Aza-cope rearrangement Mannich cyclizations for the formation of complex tricyclic amines:: Stereocontrolled total synthesis of (±)-gelsemine

被引：57

作者：

Earley, WG ^{[1
]}

Jacobsen, JE ^{[1
]}

Madin, A ^{[1
]}

Meier, GP ^{[1
]}

O'Donnell, CJ ^{[1
]}

Oh, T ^{[1
]}

Old, DW ^{[1
]}

Overman, LE ^{[1
]}

Sharp, MJ ^{[1
]}

机构：

[1] Univ Calif Irvine, Dept Chem, Irvine, CA 92697 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2005年 / 127卷 / 51期

关键词：

D O I：

10.1021/ja055710p

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A detailed examination of the use of aza-Cope rearrangement-Mannich cyclization sequences for assembling the azatricyclo[4.4.0.0(2,8)]decane core of gelsemine is described. Iminium ions and N-acyloxyiminium ions derived from endo-oriented 1-methoxy- or 1-hydroxybicyclo[2.2.2]oct-5-enylamines do not undergo the first step of this sequence, cationic aza-Cope rearrangement, to form cis-hydroisoquinolinium ions. However, the analogous base-promoted oxy-aza-Cope rearrangement does take place to form cis-hydroisoquinolones containing functionality that allows iminium ions or N-acyloxyiminium ions to be generated regioselectively in a subsequent step. Mannich cyclization of cis-hydroisoquinolones prepared in this way efficiently assembles the azatricyclo[4.4.0.02,I]decane unit of gelsemine. Using a sequential base-promoted oxy-aza-Cope rearrangement/Mannich cyclization sequence, gram quantities of azatricyclo[4.4.0.02,8]decanone 18, a central intermediate in our total of (+/-)-gelsemine, were prepared from 3-methylanisole in 12 steps and 16% overall yield.

引用

页码：18046 / 18053

页数：8

共 125 条

[1] INTRAMOLECULAR ALKENE ARYLATIONS FOR RAPID ASSEMBLY OF POLYCYCLIC SYSTEMS CONTAINING QUATERNARY CENTERS - A NEW SYNTHESIS OF SPIROOXINDOLES AND OTHER FUSED AND BRIDGED RING-SYSTEMS [J].