不对称Heck反应合成手性哌啶衍生物

SYNTHESIS OF CHIRAL PIPERIDINE DERIVATIVES VIA ASYMMETRIC HECK REACTION

手性哌啶骨架广泛存在于药物和活性天然产物分子中。本研究发展了一种新型不对称Heck反应,用于合成手性哌啶衍生物。通过对反应条件进行筛选,得到了最优反应条件:催化剂为[Pd(allyl)Cl]_(2)(5 mol%),配体为L5(10 mol%),NaOMe(3.0 equiv)作碱,在110℃的混合溶剂(PhMe/MeOH=5/1)中回流反应20 h。该不对称Heck反应显示出良好的底物普适性,可用于构建多种含有季碳中心的手性哌啶衍生物。

Chiral piperidine backbones are widely found in the drugs and bioactive natural products.In the present study,a new asymmetric Heck reaction has been developed that allows synthesis of chiral piperidine derivatives.After screening of reaction conditions,the optimal conditions were obtained:[Pd(allyl)Cl]_(2)(5 mol%)as catalyst,L5(10 mol%)as ligand,NaOMe(3.0 equiv)as base,mixed solvent(PhMe/MeOH=5/1)at 110℃for 20 hours.This method displays a good substrate scope,which could facilitate the preparation of chiral piperidine derivatives with quaternary stereogenic centers.