Catalytic enantioselective Dieckmann-type annulation: synthesis of pyrrolidines with quaternary stereogenic centers.
Catalytic enantioselective Dieckmann-type annulation: synthesis of pyrrolidines with quaternary stereogenic centers.
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DOI：
10.1002/anie.200907067
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发表时间：
2010-03
影响因子：
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通讯作者：
J. Hargrave;Joseph C. Allen;G. Kociok‐Köhn;G. Bish;C. Frost
中科院分区：
文献类型：
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作者：
J. Hargrave;Joseph C. Allen;G. Kociok‐Köhn;G. Bish;C. Frost
通过催化方法立体选择性地构建全碳四元立体中心是合成化学家非常渴望但具有挑战性的目标。一种已取得一定程度成功的方法是烷基有机金属试剂与B，b ′-二取代烯烃受体的催化对映选择性共轭加成。芳基硼酸的互补铑催化的对映选择性加成也被证明是有效的，在建立四级立体中心，虽然报告同样稀少。串联或多米诺催化反应已成为有效的有机合成，包括对映选择性过程的有价值的工具。在这种情况下，Krische和同事报道了一种优雅的去对称化方法，该方法通过对映选择性共轭加成来揭示四级立体中心。在此，我们报道了一种催化的对映选择性Dieckmann型环化反应，形成具有四元立体中心的吡咯烷。Dieckmann缩合反应为有机合成中碳-碳键的形成提供了一种简单有效的方法。对映选择性Dieckmann型环化的实例令人惊讶地限于需要两当量手性离去基团的去对称化方法。我们的方法涉及铑烯醇化物与酯的分子内反应，以在活化的烯烃上依次安装芳基和酮，伴随形成季立体中心（方案1）。不对称方法中的主要挑战是在酰化步骤测定对映选择性，而不是在插入步骤测定对映选择性，这在对映选择性缀合物加成反应中是常见的。该反应在概念上类似于以前报道的多米诺催化共轭加成-对映选择性质子化的1，1 '-烯烃。我们预期，在底物内掺入半不稳定的配位位点将使反应性中间体稳定在适合环化的构象中。为了探索该策略的可行性，我们研究了在[{RhCl（C2 H4）2}2]和rac-binap存在下将4-甲氧基苯基硼酸（4a）添加到底物1-3中而不添加质子源（方案2）。在最初的实验中，1和2的反应没有得到所需的环化产物。在不存在氮接头的情况下，观察到向缀合加成产物5a的定量转化。引入N-Boc官能团导致完全转化成丙烯酸苄酯6a。有趣的是，在相同的条件下，N-甲基类似物3被转化成环化的方案1。具有四元立体中心的吡咯烷的催化对映选择性合成。
The stereoselective construction of all-carbon quaternary stereogenic centers by catalytic methodology is a highly desirable but challenging goal for synthetic chemists. One approach that has met with some degree of success is the catalytic enantioselective conjugate addition of alkyl organometallic reagents to b,b’-disubstituted alkene acceptors. The complementary rhodium-catalyzed enantioselective addition of aryl boronic acids has also been demonstrated to be effective in establishing quaternary stereogenic centers, although reports are similarly scarce. Tandem or domino catalytic reactions have emerged as valuable tools for efficient organic synthesis, including enantioselective processes. In this context, Krische and co-workers reported an elegant desymmetrization approach triggered by an enantioselective conjugate addition to reveal a quaternary stereogenic center. Herein, we report the development of a catalytic enantioselective Dieckmann-type annulation to form pyrrolidines with quaternary stereogenic centers. The Dieckmann condensation offers a simple and effective method for the formation of carbon–carbon bonds in organic synthesis. Examples of enantioselective Dieckmann-type annulations are surprisingly limited to desymmetrization processes that require two equivalents of a chiral leaving group. Our approach involves the intramolecular reaction of a rhodium enolate with an ester to sequentially install an aryl group and a ketone across an activated alkene with the concomitant formation a quaternary stereogenic center (Scheme 1). The principal challenge in the asymmetric process is that the enantioselectivity is determined at the acylation step and not, as is common in enantioselective conjugate addition reactions, at the insertion step. This reaction is similar in concept to the previously reported domino catalytic conjugate addition–enantioselective protonation of 1,1’-alkenes. We anticipated that the incorporation of a hemilabile coordination site within the substrate would stabilize a reactive intermediate in a suitable conformation for cyclization. To explore the feasibility of this strategy, we examined the addition of 4-methoxyphenylboronic acid (4a) to substrates 1–3 in the presence of [{RhCl(C2H4)2}2] and rac-binap without an added proton source (Scheme 2). In initial experiments, the reactions of 1 and 2 afforded none of the desired cyclized product. In the absence of a nitrogen linker, quantitative conversion into the conjugateaddition product 5 a was observed. The incorporation of the N-Boc functionality led to complete conversion into the abenzyl acrylate 6a. Interestingly, under the same conditions, the N-methyl analogue 3 was converted into the cyclized Scheme 1. Catalytic, enantioselective synthesis of pyrrolidines with quaternary stereogenic centers.