Asymmetric synthesis of protoberberine alkaloids via a tandem nucleophilic addition and intramolecular cyclisation of a chiral o-toluamide anion with 3,4-dihydroisoquinoline

Abstract

The reaction of o-toluamide anions, derived from the (S)-(–)- and (R)-(+)-1-phenylethylamine, with 6,7-dimethoxy-3,4-dihydroisoquinoline gives (13aS)-(–)- and (13aR)-(+)-8-oxoprotoberberine, respectively, with enantiomeric excesses >96%.