A ruthenium/C-TunePhos catalytic system has been identified for highly efficient direct reductive amination of simple ketones. The strategy makes use of ammonium acetate as the amine source and H as the reductant and is a user-friendly and operatively simple access to industrially relevant primary amines. Excellent enantiocontrol (>90% ee for most cases) was achieved with a wide range of alkyl aryl ketones. The practicability of this methodology has been highlighted by scalable synthesis of key intermediates of three drug molecules. Moreover, an improved synthetic route to the optimal diphosphine ligand C-TunePhos is also presented.

A secondary phosphine oxide-phosphine mixed tridentate ligand and its ruthenium complex have been developed. This complex shows excellent catalytic activity for carbonyl reduction, especially for the reduction of α,β-unsaturated aldehydes. The turnover number and selectivity can reach up to 36 500 and 99%, respectively. Control experiments and DFT calculations supported an outer-sphere mechanism during the hydrogenation reaction.

The discrimination of a fluorine atom from a hydrogen atom has been challenging in asymmetric catalysis. We herein report iridium-catalyzed hydrogenation of α-fluoro ketones using a strategy of dynamic kinetic resolution. Both enantiomeric and diastereomeric selectivities were satisfactory in the preparation of β-fluoro alcohols. The DFT calculation revealed a C−F•••Na charge−dipole interaction in the transition state of hydride transfer. This noncovalent interaction would be responsible for the diastereomeric control.

A copper-catalyzed asymmetric hydrosilylation of βnitroethyl aryl ketones has been disclosed, and the corresponding chiral alcohols could be obtained in high yields (up to 99% yield) and excellent enantioselectivities (up to 96% ee). Moreover, the reaction worked well on a gram scale with 0.3 mol % of ligand loading, indicating that our protocol has potential applications in the synthesis of important pharmaceuticals such as Tranylcypromine and Ticagrelor.

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