Rhodium‐Catalyzed Asymmetric Transfer Hydrogenation of Heterocyclic Diaryl Ketones: Facile Access to Key Intermediate of Baloxavir

Comprehensive Summary Transition metal‐catalyzed asymmetric transfer hydrogenation has been proven to be a powerful approach for the synthesis of chiral alcohols. Herein, a highly efficient and enantioselective transfer hydrogenation of dibenzoheptaheterocyclic ketones catalyzed by an arene‐tethered TsDPEN‐based Rh(III) catalyst has been successfully developed, and a variety of dibenzoheptaheterocyclic ketones were reduced by a 1/1 mixture of formic acid and DBU (1,8‐diazabicyclo[5.4.0]undec‐7‐ene) with high yields and enantioselectivities. With this method, the asymmetric reduction of 7,8‐difluorodibenzo[b,e]thiepin‐11(6H)‐one has been realized, providing the key intermediate of baloxavir marboxil with >99% yield and >99% ee at a substrate/catalyst molar ratio of 1000. Herein, we have developed a highly practical and enantioselective rhodium‐catalyzed asymmetric transfer hydrogenation of heterocyclic diaryl ketones, providing the desired product with up to >99 yield and >99% ee. The synthetical potential of the current reaction was demonstrated by the gram‐scale synthesis of key intermediate of baloxavir.