HETEROCYCLES IN ASYMMETRIC-SYNTHESIS .1. CONSTRUCTION OF THE CHIRAL BUILDING-BLOCKS FOR ENANTIOSELECTIVE ALKALOID SYNTHESIS VIA AN ASYMMETRIC INTRAMOLECULAR MICHAEL REACTION

The asymmetric intramolecular Micheal reaction of acyclic compounds ethyl (E)-4-[benzyl-(3-oxobutyl)amino]but-2-enoate 9, and ethyl (E)-5-[benzyl-(3-oxobutyl)amino]pent-2-enoate 10 was investigated under a variety of conditions, and the pyrrolidine ethyl (4-acetyl-1-benzylpyrrolidin-3-yl)acetate 11 and piperidine ethyl (3-acetyl-1-benzylpiperidin-4-yl)acetate 12, versatile chiral building blocks for alkaloid synthesis, were obtained in moderate to excellent optical yield. Cyclization of the aforementioned but- and pent-2-enoate using (R)-1-phenylethylamine in THF in the presence of molecular sieves 5 angstrom gave the (+)-pyrrolidine derivative (+)-11 and the (-)-piperidine derivative (-)-12 in 60 and 90% ee, respectively. When (S)-1-phenylethylamine was used, pyrrolidine (-)-11 and piperidine derivatives (+)-12 were obtained in similar optical yields, respectively. The ee of (-)- and (+)-piperidine derivatives increased up to 98% upon recrystallization of their hydrobromide salts.