Facile access to chiral chromanone-2-carboxylic acids enabled by rhodium-catalyzed chemo- and enantioselective hydrogenation

Abstract

Rh-catalyzed highly chemo- and enantioselective hydrogenation of chromone-2-carboxylic acids was first successfully established, providing a wide range of enantiopure chromanone-2-carboxylic acids with excellent results (up to 97% yield and 99%...

Recent advances in the metal-catalyzed asymmetric alkene hydrogenation of cyclic conjugated carbonyl compounds

“…Chiral chromanones P5 bearing a carboxylic acid in the β-position with respect to the ketone were obtained by the hydrogenation of chromones S5 using a JosiPhos SL-J216-1 L16a ligated rhodium complex. 27 This catalyst exhibited high efficiency (up to 10 000 TON) and stereoselectivity (up to 99% ee). This method provides a reliable synthetic path to key skeletons of many drug candi-dates for neurocognitive deficits and also towards a novel kind of bridged [3.2.1] tricyclic lactone skeleton, that can serve as a new class of chemical entity for drug design (Scheme 5b).…”

“…More functionalized chiral cyclic ketones were prepared by contributions from Andersson, 26 Zheng & Zhang & Yao, 27 Ye & Hou cyclic nitrogen donor in the ligand backbone was made on the basis of DFT ΔpK a calculations. Chiral chromanones P5 bearing a carboxylic acid in the β-position with respect to the ketone were obtained by the hydrogenation of chromones S5 using a JosiPhos SL-J216-1 L16a ligated rhodium complex.…”

“…More functionalized chiral cyclic ketones were prepared by contributions from Andersson, 26 Zheng & Zhang & Yao, 27 Ye & Hou 14 and Tan & Ding & Chen & Zhang. 28 Baylis–Hillman adducts 26 S4 were efficiently hydrogenated by Ir/phosphine-thiazole L2b or Ir/phosphine-imidazole L12b complexes to give stereoenriched cyclic β-hydroxy ketones P4 up to 93% ee (Scheme 5a).…”

Efficient Rh-Catalyzed Chemo- and Enantioselective Hydrogenation of 2-CF3–Chromen/Thiochromen-4-ones

“…In 2018, Zhang's group developed asymmetric hydrogenation of chromones catalyzed by the RuPHOX−Ru complex, achieving both excellent diastereo-and enantioselectivities under 20 bar of H 2 . 10 Although Wang's group realized copper-catalyzed asymmetric conjugated reduction of chromones and thiochromones by DEMS (diethoxymethylsilane) to obtain chiral chromanones and thiochromanones, 11 and Yao and co-workers reported a straightforward synthetic protocol to access chiral chromanone-2-carboxylic acids via Rh-catalyzed asymmetric hydrogenation of chromone-2-carboxylic acids, 12 the chemoand enantioselective hydrogenation of flavones and chromones for direct synthesis of chiral flavanones and chromanones has not yet been developed. Moreover, up to now, 2-CF 3chromones have still not been explored in asymmetric hydrogenation, which can be attributed to two challenges: one is the control of tendencies toward the overreduction of both C�C and C�O double bonds, and the other is the rigid cyclic structure and the electron deficient C�C bond that would weaken the coordination between the substrate and the metal catalyst leading to low enantioselectivity.…”