Catalytic Asymmetric Synthesis of Secondary Nitriles via Stereoconvergent Negishi Arylations and Alkenylations of Racemic α-Bromonitriles

The first method for the stereoconvergent cross-coupling
of racemic
α-halonitriles is described, specifically, nickel-catalyzed
Negishi arylations and alkenylations that furnish an array of enantioenriched
α-arylnitriles and allylic nitriles, respectively. Noteworthy
features of this investigation include: the highly enantioselective
synthesis of α-alkyl-α-aryl nitriles that bear secondary α-alkyl substituents; the first examples
of the use of alkenylzinc reagents in stereoconvergent
Negishi reactions of alkyl electrophiles; demonstration of the utility
of a new family of ligands for asymmetric Negishi cross-couplings
(a bidentate bis­(oxazoline), rather than a tridentate pybox); in the
case of arylzinc reagents, carbon–carbon bond formation at
a remarkably low temperature (−78 °C), the lowest reported
to date for an enantioselective cross-coupling of an alkyl electrophile;
a mechanistic dichotomy between Negishi reactions of an unactivated
versus an activated secondary alkyl bromide.