Hiyama reactions of activated and unactivated secondary alkyl halides catalyzed by a nickel/norephedrine complex
Hiyama reactions of activated and unactivated secondary alkyl halides catalyzed by a nickel/norephedrine complex
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DOI：
10.1002/anie.200700440
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Fu, Gregory C.
中科院分区：
文献类型：
--
作者：
Strotman, Neil A.;Sommer, Stefan;Fu, Gregory C.
我们最近报道了基于镍/红菲咯啉的催化剂首次实现了未活化的仲烷基亲电试剂的Hiyama偶联[1][方程式：(1)DMSO=二甲基亚砜]。[2]虽然这代表了在金属催化的交叉偶联反应的范围的扩展方面向前迈进了一步，[3，4]但从至少三个观点来看，这不是一个理想的解决方案：首先，Hiyama反应的产率是中等的（60-82%）;其次，该方法对于活化的仲烷基卤化物通常不是有效的;第三，只有在氮原子邻位缺少取代基的联吡啶型配体才提供有用的催化剂（即红菲咯啉、1，10-菲咯啉和2，2 ′-联吡啶，但不提供新亚铜灵）。这种对取代的敏感性是我们实现不对称Hiyama反应的长期目标的一个重大障碍，因为几乎所有已经描述的有效手性联吡啶都具有邻位基团。[5]在2006年，我们报道了氨基醇可以用作未活化的烷基亲电试剂的交叉偶联反应的有用配体[Suzuki偶联反应：Eq. (2)，HMDS= 1，1，1，3，3，3-六甲基二硅氮烷]。[6]不幸的是，当我们尝试用反式-2-氨基环己醇[环己基溴和F3 SiPh，Eq. (1)]尽管最初的结果令人沮丧，但我们认识到各种各样的氨基醇是容易（和商业）获得的，并且我们决定探索一种这样的配体可能使我们能够解决我们的第一代用于卤代烷的Hiyama反应的催化剂的缺点的可能性。经过相当大的努力，我们很高兴地确定，在去甲麻黄碱的存在下，我们可以以非常好的产率实现环己基溴与F3 SiPh的交叉偶联（表1，条目1）。[7]所示
We recently reported that a nickel/bathophenanthrolinebased catalyst accomplishes Hiyama couplings [1] of unactivated secondary alkyl electrophiles for the first time [Eq.(1), DMSO= dimethyl sulfoxide].[2] Although this represented a step forward in the expansion of the scope of metal-catalyzed cross-coupling reactions,[3, 4] it was not an ideal solution from at least three standpoints: First, the yields of the Hiyama reactions were moderate (60–82%); second, the method was not generally effective for activated secondary alkyl halides; and third, only bipyridine-type ligands that lack a substituent ortho to the nitrogen atom furnished useful catalysts (that is, bathophenanthroline, 1, 10-phenanthroline, and 2, 2о-bipyridine, but not neocuproine). This sensitivity to substitution represented a significant impediment to our long-term goal of achieving asymmetric Hiyama reactions, since virtually all of the effective chiral bipyridines that have been described have groups in the ortho position.[5] In 2006 we reported that an amino alcohol can serve as a useful ligand for cross-coupling reactions of unactivated alkyl electrophiles [Suzuki coupling reactions: Eq.(2), HMDS= 1, 1, 1, 3, 3, 3-hexamethyldisilazane].[6] Unfortunately, when we attempted a Hiyama reaction with trans-2-aminocyclohexanol [cyclohexyl bromide and F3SiPh, Eq.(1)], we obtained none of the desired cross-coupling product.Despite this initial discouraging result, we recognized that a diverse array of amino alcohols are readily (and commercially) available, and we decided to explore the possibility that one such ligand might enable us to address the shortcomings of our first-generation catalyst for Hiyama reactions of alkyl halides. After considerable effort, we were pleased to determine that, in the presence of norephedrine, we can achieve the cross-coupling of cyclohexyl bromide with F3SiPh in very good yield (Table1, entry1).[7] As illustrated in