Heterocycles in asymmetric synthesis. Part 1. Construction of the chiral building blocks for enantioselective alkaloid synthesis via an asymmetric intramolecular Michael reaction

Abstract

The asymmetric intramolecular Michael 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 moderato 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 Å gave tha (+)-pyrrolidine derivative (+)-11 and the (–)-piperidine dsrivative (–)-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.