Indium Tribromide Catalyzed Cross-Claisen Condensation between Carboxylic Acids and Ketene Silyl Acetals Using Alkoxyhydrosilanes
Indium Tribromide Catalyzed Cross-Claisen Condensation between Carboxylic Acids and Ketene Silyl Acetals Using Alkoxyhydrosilanes
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DOI：
10.1002/anie.201104140
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发表时间：
2011-01-01
影响因子：
16.6
通讯作者：
Baba, Akio
中科院分区：
文献类型：
--
作者：
Nishimoto, Yoshihiro;Okita, Aya;Baba, Akio
碳酰化在具有羰基的碳框架的构建中发挥着重要作用。其中Claisen缩合反应是最有用的方法之一，因为它可以缩合多种β-酮酯。[1]一个经典的例子是由强碱促进的酯的均缩合。[2]最近在金属烯醇化物和活性酰化试剂（如酸酐或酰氯）之间的交叉缩合中的成功开发已经导致副反应的减少。[3-5]羧酸是作为酰化试剂的有希望的候选物，但它们的直接使用仍然是一个具有挑战性的问题，因为酸性质子经常导致催化剂的分解和不期望的副反应。大多数报道的反应需要使用苛刻的试剂如SOCl 2 [6]或N，N '-羰基二咪唑来从羧酸制备活性中间体[7]，这些反应导致产生麻烦的副产物。最近，田边和同事报道了钛和甲硅烷基烯醇化物在温和的反应条件下的交叉缩合，但该系统还需要额外的步骤来制备活性中间体。[3c在此，我们描述了一种方便的铟催化的交叉克莱森缩合，其中在InBr 3存在下简单且顺序地添加羧酸、烷氧基氢硅烷和烯酮甲硅烷基缩醛得到所需产物。由于三卤化铟具有中等的刘易斯酸性、对酸性质子的高耐受性以及与各种官能团的相容性，我们最近集中于使用三卤化铟实现醇与各种亲核试剂的直接偶联反应以及使用羧酸的Friedel-Crafts酰化反应。[8，9]这些结果促使我们尝试在三卤化铟存在下苯甲酸1a和二甲基烯酮甲基三甲基甲硅烷基缩醛（2a）之间的缩合反应。使用催化量的InBr 3几乎没有得到任何缩合产物（表1，条目1），并且Me 3SiCl的添加是无效的（表1，条目2）。接下来，使用Me 2ClSiH（其在使用羧酸的傅-克酰基化中有效）提供了所需的产物3 aa，但尽管反应转化率高，产率仅为39%（表1，条目3）。[9]这些结果表明，卤化铟和卤化甲硅烷基的组合（其通常作为强刘易斯酸）[8d，e，10]不适用于该反应。令人满意的是，使用烷氧基氢硅烷代替Me 2ClSiH加速了交叉克莱森缩合，这伴随着氢气的剧烈产生;（MeO）3SiH给出了最好的结果（表1，条目4-6）。[11]该方法具有明显的优点，即以InBr 3、1a、氢硅烷和2a的顺序连续加入所有试剂得到高产率的3 aa，并且不需要用于产生活性酰化试剂的特定步骤。当使用Et 3SiH时，发生氢气的快速放出，但仅以7%的产率获得所需产物（表1，条目7）。在不存在三卤化铟的情况下使用（MeO）3SiH没有提供产物（表1，条目8）。（MeO）3SiH与InI 3的组合得到令人满意的结果（表1，条目9），而InCl 3和In（OTf）3显示低活性（表1，条目10和11）。在包括InBr 3催化剂和（MeO）3SiH（表2）的优化的反应条件下，检查使用各种羧酸的直接酰化。带有供电子和吸电子基团的芳族羧酸与烯酮甲硅烷基缩醛2a反应，得到所需的β-酮酯3（表2，条目1-3）。脂肪族...
Carbon acylations play an important role in the construction of carbon frameworks having a carbonyl group. Among them, the Claisen condensation is one of the most useful methods, as it furnishes various β-ketoesters.[1] A classical example is the homocondensation of esters promoted by a strong base.[2] Recent successful developments in the cross-condensation between metal enolates and active acylating reagents, such as acid anhydrides or acid chlorides, have resulted in a reduction in side reactions.[3–5] Carboxylic acids are promising candidates as acylating reagents, but their direct use remains a challenging problem because the acidic proton often causes decomposition of the catalyst and undesired side reactions. Most of the reported reactions require the use of harsh reagents such as SOCl2[6] or N, N’-carbonyldiimidazole to prepare active intermediates from carboxylic acids,[7] and these reactions result in troublesome by-products being generated. Recently, Tanabe and co-workers reported the cross-condensation of titanium and silyl enolates under mild reaction conditions, but the system also required an extra step to prepare active intermediates.[3c, 4c] Herein, we describe a convenient indium-catalyzed cross-Claisen condensation, in which the simple and sequential addition of a carboxylic acid, an alkoxyhydrosilane, and a ketene silyl acetal in the presence of InBr3 gives the desired product. Owing to its moderate Lewis acidity, high tolerance to an acidic proton, and compatibility with various functional groups, we recently focused on using indium trihalides to achieve a direct coupling reaction of alcohols with various nucleophiles and the Friedel–Crafts acylation using carboxylic acids.[8, 9] These results prompted us to attempt the condensation reaction between benzoic acid 1a and dimethylketene methyltrimethylsilyl acetal (2a) in the presence of an indium trihalide. The use of a catalytic amount of InBr3 gave hardly any condensation product (Table 1, entry 1) and the addition of Me3SiCl was ineffective (Table 1, entry 2). Next, the use of Me2ClSiH, which was effective in the Friedel–Crafts acylation using carboxylic acids, furnished the desired product 3 aa, but the yield was only 39% despite a high reaction conversion (Table 1, entry 3).[9] These results indicated that the combination of an indium halide and a silyl halide, which often acts as a strong Lewis acid,[8d, e, 10] is not applicable for this reaction. Gratifyingly, the employment of alkoxyhydrosilanes, instead of Me2ClSiH, accelerated the cross-Claisen condensation, which was accompanied by the vigorous generation of hydrogen gas;(MeO) 3SiH gave the best result (Table 1, entries 4–6).[11] This method has a clear advantage that the successive addition of all the reagents in the order of InBr3, 1a, hydrosilane, and 2a gave high yields of 3 aa, and a specific step for the generation of an active acylating reagent was not required. When Et3SiH was used a rapid evolution of hydrogen gas occurred, but the desired product was obtained in only 7% yield (Table 1, entry 7). The use of (MeO) 3SiH in the absence of indium trihalide furnished no product (Table 1, entry 8). The combination of (MeO) 3SiH with InI3 gave a satisfying result (Table1, entry9), while InCl3 and In (OTf) 3 showed low activity (Table 1, entries 10 and 11). Direct acylations using a variety of carboxylic acids were examined under the optimized reaction conditions, which included InBr3 catalyst, and (MeO) 3SiH (Table 2). Aromatic carboxylic acids bearing either electron-donating and electron-withdrawing groups reacted with ketene silyl acetals 2a to give the desired β-ketoesters 3 (Table 2, entries 1–3). Aliphatic …