A Practical Method for the Synthesis of Enantiomerically Pure 4-Borono-L-phenylalanine

Abstract Enantiomerically pure L-BPA (4-borono-L-phenylalanine) was synthesized from L-tyrosine or 4-iodo-L-phenylalanine derivatives using the palladium-catalyzed cross-coupling reaction of pinacolborane (2,3-dimethyl-2,3-butanediolatoboron). Cbz-Tyr(Nf)-OBzl (2b) underwent the cross-coupling reaction with pinacolborane (1) in the presence of [PdCl2(PPh3)2] catalyst to give N-benzyloxycarbonyl-4-(2,3-dimethyl-2,3-butanediolatoboryl)-L-phenylalanine benzyl ester (3a) in 58% yield. The reaction of the 4-iodo-L-phenylalanine derivatives, such as N-benzyloxycarbonyl-4-iodo-L-phenylalanine benzyl ester (2c), N,N-dibenzyl-4-iodo-L-phenylalanine benzyl ester (2d), (4S)-3-benzyloxycarbonyl-4-(4-iodobenzyl)-5-oxazolidinone (2e), and (4S)-3-t-butyloxycarbonyl-4-(4-iodobenzyl)-5-oxazolidinone (2f), with 1 proceeded very smoothly in the presence of [PdCl2(dppf)] catalyst, giving N-benzyloxycarbonyl-4-(2,3-dimethyl-2,3-butanediolatoboryl)-L-phenylalanine benzyl ester (3a), N,N-dibenzyl-4-(2,3-dimethyl-2,3-butanediolatoboryl)-L-phenylalanine benzyl ester (3b), (4S)-3-benzyloxycarbonyl-4-[4-(2,3-dimethyl-2,3-butanediolatoboryl)benzyl]-5-oxazolidinone (3c), and (4S)-3-butyloxycarbonyl-4-[4-(2,3-dimethyl-2,3-butanediolatoboryl)benzyl]-5-oxazolidinone (3d), respectively, in high yields. Deprotection of 3a—d gave enantiomerically pure L-BPA in high total yields.