Asymmetric aldol reaction via a dinuclear zinc catalyst:: α-hydroxyketones as donors
Asymmetric aldol reaction via a dinuclear zinc catalyst:: α-hydroxyketones as donors
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DOI：
10.1021/ja003871h
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发表时间：
2001-04-11
影响因子：
15
通讯作者：
Silcoff, ER
中科院分区：
文献类型：
--
作者：
Trost, BM;Ito, H;Silcoff, ER
控制定向羟醛缩合的立体选择性的能力已经使该过程在合成由少数反应共享的复杂分子目标中变得突出。[1]然而，这些反应几乎总是需要亲核或供体配偶体的预活化。R-羟基酮供体由于多氧化产物的实用性而特别令人感兴趣，但由于化学选择性问题而代表最麻烦的供体之一。只是最近有几个报告解决了简单的羟醛加成涉及化学和对映选择性使用生物型（如催化抗体）2和非生物型3，4催化，在某些情况下，包括R-羟基丙酮和相关衍生物。2，4 b在这些情况下，必须使用供体的显著过量。我们最近报道了一种新型的不对称催化剂的发展，我们假设它涉及一个双核锌配合物。5在本文中，我们介绍了这种催化剂与R-羟基酮的有效性，它允许在不对称羟醛缩合反应中使用接近化学计量的两种伙伴，以及供体对醛的面选择性的惊人影响。在电喷雾质谱仪的入口处将络合物暴露于乙酸显示出m/e 823-833之间的一系列峰，其与对应于3a的M+ H+峰的式C45 H47 N2 O 5 Zn 2一致。这些数据与我们早期关于二乙基锌与配体的2：1化学计量的观察的组合提供了良好的结果。
The ability to control the stereoselectivity of the directed aldol condensation has raised this process to prominence in the synthesis of complex molecular targets shared by few reactions. 1 However, these reactions almost invariably require preactivation of the nucleophilic or donor partner. R-Hydroxyketone donors are particularly interesting because of the utility of the polyoxygenated products, yet represent one of the most troublesome donors because of chemoselectivity issues. Only recently have several reports addressed the simple aldol addition involving both chemoand enantioselectivity using both biological-type (eg, catalytic antibodies) 2 and nonbiological-type3, 4 catalysis and, in some cases, included R-hydroxyacetone and related derivatives. 2, 4b In these cases, significant excesses of the donor must be employed. We recently reported the development of a new type of asymmetric catalyst which we postulated involves a dinuclear zinc complex. 5 In this paper, we communicate the effectiveness of this catalyst with R-hydroxyketones that permits use of nearly stoichiometric amounts of both partners in the asymmetric aldol reaction and the surprising effect of the donor on facial selectivity with respect to the aldehyde.The catalyst is prepared by reacting the phenol 1 with diethylzinc in THF as in eq 1. Exposure of the complex to acetic acid in the inlet of an electrospray mass spectrometer shows a series of peaks between m/e 823-833 consistent with the formula C45H47N2O5Zn2 that corresponds to the M+ H+ peak of 3a. The combination of these data with our earlier observation regarding the 2: 1 stoichiometry of diethylzinc to ligand provides good