Stereoselective Electrophilic α-Alkynylation of α,α-Disubstituted N- tert-Butanesulfinyl Ketimines for Construction of Less Accessible Acyclic Quaternary Stereocenters

In order to construct less accessible acyclic quaternary stereocenters, a protocol was developed to alpha-alkynylate alpha,alpha-disubstituted N-tert-butanesulfinyl ketimines stereoselectively using 1-(2-trimethylsilylethynyl)-1,2-benziodoxol-3(1H)-one in the presence of fluoride. Despite the steric and electrical similarity between the two alpha-substituents, the entire reaction proceeded in a strongly stereoselective manner: tBuOK promoted alpha-deprotona-tion of the acyclic ketimine to generate stereodefined fully substituted aza-enolates, which stereoselectively formed C-C bonds with electrophilic alkynylation reagents, affording alpha-alkynylation products with excellent stereocontrol.

Automated summary

A protocol was developed to achieve stereoselective alpha-alkynylation of alpha,alpha-disubstituted N-tert-butanesulfinyl ketimines using a specific reagent in the presence of fluoride. This method allows the construction of less accessible acyclic quaternary stereocenters.