Synthesis of 1-amino-2-phenylethane-1-boronic acid derivatives

Article abstract of DOI:10.1021/om00082a019

The boron analogue of N-acetylphenylalanine, (R)-1-acetamido-2-phenylethane-1-boronic acid (5b), has been synthesized from (+)-pinanediol phenylmethane-1-boronate (1b), which was converted by (dichloromethyl)lithium to the (S)-1-chloro-2-phenylethane-1-boronate (2b), then with N-lithiohexamethyldisilazane to the silylated 1-amino-2-phenylethane-1-boronic ester 3b, which was desilylated and acetylated in situ to (+)-pinanediol (R)-1-acetamido-2-phenylethane-1-boronate (4b) and then cleaved to the free boronic acid 5b with boron trichloride. 1-Amino-2-phenylethane-1-boronic esters (6) were found to be isolable but unstable, deboronating to 2-phenylethylamine under the influence of heat or hydroxylic solvents. 1-Amino-2-phenylethane-1-boronic acid, though not isolable, partially survives for an hour in cold aqueous solution. Attempts to synthesize the stable α-acetamido boronic esters (4) directly by reaction of lithioacetamide with 1-halo-2-phenylethane-1-boronic esters (2) have resulted in a major proportion of O-alkylation to form imino esters. Pinacol 1-acetamidino-2-phenylethane-1-boronate (8) has been obtained from the α-iodo boronic ester 2d and acetamidine.