Asymmetric Lithiation−Substitution Sequences of Substituted Allylamines

(−)-Sparteine-mediated asymmetric lithiation−substitution sequences of 2- and 3-substituted
N-(Boc)-N-(p-methoxyphenyl) allylic amines with electrophiles have been investigated. Asymmetric
lithiation−substitutions of N-(Boc)-N-(p-methoxyphenyl) allylic amines 11, 12, 13, 14, and 15 provide
highly enantioenriched enecarbamates in good yields. Further transformations to give aldehydes,
acids, ketones, and a Diels−Alder adduct are reported. The 1,4-addition products from reactions of
the lithiated allylic amines from 14 and 15 with conjugated activated alkenes gives enecarbamates
with two and three stereogenic centers in good yields with high diastereomeric and enantiomeric
ratios. Synthetic transformation of these products by acid hydrolysis and subsequent cyclization
provide stereoselective access to bicyclic compounds containing four and five stereogenic centers
with high diastereoselectivity and enantioselectivity. It is suggested that allyllithium complexes
generated by asymmetric deprotonation react with most electrophiles with inversion of configuration.

本研究系统考察了以(-)-鹰爪豆碱((-)-Sparteine)为手性介导试剂的2-位及3-位取代N-(Boc)-N-(对甲氧基苯基)烯丙基胺与亲电试剂的不对称锂化-取代反应序列。针对N-(Boc)-N-(对甲氧基苯基)烯丙基胺11、12、13、14及15开展的不对称锂化-取代反应，可获得收率优良且对映体高度富集的烯基氨基甲酸酯产物。本文同时报道了该类产物进一步转化为醛、羧酸、酮及狄尔斯-阿尔德(Diels−Alder)加合物的合成路径。由底物14和15衍生的锂化烯丙基胺与共轭活化烯烃发生反应得到的1,4-加成产物，可生成带有两个及三个手性中心的烯基氨基甲酸酯，且反应兼具良好收率与优异的非对映异构体比例及对映异构体比例。通过酸水解及后续环化对上述产物进行合成转化，可立体选择性构建含有四个及五个手性中心的双环化合物，该过程展现出极高的非对映选择性与对映选择性。研究证实，经不对称去质子化生成的烯丙基锂配合物与绝大多数亲电试剂发生反应时，均遵循构型翻转的反应机制。