Department of Chemistry, University of Sheffield, Brook Hill, Sheffield S3 7HF, UK.
J Org Chem. 2010 Jun 18;75(12):4069-77. doi: 10.1021/jo100415x.
Copper salts have been screened for transmetalation and electrophilic quench of N-tert-butoxycarbonyl-2-lithiopyrrolidine (N-Boc-2-lithiopyrrolidine) and N-Boc-2-lithiopiperidine, formed by deprotonation of N-Boc-pyrrolidine and N-Boc-piperidine, respectively. Transmetalation with zinc chloride then (lithium chloride solubilized) copper cyanide followed by allylation typically gives mixtures of regioisomers (S(N)2 and S(N)2' products), whereas transmetalation with copper iodide.TMEDA then allylation occurs regioselectively (S(N)2 mechanism). Addition to an enone or alpha,beta-unsaturated ester occurs by 1,4-addition. Asymmetric deprotonation of N-Boc-pyrrolidine or dynamic resolution in the presence of a chiral ligand of N-Boc-2-lithiopiperidine followed by the zinc/copper chemistry was successful and gave the allylated pyrrolidine and piperidine products with good enantioselectivity, although use of the copper iodide chemistry resulted in some loss of enantiopurity. The chemistry provides formal syntheses of (+)-allosedridine, (+)-lasubine II, and (+)-pseudohygroline and has been used for the synthesis of (+)-coniine, (-)-pelletierine, (+)-coniceine, (-)-norhygrine, and the ant extract alkaloids cis- and trans-2-butyl-5-propylpyrrolidine.
铜盐已被筛选用于 N-叔丁氧羰基-2-锂吡咯烷（N-Boc-2-锂吡咯烷）和 N-Boc-2-锂哌啶的转金属化和亲电淬灭，这两种化合物分别由 N-Boc-吡咯烷和 N-Boc-哌啶脱质子形成。然后用氯化锌进行转金属化（溶解在氯化锂中），接着用氰化铜和烯丙基化反应通常得到区域异构体的混合物（S(N)2 和 S(N)2'产物），而用碘化铜.TMEDA 进行转金属化然后烯丙基化则是区域选择性的（S(N)2 机制）。与烯酮或α，β-不饱和酯的加成通过 1,4-加成发生。N-Boc-吡咯烷的不对称脱质子或在手性配体存在下的 N-Boc-2-锂哌啶的动态拆分，然后进行锌/铜化学，是成功的，并得到了具有良好对映选择性的烯丙基化吡咯烷和哌啶产物，尽管使用碘化铜化学会导致对映纯度的一些损失。该化学提供了（+）-allosedridine、（+）-lasubine II 和（+）-pseudohygroline 的正式合成方法，并已用于（+）-coniine、（-）-pelletierine、（+）-coniceine、（-）-norhygrine 和抗提取物生物碱顺式和反式 2-丁基-5-丙基吡咯烷的合成。
