An enantioselective formal synthesis of 4-demethoxydaunomycin using the catalytic asymmetric ring opening reaction of meso-epoxide with p-anisidine

A catalytic asymmetric formal synthesis of 4-demethoxydaunomycin (3) was achieved using a catalytic asymmetric ring opening reaction of meso-epoxide 9 as a key step. The epoxide opening reaction was promoted by 10 mol% of Pr-(R)-BINOL-Ph₃P=O complex to give the β-amino alcohol 11 in 80% yield with 65% enantiomeric excess (ee). Single recrystallization enhanced the enantiomeric purity of the β-amino alcohol 11 to 95% ee. The β-amino alcohol 11 was then converted to the known key intermediate 6 through several steps, including a methylation, Hofmann elimination, an oxymercuration, and addition of an ethynyl group in a highly diastereoselective manner.