“金属-配体部分电荷转移”及轴手性诱导实现高活性、高对映选择性的铁催化不对称转移加氢反应

The abundance on earth and its non-toxicity has made iron catalysis important both economically and environmentally. We have developed an amido(ene-amido) diphosphane carbonyl (PNNP) iron catalyst in efficiently catalyzing transfer hydrogenation of polar double bonds with turn-over frequency greater than 200 s-1, which rivals that of the famous Noyori’s ruthenium based catalyst, and it is currently the most active hydrogenation catalyst. Initial mechanistic studies revealed that the partial charge transfer between iron and ligand is important in stabilizing the transition state of the turnover-limiting step and thus leads to reduced activation barrier of the catalytic reaction, which is the real reason to obtain high reactivity. However, the relative low stereo-selectivity of the PNNP iron catalysts has hampered their wide industry applications. This project is aimed to synthesize new iron catalysts that combine the “metal-ligand partial charge transfer” effect which would maintain the high catalytic activity, and the excellent stereoinduction capabilities of axially chiral diphosphanes and axially chiral counterions, thereby affording high enantioselectivity. Two strategies were utilized. Neutral ligands that have the “metal-ligand partial charge transfer” effect which would maintain the high catalytic activity, and the excellent stereoinduction capabilities imparted by axially chiral diphosphanes thereby affording high enantioselectivity are first synthesized and then complexed to iron to form chiral iron complexes as the catalyst precursors. Amido(ene-amido) diphosphane carbonyl iron complexes having a cationic ammonium substituent on the ligand backbone are paired with a chiral boron-substituted binaphtholate anion to form the new chiral iron catalysts. It is hoped that the chiral counterion may impart a remarkable stereocontrolling ability to its iron complex which catalyzes highly enantioselective hydrogenation reactions. The new iron catalysts are expected to have catalytic activity greater than 100 s-1, and enantiomeric excess higher than 99% for acetophenone.

手性醇、胺在工业上的广泛应用和铁元素低毒、廉价的特点使得铁催化酮、亚胺不对称（转移）加氢反应具有重要的环境及经济意义。申请者前期发现烯胺-胺-双膦（PNNP）配体具有“金属-配体部分电荷转移”功能，能够活化铁元素并稳定活性中心，实现高活性的铁催化不对称转移加氢反应。然而，此类PNNP铁催化剂所使用的、基于中心手性的配体未能使得催化剂的对映选择性达到实际应用水平，阻碍了其大规模应用。本项目拟设计、合成高活性、高对映选择性的手性铁催化剂应用于酮、亚胺的不对称转移加氢反应：1、设计含有轴手性联萘基团和具有“金属-配体部分电荷转移”功能的基团的中性配体，将其与铁配位生成铁配合物作为催化剂前驱体；2、通过在原PNNP配体上引入季铵盐基团引入轴手性反离子，利用PNNP配体保持高活性，而利用手性反离子构建的立体环境实现高对映选择性。新催化剂的活性可达100 s-1，产物的手性纯度可达99%（苯乙醇）。

针对3d金属（铁、钴、镍）催化剂催化酮、亚胺的不对称氢化反应的重要意义，同时当前缺少有效的理论指导高性能催化剂的合成导致目前3d金属催化剂在催化反应活性及产物选择性与贵金属催化剂相距较远的关键问题，本项目开展了以下3方面研究：1、含有亚胺（胺）双磷配体铁催化剂的催化反应机理研究；2、在上述机理研究的基础上，设计合成新的高活性、高选择性的铁催化剂；3、在上述机理研究的指导下，设计合成新的高活性、高选择性的钴催化剂。取得以下成果：1、成功揭示了3d金属由于具有与贵金属不同的电子结构而导致的、独特的金属中心活化机制。原创性地提出了“π-型活化”原理，即本项目申请时项目负责人所提出的“金属-配体部分电荷转移”原理。同时在该原理的指导下，成功合成了既具有高活性、又具有高对映选择性的新型铁系催化剂，验证了该新原理的正确性；2、应用上述原理成功地预测并合成了新型既具有良好活性、又具有高对映选择性的新型钴系催化剂，进一步验证了该原理的普适性；3、在合成高活性、高对映选择性铁系催化剂时发现了一种新的、含有多种手性中心的手性配体的合成方法。该类既具有联萘轴手性、又含有磷中心手性的新型手性配体在解决烷基-烷基酮不对称氢化反应所面临的对映选择性低的关键问题时具有一定优势。上述研究成果的意义包括：1、所提出的新的3d金属活化机制成功预测并实现了高活性、高选择性钴、镍催化剂（部分工作已发表，部分工作还未发表）。钴催化剂具有广泛的底物范围，比现在报道的钴催化剂活性提高一个数量级，且具有优异的对映选择性（>90% e.e）；2、本项目的研究中意外发现一类新的、既具有联萘轴手性、又含有磷中心手性的新型手性配体及其合成方法。该类配体的发现为解决现阶段某些不对称催化反应所面临的对映选择性低的问题提供一种新的思路。

内容获取失败，请点击重试