Anion radical [2+2] cycloaddition as a mechanistic probe:: Stoichiometry- and concentration-dependent partitioning of electron-transfer and alkylation pathways in the reaction of the gilman reagent Me2CuLi•LiI with bis(enones)
Anion radical [2+2] cycloaddition as a mechanistic probe:: Stoichiometry- and concentration-dependent partitioning of electron-transfer and alkylation pathways in the reaction of the gilman reagent Me2CuLi•LiI with bis(enones)
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DOI：
10.1021/jo048499t
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发表时间：
2004-11-12
影响因子：
3.6
通讯作者：
Krische, MJ
中科院分区：
文献类型：
--
作者：
Yang, JK;Cauble, DF;Krische, MJ
在0 ℃下，在四氢呋喃溶剂中，将容易还原的芳族双（烯酮）1a-1 e暴露于甲基Gilman试剂Me 2CuLi·LiI，得到串联共轭加成-迈克尔环化的产物2a-2 e，沿着[2 + 2]环加成的产物3a-3e。Gilman烷基化和[2 + 2]环加成途径的完全分配可以通过调节Gilman试剂的加载量、Gilman试剂的添加速率和反应混合物的浓度来实现。在较高的底物浓度下快速添加过量的吉尔曼试剂有利于吉尔曼烷基化歧管，而在较低的浓度和载量下缓慢添加相同的吉尔曼试剂有利于[2 + 2]环加成歧管。值得注意的是，形成3a-3e的[2 + 2]环加成在吉尔曼试剂中是催化的。动力学数据表明，2a和3a的比例发生变化，使得环加成途径在Gilman试剂消耗增加时变得占主导地位。这些数据表明，浓度依赖性形态的吉尔曼试剂和差异反应的聚集体存在于较高和较低的浓度。虽然以较高浓度存在的物质在生成产物2a-2 e的过程中诱导Gilman烷基化，但以较低浓度存在的物质提供催化[2 + 2]环加成的产物3a-3e。此外，在his（烯酮）la-le的电化学还原或来自芳烃阴离子自由基的化学诱导的单电子转移时，形成非常相同的[2 + 2]环加合物3a-3e。集体数据表明，在Gilman条件下产生的[2 + 2]环加合物3a-3e可能是阴离子自由基链式环丁烷化的产物，其通过电子转移（ET）从低浓度存在的Me 2CuLi. LiI聚集体衍生。这些观察结果提供了吉尔曼烷基化反应和相关的ET化学之间的联系，并表明这些反应路径是不同的机械。这种分析是可能的，最近的观察，容易减少的双（烯酮）受到分子内[2 + 2]环加成阴极还原或化学诱导的ET从芳烃阴离子自由基，并在此展示作为一种新的方法测试的中间体烯酮阴离子自由基。
Exposure of easily reduced aromatic bis(enones) 1a-1e to the methyl Gilman reagent Me2CuLi.LiI at 0 degreesC in tetrahydrofuran solvent provides the products of tandem conjugate addition-Michael cyclization, 2a-2e, along with the products of [2 + 2] cycloaddition, 3a-3e. Complete partitioning of the Gilman alkylation and [2 + 2] cycloaddition pathways may be achieved by adjusting the loading of the Gilman reagent, the rate of addition of the Gilman reagent, and the concentration of the reaction mixture. The Gilman alkylation manifold is favored by the rapid addition of excess Gilman reagent at higher substrate concentrations, while the [2 + 2] cycloaddition manifold is favored by slow addition of the same Gilman reagent at lower concentrations and loadings. Notably, [2 + 2] cycloaddition to form 3a-3e is catalytic in Gilman reagent. Kinetic data reveal that the ratio of 2a and 3a changes such that the cycloaddition pathway becomes dominant upon increased consumption of Gilman reagent. These data suggest a concentration-dependent speciation of the Gilman reagent and differential reactivity of the aggregates present at higher and lower concentrations. While the species present at higher concentration induce Gilman alkylation en route to products 2a-2e, the species present at lower concentration provide products of catalytic [2 + 2] cycloaddition, 3a-3e. Moreover, upon electrochemical reduction of the his(enones) la-le, or chemically induced single-electron transfer from arene anion radicals, the very same [2 + 2] cycloadducts 3a-3e are formed. The collective data suggest that [2 + 2] cycloadducts 3a-3e arising under Gilman conditions may be products of anion radical chain cyclobutanation that derive via electron transfer (ET) from the Me2CuLi.LiI aggregate(s) present at low concentration. These observations provide a link between the Gilman alkylation reaction and related ET chemistry and suggest these reaction paths are mechanistically distinct. This analysis is made possible by the recent observation that easily reduced bis(enones) are subject to intramolecular [2 + 2] cycloaddition upon cathodic reduction or chemically induced ET from arene anion radicals, and is herewith showcased as a novel method of testing for the intermediacy of enone anion radicals.