A practical method to access enantiopure beta-perfluoroalkyl-beta-amino acids: diastereoselective reduction of cyclic enamino-esters

作者：Ishida Yasuhiro^*; Iwahashi Nobutaka; Nishizono Nao; Saigo Kazuhiko

来源：Tetrahedron Letters, 2009, 50(17): 1889-1892.

DOI：10.1016/j.tetlet.2009.01.159

A highly practical method to access enantiopure beta-perfluoroalkyl-beta-amino acids was developed, which Could be conducted Without any expensive reagent, special apparatus/technique, nor tedious chromatographic separation. The condensation of methyl 4,4,4-trifluoro-3-oxobutanoate with (S)-2-amino-2-phenylethanol, followed by an intramoleculer transesterification, gave an enamino-ester with a seven-membered ring structure. The hydride reduction of the cyclic enamino-ester proceeded with excellent diastereoselectivity (dr = 95:5-97:3) to give the corresponding cyclic amino-ester. The major isomer of the cyclic amino-ester was readily separated from the minor one and successfully converted into (S)-3-amino-4,4,4-trifluorobutanoic acid (five steps, 38% overall yield, >99% ee). Concerning the key step of this synthesis, the same strategy was applicable to another substrate: the asymmetric hydride reduction of a cyclic enamino-ester with a pentafluoroethyl group also proceeded in excellent diastereoselectivity (dr = 96:4).

• 出版日期2009-4-29