Kinetics and mechanism of the (-)-sparteine-mediated deprotonation of (E)-N-Boc-N-(p-methoxyphenyl)-3-cyclohexylallylamine.
Kinetics and mechanism of the (-)-sparteine-mediated deprotonation of (E)-N-Boc-N-(p-methoxyphenyl)-3-cyclohexylallylamine.
复制标题
(-)-金雀花碱介导的 (E)-N-Boc-N-(对甲氧基苯基)-3-环己基烯丙胺去质子化的动力学和机制。
DOI：
10.1021/ja001955k
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发表时间：
2001
影响因子：
15
通讯作者：
Beak,P
中科院分区：
文献类型：
--
作者：
Pippel,DJ;Weisenburger,GA;Faibish,NC;Beak,P
报道了（E）-N-Boc-N-（p-甲氧基苯基）-3-环己基烯丙胺（（E）-5）的（−）-鹰爪豆碱介导的不对称锂化−取代反应，得到γ-取代的对映体富集产物6。在这些反应中，锂化中间体8·1的溶液结构通过Heter-NMR确定为构型稳定的α-锂代η1配位单体。该中间体被提议作为两种旋转异构体存在，它们在NMR时间尺度上迅速平衡;每个构象的竞争性亲电取代导致形成ofZorE产物。动力学测量的锂化原位红外光谱提供了伪一级反应速率常数与各种浓度的胺，（-）-金雀花碱，和n-BuLi。该反应在胺中为一级反应，在1：1碱-配体络合物中为零级反应。当n-BuLi的浓度与（-）-金雀花碱的浓度无关时，反应速率与n-BuLi的浓度呈负相关。反应的氘同位素效应在−75 °C下被确定为86，这一结果与速率决定步骤中的C-H键断裂一致，并表明隧道效应。涉及预锂化复合物的反应途径的动力学模拟的支持。
The (−)-sparteine-mediated asymmetric lithiation−substitution of (E)-N-Boc-N-(p-methoxyphenyl)-3-cyclohexylallylamine ((E)-5) to afford γ-substituted enantiomerically enriched products6is reported. The solution structure for the lithiated intermediate8·1in these reactions was determined by heteronuclear NMR to be a configurationally stable, α-lithio, η1-coordinated monomer. This intermediate is proposed to exist as two rotamers that are rapidly equilibrating on the NMR time scale; competitive electrophilic substitution of each conformation results in the formation ofZorEproducts. Kinetic measurements of the lithiation by in situ infrared spectroscopy provide pseudo-first-order rate constants for reactions with a variety of concentrations of amine, (−)-sparteine, andn-BuLi. The reaction is first order in amine and zero order in 1:1 base−ligand complex. When the concentration ofn-BuLi is varied independently of (−)-sparteine concentration, the reaction rate exhibits an inverse dependence onn-BuLi concentration. The deuterium isotope effect for the reaction was determined to be 86 at −75 °C, a result consistent with C−H bond breaking in the rate-determining step and indicative of tunneling. A reaction pathway involving a prelithiation complex is supported by kinetic simulations.