Organocuprate cross-coupling: The central role of the copper(III) intermediate and the importance of the Copper(I) precursor
Organocuprate cross-coupling: The central role of the copper(III) intermediate and the importance of the Copper(I) precursor
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DOI：
10.1002/anie.200703035
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Ogle, Craig A.
中科院分区：
文献类型：
--
作者：
Bertz, Steven H.;Cope, Stephen;Ogle, Craig A.
铜是最不起眼的钴金属，但在合成方面却最有用。化学家使用有机铜化合物，例如，有机铜酸盐（吉尔曼试剂）R2 CuLi，用于大量涉及选择性产生碳-碳键的转化。[1，2]有机铜试剂的两个典型反应是与α，β-不饱和羰基化合物的共轭加成和与有机卤化物的交叉偶联[3-5]，其已被推广到包括各种离去基团，并进一步从SN 2扩展到SN 2 '过程。化学计量和催化铜介导的反应中的关键中间体一直被认为是所谓的“铜（III）中间体"，[3a，4-6]并且理论计算支持这一假设。[7，8]我们最近报道了在共轭加成反应（2-环己烯酮+Me 2CuLi· LiI+ Me 3SiCN）中，通过在1008 ℃下使用快速注入NMR光谱（RI-NMR）观察到这种四配位正方形平面（TCSP）中间体的第一个例子，氰基双（甲基）（3-三甲基环己基环己-2-烯-1-基）铜（III）酸锂。[9]它在808 ℃下迅速分解，得到预期的烯醇化物。我们现在已经研究了各种甲基Gilman试剂Me 2CuLi· LiX（1，X= I，CN，SCN，SPh）与简单卤代烷EtI在RI-NMR条件下的反应，并且我们已经能够观察到许多具有令人惊讶的稳定性范围的TCSP中间体。其中最稳定的是乙基三甲基铜（III）酸锂（2），它是第一个没有氟化取代基的四烷基铜（III）配合物。[10]自乌尔曼反应的早期以来，铜介导的交叉偶联过程一直难以控制和优化，[5]我们在这一领域的观察具有合成衍生物和机械意义。当Me 2CuLi· LiI（1a）或Me 2CuLi· LiCN（1b;在[D8] THF中，在氮气下，在NMR管中，在100 ℃下在NMR光谱仪的探针中旋转）注入EtI的[D8] THF溶液时，在NMR光谱中观察到瞬态新信号。基于NMR光谱研究，包括2D技术（见支持信息）和13 C标记的类似物（见下文），分别将它们分配为3（来自1a）和4（来自1b）（方案1）。化学位移数据总结在表1中;值得注意的是，与铜键合的碳原子具有极强的去屏蔽性质。
Copper, the humblest of the coinage metals, has nevertheless been the most useful synthetically. Chemists use organocopper compounds, for exmaple, organocuprates (Gilman reagents) R2CuLi, for a plethora of transformations involving the selective creation of carbon–carbon bonds.[1, 2] The two prototypical reactions of organocopper reagents are conjugate addition to α, β-unsaturated carbonyl compounds and cross-coupling with organic halides,[3–5] which has been generalized to include a variety of leaving groups and further extended from SN2 to SN2’processes. The key intermediate in both stoichiometric and catalytic copper-mediated reactions has long been believed to be a socalled “copper (III) intermediate,”[3a, 4–6] and theoretical calculations have supported this hypothesis.[7, 8] We recently reported the observation of the first example of such a tetracoordinate, square-planar (TCSP) intermediate, lithium cyanobis (methyl)(3-trimethylsiloxycyclohex-2-en-1-yl) cuprate (III), in a conjugate addition reaction (2-cyclohexenone+ Me2CuLi· LiI+ Me3SiCN) by using rapid-injection NMR spectroscopy (RI-NMR) at À1008C.[9] It decomposed rapidly at À808C to yield the expected enolate. We have now investigated the reactions of a variety of methyl Gilman reagents, Me2CuLi· LiX (1, X= I, CN, SCN, SPh), with a simple alkyl halide, EtI, under RI-NMR conditions, and we have been able to observe a number of TCSP intermediates with a surprising range of stabilities. The most stable of them, lithium ethyltrimethylcuprate (III)(2), is the first example of a tetraalkyl copper (III) complex without fluorinated substituents.[10] Since the earliest days of the Ullmann reaction, copper-mediated cross-coupling processes have been notoriously difficult to control and optimize,[5] and our observations in this area have synthetic ramifications as well as mechanistic significance. When Me2CuLi· LiI (1a) or Me2CuLi· LiCN (1b; in [D8] THF under nitrogen in an NMR tube, spinning in the probe of an NMR spectrometer at À1008C) was injected with a [D8] THF solution of EtI, transient new signals were observed in the NMR spectrum. They were assigned to 3 (from 1a) and 4 (from 1b), respectively (Scheme 1), on the basis of NMR spectroscopy studies, including 2D techniques (see the Supporting Information) and 13C-labeled analogs (see below). Chemical shift data are summarized in Table 1; they are notable for the extremely deshielded nature of the carbon atom bonded to copper.