Electrophile-Directed Diastereoselective Oxonitrile Alkylations.

Diastereoselective alkylation of prochiral oxonitrile dianions with secondary alkyl halides efficiently installs two contiguous stereogenic centers. The confluence of nucleophilic trajectory and the electrophile chirality causes distinct steric differences that allow efficient discrimination for one of the six possible conformers. Numerous oxonitrile-derived dianions efficiently displace secondary alkyl halides propagating the electrophile chirality to efficiently install two contiguous tertiary centers. The prevalence of chiral, secondary electrophiles makes the interdigitated alkylation of chiral electrophiles a particularly attractive route because the resulting oxonitriles are readily transformed into bioactive heterocycles.

Metalated nitrile and enolate chlorinations.

Metalated nitriles and enolates rapidly and efficiently abstract chlorine from 2-chloro-2-fluoro-2-phenylacetonitrile to afford a diverse range of chloronitriles and chloroesters. The method provides the first general anionic chlorination of alkylnitriles, tolerates numerous functional groups, and addresses the challenge of synthesizing alpha-chloronitriles under mild conditions.