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We disclose herein an atroposelective synthesis of novel bridged biaryls containing medium-sized rings via N-heterocyclic carbene organocatalysis. The reaction starts with addition of the carbene catalyst to the aminophenol-derived aldimine substrate. Subsequent oxidation and intramolecular desymmetrization lead to the formation of 1,3-oxazepine-containing bridged biaryls in good yields and excellent enantioselectivities. These novel bridged biaryl products can be readily transformed into chiral phosphite ligands. Preliminary density function theory calculations suggest that the origin of enantioselectivity arises from the more favorable frontier molecular orbital interactions in the transition state leading to the major product. Agency for Science, Technology and Research (A*STAR) Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Submitted/Accepted version We acknowledge financial supports of the starting-up funding from Hunan Normal University, the National Natural Science Foundation of China (21901233, 22201071), 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 Tier1 Award (RG108/16, RG5/19, RG1/18), MOE AcRF Tier 2 (MOE2019-T2-2-117), MOE AcRF Tier 3 Award (MOE2018-T3-103); the Agency for Science, Technology and Research (A*STAR) under its A*STAR AMEIRG Award (A1783c0008, A1783c0010); GSK-EDB Trust Fund; Nanyang Research Award Grant, Nanyang Technological University; X.Z. acknowledges the support from IHPC, A*STAR, and thanks the Deputy Chief Executive Research Office (DCERO), A*STAR, for a Career Development Fund (CDF Project Number C210812008) for this work.

An enantioselective functionalization of the indole NH group is developed. The reaction stereoselectivity is controlled by an N-heterocyclic carbene catalyst that adds to an aldehyde moiety at the C7-carbon of indole. The NH group participating in the carbene-catalyzed reaction is part of the heteroaromatic rings of the indole substrate. Our reactions afford multicyclic products bearing pyrroloquinazoline or oxazinoindole scaffolds widely present in bioactive molecules. Our study will encourage further exploration of carbene-catalyzed reactions of aromatic molecules and asymmetric transformation of heteroatoms in various functional molecules. NRF (Natl Research Foundation, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Accepted version

A new catalytic approach for rapid asymmetric access to spirocycles is disclosed. The reaction involves a carbene- and thiourea-cocatalyzed desymmetrization process with the simultaneous installation of a spirocyclic core. The use of a thiourea cocatalyst is critical to turn on this reaction, as no product was formed in the absence of a thiourea. Our study constitutes the first success in the carbene-catalyzed enantioselective synthesis of all-carbon spirocycles. The reaction products can be readily transformed into sophisticated multicyclic molecules and chiral ligands. NRF (Natl Research Foundation, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Accepted version

A carbene and sulfinate co-catalyzed intermolecular Rauhut-Currier reaction between enals and nitrovinyl indoles is disclosed. The carbene catalyst activates the enal and the sulfinate co-catalyst activates the nitrovinyl indole. Both activation processes are realized via the formation of covalent bonds between the catalysts and substrates to generate catalyst-bound intermediates. The dual catalytic reaction affords azepino[1,2-a]indole products with excellent stereoselectivity. Our study demonstrates the unique involvement of sulfinate as an effective nucleophilic catalyst in activating electron-deficient alkenes for asymmetric reactions. This dual catalytic approach should also encourage future explorations of both sulfinate and carbene catalysts for new reactions. NRF (Natl Research Foundation, S’pore) ASTAR (Agency for Sci., Tech. and Research, S’pore) MOE (Min. of Education, S’pore) Accepted version

Facile and efficient conjugate additions of carbon nucleophiles, such as ?-dicarbonyl compounds and nitroalkanes, to 4-aryl-4-oxobut-2-enoates have been achieved under simple base catalysis. A variety of multi-functional ?-keto esters could be conveniently obtained in good to excellent yields with complete regioselectivity.