Catalytic, enantioselective addition of substituted allylic trichlorosilanes using a rationally-designed 2,2′-bispyrrolidine-based bisphosphoramide
Catalytic, enantioselective addition of substituted allylic trichlorosilanes using a rationally-designed 2,2′-bispyrrolidine-based bisphosphoramide
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DOI：
10.1021/ja016552e
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发表时间：
2001-09-26
影响因子：
15
通讯作者：
Fu, JP
中科院分区：
文献类型：
--
作者：
Denmark, SE;Fu, JP
烯丙基金属试剂在醛上的对映选择性加成是一种常用的立体选择性碳-碳键形成的有效方法。绝大多数催化作用的例子是手性路易斯酸促进的烯丙基硅烷和锡烷的加成，这些加成通常具有优异的对映选择性。2然而，这些转化对于引入γ-取代的烯丙基物种不太有用，因为这些反应的开放过渡结构特征不允许控制非对映选择。解决相对非对映控制问题的一种机制上的独特方法是路易斯碱促进的烯丙基三氯硅烷与醛的加成。4,5 1994年，这些实验室报告了使用手性磷酰胺催化三氯硅烷对醛的对映选择性加成的第一个例子（方案1）。6从那时起，一些小组报告了手性磷酰胺、7a、b甲酰胺、7c、d n -氧化物、7e脲、7f和二胺促进的对映选择性加成。尽管在对映体选择性的经验优化方面做了大量的努力，但尚未发现一种高选择性和活性的催化剂。在此，我们报道了一种新的2,2 ' -双吡咯烷基双磷酰胺的设计和实现，它催化多种烯丙基三氯硅烷与醛的加成，具有优异的非对映和对映选择性。我们还报道了用该技术催化、对映选择性构建季碳中心的第一个例子。对磷酰胺3促进烯丙化的机理研究表明，该反应可通过两种途径进行，其中一种或两种磷酰胺与氯硅烷结合。这种二元性的一个重要结果是，更具选择性的“双磷酰胺”途径的速率随着[cat] 2而降低。因此，在催化负载下，加成的速率和选择性（由于单磷酰胺途径的干预）受到不利影响。这个问题通过使用双磷酰胺5来解决，期望通过接近来增加第二个催化剂分子的有效浓度（图1）。对系链的系统研究表明，双磷酰胺5d（其中两个碱基功能被一个5 -亚甲基单元分开）能够提供更高的ee，但仍然适中（72%）。对催化剂结构的进一步改进集中在以各种手性二胺为骨架的二聚体磷酰胺的评价上。二聚体催化剂在其他工艺中使用效果很好，但在这里基本上是无效的。为了完善我们对不对称诱导起源的理解并帮助设计更具选择性的催化剂，我们使用SnCl4作为硅的替代品来研究双磷酰胺与路易斯酸的络合作用。10对5d， sncl411的x射线晶体结构的检查显示，内部n -甲基取代基的配置受到手性骨架的显著影响（图1a）。我们推断，将立体中心上的取代基与氮原子连接在一个环中，应该加强对n取代基取向的更严格控制，从而施加更高度不对称的配位环境。图1b、c给出了骨架诱导的氮畸变的概念，因此建议使用从2,2 ' -双吡咯烷衍生的磷酰胺。12
The enantioselective addition of allylmetal reagents to aldehydes is an often-employed and powerful method for stereoselective carbon-carbon bond formation. 1 The overwhelming majority of examples that operate catalytically are chiral Lewis acid-promoted additions of allylic silanes and stannanes which often proceed with excellent enantioselectivity. 2 However, these transformations are less useful for the introduction of γ-substituted allylic species, because the open-transition structure characteristic of these reactions does not allow for controlled diastereoselection. 3 A mechanistically distinct approach that addresses the problem of relative diastereocontrol is the Lewis base-promoted addition of allylic trichlorosilanes to aldehydes. 4, 5 In 1994, the first examples of catalytic enantioselective addition of allylic trichlorosilanes to aldehydes by the use of chiral phosphoramides was reported from these laboratories (Scheme 1). 6 Since then, a number of groups have reported enantioselective additions promoted by chiral phosphoramides, 7a, b formamides, 7c, d N-oxides, 7e ureas, 7f and diamines. 7g Despite significant efforts at empirical optimization of the enantioselectivity, a highly selective and reactive catalyst has yet to be discovered. Herein, we report the design and implementation of a new 2, 2′-bispyrrolidine-based bisphosphoramide that catalyzes the addition of many kinds of allylic trichlorosilanes to aldehydes with excellent diastereo-and enantioselectivity. We also report the first examples of catalytic, enantioselective construction of quaternary carbon centers by this technology. Mechanistic studies on the allylation promoted by phosphoramide 3 indicated that the reaction can proceed by two pathways involving either one or two phosphoramides bound to the chlorosilane. 8 An important consequence of this duality is that the rate of the more selective “two-phosphoramide” pathway decreases as [cat] 2. Thus, at catalytic loadings, the rate and selectivity (due to the intervention of the one-phosphoramide pathway) of the addition are adversely affected. This problem was addressed by utilizing bisphosphoramide 5 with the expectation of increasing the effective concentration of the second catalyst molecule through proximity (Chart 1). A systematic investigation of the tether revealed that bisphosphoramide 5d (in which the two base functions are separated by a five-methylene unit) was able to provide a higher, yet still modest ee (72%).Further modifications of the catalyst structure focused on the evaluation of dimeric phosphoramides with various chiral diamines as backbones. Employment of dimeric versions of catalysts that have served well in other processes were largely ineffective here. 9 To refine our understanding of the origin of asymmetric induction and assist in the design of more selective catalysts, we utilized SnCl4 as a surrogate for silicon to study the complexation of a bisphosphoramide to a Lewis acid. 10 Examination of the X-ray crystal structure of 5d ‚SnCl4 11 revealed that the disposition of the internal, N-methyl substituents was significantly influenced by the chiral skeleton (Figure 1a). We reasoned that connecting the substituent on the stereogenic center to the nitrogen atom by enclosure in a ring should enforce a more rigid control of the orientation of the N-substituents and thus impose a more highly dissymmetric coordination environment. This notion of backboneinduced nitrogen distortion is presented in Figure 1b, c, and thus suggested the use of a phosphoramide derived from 2, 2′-bispyrrolidine. 12