Rhodium-Catalyzed Asymmetric Transfer Hydrogenation of Heterocyclic
Diaryl Ketones: Facile Access to Key Intermediate of Baloxavir
Transition metal-catalyzed asymmetric transfer hydrogenation has been
proved 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.