FORMAL ALPHA-VINYLATION OF AMINO-ACIDS - USE OF A NEW BENZENESELENOLATE EQUIVALENT

A new synthetic approach to the formal alpha-vinylation of alpha-amino acids is described, in which the readily available electrophile, ethy lene oxide, serves as the vinyl cation equivalent. N-Benzoyl alpha-ami no esters bearing appropriate side-chain protecting groups are deproto nated with lithium diisopropylamide lamide in THF/TMEDA at -78-degrees -C to generate the corresponding dianions. Exposure of these to ethyle ne oxide results in C-alkylation and lactonization to give the corresp onding racemic, alpha-substituted homoserine lactones 2a-j in 61-85% y ield. Next, reduction of diphenyl diselenide with sodium trimethoxybor ohydride generates a benzeneselenolate anion equivalent which efficien tly cleaves the alpha-substituted homoserine lactones without competin g lactone reduction (69-97% yields for 3a-j following diazomethane wor kup). The protected alpha-[2-(phenylseleno)ethyl] amino acids thereby obtained are oxidized to the corresponding selenoxides through the age ncy of ozone at -78-degrees-C. Pyrolysis of these in refluxing benzene or carbon tetrachloride gives the protected alpha-vinyl amino acids 4 a-c and 4e-j in 95-100% yield. In the case of methyl -[2'-(phenylselen o)ethyl]-N(tau)-tritylhistidinate (3d), oxidation and pyrolysis (80%) are carried out in one pot by refluxing with tetrabutylammonium period ate in chloroform. Finally, deprotection is achieved by acidic hydroly sis. This methodology has been successfully applied to the synthesis, in racemic form, of the alpha-vinyl amino acids derived from phenylala nine (5a), DOPA (5b), histidine (5c), lysine (5d), ornithine (5e), val ine (5f), alanine (5g), and homoserine (5h). In addition, alpha-vinyla spartic acid (9) and alpha-vinylargine (10) could be obtained from alp ha-vinylhomoserine derivative 4j and alpha-vinylornithine (5f), respec tively.