A highly enantioselective intramolecular Michael reaction catalyzed by N-heterocyclic carbenes
A highly enantioselective intramolecular Michael reaction catalyzed by N-heterocyclic carbenes
复制标题
DOI：
10.1002/anie.200605235
复制
发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Scheidt, Karl A.
中科院分区：
文献类型：
--
作者：
Phillips, Eric M.;Wadamoto, Manabu;Scheidt, Karl A.
烯醇化物或烯醇亲核试剂与活化双键的共轭加成反应（Michael反应）是合成1，5-二羰基化合物的有效方法。[1]直接形成新的碳-碳键并控制多达三个新的立体异构中心的潜力推动了该反应的持续和重大发展。两个核心策略是使用金属烯醇化物和添加潜在的亲核试剂如烯醇硅烷与刘易斯酸的组合。[2]Yamaguchi，[3] MacMillan，[4] Jørgensen，[5]和List [6]的研究小组的研究表明，仲胺通过亚胺离子产生活化的不饱和亲电试剂来催化迈克尔反应。亚胺方法的相应策略是催化生成烯醇化物或烯醇亲核试剂。[7，8]在此，我们报道了N-杂环卡宾（NHC）是用于底物1的分子内迈克尔反应的高选择性催化剂，以在添加外源亲核试剂后得到二羰基化合物2 [Eq.①]。
The conjugate addition of enolate or enol nucleophiles to activated double bonds (the Michael reaction) is an efficient method for the synthesis of 1, 5-dicarbonyl compounds.[1] The potential for the direct formation of a new carbon–carbon bond with control of up to three new stereogenic centers has driven continued and significant development of this reaction. Two central strategies are the use of metalloenolates and the addition of latent nucleophiles such as enol silanes in combination with a Lewis acid.[2] Studies by the research groups of Yamaguchi,[3] MacMillan,[4] Jørgensen,[5] and List [6] have demonstrated that secondary amines catalyze Michael reactions by the generation of activated unsaturated electrophiles through iminium ions. The corresponding strategy to the iminium approach is the catalytic generation of an enolate or enol nucleophile.[7, 8] Herein we report that N-heterocyclic carbenes (NHCs) are highly selective catalysts for the intramolecular Michael reaction of substrates 1 to afford dicarbonyl compounds 2 after the addition of an exogenous nucleophile [Eq.(1)].