Enantioselective Alkyl-Alkyl Coupling by Ni-Catalyzed Asymmetric Cross-Hydrodimerization of Alkenes

Abstract Saturated tertiary stereogenic carbon centers consist of much of the frameworks of small molecules and organic materials. Transition-metal-catalyzed asymmetric alkyl-alkyl bond-formation processes represent contemporary techniques for the straightforward and efficient construction of saturated tertiary stereogenic carbon centers. However, reaction modes for asymmetric alkyl-alkyl bonds (Csp3-Csp3) formation between sp3 hybridized carbons are extremely limited and highly desirable. Herein, an unprecedented mode for asymmetric alkyl-alkyl bond-forming process enabled by Ni-catalyzed asymmetric alkyl-alkyl cross-coupling from alkenes has been developed to construct tertiary stereogenic carbon centers. Ni-catalyzed asymmtric cross-hydrodimerization of N-acyl enamines and unactivated alkenes to enables head-to-tail regioselectivity and exellent levels of chemo- and enantioselectivity, providing a new reaction mode to achieve asymmetric alkyl-alkyl bond-forming event. Notably, the reaction proceeds in the presence of both reducing and oxidizing reagents, rendering alkenes as the sole precursors to forge enantioselective alkyl-alkyl bonds. The exclusive head-to-tail cross-hydrodimerization of distinct alkenes, opening a new avenue to access saturated tertiary stereogenic carbon centers from alkenes.