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

Abstract

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 C₂-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 η²-aldehyde η²-alkyne Ni five-centered transition state. We expected that the enantioselective η²-activation mode be widely applicable in other Ni-catalyzed carbonyl couplings.