A facile synthesis of tert-butyl 2'[(benzyloxycarbonyl)amino]-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propionate: An orthogonally protected boronic acid analog of aspartic acid

tert-Butyl 2-[(benzyloxycarbonyl)amino]-3-(4,4,5,5-tetramethyl-1,3,2- dioxaborolan-2-yl)propionate, an orthogonally protected analog of aspartic acid wherein the side chain carboxylic acid is replaced with a boronic acid moiety, was conveniently synthesized by alkylation of N- (diphenylmethylene)glycine tert-butyl ester with pinacol (chloromethyl)boronate as the key step. After selective cleavage of the tert- butyl ester this unnatural amino acid was coupled with L-isoleucinamide using a mixed anhydride method. The two diastereomers of the resulting dipeptides were separated by reversed phase HPLC and their absolute configurations were established by oxidizing the boronic acids to the corresponding hydroxy groups followed by NMR and HPLC correlation with authentic Cbz-L-Ser-L-Ile- NH₂.