Asymmetric Synthesis of Pyrrolidinoindolines. Application for the Practical Total Synthesis of (−)-Phenserine

A versatile route to enantiopure 3,3-disubstituted oxindoles and 3a-substituted pyrrolidinoindolines
is described in which diastereoselective dialkylation of enantiopure ditriflate 10 with oxindole enolates is
the central step. These reactions are rare examples of alkylations of prostereogenic enolates with chiral
sp3 electrophiles that proceed with high facial selectivity (10−20:1). The scope of this method is explored,
and a model to rationalize the sense of stereoselection is advanced. This dialkylation chemistry was used
to synthesize (−)-phenserine on a multigram scale in six steps and 43% overall yield from 5-methoxy-1,3-dimethyloxindole (27) and to complete a short formal total synthesis of (−)-physostigmine (2).