Synthesis of cyclic amino acid baikiain via asymmetric phase transfer catalysis

Abstract

The synthesis of the cyclic, naturally occurring amino acid baikiain from glycine and cis-1,4-butenediol is reported. The key step of the synthesis is an enantioselective phase transfer catalyzed allylation of the benzophenone imine of glycine t-butyl ester, catalyzed by a cinchonidine quaternary ammonium salt, which provided the allylated glycine in 82% yield and 80% e.e. Further deprotection and hydrolysis of the Schiff base followed by an intramolecular Mitsunobu ring closure reaction yielded the corresponding piperidine ring system in 77% yield, which by hydrolysis yielded baikiain hydrochloride in 36% overall yield. Hydrogenation of the double bond could provide access to (S)pipecolic acid, which is also an important chiral synthon.

Recent Advances in Chiral Schiff Base Compounds in 2023

“…They are used exclusively as catalysts in reactions, including both organic substances [6,7] and metal complexes [8][9][10]. A summary of the paper title exemplifies the target response of the latest report.…”

“…Synthesis of cyclic amino acid using asymmetric phase transfer catalyst [7]. Spectroscopic characterization, catalytic activity, and biological activity of vanadium(V) oxide complexes with chiral tetradentate Schiff bases [8].…”