Enantioselective C(sp(3))–C(sp(3)) cross-coupling of non-activated alkyl electrophiles via nickel hydride catalysis

Cross-coupling of two alkyl fragments is an efficient method to produce organic molecules rich in sp(3)-hybridized carbon centers, which are attractive candidate compounds in drug discovery. Enantioselective C(sp(3))–C(sp(3)) 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-catalyzed alkyl-alkyl coupling. This strategy enables 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.