Chemodivergent, enantio- and regioselective couplings of alkynes, aldehydes and silanes enabled by nickel/N-heterocyclic carbene catalysis

Divergent synthesis of valuable molecules through common starting materials and metal catalysis represents a longstanding challenge and a significant research goal. We here describe chemodivergent, highly enantio- and regioselective nickel-catalyzed reductive and dehydrogenative coupling reactions of alkynes, aldehydes, and silanes. A single chiral Ni-based catalyst is leveraged to directly prepare three distinct enantioenriched products (silyl-protected trisubstituted chiral allylic alcohols, oxasilacyclopentenes, and silicon-stereogenic oxasilacyclopentenes) in a single chemical operation. The use of a bulky C-2-symmetric N-heterocyclic carbene (NHC) ligand for nickel catalyst is the key to enable simultaneous exceptional control of stereo- and regioselectivity (up to 99% enantiomeric excess (ee), >99:1 regiomeric ratio (rr), >99:1 E/Z) and high efficiency (up to 99% yield). Computational studies elucidate the origin of chemodivergency and reveal the critical role of NHC in the enantioselectivity- and rate-determining oxidative cyclization step via an eta(2)-aldehyde eta(2)-alkyne Ni five-centered transition state. We expected that the enantioselective eta(2)-activation mode be widely applicable in other Ni-catalyzed carbonyl couplings. (c) 2024 Science China Press. Published by Elsevier B.V. and Science China Press. All rights are reserved, including those for text and data mining, AI training, and similar technologies.