Fustero Santos, Pina Belén, Salavert Esther, Navarro Antonio, Ramírez de Arellano M Carmen, Fuentes Antonio Simón
Departamento de Química Orgánica, Facultad de Farmacia, Universidad de Valencia, 46100-Burjassot, Valencia, Spain.
J Org Chem. 2002 Jul 12;67(14):4667-79. doi: 10.1021/jo025621k.
Racemic and chiral nonracemic alpha-substituted and alpha-unsubstituted beta-fluoroalkyl beta-amino acid derivatives 6 and 9 have been synthesized in two steps starting from fluorinated imidoyl chlorides 1 and ester enolates. This approach is based on the chemical reduction of previously obtained gamma-fluorinated beta-enamino esters 4 by using ZnI(2)/NaBH(4) in a nonchelated aprotic medium (dry CH(2)Cl(2)) as the reducing agent. A metal-chelated six-membered model has been suggested to explain the stereochemical outcome of the reduction reaction. The process takes place with high yields and with moderate to good diastereoselectivity. The best results related to diastereoselective reduction of chiral beta-enamino esters 4 were provided by the use of (-)-8-phenylmenthol as a chiral auxiliary.
从氟化亚胺酰氯1和酯烯醇盐出发，通过两步反应合成了外消旋和手性非外消旋的α-取代和α-未取代的β-氟烷基β-氨基酸衍生物6和9。该方法基于在非螯合非质子介质（干燥的二氯甲烷）中使用碘化锌/硼氢化钠作为还原剂，对先前得到的γ-氟化β-烯胺酯4进行化学还原。有人提出了一个金属螯合的六元模型来解释还原反应的立体化学结果。该过程产率高，非对映选择性中等至良好。使用(-)-8-苯基薄荷醇作为手性助剂，在手性β-烯胺酯4的非对映选择性还原方面取得了最佳结果。
