Highly diastereoselective approach to novel phenylindolizidinols via benzothieno analogues of tylophorine based on reductive desulfurization of benzo[ b]thiophene

Abstract

Chiral tetra- and hexahydro[1]benzothieno[2,3- f]indolizines 3– 5, 9, and 11 were synthesized easily from benzo[ b]thiophene-2-carboxaldehyde ( 1) and ( S)-glutamic acid ( 2) in good overall yields and both high enantio- and diastereomeric purities. Applying a diastereoselective reductive desulfurization of benzo[ b]thiophene followed by lactam reduction, epimeric alcohols 4a and 4b were readily converted into (7 R or S,8a S)-phenylindolizidinols 6a, c. During these studies, the reduction of benzothienoindolizines 3– 5, 9, 11, and 12, was investigated and the results obtained are also discussed.