Cooperative catalysis through noncovalent interactions.
Cooperative catalysis through noncovalent interactions.
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DOI：
10.1002/anie.201208774
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发表时间：
2013-02
影响因子：
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通讯作者：
Weijun Tang;S. Johnston;J. Iggo;N. Berry;M. Phelan;Lu-Yun Lian;J. Bacsa;Jianliang Xiao
中科院分区：
文献类型：
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作者：
Weijun Tang;S. Johnston;J. Iggo;N. Berry;M. Phelan;Lu-Yun Lian;J. Bacsa;Jianliang Xiao
非共价相互作用，如氢键、静电、p-p、CH-p和疏水力，在自然界的催化剂、酶的作用中起着重要作用。在过去的十年中，这些相互作用已成功地用于有机小分子的有机催化。相比之下，这种相互作用很少在有机金属催化的成熟领域进行研究，其中通过共价键和结合配体施加的空间效应的电子相互作用决定了金属催化剂的活性和选择性。一个有趣的问题是：当有机催化剂遇到有机金属催化剂时会发生什么？这种统一已经为这两个领域创造了一个令人兴奋的新空间：协同催化，反应物同时被两种类型的催化剂激活，从而实现单独在每个领域无法实现的反应性和选择性模式。然而，两种催化剂协同作用的机理仍有待研究。我们最近发现，将一种非手性铱催化剂与一种手性磷酸结合，可以实现亚胺的高度对映选择性氢化（方案1）。为了深入了解这种金属-有机协同催化的机理，我们使用一系列技术研究了催化体系，包括高压2D-NMR光谱，扩散测量和nol约束计算。在此我们报告我们的发现。为了评价其机理，我们使用了一种简化的非手性配合物C，通过在氨基氮上的质子化作用，将其与手性磷酸HA原位或非原位混合，得到[C][a]（方案1）。模型氯胺酮1a的不对称加氢反应[C][A]获得95% ee和完全转化率。根据相关研究，氢化反应可以用方案1所示的催化循环来解释，即[C][A]活化H2得到氢化物D和质子化的1a，与提供磷酸盐的[1a][A]形成离子对；[C][A]。与可能的铱-磷酸合作相关的问题随之出现：1)手性磷酸如何在加氢过程中诱导不对称？2) D的对映体选择性是由[C][A]、磷酸盐[1a][A]、还是由三种组分的相互作用产生的？我们首先研究了氢化物D的形成及其向底物的转移如何受到手性酸HA的影响。由于各种金属配合物在甲苯中的溶解度较低，因此在CH2Cl2或CD2Cl2中进行了研究。在两种溶剂中催化加氢都是可行的，在方案1中，当1a与C和HA加氢时，在甲苯中产生95%的ee，在CH2Cl2中产生85%的ee。溶液核磁共振研究表明，离子络合物[C][A]在CD2Cl2 （0.5 mL）中，C （0.05 mmol）与1个等量HA发生质子化反应，立即形成。在H2压力（bbb1bar）下，质子从[C] -H2二氢中间体（未观察到）转移到1a，将[C]转化为氢化物D，生成盐[1a] [a]。D的生成即使在78 8C时也能立即发生，并且在催化翻转过程中观察到，这表明氢化物转移步骤限制了氢化反应的速率。方案1。亚胺与非手性C和手性酸HA的加氢反应（PMP =对甲氧基苯基，Ar= 2,4,6-三异丙基苯基，Ts = tosyyl, Bn = benzyl）。
Noncovalent interactions, such as hydrogen bonding, electrostatic, p–p, CH–p, and hydrophobic forces, play an essential role in the action of nature s catalysts, enzymes. In the last decade these interactions have been successfully exploited in organocatalysis with small organic molecules. In contrast, such interactions have rarely been studied in the wellestablished area of organometallic catalysis, where electronic interactions through covalent bonding and steric effects imposed by bound ligands dictate the activity and selectivity of a metal catalyst. An interesting question is: What happens when an organocatalyst meets an organometallic catalyst? This unification has already created an exciting new space for both fields: cooperative catalysis, where reactants are activated simultaneously by both types of catalyst, thereby enabling reactivity and selectivity patterns inaccessible within each field alone. However, the mechanisms by which the two catalysts cooperatively effect the catalysis remain to be delineated. We recently found that combining an achiral iridium catalyst with a chiral phosphoric acid allows for highly enantioselective hydrogenation of imines (Scheme 1). To gain insight into the mechanism of this metal–organo cooperative catalysis, we studied the catalytic system with a range of techniques, including high pressure 2D-NMR spectroscopy, diffusion measurements, and NOEconstrained computation. Herein we report our findings. To evaluate the mechanism, a simplified achiral complex C was used, which leads to [C][A ] upon mixing, in situ or ex situ, with the chiral phosphoric acid HA through protonation at the amido nitrogen (Scheme 1). In the asymmetric hydrogenation of the model ketimine 1a, [C][A ] afforded 95% ee and full conversion. On the basis of related studies, the hydrogenation can be broadly explained by the catalytic cycle shown in Scheme 1, that is, [C][A ] activates H2 to give the hydride D and protonated 1a, which forms an ion pair with the phosphate affording [1a][A ]; hydride transfer furnishes the amine product 2a while regenerating [C][A ]. Questions pertinent to possible iridium–phosphate cooperation then arise: 1) How does the chiral phosphoric acid induce asymmetry in the hydrogenation? and 2) Does the enantioselectivity result from D being formed enantioselectively from [C][A ], from the phosphate salt [1a][A ], or from interactions involving all three components? We looked first at how the formation of hydride D and its transfer into the substrate are influenced by the chiral acid HA. The studies were carried out in CH2Cl2 or CD2Cl2 owing to the low solubility of the various metal complexes in toluene. The catalytic hydrogenation is feasible in both solvents, giving a 95% ee in toluene and 85 % ee in CH2Cl2 in the case of hydrogenation of 1a with C and HA under the conditions given in Scheme 1. The solution NMR studies show that the ionic complex [C][A ] is formed instantly on protonation of C (0.05 mmol) with one equivalent HA in CD2Cl2 (0.5 mL). Under H2 pressure (> 1 bar), proton transfer from a [C]–H2 dihydrogen intermediate (not observed) to 1a converts [C] into the hydride D and affords the salt [1a] [A ]. Formation of D took place instantly even at 78 8C, and it is observed during catalytic turnover, thus indicating that the hydrogenation is rate-limited by the hydride transfer step. Scheme 1. Hydrogenation of imine with achiral C and chiral acid HA (PMP = p-methoxyphenyl, Ar= 2,4,6-triisopropylphenyl, Ts = tosyl, Bn = benzyl).