Asymmetric Hydrogenation of Trisubstituted Olefins with Iridium−Phosphine Thiazole Complexes: A Further Investigation of the Ligand Structure

New chiral bidentate phoshine thiazoles have been prepared and successfully applied as ligands
in the homogeneous iridium-catalyzed asymmetric hydrogenation of aryl alkenes and aryl alkene esters.
The ligands are designed to be highly modular and have one common chiral intermediate, from which
diversity can be introduced at a late stage in the synthetic pathway. It was found that a six-member-ring
backbone of the rigid ligand structure was preferred over seven- or five-member rings. In this study it is
shown that the substituent pattern of the ligands has a major influence on the stereochemical outcome of
the products. By applying the selectivity model proposed in this study, it is possible to match different
substrates against different catalysts. In this way, good to excellent enantioselectivity can be obtained for
typically difficult substrates. Geometrically different derivatives of α- and β-methyl cinnamic acid ethyl esters
were hydrogenated, to demonstrate the validity of the selectivity model and to verify the importance of
steric and electronic matching of the catalyst and the substrate.

本研究合成了新型手性双齿膦噻唑类配体，并将其成功用作均相铱催化芳基烯烃与芳基烯烃酯不对称氢化反应的配体。该类配体具备高度模块化的设计特性，且拥有共同的手性中间体，可在合成后期引入结构多样性。研究发现，刚性配体骨架采用六元环时，其性能优于五元环或七元环骨架。本研究证实，配体的取代基模式对产物的立体化学结果具有显著影响。通过运用本研究提出的选择性模型，可实现不同底物与不同催化剂的精准匹配，由此可针对常规较难转化的底物获得良好至优异的对映选择性。为验证该选择性模型的有效性，并证实催化剂与底物的空间位阻和电子效应匹配的重要性，本研究对α-甲基肉桂酸乙酯与β-甲基肉桂酸乙酯的不同几何异构体衍生物进行了氢化反应测试。