Enamide synthesis by copper-catalyzed cross-coupling of amides and potassium alkenyltrifluoroborate salts
Enamide synthesis by copper-catalyzed cross-coupling of amides and potassium alkenyltrifluoroborate salts
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DOI：
10.1002/anie.200704711
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发表时间：
2008-01-01
影响因子：
16.6
通讯作者：
Batey, Robert A.
中科院分区：
文献类型：
--
作者：
Bolshan, Yuri;Batey, Robert A.
烯酰胺是各类天然产物中的关键结构基序[1，2]，也是有价值的合成中间体。[3，4]除了一些传统采用的方法外，[5-9]最近出现了几种用于合成酰胺的过渡金属催化方法。[10-12]迄今为止开发的最广泛应用的金属催化方法可能是铜催化的烯基卤化物与酰胺的偶联[13]，[14]这是Goldberg反应的现代变体。[15]Porco、Buchwald、Ma和其他人已经表明，酰胺和烯基溴的偶联可以使用催化量的铜盐来实现。[16]尽管有这些进展，但仍然需要用于烯酰胺形成的通用方法，特别是因为现有方法通常具有有限的底物范围并且通常需要升高的温度、严格排除空气和水以及使用两个或更多个当量的强碱。Lam等人已经报道了使用（E）-1-己烯基硼酸作为替代偶联配偶体。[17不幸的是，该方法缺乏通用性，并且仅报道了酰胺样底物（1-乙基-1，3-二氢苯并咪唑-2-酮、2-羟基吡啶和邻苯二甲酰亚胺）的三个实例，其在五组不同的反应条件下得到可变的产率。与芳基硼酸的类似反应相比，该途径的潜在问题之一[18，19]是烯基硼酸的稳定性较低，特别是在氧化条件下。我们之前已经证明，在铜催化的与醇[20]和胺[21]的交叉偶联反应中使用有机三氟硼酸钾盐提供了优于硼酸的相应反应的几个优点。该四配位盐具有增加的对空气和水的稳定性，并且易于制备。[22]许多现在都是商业上可获得的，[23]并且它们被广泛用于其他类型的金属催化转化。[23-25]在此，我们报道了烯基三氟硼酸钾盐可用于在温和的无碱条件下与酰胺的铜催化的交叉偶联反应。邻苯二甲酰亚胺被选为测试基板在最初的实验中，以优化反应条件，因为它已被用于Lam等人。[17]在化学计量量的Cu II盐存在下，在己烯基硼酸的偶联中以良好的产率（79%）得到相应的烯酰胺产物2，但是在催化条件（Cu（OAc）2，10摩尔%）下提供了差的产率（13%）。在Lam所用的相同催化条件下，除了在408 ℃下，使用己烯基三氟硼酸盐1a进行偶联，类似地以低收率得到2（表1，条目1）。反应效率在除去过量碱（Et 3 N）后得到改善，并且强烈依赖于配体的选择（表1，条目2-7）。在富电子单齿胺配体的存在下获得最高的产率。令人感兴趣的是，使用N-甲基咪唑作为配体（其之前未在铜催化的偶联反应中使用）得到最好的结果，以定量产率提供2（表1，条目7）。在相同条件下尝试（E）-1-己烯基硼酸的反应是不成功的。
Enamides are key structural motifs in various classes of natural products [1, 2] and are also valuable synthetic intermediates.[3, 4] In addition to a number of traditionally employed approaches,[5–9] several transition-metal-catalyzed methods for the synthesis of enamides have recently emerged.[10–12] Perhaps the most widely applicable metalcatalyzed method developed to date is the copper-catalyzed coupling [13] of alkenyl halides with amides,[14] a modern variant of the Goldberg reaction.[15] Porco, Buchwald, Ma, and others have shown that the coupling of amides and alkenyl bromides can be achieved using catalytic quantities of copper salts.[16] Despite these advances general methods are still needed for enamide formation, particularly since existing methods often have limited substrate scope and typically require elevated temperatures, rigorous exclusion of air and water, and the use of two or more equivalents of strong base. Lam et al. have reported the use of (E)-1-hexenylboronic acid as an alternative coupling partner.[17, 18] Unfortunately, this method lacks generality, and only three examples of amidelike substrates (1-ethyl-1, 3-dihydrobenzoimidazol-2-one, 2-hydroxypyridine, and phthalimide) were reported, which gave variable yields under five different sets of reaction conditions. One of the potential problems with this route, compared to similar reactions of arylboronic acids,[18, 19] is the lower stability of alkenylboronic acids, particularly under oxidative conditions. We have previously demonstrated that the use of potassium organotrifluoroborate salts in copper-catalyzed cross-coupling reactions with alcohols [20] and amines [21] offer several advantages over the corresponding reactions of boronic acids. The tetracoordinate salts possess increased stability toward air and water, and are readily prepared.[22] Many are now commercially available,[23] and they are widely used for other classes of metal-catalyzed transformations.[23–25] Herein we report that potassium alkenyltrifluoroborate salts can be used in copper-catalyzed cross-coupling reactions with amides under mild base-free conditions. Phthalimide was chosen as a test substrate in the initial experiments to optimize the reaction conditions, because it had been used by Lam et al.[17] in the coupling of hexenylboronic acid to give the corresponding enamide product 2 in good yield (79%) in the presence of stoichiometric amounts of CuII salts, but had provided poor yield (13%) under catalytic conditions (Cu (OAc) 2, 10 mol%). Coupling under the same catalytic conditions employed by Lam, except at 408C, using hexenyltrifluoroborate salt 1a similarly gave 2 in low yield (Table 1, entry 1). The efficiency of the reaction improved on removal of the excess base (Et3N) and was strongly dependant upon the choice of ligand (Table 1, entries 2–7). The highest yields were obtained in the presence of electron-rich monodentate amine ligands. Interestingly, the use of N-methylimidazole as ligand, which has not been used before in copper-catalyzed coupling reactions, gave the best results, affording 2 in quantitative yield (Table 1, entry 7). Attempted reaction of (E)-1-hexenylboronic acid under the same conditions was unsuccessful.