Enantio- and Diastereodivergent N-Heterocyclic Carbene/Nickel Dual-Catalyzed Umpolung Propargylic Substitutions of Enals
Lingzi Peng, Mingxu Wang, Jianming Huang, Chang Guo, Liu‐Zhu Gong, Jin Song
Abstract
The creation of full stereoisomers of an organic compound comprising multiple contiguous stereocenters with simultaneous control over both relative and absolute configurations remains a significant challenge in synthetic chemistry. Using a cooperative catalysis strategy, we established an N-heterocyclic carbene/nickel-catalyzed enantio- and diastereodivergent propargylation reaction to access 3,3′-disubstituted oxindoles, enabling the incorporation of internal alkyne functionality and the introduction of a single quaternary or vicinal quaternary/tertiary stereogenic center. By selecting the appropriate combination of catalyst chirality, all four potential stereoisomers of α-quaternary propargylated oxindoles were synthesized in a predictable and precise way with remarkable yields, diastereoselectivities, and enantioselectivities from identical starting materials. The synthetic utility of this method was demonstrated in the concise asymmetric total synthesis of (−)-debromoflustramine B and (−)-C (β-Me) -debromoflustramine B.