EFFICIENT SYNTHESIS OF BETA-HALOGENO PROTECTED L-ALANINES AND THEIR BETA-PHOSPHONIUM DERIVATIVES

Ring opening of oxazolines, prepared from L-serinates, with trimethylsilyl halides (TMSX) led to -halogeno-N-benzoyl- -amino esters in good to excellent yields. Quaternization of triphenylphosphine by the -bromo or -iodo amino esters gave the corresponding -phosphonium salts in overall yields of up to 93% and with e.e. >96%. Hydrolysis of the ester function afforded the phosphonium salt bearing an N-benzoyl--amino acid substituent, with partial racemization. However, the reaction of the TMSX with the carboxylic salt, prepared by saponification of the starting oxazoline ester, furnished the corresponding -halogeno-N-benzoyl--amino acids in 70–95% yields. Quaternization of triphenylphosphine by the bromo or iodo derivatives led to the phosphonium salts bearing a free acid function in 95% yield, without racemization. The efficiency of this synthesis was demonstrated by the preparation of these phosphonium salts in excellent overall yields, by a one-pot procedure starting from the oxazoline.