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 sp(3) 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).
Huang
Audris
A
Department of Chemistry, 516 Rowland Hall, University of California, Irvine, California 92697-2025, USA.
Kodanko
Jeremy J
JJ
Overman
Larry E
LE
D000478:Alkylation; D007211:Indoles / Q000138:chemical synthesis*; D010830:Physostigmine / Q000031:analogs & derivatives* / Q000138:chemical synthesis*; D011759:Pyrrolidines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D007211:Indoles; D011759:Pyrrolidines; C057812:indoline; D010830:Physostigmine; C092280:phenserine