Enantioselective C(sp³)-C(sp³) cross-coupling of non-activated alkyl electrophiles via nickel hydride catalysis.

ABSTRACT: Cross-coupling of two alkyl fragments is an efficient method to produce organic molecules rich in sp³-hybridized carbon centres, which are attractive candidate compounds in drug discovery. Enantioselective C(sp³)-C(sp³) coupling is challenging, especially of alkyl electrophiles without an activating group (aryl, vinyl, carbonyl). Here, we report a strategy based on nickel hydride addition to internal olefins followed by nickel-catalysed alkyl-alkyl coupling. This strategy enables the enantioselective cross-coupling of non-activated alkyl halides with alkenyl boronates to produce chiral alkyl boronates. Employing readily available and stable olefins as pro-chiral nucleophiles, the coupling proceeds under mild conditions and exhibits broad scope and high functional-group tolerance. Applications for the functionalization of natural products and drug molecules, as well as the synthesis of chiral building blocks and a key intermediate to (S)-(+)-pregabalin, are demonstrated.

SUBMITTER: Bera S 

PROVIDER: S-EPMC7610379 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature