N-heterocyclic carbene catalyzed C-C bond cleavage in redox esterifications of chiral formylcyclopropanes
N-heterocyclic carbene catalyzed C-C bond cleavage in redox esterifications of chiral formylcyclopropanes
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DOI：
10.1002/anie.200601919
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发表时间：
2006-01-01
影响因子：
16.6
通讯作者：
Bode, Jeffrey W.
中科院分区：
文献类型：
--
作者：
Sohn, Stephanie S.;Bode, Jeffrey W.
小的，紧张的分子的开环反应转化为在非环状系统中建立绝对的立体化学的不同的环状结构的合成中固有的高度的立体选择性。[1]许多开环过程（形式上是还原反应）的缺点是需要化学计量的试剂，这些试剂通常是昂贵或有毒的金属。为了解决这个问题，我们最近开发了一种有机催化氧化还原开放的α，β环氧醛伴随氧化的醛和随后的酯化。[2，3]这种高效的工艺将广泛可用的对映体富集的环氧化物转化为各种增值产品，包括在温和的实际条件下的抗丙酸羟醛加合物。在寻求扩展容易制备的对映体纯的起始材料的催化环状至非环状立体化学转化的概念时，我们被Kunz和MacMillan在用市售有机催化剂（2S）-二氢吲哚-2-羧酸直接、高对映体选择性合成甲酰基环丙烷方面的最新进展所吸引。[4]我们推断，涉及打开环丙烷单元的氧化还原异构化的有效方法将导致对映体富集的β取代的羧酸衍生物的简洁方法，这是一类有吸引力的手性结构单元，其一般的不对称制备方法很少。[5]然而，为了实现这种转化，我们需要裂解缺乏杂原子官能团的碳-碳键，[6]这一过程通常需要强还原剂和剧烈的条件，即使在高度紧张的系统中。[7]我们现在报道了通过N-杂环卡宾（NHC）有机催化剂介导的甲酰基环丙烷的C12 C-键断裂开环的成功开发，从而经由催化产生的活化羧酸酯的中间作用产生酯和硫酯[Eq. (1)DBU= 1，8-二氮杂双环[5.4. 0]十一碳-7-烯，吸电子基团（EWG）=酮、酯、酰胺或硝基]。在我们的研究开始时，不清楚预期通过将NHC催化剂添加到甲酰基环丙烷中形成的稳定的酰基阴离子当量是否会导致开环反应优先于苯偶姻二聚，[8]特别是在氧化还原酯化过程所要求的质子条件下。我们选择容易制备的，对映体富集的甲酰基环丙烷1作为反应发展的模型底物。最初的努力证实了我们的担忧，简单的噻唑和三唑衍生的NHC将证明是低效的或更喜欢竞争途径（方案1）。然而，我们很高兴地发现，我们的均三甲苯基取代的三唑鎓盐7 [3b]，
Ring-opening reactions of small, strained molecules translate the high degree of stereoselectivity inherent in the synthesis of diverse cyclic structures into the establishment of absolute stereochemistry in acyclic systems.[1] A disadvantage of many ring-opening processes, which are formally reduction reactions, is the necessity of stoichiometric reagents that are often expensive or toxic metals. To address this limitation, we recently developed an organocatalytic redox opening of α, βepoxyaldehydes with concomitant oxidation of the aldehyde and subsequent esterification.[2, 3] This efficient process transforms widely available, enantioenriched epoxides into a variety of value-added products, including anti-propionate aldol adducts under mild, practical conditions. In seeking to extend the concept of catalytic cyclic-toacyclic stereochemical translation of readily prepared, enantiopure starting materials, we were attracted to the recent advances made by Kunz and MacMillan on the direct, highly enantioselective synthesis of formylcyclopropanes with the commercially available organocatalyst (2S)-indoline-2-carboxylic acid.[4] We reasoned that an efficient method for redox esterifications that involves opening the cyclopropane unit would result in a concise approach to enantioenriched βsubstituted carboxylic acid derivatives, an attractive class of chiral building blocks with few methods for their general, asymmetric preparation.[5] To achieve this transformation, however, we required the cleavage of a carbon–-carbon bond lacking heteroatom functionalities,[6] a process that normally requires strong reducing agents and vigorous conditions even in highly strained systems.[7] We now report the successful development of CÀC-bond-cleaving ring-openings of formylcyclopropanes mediated by an N-heterocyclic carbene (NHC) organocatalyst, thus leading to esters and thioesters via the intermediacy of catalytically generated activated carboxylates [Eq.(1); DBU= 1, 8-diazabicyclo [5.4. 0] undec-7-ene, electron-withdrawing group (EWG)= ketone, ester, amide, or nitro].At the onset of our studies, it was unclear if the stabilized acyl anion equivalents expected to be formed by addition of an NHC catalyst to a formylcyclopropane would lead to ringopening reactions in preference to benzoin dimerizations,[8] especially under the protic conditions mandated by redox esterification processes. We selected readily prepared, enantiomerically enriched formylcyclopropane 1 as a model substrate for reaction development. Initial efforts confirmed our trepidation that simple thiazolium-and triazoliumderived NHCs would prove inefficient or prefer competing pathways (Scheme 1). However, we were pleased to find that our mesityl-substituted triazolium salt 7,[3b] which deters