PPM Ir-f-phamidol-Catalyzed Asymmetric Hydrogenation of γ-Amino Ketones Followed by Stereoselective Cyclization for Construction of Chiral 2-Aryl-pyrrolidine Pharmacophores.

Transition metal catalysts with a million turnovers and excellent selectivity are rarely reported but are crucial for the industrial manufacture of optical pure pharmaceuticals, natural products, and fine chemicals. In this paper, we report an unprecedented aninoic Ir-f-phamidol catalyst for asymmetric hydrogenation of γ-amino ketones followed by stereoselective cyclization for construction of valuable chiral 2-aryl-pyrrolidine pharmacophores. The Ir-f-phamidol catalyst showed up to 1,000,000 TON and >99% ee, as well as excellent tolerance of substrates and protecting groups, providing various chiral amino alcohol intermediates.

A 13-million turnover-number anionic Ir-catalyst for a selective industrial route to chiral nicotine.

Developing catalysts with both useful enantioselectivities and million turnover numbers (TONs) for asymmetric hydrogenation of ketones is attractive for industrial production of high-value bioactive chiral entities but remains a challenging. Herein, we report an ultra-efficient anionic Ir-catalyst integrated with the concept of multidentate ligation for asymmetric hydrogenation of ketones. Biocatalysis-like efficacy of up to 99% ee (enantiomeric excess), 13,425,000 TON (turnover number) and 224 s TOF (turnover frequency) were documented for benchmark acetophenone.

Catalytic Asymmetric Hydrogenation of Tetrasubstituted Unsaturated Lactams: An Efficient Approach to Enantioenriched 3,4-Disubstituted Piperidines.

Asymmetric hydrogenation of tetrasubstituted alkenes remains a formidable challenge in asymmetric catalysis. We report herein an unprecedented Rh-catalyzed enantioselective and diastereoselective hydrogenation of easily accessed α,β-disubstituted unsaturated lactams to afford synthetically valuable chiral lactams with 1,2-consecutive stereocenters. The reaction could be performed on the gram scale, and the products could be concisely transformed to enantiomerically pure -3,4-disubstituted piperidines, which are prevalent structural units in medicinal agents.

Direct reductive amination of ketones with ammonium salt catalysed by Cp*Ir(III) complexes bearing an amidato ligand.

A series of half-sandwich Ir(III) complexes 1-6 bearing an amidato bidentate ligand were conveniently synthesized and applied to the catalytic Leuckart-Wallach reaction to produce racemic α-chiral primary amines. With 0.1 mol% of complex 1, a broad range of ketones, including aryl ketones, dialkyl ketones, cyclic ketones, α-keto acids, α-keto esters and diketones, could be transformed to their corresponding primary amines with moderate to excellent yields (40%-95%).

Rh-Catalyzed Asymmetric Hydrogenation of Unsaturated Medium-Ring NH Lactams: Highly Enantioselective Synthesis of N-Unprotected 2,3-Dihydro-1,5-benzothiazepinones.

A straightforward method to prepare 1,5-benzothiazepines was reported. Catalyzed by a Rh/Zhaophos complex, unsaturated cyclic NH lactams with a medium-size ring were hydrogenated smoothly, giving remarkably high enantioselectivities. The sulfur atom in the substrates did not bring an inhibition which was observed with commercially available bisphosphine ligands.