Synthesis of cyclic amino acid baikiain via asymmetric phase transfer catalysis

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.