基于β-氨基自由基的6-外向-三自由基环化反应合成（+）-异杷碱

Synthesis of (+)-Ipalbidine Based on 6-exo-trig Radical Cyclization of a β-Amino Radical.

作者信息

Chea JongMyoung, Clive Derrick L J

机构信息

Chemistry Department, University of Alberta , Edmonton, Alberta T6G 2G2, Canada.

出版信息

J Org Chem. 2015 Oct 16;80(20):10294-8. doi: 10.1021/acs.joc.5b01890. Epub 2015 Oct 7.

DOI:10.1021/acs.joc.5b01890

PMID:26402510

Abstract

N-Boc (S)-proline was converted into (2S)-2-[(phenylselanyl)methyl]pyrrolidine, which was alkylated on nitrogen with 2-bromo-1-(4-methoxyphenyl)ethan-1-one. Reaction with vinyllithium, 6-exo-trig radical cyclization (Bu3SnH, AIBN, PhMe, 110 °C), dehydration (P2O5, H3PO4), and demethylation (BBr3) gave (+)-ipalbidine with ee >99%.

摘要

N-叔丁氧羰基-(S)-脯氨酸被转化为(2S)-2-[(苯基硒基)甲基]吡咯烷，其在氮原子上用2-溴-1-(4-甲氧基苯基)乙-1-酮进行烷基化反应。与乙烯基锂反应、6-外式-三自由基环化反应（三丁基氢化锡、偶氮二异丁腈、甲苯，110℃）、脱水反应（五氧化二磷、磷酸）以及脱甲基反应（三溴化硼）得到对映体过量大于99%的(+)-伊波加因。