Photoexcited Chiral Copper Complex-Mediated Alkene E → Z Isomerization Enables Kinetic Resolution

Abstract

While asymmetric synthesis has been established as a powerful synthetic tool for the construction of versatile enantioenriched molecules in the most efficient and practical manner, the resolution of racemates is still the most universal industrial approach to the synthesis of chiral compounds. However, the direct formation of enantiopure Z-isomers through the catalytic nonenzymatic kinetic resolution of racemic E-alkenes remains challenging. Herein, we disclose an unprecedented enantioselective E → Z isomerization mediated by a photoexcited chiral copper complex. This catalytic system enables kinetic resolution of 2-styrylpyrrolidines. This process is difficult to realize under thermal conditions. Mechanistic experiments and density functional theory (DFT) calculations revealed that different overall sensitization rates of the substrate–catalyst complex of the two enantiomers led to the observed excellent kinetic resolution efficiency. This photochemical transformation expands the potential of kinetic resolution beyond their established ground-state reactivity, furnishing a novel reaction mode for enantioselective catalysis at its excited state.

Excited-State Copper-Catalyzed [4 + 1] Annulation Reaction Enables Modular Synthesis of α,β-Unsaturated-γ-Lactams

“…Visible-light-induced excited-state catalysis is becoming a versatile tool in organic synthesis because it allows access to an excited-state reaction landscape for the discovery of novel chemical transformations . The use of ecologically benign and cost-effective copper complexes (Cu: US$0.512/mol) replacing precious metal Ru II polypyridine (Ru: US$2,015/mol) or cyclo-metallated Ir III complexes (Ir: US$30,282/mol) as photocatalysts has recently attracted increasing attention. − In addition to the economic benefits of their use, copper photocatalysts have dual catalytic reactivity and can serve as both photocatalysts and coupling catalysts, participating in inner-sphere catalysis through direct engagement with radical intermediates. We have a continuing interest in advancing fundamental knowledge in excited-state and radical chemistry, expanding the reaction profile of Cu catalysis, and exploring synthetic applications of the umpolung reactivity of acyl radicals. − , Accordingly, we questioned if a copper catalyst could capture a radical intermediate generated from the addition of a nucleophilic acyl radical to acrylamide and undertake a reaction pathway distinct from the Ir-photocatalyst-mediated reaction (Scheme C) .…”

Photoexcited Palladium-Initiated Remote Desaturation of N-Alkoxypyridinium Salts

“…Our group has always been passionate about introducing a CC double bond directly into a saturated system and recently established an excited Pd-catalyzed remote desaturation of O-acyl hydroxamides via N-radical-mediated 1,5-HAT (Figure b) . Based on the aforementioned achievements, as well as our continuing interests in excited-state transition metal catalysis, we decided to work on excited Pd-induced remote desaturation of N -alkoxypyridinium salts leading to unsaturated alcohols (Figure c).…”

Photoactive Copper Complexes: Properties and Applications

“…The emerging field of asymmetric copper-photocatalyzed reactions has been expanded, notably with an efficient kinetic resolution of styrylpyrrolidines relying on the use of [Cu­(MeCN) 4 ]­BF 4 and a chiral BOX ligand under irradiation at 427 nm. A different sensitization of the two diastereomeric substrate-chiral catalyst complexes is being proposed to rationalize the excellent enantiomeric excesses that could be obtained . A visible-light-promoted stereoselective C­(sp 3 )-H glycosylation of quinolinyl-8 glycinates with modified carbohydrates bearing a redox active ester has been moreover shown to be promoted by a combination of copper­(II) triflate and (S)-PHANEPhos .…”