Fujian Provincial Key Laboratory of Chemical Biology, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University , Xiamen, Fujian 361005, People's Republic of China.
Acc Chem Res. 2013 Nov 19;46(11):2635-44. doi: 10.1021/ar400083u. Epub 2013 Jun 3.
An octahedral metal complex with 6 different monodentate ligands can form 15 diastereomers as pairs of enantiomers. As a result, the elaborate stereochemistry of octahedral coordination geometries provides tremendous opportunities in the fields of catalysis, the materials sciences, and the life sciences. The demand for enantiomerically pure coordination complexes for tasks related to the selective molecular recognition of biomacromolecules led us to develop synthetic methods to control the absolute stereochemistry at octahedral metal centers. A few years ago our laboratory therefore embarked on a project exploring new and general synthetic strategies for the asymmetric synthesis of inert octahedral transition metal complexes. We initially used the example of thermally inert ruthenium polypyridyl complexes and developed a family of chiral bidentate ligands, including salicyloxazolines, (mercaptophenyl)oxazolines, sulfinylphenols, N-acetylsulfinamides, a phosphinohydroxybinaphthyl, and even the amino acid proline to serve as chiral auxiliaries for asymmetric coordination chemistry. All these chiral auxiliaries strongly coordinate to ruthenium(II) in a bidentate, deprotonated fashion, allowing them to control the absolute metal-centered configuration in the course of subsequent ligand exchange reactions. Finally, we can remove them from the metal without any loss of chiral information and without leaving a chemical trace. A key feature of these chiral auxiliary ligands is their switchable binding strength. A chelate effect ensures that the chiral ligands coordinate very tightly to the metal center, placing their carbon-based, sulfur-based, or axial chirality in a well-defined position close to the metal center to efficiently establish the absolute metal-centered configuration. At the same time a coordinating phenolate, carboximidate, carboxylate, or thiophenolate moiety makes the coordination reversible by weakening the binding strength through protonation or methylation. Following this strategy, we synthesized a large number of homoleptic, bis-heteroleptic, and tris-heteroleptic ruthenium polypyridyl complexes in an asymmetric fashion with enantiomeric ratios that routinely reached or exceeded 96:4. Our approach should serve as a blueprint for the asymmetric synthesis of different classes of ruthenium complexes and chiral coordination complexes of other metals.
一个具有 6 个不同单齿配体的八面体金属配合物可以形成 15 对对映异构体的非对映异构体。因此，八面体配位几何的精细立体化学在催化、材料科学和生命科学领域提供了巨大的机会。对用于与生物大分子选择性分子识别相关任务的对映体纯配位配合物的需求促使我们开发了控制八面体金属中心绝对立体化学的合成方法。几年前，我们实验室因此开始了一个项目，探索用于惰性八面体过渡金属配合物不对称合成的新的和通用的合成策略。我们最初使用热惰性钌多吡啶配合物的例子，开发了一系列手性双齿配体，包括水杨醛恶唑啉、（巯基苯基）恶唑啉、亚砜酚、N-乙酰亚磺酰胺、膦羟基联萘，甚至氨基酸脯氨酸作为不对称配位化学的手性辅助剂。所有这些手性辅助剂都以双齿、去质子化的方式强烈地与钌（II）配位，允许它们在随后的配体交换反应中控制绝对的金属中心构型。最后，我们可以在不损失手性信息且没有留下化学痕迹的情况下将它们从金属中去除。这些手性辅助配体的一个关键特征是它们的可切换结合强度。螯合效应确保手性配体与金属中心非常紧密地配位，将其基于碳、基于硫或轴向的手性置于靠近金属中心的明确定义位置，以有效地建立绝对的金属中心构型。同时，配位的酚盐、羧亚胺盐、羧酸盐或硫酚盐部分通过质子化或甲基化来削弱结合强度，使配位可逆。根据该策略，我们以不对称的方式合成了大量同单核、双杂核和三杂核钌多吡啶配合物，对映体过量比通常达到或超过 96:4。我们的方法应该作为其他金属的不同类别的钌配合物和手性配位配合物的不对称合成的蓝图。
