Cross-coupling of two alkyl fragments is an
efficient method to produce organic molecules rich in sp<sup>3</sup>-hydridized
carbon centers, which are attractive candidate compounds in drug discovery.
Enantioselective C(sp<sup>3</sup>)-C(sp<sup>3</sup>) coupling, especially of
alkyl electrophiles without an activating group (aryl, vinyl, carbonyl) is
challenging. 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 iodides
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 in late-stage functionalization of natural products and
drug molecules, synthesis of chiral building blocks, and enantioselective
formal synthesis of (<i>S</i>)-(+)-Pregabalin are demonstrated.<br>
Publisher Correction: Enantioselective C(sp3)–C(sp3) cross-coupling of non-activated alkyl electrophiles via nickel hydride catalysis