Enantioselective Hydrogenation of Endocyclic Enones: the Solution to a Historical Problem^†

Abstract

Asymmetric catalysis | Hydrogenation | Cyclic enone | Rhodium | Citral reduction The enantioselective hydrogenation of endocyclic enones has been a historical problem for homogeneous catalysis. We herein report an efficient method to reduce endocyclic enones with molecular hydrogen. Catalyzed by a rhodium/Zhaophos complex, a variety of enones with five-, six-or seven-member ring were hydrogenated with high enantioselectivity (92%-99% ee). Excellent chemo-and enantioselectivity demonstrated this method was successfully applied in the enantioselective hydrogenation of citral to produce enantio-enriched citronellal.

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

“…In 2021, Wen & Zhang 23 developed an efficient rhodium/ ZhaoPhos L8 catalytic system for the asymmetric hydrogen-ation of predominantly β-prochiral cyclopentenones S3 (up to 99% ee, Scheme 4). Efficient catalysts for this transformation had not been established prior to this report and a long-standing interest was thus realized.…”

Concise Total Synthesis of Salimabromide

“…Initially, we attempted to realize an enantioselective version of the tandem Michael/Mukaiyama aldol reaction of cycloheptadienone 4 to produce chiral 8 . Unfortunately, the initial conjugate addition proved extremely challenging with an aryl Grignard reagent 5 or an aluminum or boronic acid reagent, and only racemic adducts were obtainable in our hands. − Inspired by a recent advance achieved by Zhang and co-workers on enantioselective hydrogenation of endocyclic enones, we turned our attention to the enantioselective hydrogenation of cycloheptenone derivative 14 . To our delight, when we used ( R , S )-ZhaoPhos as a ligand, reduction product (−)- 15 was obtained in 86% yield with 97% ee, for which the absolute configuration was determined by single-crystal X-ray analysis of its later intermediate (+)- 8 .…”

Iridium-Catalyzed Double Asymmetric Hydrogenation of 2,5-Dialkylienecyclopentanones for the Synthesis of Chiral Cyclopentanones

“…There are several excellent results for the asymmetric hydrogenation of the endo- and exocyclic CC bonds of the six-membered ring. − , However, for the asymmetric hydrogenation of five-membered ring bearing exocyclic CC bonds, only our developed BiphPHOX ligand showed good results, so the BiphPHOX was selected as the ligand and compound 1a was taken as a model substrate for the reaction conditions optimization (Table ). First, different solvents for the reaction were investigated using L1 as a ligand.…”