N-Heterocyclic carbene catalyzed radical coupling of aldehydes with redox-active esters

N-Heterocyclic carbene catalyzed radical reactions are challenging and underdeveloped. In a recent study, Ohmiya, Nagao and co-workers found that aldehyde carbonyl carbon centers can be coupled with alkyl radicals under NHC catalysis. An elegant aspect of this study is the use of a redox-active carboxylic ester that behaves as an single-electron oxidant to convert the Breslow intermediate into a radical adduct and concurrently release an alkyl radical intermediate as a reaction partner.NRF (Natl Research Foundation, S’pore)ASTAR (Agency for Sci., Tech. and Research, S’pore)MOE (Min. of Education, S’pore)Accepted versio

Exploring molecular complexity by N-heterocyclic carbene organocatalysis: new activation and reaction diversity

The development of catalytic synthetic approaches towards molecular complexity from simple materials continues to be an ultimate goal in synthetic chemistry. Over the past decades, N-heterocyclic carbene (NHC) organocatalysis has been extensively investigated to provide opportunities for a vast number of novel chemical transformations. Various activation modes and reactive intermediates enabled by NHC small-molecule catalysts, such as Breslow intermediates, (homo)enolates, acyl azoliums and their derived unsaturated azoliums exhibit great potential in the construction of complicated skeletons. This personal account will summarize our group's recent work in the exploration of new activation modes of NHC catalysis towards molecular complexity with a focus on the development and applications of NHC to achieve diversity and enantioselectivity in the preparation of functional molecules.Ministry of Education (MOE)Nanyang Technological UniversityNational Research Foundation (NRF)We acknowledge financial support from the National Natural Science Foundation of China (21772029, 21801051, 21961006, 22001173), National Natural Science Fund for Excellent Young Scientists Fund Program (Overseas), The 10 Talent Plan (Shicengci) of Guizhou Province ([2016]5649), the Science and Technology Department of Guizhou Province ([2019]1020, Qianke‐hejichu‐ZK[2021]Key033), the starting grant of Guizhou University [(2022)47)], Frontiers Science Center for Asymmetric Synthesis and Medicinal Molecules, Department of Education, Guizhou Province [Qianjiaohe KY (2020)004], the Basic and Applied Research Foundation of Guangdong Province (2019A1515110906), the Guizhou Province First‐Class Disci‐plines Project [(Yiliu Xueke Jianshe Xiangmu)‐GNYL(2017)008], Guizhou University of Traditional Chinese Medicine, and Guizhou University (China). Singapore National Research Foundation under its NRF Investigatorship (NRF‐NRFI2016‐06) and Competitive Research Program (NRF‐CRP22‐2019‐0002); the Ministry of Education, Singapore, under its MOE AcRF Tier 1 Award (RG7/20, RG5/19), MOE AcRF Tier 2 (MOE2019‐T2‐2‐117), MOE AcRF Tier 3 Award (MOE2018‐T3‐1‐003); Nanyang Research Award Grant, Chair Professorship Grant, Nanyang Technological University

NHC-catalyzed covalent activation of heteroatoms for enantioselective reactions

Covalent activation of heteroatoms enabled by N-heterocyclic carbene (NHC) organic catalysts for enantioselective reactions is evaluated and summarized in this review. To date, sulfur, oxygen, and nitrogen atoms can be activated in this manner to react with another substrate to construct chiral carbon–heteroatom bonds with high optical enantioselectivities. The activation starts with addition of an NHC catalyst to the carbonyl moiety (aldehyde or imine) of substrates that contain heteroatoms. The key in this approach is the formation of intermediates covalently bound to the NHC catalyst, in which the heteroatom of the substrate is activated as a nucleophilic reactive site.Ministry of Education (MOE)National Research Foundation (NRF)Published versionWe acknowledge financial support from the National Natural Science Foundation of China (21772029, 21801051, 21961006, 82360589, and 81360589), The 10 Talent Plan (Shicengci) of Guizhou Province ([2016]5649), the Guizhou Province Returned Oversea Student Science and Technology Activity Program [(2014)-2], the Science and Technology Department of Guizhou Province ([2018]2802, [2019]1020), the Program of Introducing Talents of Discipline to Universities of China (111 Program, D20023) at Guizhou University, Frontiers Science Center for Asymmetric Synthesis and Medicinal Molecules, Department of Education, Guizhou Province [Qianjiaohe KY (2020)004], and Guizhou University. We also acknowledge Singapore National Research Foundation under its NRF Investigatorship (NRFNRFI2016-06) and Competitive Research Program (NRFCRP22-2019-0002), the Ministry of Education, Singapore, under its MOE AcRF Tier 1 Award (RG108/16, RG5/19, RG1/18), MOE AcRF Tier 2 (MOE2019-T2-2-117), MOE AcRF Tier 3 Award (MOE2018-T3-1-003), the Agency for Science, Technology and Research (A*STAR) under its A*STAR AME IRG Award (A1783c0008, A1783c0010), Nanyang Research Award Grant, and Nanyang Technological University

N-heterocyclic carbene-catalyzed arene formation reactions

N-heterocyclic carbene-catalyzed reactions for the formation of aromatic compounds are reviewed. The reactions are subdivided into 4 types based on their activation modes. A brief summary on the achievements and the challenges remaining in N-heterocyclic carbene (NHC)-catalyzed arene construction processes is provided at the end of this review. An outlook into the future research direction within this field is also given based on our own opinion and knowledge on the trends of the development of NHC organocatalysis.Submitted/Accepted versio

N-Heterocyclic carbene catalyzed aza-benzoin reaction for access to α-aminoketone molecules containing benzothiazole fragments

An N-Heterocyclic carbene (NHC) catalyzed aza-benzoin reaction of benzothiazole-2-carboxaldehydes and N-sulfonylimines is reported for the first time. The target benzothiazole-containing aminoketone products bearing different substituents and substitution patterns can be obtained in good to excellent yields under mild conditions.Agency for Science, Technology and Research (A*STAR)Ministry of Education (MOE)National Research Foundation (NRF)Accepted versionWe acknowledge financial support from the National Natural Science Foundation of China (21772029, 21801051, 21961006, 22001173), The 10 Talent Plan (Shicengci) of Guizhou Province ([2016]5649), the Guizhou Province Returned Oversea Student Science and Technology Activity Program [(2014)-2], the Science and Technology Department of Guizhou Province ([2018]2802, [2019]1020, Qiankehejichu-ZK[2021]Key033), the Program of Introducing Talents of Discipline to Universities of China (111 Program, D20023) at Guizhou University, Frontiers Science Center for Asymmetric Synthesis and Medicinal Molecules, Department of Education, Guizhou Province [Qianjiaohe KY (2020)004], the Basic and Applied Research Foundation of Guangdong Province (2019A1515110906), the Guizhou Province First-Class Disciplines Project [(Yiliu Xueke Jianshe Xiangmu)-GNYL(2017)008], Guizhou University of Traditional Chinese Medicine, and Guizhou University (China). Singapore National Research Foundation under its NRF Investigatorship (NRF-NRFI2016-06), the Ministry of Education, Singapore, under its MOE AcRF Tier 1 Award (RG108/16, RG5/19, RG1/18), MOE AcRF Tier 3 Award (MOE2018-T3-1-003), the Agency for Science, Technology and Research (A*STAR) under its A*STAR AME IRG Award (A1783c0008, A1783c0010), GSK-EDB Trust Fund, Nanyang Research Award Grant, Nanyang Technological University

Organocatalytic enantioselective γ-aminoalkylation of unsaturated ester : access to pipecolic acid derivatives

The direct γ-carbon functionalization of α,β-unsaturated esters via N-Heterocyclic Carbene (NHC) catalysis is disclosed. This catalytically generated nucleophilic γ-carbon undergoes highly enantioselective additions to hydrazones. The resulting δ-lactam products can be readily transformed to optically enriched pipecolic acid derivatives

cis-Enals in N-heterocyclic carbene-catalyzed reactions : distinct stereoselectivity and reactivity

The first successful generation of cis-homoenolate equivalents from cis-enals under the catalysis of N-heterocyclic carbenes (NHCs) has been realized. The cis-homoenolate intermediates undergo effective reactions with α,β-unsaturated imines to afford chiral cyclic ketone products. Compared to the trans-enals, cis-enals show different stereoselectivities and new reactivity patterns

Enantioselective dual catalysis of N-heterocyclic carbene and hydrogen-bond donor organocatalysts

N-heterocyclic carbene (NHC) catalysis has become a versatile catalysis strategy for building molecules via unique reaction modes. Dual catalytic processes using NHCs in combination with additional modulating agents such as another organocatalyst or transition-metal catalyst have also been studied. The clear selection of cocatalysts has led to enhanced reactivity, increased yields, and/or improved stereoselectivity. This minireview is to provide readers with a brief overview of the development and applications of NHC and hydrogen-bond donor for dual catalytic reactions.We acknowledge financial support from the National Natural Science Foundation of China (No. 22001173), Basic and Applied Research Foundation of Guangdong (No. 2019A1515110906) and the Project of Department of Education of Guangdong Province (No. 2020KTSCX116), the Shenzhen Science and Technology Foundation (No. KQJSCX20180328100401788) and the Principal Foundation of SZU (No. 8570700000307)

Enantioselective Diels–Alder reactions of enals and alkylidene diketones catalyzed by N-heterocyclic carbenes

An electron-withdrawing group was introduced to the α-position of chalcones, and the resulting alkylidene diketones showed new reactivities with enals under the catalysis of N-heterocyclic carbenes (NHCs). Selective activation of enals affords enolate equivalents that undergo highly enantioselective intermolecular Diels–Alder reactions with the alkylidene diketones. No products that might have resulted from typical homoenolate pathways were observed

Rapid access to bicyclic δ-lactones via carbene-catalyzed activation and cascade reaction of unsaturated carboxylic esters

Carboxylic esters are an excellent choice of substrates in organic synthesis. Here we demonstrate that carbene-catalyzed activation of α,β-unsaturated ester can be developed to synthesize sophisticated multi-cyclic molecules in a single step cascade process. The iridoid-type lactone products are obtained with high stereo-selectivities, and can readily undergo further transformations.NRF (Natl Research Foundation, S’pore)MOE (Min. of Education, S’pore)Accepted versio