Enantioselective Hydrogenation of Activated Aryl Imines Catalyzed by an Iron(II) P‑NH-P′ Complex

Chiral amines are key building blocks in synthetic chemistry with numerous applications in the agricultural and pharmaceutical industries. Asymmetric imine hydrogenation, particularly with iridium catalysts, is well developed. However, imine reduction still remains challenging in the context of replacing such a precious metal with a cheap, nontoxic, and environmentally friendly substitute such as iron. Here, we report that an unsymmetrical iron P-NH-P′ catalyst that was previously shown to be effective for the asymmetric hydrogenation of aryl ketones is also a very effective catalyst for the asymmetric hydrogenation of prochiral aryl imines activated with N-diphenylphosphinoyl or N-tosyl groups. The P-NH-P′ abbreviation stands for (S,S)-PPh2CHPhCHPhNHCH2CH2PiPr2. Density functional theory results suggest that, surprisingly, the NH group on the catalyst activates and orients the imine to hydride attack by hydrogen bonding to the PO or SO group on the imine nitrogen, as opposed to the imine nitrogen itself. This may explain why N-Ph and N-Bu imines are not hydrogenated.手性胺（chiral amines）是合成化学中的核心结构砌块，在农业与制药工业领域拥有广泛应用。不对称亚胺氢化反应——尤其是依托铱催化剂的反应路径——已发展得较为成熟。然而，若要以廉价、无毒且环境友好的替代金属（如铁）替代这类贵金属，亚胺还原反应仍存在诸多挑战。本文报道，一种此前被证实可高效催化芳基酮不对称氢化的不对称铁基P-NH-P′型催化剂，同样可高效催化被N-二苯基膦酰基或N-对甲苯磺酰基活化的前手性芳基亚胺的不对称氢化反应。其中P-NH-P′的缩写对应结构为(S,S)-PPh₂CHPhCHPhNHCH₂CH₂PiPr₂。密度泛函理论结果出人意料地显示，该催化剂上的NH基团并非通过与亚胺氮原子本身相互作用，而是通过与亚胺氮上的PO或SO基团形成氢键，来活化亚胺并使其定向以利于氢负离子进攻。这一机制或可解释为何N-苯基与N-丁基亚胺无法发生氢化反应。