分子内叠氮酰氯的Schmidt反应合成(R)-苯并吲哚里西定

Synthesis of(R)-benzoindolizidine by Intramolecular Schmidt Reaction of ω-Azido Acyl Chloride

5-溴戊酰氯与手性助剂(S)-4-苄基-2-噁唑烷酮经酰胺化反应制得手性酰胺(3);3与叠氮钠反应得烷基化前体(4);以苄溴为烷基化试剂,碱辅助在酰胺羰基邻位引入苄基高立体选择性地制得手性酰胺[(R)-5],dr>99/1。用H2O2脱除(R)-5中的助剂结构单元得多米诺反应的前体手性叠氮羧酸[(R)-6];用草酰氯预处理(R)-6,原位制得叠氮酰氯,随即以四氯化锡来实现分子内Schmidt反应,苯环原位捕获重排中间体合成内酰胺[(R)-7],92%ee;用红铝还原(R)-7合成了(R)-苯并吲哚里西啶,收率85%,总收率40.6%,其结构经1H NMR,13C NMR和IR确证。

The chiral arnide （3） was prepared by amidation of 5-bromopetanoyl chloride with the ehiral auxiliary （S） -（ - ） -4-benzyl-2-oxazolidinone. The azido carboxylic acid[ （R） -6] was synthe- sized by reaction of 3 with sodium azide, then introducing of benzyl and removel of the auxiliary. Treatment of （R）-6 with oxalyl chloride followed with stannie chloride gave the benzo fused lactam [ （R）-7 ] in good yield with 92% ee. （R）-benzoindolizidine with the yield of 85% was synthesized by reudetion of （R）-7 with red aluminum. The total yield was 40.6%. The structure was confirmed by l H NMR, 13C NMR and IR.