Asymmetric Alkyl-Alkyl Cross-Coupling Enabled by Ni-Catalyzed Cross-Hydrodimerization of Enamides with Unactivated Alkenes

Abstract

Saturated stereogenic centers containing C(sp³)–C(sp³) bonds comprise a major portion of organic molecules. Over the past decades, transition-metal-catalyzed asymmetric C(sp³)–C(sp³) cross-coupling has evolved into an efficient strategy for constructing such stereogenic centers. However, reaction modes to build asymmetric C(sp³)–C(sp³) bonds remain limited. Herein, a nickel-catalyzed enantioselective cross-hydrodimerization between distinct alkenes to enable the enantioselective construction of alkyl–alkyl bonds has been developed. In this reaction mode, N-acyl enamines (enamides) and unactivated alkenes undergo oxidative enantioselective cross-hydrodimerization with excellent levels of chemo- and head-to-tail regioselectivity to give enantioenriched N-acyl α-branched amines by forging the C(sp³)–C(sp³) bond with control of the enantioselectivity. The presence of both reducing and oxidizing reagents in the reaction allows the use of alkenes as sole precursors to forge enantioselective C(sp³)–C(sp³) bonds, representing a new reaction mode for asymmetric alkyl–alkyl cross-coupling. The asymmetric cross-hydrodimerization between distinct alkenes provides a new strategy for constructing saturated stereogenic centers containing C(sp³)–C(sp³) bonds.

Key words

asymmetric hydrodimerization of alkenes - asymmetric alkyl–alkyl coupling - nickel catalysis - saturated stereogenic centers - alkyl electrophile free

Publication History

Received: 07 August 2024

Accepted after revision: 28 August 2024

Accepted Manuscript online:
28 August 2024

Article published online:
26 September 2024

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