Multicenter strategy for the development of catalytic enantioselective nucleophilic alkylation of ketones:: Me2Zn addition to α-ketoesters
Multicenter strategy for the development of catalytic enantioselective nucleophilic alkylation of ketones:: Me2Zn addition to α-ketoesters
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DOI：
10.1002/anie.200351650
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发表时间：
2003-01-01
影响因子：
16.6
通讯作者：
Shibasaki, M
中科院分区：
文献类型：
--
作者：
Funabashi, K;Jachmann, M;Shibasaki, M
通过将碳亲核试剂加成到酮或酮亚胺上来催化构建立体四取代的碳中心是非常具有挑战性的，部分原因是这些底物相对于醛和醛亚胺的反应性较低。[1]该任务需要通过不对称催化剂强烈活化底物和/或亲核试剂。我们开发了刘易斯酸-刘易斯碱双中心不对称催化剂（1的钛和镧系元素络合物），其促进具有广泛底物通用性的酮和酮亚胺的氰基硅烷化。[2]催化剂设计的基本概念是刘易斯酸金属和刘易斯碱（膦氧化物）在过渡态的限定位置同时活化底物和亲核试剂（TMSCN）。这一概念的逻辑延伸是将二有机锌加成到酮上，[3]因为需要底物的刘易斯酸活化和试剂的刘易斯碱活化来促进反应。[4]本文报道了我们对这一目标的初步研究：Me 2 Zn对α-酮酯的催化对映选择性加成。我们新设计的催化剂2，
The catalytic construction of stereogenic tetrasubstituted carbon centers through the addition of carbon nucleophiles to ketones or ketoimines is very challenging, partly because of the lower reactivity of these substrates relative to aldehydes and aldoimines.[1] This task requires strong activation of the substrate and/or the nucleophile by an asymmetric catalyst. We developed Lewis acid–Lewis base two-center asymmetric catalysts (titanium and lanthanide complexes of 1) that promote the cyanosilylation of ketones and ketoimines with broad substrate generality.[2] The fundamental concept for the catalyst design was that the Lewis acid metal and the Lewis base (the phosphane oxide) activate both the substrate and the nucleophile (TMSCN) simultaneously at defined positions in the transition state. A logical extension of this concept is to target the diorganozinc addition to ketones,[3] because both Lewis acid activation of the substrate and Lewis base activation of the reagent are required to promote the reaction.[4] We report herein our initial investigations toward this goal: the catalytic enantioselective addition of Me2Zn to α-ketoesters. Our newly designed catalyst 2, which