Electrophile-Dependent Alkylations of Lithiated 4‑Alkoxyalk-4-enenitriles

Alkylations of acyclic, lithiated
4-alkoxyalk-4-enenitriles are
highly diastereoselective with an unusual electrophile-dependent preference.
Alkyl halides, sulfur, chlorine, and acyl cyanide electrophiles intercept
a series of lithiated 4-alkoxyalk-4-enenitriles to install contiguous
tertiary–quaternary stereocenters with high diastereoselectivity,
whereas acylations with ester and carbonate electrophiles are modestly
selective. The diastereoselectivity is consistent with electrophilic
attack on the most accessible face of the lithated nitrile for most
electrophiles except ester and carbonate electrophiles, which likely
precoordinate the lithiated nitrile before acylation. Intercepting
the lithiated 4-alkoxyalk-4-enenitriles with a range of electrophiles
provide insight into the criteria for otherwise challenging diastereoselective
alkylations and acylations of acyclic nitriles.