Iridium-catalyzed enantioselective transfer hydrogenation of ketones with formic acid was developed using a prolinol-phosphine chiral ligand. Cooperative action of the iridium atom and the ligand through alcohol-alkoxide interconversion is crucial to facilitate the transfer hydrogenation. Various ketones including alkyl aryl ketones, ketoesters, and an aryl heteroaryl ketone were competent substrates. An attractive feature of this catalysis is efficient discrimination between the alkyl and aryl substituents of the ketones, promoting hydrogenation with the identical sense of enantioselection regardless of steric demand of the alkyl substituent and thus resulting in a rare case of highly enantioselective transfer hydrogenation of tert-alkyl aryl ketones. Quantum chemical calculations revealed that the sp 3-CÀ H/π interaction between an sp 3-CÀ H bond of the prolinol-phosphine ligand and the aryl substituent of the ketone is crucial for the enantioselection in combination with OÀ H•••O/sp 3-CÀ H•••O two-point hydrogen-bonding between the chiral ligand and carbonyl group.
The front cover picture, designed by three groups from Hokkaido (Japan: ramanus rose), Ibaraki (Japan: plum), and Ubon Ratchathani (Thailand: lotus) illustrates the enantioselective transfer hydrogenation reactions of ketones with formic acid under iridium catalysis. Rationally designed prolinol‐phosphine chiral ligands are highly effective for the hydrogenation of ketones including tert‐alkylaryl ketones in up to 99% yield and with up to 99.8% ee. DFT calculations showed non‐covalent interactions including O–H⋅⋅⋅O/sp3‐C–H⋅⋅⋅O two‐point hydrogen‐bonding and C–H/π interactions. Details of this work can be found in the communication on pages 4655–4661 (H. Murayama, Y. Heike, K. Higashida, Y. Shimizu, N. Yodsin, Y. Wongnongwa, S. Jungsuttiwong, S. Mori, M. Sawamura, Adv. Synth. Catal. 2020, 362, 4655–4661; DOI: 10.1002/adsc.202000615).
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