Enantioselective, palladium-catalyzed α-arylation of N-Boc-pyrrolidine
Enantioselective, palladium-catalyzed α-arylation of N-Boc-pyrrolidine
复制标题
DOI：
10.1021/ja0605265
复制
发表时间：
2006-03-22
影响因子：
15
通讯作者：
Chen, CY
中科院分区：
文献类型：
--
作者：
Campos, KR;Klapars, A;Chen, CY
This communication discloses the first instance of the enantioselective Pd-catalyzed α-arylation ofN-Boc-pyrrolidine. The methodology relies on Beak's sparteine-mediated, enantioselective deprotonation ofN-Boc-pyrrolidine to form the 2-pyrrolidinolithium specices in high enantiomeric ratio (er). Transmetalation of this intermediate with zinc chloride generates the stereochemically rigid, 2-pyrrolidinozinc reagent, which was readily coupled to a variety of functionalized aryl halides at room temperature using a catalyst generated from Pd(OAc)2and PtBu3−HBF4. A diverse array of 2-aryl-N-Boc-pyrrolidines was synthesized using this methodology, providing adducts consistently in a 96:4 er. A survey of the stoichiometry revealed that as little as 0.3 equiv of zinc could be used in the coupling reaction, and the 2-pyrrolidinozinc reagent was found to exhibit stereochemical stability up to 60 °C. The method allows for the most convergent and reliable preparation of a broad range of functionalized 2-aryl-N-Boc-pyrrolidines in high enantioselectivity, which is highlighted in this report by the enantioselective synthesis of (R)-nicotine.
