ASYMMETRIC SYNTHESIS OF 2,3-DIMETHOXY-8-OXOBERBINE, PRECURSOR OF O-METHYLBHARATAMINE

摘要

The enantiospecific and-enantioselective syntheses of 2,3-dimethoxy-8-oxoberbine were performed using the lateral metallation methodology. In the enantiospecific synthesis (4S)-2,2,4-trimethyl-3-(o-toluoyl)-oxazolidine incorporating (S)-alaninol as the chiral auxiliary was applied. The addition reaction of benzylic anion generated in situ from chiral oxazolidine into 6,7-dimethoxy-3,4-dihydroisoquinoline led to the protoberberine with high enantiomeric excess. Enantioselective synthesis of 2,3-dimethoxy-8-oxoberbine was performed with achiral 2,2-dimethyl-3-(o-toluoyl)oxazolidine in the presence of chiral ligands. Among them (-)-sparteine and (+)-sparteine surrogate turned out to be the most efficient ones.