Regio- and Enantioselective Hydroalkylations of Unactivated Olefins Enabled by Nickel Catalysis: Reaction Development and Mechanistic Insights

Abstract

Direct construction of fully alkyl-substituted tertiary chiral centers remote to activating groups is highly challenging and desirable. Herein, a Ni-catalyzed enantioselective hydroalkylation of unactivated alkenes with unactivated alkyl halides at room temperature is reported, providing a general and practical access to fully alkyl-substituted tertiary stereogenic carbon centers not adjacent to activating groups. This reaction undergoes the regio- and stereoselective hydrometalation of unactivated alkenes with a nontrivial Markovnikov selectivity, followed by the cross-coupling with unactivated alkyl electrophiles to access trialkyl tertiary saturated stereogenic centers not adjacent to activating groups. The mild and robust conditions enable the use of terminal and internal unactivated alkenes and unactivated primary and secondary alkyl, benzyl, and propargyl halides to construct diverse trialkyl tertiary stereogenic carbon centers with broad functional group tolerance. Moreover, experimental investigations support the reaction undergoing irreversible and stereoselective hydrometalation of alkenes. Density functional theory calculations provide further insights into the reaction mechanism, suggesting a stereoselective migration insertion of alkenes with Ni(II)–H species. Finally, the origin of the regio- and enantioselectivities is also investigated.