Direct β-Activation of Saturated Aldehydes to Formal Michael Acceptors through Oxidative NHC Catalysis
Direct β-Activation of Saturated Aldehydes to Formal Michael Acceptors through Oxidative NHC Catalysis
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DOI：
10.1002/anie.201302152
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发表时间：
2013-08-12
影响因子：
16.6
通讯作者：
Chi, Yonggui Robin
中科院分区：
文献类型：
--
作者：
Mo, Junming;Shen, Liang;Chi, Yonggui Robin
饱和羰基化合物，如醛和酯，是合成有机分子和材料的基本组成部分。羰基化合物作为底物的反应主要发生在羰基碳原子（作为亲电中心）或α-碳原子（作为亲核前试剂）上。在有机催化中，已经开发了几种有效的方法用于醛和酯的α-CH的不对称功能化。例如，利用烯胺[1]或SOMO[2]催化，在醛的α-碳原子上实现了许多优雅的转化。最近，Rovis及其同事[3]和我们的实验室[4]独立报道了n -杂环碳（NHCs）介导的氧化催化饱和醛的α-碳功能化我们还实现了nhc介导的饱和酯α-功能化为了使羰基化合物的β-碳原子功能化，通常使用相应的α， β-不饱和化合物。例如，几个研究小组已经开发出NHC催化[7 - 9]，用于激活α， β-不饱和醛（烯醛和α-溴烯醛）[7,8]和ynals，[9]，形成不饱和酯[7,9a]或正式的Michael受体。[8,9b - e， 20]特别是Studer率先将1,3 -二羰基化合物添加到由α， β不饱和醛生成的α， β-不饱和酰基三唑中。[8a] Lupton等人最近率先研究了nhc介导的α、β不饱和烯醇酯和酰基氟化物的活化，最终实现β-sp2碳原子的功能化烯醛βsp2碳原子也可以通过微量有机催化被激活，这是由麦克米伦和他的同事开创的。有几种催化方法可用于直接活化羰基化合物的α-碳原子（和不饱和羰基化合物的βsp2碳原子），但直接活化饱和羰基化合物的典型惰性β-C （sp3）是具有挑战性的。值得注意的是，CÀH活化涉及饱和酯和β-碳原子
Saturated carbonyl compounds, such as aldehydes and esters, are basic building blocks for the synthesis of organic molecules and materials. Reactions with carbonyl compounds as substrates primarily occur at the carbonyl carbon atom (as an electrophilic center) or the α-carbon atom (as a prenucleophile). In organocatalysis, several powerful approaches have been developed for the asymmetric functionalization of α-CH of aldehydes and esters. For example, many elegant transformations at the α-carbon atom of aldehydes have been realized by employing enamine [1] or SOMO [2] catalysis. Very recently, Rovis and co-workers [3] and our laboratory [4] independently reported α-carbon functionalization of saturated aldehydes through oxidative catalysis mediated by N-heterocyclic carbenes (NHCs).[5] We have also realized NHC-mediated α-functionalization of saturated esters.[6] To functionalize the β-carbon atoms of carbonyl compounds, the corresponding α, β-unsaturated compounds are typically used. For example, several groups have developed NHC catalysis [7–9] for the activation of α, β-unsaturated aldehydes (enals and α-bromoenals)[7, 8] and ynals,[9] to form unsaturated esters [7, 9a] or formal Michael acceptors.[8, 9b–e, 20] In particular, Studer pioneered the addition of 1, 3-dicarbonyl compounds to α, β-unsaturated acyl triazoliums generated from α, βunsaturated aldehydes.[8a] Lupton and co-workers have recently pioneered the NHC-mediated activation of α, βunsaturated enol ester and acyl fluorides for eventual functionalizations of the β-sp2 carbon atoms.[10] The enal βsp2 carbon atom can also be activated through iminium organocatalysis, as pioneered by MacMillan and co-workers.[11]Several catalytic approaches are available for the direct activation of α-carbon atoms of carbonyl compounds (and βsp2 carbon atoms of unsaturated carbonyl compounds), but the direct activation of the typically inert β-C (sp3) of saturated carbonyl compounds is challenging. Notably, CÀH activation involving the β-carbon atom of saturated esters and