Enantioselective Synthesis of Chiral 1,5-Benzodiazepin-2-ones by Pd-Catalyzed Asymmetric Hydrogenation and Reductive Amination.

The enantioselective synthesis of chiral 4-substituted 4,5-dihydro-1-[1,5]benzodiazepin-2(3)-ones via asymmetric hydrogenation catalyzed by the Pd/f-spiroPhos complex in the presence of hydrochloric acid as an additive has been developed, achieving excellent enantioselectivities and high turnover numbers, up to 99% ee and TON = 4600. More significantly, the asymmetric reductive amination of β-keto esters with 1,2-phenylenediamine has also been successfully realized to afford chiral 4-substituted 4,5-dihydro-1-[1,5]benzodiazepin-2(3)-ones with comparable enantioselectivities of up to 99% ee.

Ir-Catalyzed Asymmetric Hydrogenation of -Fused Heteroarenes with High Nitrogen Density: An Access to Chiral 2,5-Disubstituted 5,6-Dihydropyrrolo[1,2-][1,2,4]triazolo[5,1-]pyrazines.

A highly enantioselective Ir-catalyzed asymmetric hydrogenation of 2,5-disubstituted pyrrolo[1,2-][1,2,4]triazolo[5,1-]pyrazines containing four nitrogen atoms has been first realized. Under additive-free conditions, a variety of chiral 2,5-disubstituted 5,6-dihydropyrrolo[1,2-][1,2,4]triazolo[5,1-]pyrazines can be afforded in high yields (86-98%) with excellent enantioselectivities of up to 99% ee. This method provides a straightforward strategy for the efficient synthesis of chiral multinitrogen polyheterocyclic compounds.

Rh-Catalyzed Asymmetric Hydrogenation of 2-Substituted 4-(Thio)chromenes for Synthesis of Chiral (Thio)chromanes.

Rh-catalyzed asymmetric hydrogenation of 2-substituted 4-thiochromenes and 4-chromenes was successfully developed. This method provided highly efficient access to a series of chiral 2-substituted thiochromanes and chromanes in high yields with excellent enantioselectivities (up to 99% yield, 86-99% ee). The obtained chiral 2-substituted thiochromane products were also successfully transformed to corresponding chiral substituted sulfoxides and sulfones with excellent enantioselectivities.

Efficient Rh-Catalyzed Chemo- and Enantioselective Hydrogenation of 2-CF-Chromen/Thiochromen-4-ones.

A Rh-catalyzed highly chemo- and enantioselective hydrogenation of 2-CF-chromen/thiochromen-4-ones was successfully established achieving excellent selectivity and high turnover numbers. Under mild conditions, a series of 2-CF-chromen-4-ones were hydrogenated to provide the corresponding chiral 2-CF-chroman-4-ones with excellent enantioselectivities (up to 99.9% ee) and achieve high turnover numbers (TON of up to 11,800).

Highly enantioselective Rh-catalyzed asymmetric reductive dearomatization of multi-nitrogen polycyclic pyrazolo[1,5-]pyrimidines.

A highly enantioselective rhodium-catalyzed reductive dearomatization of 7-substituted pyrazolo[1,5-]pyrimidines has been realized for the first time by two strategies to afford chiral 4,5,6,7-tetrahydropyrazolo[1,5-]pyrimidines with excellent enantioselectivities of up to 98% ee. This method also provides an efficient approach for the synthesis of the powerful BTK inhibitor, zanubrutinib.

Nickel-Catalyzed Asymmetric Hydrogenation of γ-Keto Acids, Esters, and Amides to Chiral γ-Lactones and γ-Hydroxy Acid Derivatives.

A highly efficient asymmetric hydrogenation of a series of γ-keto acid derivatives, including γ-keto acids, esters, and amides, using a Ni-(,)-QuinoxP* complex as the catalyst has been developed to afford chiral γ-hydroxy acid derivatives with excellent enantioselectivities, up to 99.9% ee. This method provides not only an economical one-pot approach for the synthesis of chiral γ-lactones but also access to ()-norfluoxetine, an inhibitor of neural serotonin reuptake and an essential intermediate for pharmaceutical synthesis.

Enantioselective Synthesis of Chiral Phosphonates via Rh/f-spiroPhos Catalyzed Asymmetric Hydrogenation of β,β-Disubstituted Unsaturated Phosphonates.

The first asymmetric hydrogenation of β,β-diaryl unsaturated phosphonates has been realized for synthesis of β,β-diaryl chiral phosphonates with excellent enantioselectivities (up to 99.9% ee) catalyzed by the Rh-(,)-f-spiroPhos complex. Furthermore, this catalyst also exhibits comparably excellent performance for β-aryl-β-alkyl unsaturated phosphonates providing the corresponding chiral phosphonates with up to 99.