通过不对称钐介导的酮基-烯烃偶联反应一步高非对映选择性合成γ-氨基烷基取代的γ-丁内酯

One-step highly diastereoselective synthesis of gamma-aminoalkyl-substituted gamma-butyrolactones by an asymmetric samarium-mediated ketyl-alkene coupling reaction.

作者信息

Fukuzawa Shin-ichi, Miura Manabu, Saitoh Takahide

机构信息

Department of Applied Chemistry, Institute of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.

出版信息

J Org Chem. 2003 Mar 7;68(5):2042-4. doi: 10.1021/jo020574h.

DOI:10.1021/jo020574h

PMID:12608834

Abstract

The samarium(II) iodide mediated reaction of N,N-dibenzyl-protected (S)-alpha-amino aldehydes with (1S,2R)-N-methylephedrinyl acrylate gave the (4R,1'S)-gamma-(aminoalkyl)-gamma-butyrolactones in good yields with high diastereoselectivities (up to 80% de); (4R,1'S)-gamma-amino-(2-phenylethyl)-gamma-butyrolactone (6a), which should be a potent precursor for gamma-secretase inhibitors, was obtained with high de value.

摘要

碘化钐（II）介导的N，N - 二苄基保护的（S）-α-氨基醛与（1S，2R）-N - 甲基麻黄碱丙烯酸酯的反应以良好的产率和高非对映选择性（高达80%的非对映体过量）得到了（4R，1'S）-γ-（氨基烷基）-γ-丁内酯；以高非对映体过量值得到了（4R，1'S）-γ-氨基-（2-苯乙基）-γ-丁内酯（6a），它应该是γ-分泌酶抑制剂的有效前体。