THE SYTHESIS OF γ-FLUOROISOLEUCINE

Article abstract of DOI:10.1016/S0022-1139(00)82317-9

Condensation of 3-fluoro-2-butanone (2) with alkyl diethylphosphonoacetates (4a-d) gave alkyl 4-fluoro-3-methyl-2-pentenoates (5a-d).Addition of bromine yielded alkyl-2,3-dibromo-4-fluoro-3-methylpentanoates (6a,b) which were dehydrobrominated to alkyl 2-bromo-4-fluoro-3-methyl-2-pentenoates (7a,b).Since these compounds could not be hydrogenated to the desired alkyl 2-bromo-4-fluoro-3-methylpentanoates (8a,b), another route was taken.The esters 5a-d were hydrogenated to alkyl 4-fluoro-3-methylpentanoates (11a-c) which were converted to their carbanions.Treatment with bromine gave esters 8a-c, and iodine gave alkyl 4-fluoro-2-iodo-3-methylpentanoates (12a,b).Esters 8a-c and 12a,b were converted to alkyl 2-azido-4-fluoro-3-methylpentanoates (13a-c) whose hydrogenation gave alkyl 2-amino-4-fluoro-3-methylpentanoates (14a-c).Hydrolysis afforded γ-fluoroisoleucine (1).