Ml. Pedersen et Db. Berkowitz, FORMAL ALPHA-VINYLATION OF AMINO-ACIDS - USE OF A NEW BENZENESELENOLATE EQUIVALENT, Journal of organic chemistry, 58(25), 1993, pp. 6966-6975
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.