N-Cbz-3,3-二氟-2-二氟亚甲基吡咯烷的选择性脱氟方法及其在3,3-二氟脯氨酸二肽合成中的应用。

Selective defluorination approach to N-Cbz-3,3-difluoro-2-difluoromethylenepyrrolidine and its application to 3,3-difluoroproline dipeptide synthesis.

作者信息

Guo Yong, Fujiwara Kana, Amii Hideki, Uneyama Kenji

机构信息

Department of Applied Chemistry, Faculty of Engineering, Okayama University, 3-3-1 Tsushima-naka, Okayama, 700-8530 Japan.

出版信息

J Org Chem. 2007 Oct 26;72(22):8523-6. doi: 10.1021/jo070719q. Epub 2007 Oct 3.

DOI:10.1021/jo070719q

PMID:17914839

Abstract

Mg-promoted defluorination of N-(p-methoxyphenyl)bis(trifluoromethyl)imine 1 gave perfluoroenamine 2, which was readily transformed to N-Cbz-2-trifluoromethyl-3,3-difluoropyrrolidine 10. Chemoselective defluorination from the trifluoromethyl group of 10 by LHMDS-promoted dehydrofluorination in THF provided 3,3-difluoro-2-difluoromethylenepyrrolidine 11. The product 11 was converted to 3,3-difluoroproline dipeptides 16 upon treatment with aminoesters.

摘要

镁促进的N-（对甲氧基苯基）双（三氟甲基）亚胺1的脱氟反应生成了全氟烯胺2，其很容易转化为N-Cbz-2-三氟甲基-3,3-二氟吡咯烷10。在四氢呋喃中通过LHMDS促进的脱氢氟化反应从10的三氟甲基进行化学选择性脱氟得到3,3-二氟-2-二氟亚甲基吡咯烷11。产物11在用氨基酯处理后转化为3,3-二氟脯氨酸二肽16。