A novel and versatile method for the enantioselective syntheses of tropane alkaloids  

作　　者：MAO ZhongYi HUANG SuYu GAO LongHui WANG AiE HUANG PeiQiang 

机构地区：[1]Department of Chemistry and Fujian Provincial Key Laboratory of Chemical Biology,College of Chemistry and Chemical Engineering,Xiamen University

出　　处：《Science China Chemistry》2014年第2期252-264,共13页中国科学（化学英文版）

基　　金：the National Basic Research Program of China(973 Program,2010CB833200);the National Natural Science Foundation of China(21072160,21332007);the Program for Changjiang Scholars and Innovative Research Team at the University of the MOE for financial support

摘　　要：A full account of the novel and flexible approach to hydroxylated 8-azabicyclo[3,2,1]octan-3-ones and 9-azabicyclo[3,3,1] nonan-3-ones is presented. Using keto-lactams as the starting materials, this two-step method consists of silyl enol ether for mation with TBDMSOTf, lactam activation with Tf20/DTBMP, and halide-promoted cyclization. Radical dechlorination of the resulting 1-halotropan-3-ones led to the corresponding hydroxylated tropan-3-ones, which can be hydrogenated to yield 3ct,613-dihydroxytropanes. Starting from optically active keto-lactams, the method has been applied to the enantioselective syntheses of （＋）-（1S,3S,5R,6S）-pervilleine C （6）, （＋）-（1S,3R,5S,6R）-valeroidine （3）, （＋）-（1S,3S,5R,6S）-dibenzoyloxytropane （8） and （＋）-（1S,3S,5R,6S）-merredissine （9）.A full account of the novel and flexible approach to hydroxylated 8-azabicyclo[3,2,1]octan-3-ones and 9-azabicyclo[3,3,1]nonan-3-ones is presented.Using keto-lactams as the starting materials,this two-step method consists of silyl enol ether formation with TBDMSOTf,lactam activation with Tf2O/DTBMP,and halide-promoted cyclization.Radical dechlorination of the resulting 1-halotropan-3-ones led to the corresponding hydroxylated tropan-3-ones,which can be hydrogenated to yield3,6-dihydroxytropanes.Starting from optically active keto-lactams,the method has been applied to the enantioselective syntheses of(+)-(1S,3S,5R,6S)-pervilleine C(6),(+)-(1S,3R,5S,6R)-valeroidine(3),(+)-(1S,3S,5R,6S)-dibenzoyloxytropane(8),and(+)-(1S,3S,5R,6S)-merredissine(9).

关 键 词：synthetic methods tropane alkaloids CYCLIZATION ACTIVATION AMIDES 

分 类 号：O621.25[理学—有机化学]