydride source. Oxidative ketonylation was feasible with a number of organometallic partners, especially dialkylzinc or organostannanes. An interesting finding regarding the fate of various acylpalladium intermediates is discussed. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579550834009-93MM95UDJ83U54TBUTKL/mesylation.gif Publications - Nacsa, E. D.; Lambert, T. H. Org. Lett. 2013, 15, 38-41. The cyclopropenone catalyzed nucleophilic substitution of alcohols by methanesulfonate ion with inversion of configuration is described. This work provides an alternative to the Mitsunobu reaction that avoids the use of azodicarboxylates and generation of hydrazine and phosphine oxide byproducts. This transformation is shown to be compatible with a range of functionality. A cyclopropenone scavenge strategy is demonstrated to aid purification. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579550649254-0XK9D4LMSG4XR536WCQ2/metathesis.gif Publications - Griffith, A. K.; Vanos, C. M.; Lambert, T. H. J. Am. Chem. Soc. 2012, 134, 18581-18584. The development of a catalytic carbonyl-olefin metathesis strategy is reported, in the context of the ring-opening metathesis of cyclopropenes with aldehydes using a simple hydrazine catalyst. The key to this reaction is a conceptual blueprint for metathesis chemistry that forgoes the traditional reliance on [2 + 2] cycloaddition modes in favor of a [3 + 2] paradigm. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1583427918610-4K08ELM7T3PGNG8ZQIW1/ionic+liquids.gif Publications - Litterscheidt, J.; Bandar, J. S.; Ebert, M.; Forschner, R.; Bader, K.; Lambert, T. H.; Frey, W.; Bühlmeyer, A.; Brändle, M.; Schulz, F.; Laschat. S. Angew. Chem. Int. Ed. 2020, 59, 10557-10565. Aminocyclopropenium ions have raised much attention both as organocatalysts as well as redoxactive polymers. The self‐assembly of amphiphilic aminocyclopropenium ions remains challenging however. Here the first deltic ionic liquid crystals based on aminocyclopropenium ions have been developed. Differential scanning calorimetry (DSC), polarizing optical microscopy (POM) and X‐ray diffraction (WAXS, SAXS) provided insight into the unique self‐assembly and nanosegregation of these liquid crystals. While the combination of small headgroups with linear p ‐alkoxyphenyl units led to bilayer‐type smectic mesophases, wedge‐shaped units resulted in columnar mesophases. Upon increasing the size and polyphilicity of the aminocyclopropenium headgroup again a lamellar phase was formed. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/6470dffc-a92b-4846-bcec-416154312907/diazenecoupling.jpeg Publications - Steiniger, K. A.; Lamb, M. C.; Lambert, T. H. J. Am. Chem. Soc. 2023, 145, 11524-11529. A method for C(sp3)–C(sp3) cross-coupling of amines is described. Primary amines are converted to 1,2-dialkyldiazenes by treatment with O-nosylhydroxylamines in the presence of atmospheric oxygen. Denitrogenation of the diazenes with an iridium photocatalyst then forges the C–C bond. The substrate scope accommodates a broad latitude of functionality, including heteroaromatics and unprotected alcohols and acids. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579614809733-P85KXNWQOAU2SSYU09HA/SAR+cyclopropenimines.gif Publications - Bandar, J. S.; Barthelme, A. P.; Mazori, A. Y.; Lambert, T. H. Chem. Sci. 2015, 6, 1537-1547. We recently demonstrated that chiral cyclopropenimines are viable Brønsted base catalysts in enantioselective Michael and Mannich reactions. Herein, we describe a series of structure–activity relationship studies that provide an enhanced understanding of the effectiveness of certain cyclopropenimines as enantioselective Brønsted base catalysts. These studies underscore the crucial importance of dicyclohexylamino substituents in mediating both reaction rate and enantioselectivity. In addition, an unusual catalyst CH⋯O interaction, which provides both ground state and transition state organization, is discussed. Cyclopropenimine stability studies have led to the identification of new catalysts with greatly improved stability. Finally, additional demonstrations of substrate scope and current limitations are provided herein. https://www.cyclopropenium.com/home daily 1.0 2023-06-01 https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/705a752e-a7ea-4240-bb87-545711a2f5a3/group052023.png Home https://www.cyclopropenium.com/com daily 0.75 2022-05-18 https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1594829120807-WT1NEB5JAM6GUINFUFEZ/image-asset.gif COM - ROCOM of Norbornenes With the help of computational design, we have identified a second-generation catalyst that allows for the ROCOM of norbornenes (Chem. Sci. 2020, 11, 7884). Further catalyst optimizations should enable the expansion to other, less-strained olefins. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/7dcc06c8-4962-4b9a-a48e-93b8c41bb5c5/cyclopropene+ROMP.jpg COM - A New System for Olefin Metathesis and ROMP The same logic that enables carbonyl-olefin metathesis can be applied to achieve olefin metathesis without the need for metals. We demonstrated this idea with the hydrazonium-mediated ring-opening metathesis polymerization (ROMP) of cyclopropenes in a collaborative paper with Brett Fors (Angew. Chem. Int. Ed. 2022, 61, Early view). https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1594828533984-GX9AOEXHHQGJ4C0T8Q9Q/COM.png COM - Catalytic Carbonyl-Olefin Metathesis Double bond metathesis reactions, especially catalytic olefin metathesis and the Wittig reaction, have had a large impact on the field of chemical synthesis. Despite an equally high synthetic potential, carbonyl-olefin metathesis has seen relatively little progress until very recently, particularly in the context of catalysis. Our group developed the first catalytic strategy for carbonyl-olefin metathesis by using a paradigm of [3+2] cycloaddition/cycloreversion rather than the ubiquitous [2+2] manifold employed by existing strategies. The catalytic design centered on the use of simple symmetric hydrazines as catalysts, which effect metathesis through a sequence of reversible condensation and cycloaddition steps. For a review on this catalysis, see SynLett 2019, 30, 1954. For a general review on carbonyl-olefin metathesis we published with Corinna Schindler, see Chem. Rev. 2021, 121, 9359. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1594829359741-RTDRTBHK3JBCH7QP10BL/Yunfei-TS.gif COM - Ring-Closing Carbonyl-Olefin Metathesis We have also shown that hydrazine catalysis can be used for ring-closing carbonyl-olefin metathesis (RCCOM), for example to generate 2H-chromenes (ACS Catal. 2019, 9, 9259), dihydroisoquinolines (Org. Lett. 2020, 22, 6026), or polycyclic heteroaromatics (Chem. Sci. 2022, 13, 2418). Particularly for the latter work, we showed that hydrazine catalysis is compatible with strongly Lewis basic functionality, which strongly inhibits acid-catalyzed approaches. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/56b042d8-5333-4ab2-8baf-fd95e4a31d94/cyclobutene.jpg COM - ROCOM of Small-Ring Olefins We first reported the implementation of this strategy with the ring-opening carbon-olefin metathesis (ROCOM) of cyclopropenes using a [2.2.1]-bicyclic hydrazine as the catalyst (J. Am. Chem. Soc. 2012, 134, 18581; Chem. Sci. 2014, 5, 471). More recently, we extended this concept to cyclobutenes, which delivers formal Claisen rearrangement products (ACS Catal. 2022, 12, 4813). https://www.cyclopropenium.com/news daily 0.75 2023-04-17 https://www.cyclopropenium.com/photos daily 0.75 2023-06-01 https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/0d0c416e-95a4-4fb2-8f4e-52fa36f6fb7e/Nobel1.png Photos - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580919015870-4NRBW6HFYOVKHJK5SXCW/group+night+out.jpeg Photos https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/b1924243-9937-49e6-9f14-30d97f3b84c8/Nobel2.png Photos - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/701c63d9-4a28-4f49-ad1f-54c651b6f60c/birthday_0623.png Photos - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580919086102-7KIG9Z3VVRAHWOMN2VV8/He_celebration.jpeg Photos https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1175a601-a0a2-47d8-bcfe-c1a11652d929/groupphoto2021.jpg Photos - Make it stand out Whatever it is, the way you tell your story online can make all the difference. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580919235298-4JWHQZIH9584F1WDV7O9/he+paper+toast.jpeg Photos https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580919266792-NPPX8M31QUUAYGVCA5AY/Zack+defense.jpeg Photos https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580919300690-SOMMAUYEZW13T3PDDR9S/Dmac+Jlong.jpeg Photos https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580919953106-XS5R395EP7WXW47O3NFL/japan+trip.JPG Photos https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580920019649-5ILHFSQKJ4XJZR2RLQBT/Matcha.JPG Photos https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580919999939-HZQ5HK8JIXGBGKPFUGBI/ishhihara.JPG Photos https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580921059761-5IEM76MV1OCZUXEAB63I/vienna.jpeg Photos https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580921094222-G3FK8I1EI283UZPEN0UU/maxplank.jpeg Photos https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580921120329-Y9P8P6UV0P5LXH1I8381/london.jpeg Photos https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580921144321-8AA3UDOQBQDNJVVH3ZMO/oxford.jpeg Photos https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1581348670735-DS580L7138MKDCN3SEYA/Caroline_Ilana.jpeg Photos Lambert group upstate meets Lambert group downstate. https://www.cyclopropenium.com/pccps daily 0.75 2022-10-25 https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580840554211-SB5ET85YAEA2LM40803J/second+fig.png PCCPs - Simple Access to PCCP Derivatives To maximize the utility of these species, we devised simple procedures to convert the Diels PCCP, which can be made on large scale (Synthesis 2019, 51, 1135), into a variety of derivatives including chiral esters, amides, and highly stabilized fluorinated species (Org. Lett. 2017, 19, 4227). https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580840376261-3HCKBGTTNUXARRG55NU5/first+fig.png PCCPs - PCCPs Motivated by a desire to develop a new class of strong acid catalysts that would be easy to synthesize, trivial to derivatize, and structurally distinct, we showed that pentacarboxycyclopentadienes or “PCCPs” were a viable aromatic ion-based option (Science 2016, 351, 961). The parent compound—the penta methyl ester—was originally made by Otto Diels. We found that a simple transesterification of this readily available material could furnish chiral derivatives that were highly effective for asymmetric catalysis. For example, we showed that the PCCP acid derived from menthol was an effective catalyst for enantioselective Mannich and oxocarbenium aldol reactions. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580841523283-LEVAWEXZX6U33KE7HE88/third+fig.png PCCPs - Enantioselection via a Helically Chiral Anion We found that chiral PCCPs could catalyze the enantioselective inverse electron-demand Diels-Alder cycloaddition of oxocarbenium ions (J. Am. Chem. Soc. 2018, 140, 3523). Working with the group of Prof. Mathew Vetticatt at SUNY-Binghamton, we discovered that the asymmetric induction occurs by way of a helically chiral PCCP anion. Among the several key organization elements implicated by our study was a C–H to aryl anion interaction between the vinyl ether component and the cyclopentadienyl anion ring. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/a8252b32-5a4a-4fca-a433-94e3fe62c8d2/Fors+HBD.jpg PCCPs - Cationic Polymerization Under Ambient Conditions In collaboration with Brett Fors and his group, we have found that PCCPs initiate controlled cationic polymerizations of vinyl ethers, even in the presence of impurities such as water (J. Am. Chem. Soc. 2019, 141, 10605). With the addition of a three-point hydrogen bond donor, the rates of polymerization are greatly increased but without decreasing robustness to impurities, leading to the ability to make high molecular weight polymers (Angew. Chem. Int. Ed. 2021, 60, 4535). Recently, this chemistry has been applied to the synthesis of high molecular weight poly(2,3-dihydrofuran) (J. Am. Chem. Soc. 2022, 144, 15727) and to the development of a moisture-tolerant cationic RAFT polymerization (Polymer Chem. 2022, 13, Advance Article. https://www.cyclopropenium.com/electrophotocatalysis daily 0.75 2022-10-25 https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/b1d416fb-96c0-4712-8939-d18fa8d7e29d/diamination+revised.jpg Electrophotocatalysis - Amination of C–H Bonds TAC electrophotocatalysis can be used to achieve a Ritter-type amination of benzylic C–H bonds, using simple acetonitrile as the nitrogen source (J. Am. Chem. Soc. 2021, 143, 8597). With modified conditions, a remarkable vicinal C–H diamination occurs, leading to the production of 3,4-dihydroimidazoles from the saturated precursors (Science 2021, 371, 620). https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/da28d605-5328-4e31-84d8-614e31f398d1/acetoxyhydroxylation_TOC.jpg Electrophotocatalysis - Aryl Olefin Functionalization Electrophotocatalysis can also lead to the difunctionalization of aryl olefins, even though such substrates can be sensitive to oxidizing and acidic conditions. For example, we have shown the acetoxyhydroxylation (J. Am. Chem. Soc. 2021, 143, 7247) and the regiodivergent aminooxygenation (J. Am. Chem. Soc. 2022, 144, ASAP) of aryl olefins. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1581449606874-AFWQT2ZWRPNWE2XFJUT9/reductive.png Electrophotocatalysis - Reductive Electrophotocatalysis In collaboration with the group of Prof. Song Lin, we have also demonstrated electrophotocatalysis is effective for realizing very strongly reducing conditions as well (J. Am. Chem. Soc. 2020, 142, 2087). Specifically, we showed that the mild cathodic reduction of dicyanoanthracene generates the corresponding radical anion, which when photoexcited is nearly as reducing as lithium metal. The secret sauce behind both the oxidative and reductive electrophotocatalytic strategies is the use of open-shell, doublet photocatalytic intemediates to achieve extreme redox potentials with only mild inputs of light and electrical energy. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580072784002-ZV8ZWURP9BST0H391YRZ/electrophotocatalysis.png Electrophotocatalysis - Electrophotocatalysis Both photocatalysis and electrocatalysis have had a transformational effect on organic synthetic chemistry over the last decade. Given this impact, a natural question to ask is how might the energy of light and electricity be combined within a single catalytic process? Until recently, very few examples of such “electrophotocatalysts” had been described. We have shown that trisaminocyclopropenium (TAC) ions can serve as electrophotocatalysts for potent oxidation reactions (Angew. Chem. Int. Ed. 2019, 58, 13318). This catalysis is based on the mild electrochemical oxidation of the TAC to form a stable radical dication, which can then be photoexcited with visible light to generate an excited state with an estimated reduction potential of well over 3 V. We have shown that this level of oxidizing power is enough to functionalize benzene and halobenzenes cleanly and selectively. We have also shown that ethers can be electrophotocatalytically functionalized with high regioselectivity (J. Am. Chem. Soc. 2020, 142, 1698). A key aspect of the TAC catalyst is the cis-dimethylpiperidine units, which protect the ion from photodegradation due to its all-cis conformation. For a perspective article on Electrophotocatalysis, see J. Am. Chem. Soc. 2022, 144, 12567). https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1581450253130-XHZ9C7SOSNDFL30W1YWM/image-asset.png Electrophotocatalysis - Electrophotocatalytic SnAr In addition to the open-shell work, we have also found that potent photooxidants like DDQ can be engaged as useful electrophotocatalysts as well (Angew. Chem. Int. Ed. 2020, 59, 658). For example, we showed that classically unactivated aryl fluorides can undergo nucleophilic substitution with pyrazoles, alcohols, or other nucleophiles at room temperature and without strong base (in fact in the presence of acetic acid). The peculiarities of the process enabled us to achieve selective SnAr reactions of chlorofluorobenzene in the presence of either an electron-deficient arene (2,4-dinitrofluorobenzene) or an electron-rich arene (4-methoxyfluorobenzene). https://www.cyclopropenium.com/cyclopropenimines daily 0.75 2020-01-26 https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580483199597-DQ8MJKIDSRI8KZP96WSZ/basicity.png Cyclopropenimines - Cyclopropenimines Our group has introduced cyclopropenimines as a novel class of strong organic Brønsted base (J. Am. Chem. Soc. 2012, 134, 5552; J. Am. Chem. Soc. 2013, 135, 11799). The signature feature of the cyclopropenimine scaffold is the presence of a latent cyclopropenium ion, which is revealed upon protonation of the imino nitrogen. As the smallest ring system that satisfies Hückel’s rules for aromaticity, the 2π-electron cyclopropenium ion provides substantial resonance stability to the conjugate acid of the cyclopropenimine. In comparison to the analogous guanidines, this additional aromatic stabilization renders cyclopropenimines significantly more basic, and places them directly on par with the phosphazenes in terms of basicity. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580483261588-ELLO1B7PQ7INTIV7DOVR/cyclopropenimine+structure.png Cyclopropenimines - Enantioselective Catalysis One of our primary interests with cyclopropenimines has been in regard to their capacity to serve as highly effective enantioselective Brønsted base catalysts. An interesting finding for this program arose from a detailed mechanistic and computational study, performed in collaboration with the group of Prof. Mathew Vetticatt at SUNY-Binghamton, which revealed several notable features of these structures and provided crucial insight into their high efficiencies (J. Am. Chem. Soc. 2014, 136, 10700 and Chem. Sci. 2015, 6, 1537). Specifically, we discovered the profound impact the dicyclohexylamino substituents have on the efficiency of this catalyst. A combination of X-ray crystallography and computational analysis revealed the unique role these substituents play. Due to their significant steric demand, the four cyclohexyl substituents do not have the freedom of rotation that less demanding substituents have, but are instead geared to one another. This restriction reinforces a long-range, noncovalent C-H---O interaction between one of the cyclohexylamino a-C-H bonds and the hydroxyl group, which in turn constrains the conformational freedom of this key hydrogen bonding functionality. In this way, facile transition state organization is achieved, helping to enable high levels of enantioselection. In addition to our first generation catalyst, we have reported an improved, second generation catalyst that offers significantly enhanced reactivity, selectivity, and stability (Chem. Sci. 2015, 6, 1537). https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580482190679-FOO6DLVQ33OANBZRML4T/higher+order.png Cyclopropenimines - Higher-Order Cyclopropenimine Superbases We have also developed a series of higher-order superbases using cyclopropenimines (J. Am. Chem. Soc. 2015, 137, 10246). These species have enhanced basicities and unique structural characteristics, which serve to significantly expand the repertoire of this class of molecules. Many of these bases are also reasonably easy to synthesize and handle, especially the GC2 bases. https://www.cyclopropenium.com/group-members daily 0.75 2024-11-13 https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/efbecec3-5236-44fe-94f3-3d3cc0451222/Trigoura_Leslie.jpg Group Members - Leslie Trigoura BS, William Paterson University of New Jersey (2019) MS, William Paterson University of New Jersey (2021) https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/df39e431-b1e2-48d7-82ac-defbc03e9580/Fan_Chengyi.jpg Group Members - Chengyi Fan BS, Chemistry, Purdue (2024) https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1603909705797-25FE4EEMUCYVXOKYVX5L/Julian.jpeg Group Members - Julian Kellner-Rogers BS, Chemistry, Ithaca College (2020) https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1603368261113-R5CXODLLKLN1KYOE3T5S/JoseDeLaRosa.jpg Group Members - Jose De La Rosa BS, Chemistry, Rutgers (2020) https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/2b64257b-4d94-451e-b0c4-06a8b5fe6b1a/Goclon_Jakub.jpg Group Members - Jakub Goclon Tobias Keene, D.D.S. Hailing from Richmond, Virginia, Dr. Tobias Keene brings a bit of unabashed Southern hospitality to all his patients. He moved to Washington, D.C. over thirty years ago as a freshman at Ivy College. Right after graduation, he attended World University’s School of Dentistry. Before opening Keene Dental in 1994, he worked for free clinics and some of the finest practices in the District. He is part of the 123 Dental Association and stays up-to-date on the latest dental discoveries. When not striving to keep his patients happy and healthy, he’s enjoys hiking with his family in Rock Creek Park. https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/adbcc2c2-568b-4161-93e6-35b63aa23a0a/Wu_Jason.jpg Group Members - Jason Wu BS, UCLA (2021) https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/bb30667f-0a3a-4314-b6ff-33a117856be6/lamb_matthew.jpg Group Members - Matthew Lamb BS, Franklin and Marshall College (2021) https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/ba27a2d6-80fa-4852-82c7-cd85c45ef822/Hoshi_Kaede.jpg Group Members - Kaede Hoshi BS, University of California at Berkeley (2021) https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1579369544107-PCVWVF50RDIKN3KWS9W4/Zoe.png Group Members - Zoe Meng BS Chemistry, UC-San Diego (2019) https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/7c6a330d-eef0-4dcd-9a91-82ddc47e0cc7/Oku_Naoki.jpg Group Members - Dr. Naoki Oku Ph.D. Okayama University (2024) https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/3fd6a4b8-eccf-482c-9e27-8abfc43a3307/Ariana.jpeg Group Members - Ariana Wanvig Dot Cornell 2025 https://www.cyclopropenium.com/research daily 0.75 2021-11-23 https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580064443644-L4S5J3UNW8NLDIM5CME7/222.gif Research - Catalytic carbonyl-olefin metathesis New reactions and strategies for complex molecule synthesis https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580067869916-SR1WPGG1RLLUAD0GFWHT/TAC+SOMO.png Research - Electrophotocatalysis Combining light and electricity to achieve very high redox potentials https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580069492538-MUH1QNGLJJ63Y5LOME2O/PCCP_TS-1.gif Research - Pentacarboxycyclopentadienes (PCCPs) A novel class of strong carbon acids https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/1580067439193-YUHFXSPNNR2RXU9ALMXZ/movieLR+copy.gif Research - Cyclopropenimines A new class of high potency superbase https://www.cyclopropenium.com/aromatic-ions daily 0.75 2020-01-26 https://images.squarespace-cdn.com/content/v1/5c5a514d65019f01a2cb2be5/1562685656804-Q9GBRN0NAL6DVNVQUCHS/20140301_Trade-151_0124-copy.jpg Aromatic Ions - Aromatic Ions Coming soon! 1/26/2020 https://www.cyclopropenium.com/about-tristan daily 0.75 2023-07-19 https://images.squarespace-cdn.com/content/v1/5e232ba9ee2964277b03178e/a96e8a9d-8946-41c8-8b37-7bc6fc532742/Lambert+Tristan+20230412+Chemistry+07+small.JPG About Tristan - Tristan H. Lambert Tristan was born in Madison, WI, in 1976 and grew up in the small town of Black Earth. He graduated from the University of Wisconsin at Platteville in 1998 with a B.S. in chemistry. The same year he began graduate studies at UC-Berkeley as one of Dave MacMillan’s first students. In 2000, Tristan moved with the MacMillan group to Caltech where he earned his Ph.D. for the development and application of novel Claisen rearrangements. In 2004, he began postdoctoral studies with Sam Danishefsky at the Memorial Sloan-Kettering Cancer Center in New York. At Sloan-Kettering he completed a total synthesis of UCS1025A, a putative telomerase inhibitor. In 2006, Tristan accepted a faculty position in the Department of Chemistry at Columbia University. In 2011 he was promoted to Associate Professor and in 2016 to Full Professor. In January 2018, he moved to the Department of Chemistry and Chemical Biology at Cornell University where he now serves as Department Chair. In 2023, he was named the William T. Miller Professor of Chemistry. His research group focuses on the study of intriguing chemical building blocks such as aromatic ions and their application to problems in the areas of catalysis, reaction design, and polymers.