Photoredox-catalyzed C–C bond cleavage of cyclopropanes for the formation of C(sp3)–heteroatom bonds

Abstract

Sterically congested C–O and C–N bonds are ubiquitous in natural products, pharmaceuticals, and bioactive compounds. However, the development of a general method for the efficient construction of those sterically demanding covalent bonds still remains a formidable challenge. Herein, a photoredox-driven ring-opening C(sp3)–heteroatom bond formation of arylcyclopropanes is presented, which enables the construction of structurally diversified while sterically congested dialkyl ether, alkyl ester, alcohol, amine, chloride/fluoride, azide and also thiocyanate derivatives. The selective single electron oxidation of aryl motif associated with the thermodynamic driving force from ring strain-release is the key for this transformation. By this synergistic activation mode, C–C bond cleavage of otherwise inert cyclopropane framework is successfully unlocked. Further mechanistic and computational studies disclose a complete stereoinversion upon nucleophilic attack, thus proving a concerted SN2-type ring-opening functionalization manifold, while the regioselectivity is subjected to an orbital control scenario.

Photoredox-Catalysis-Enabled Ring-Opening Functionalization of Aryl Cyclopropanes

“…This method permits the expedient construction of a host of structurally diverse, sterically congested, dialkyl ether, alkyl ester, alcohol, amine, chloro, fluoro, azide, or thiocyanate derivatives (Scheme 4a ). 11 The synthetic utility of this method was further showcased by a late-stage functionalization of several natural products and derivatives of pharmaceutical molecules. In accordance with our previous report, reactions of two enantioenriched cyclopropanes also afforded the desired products with full conservation of their enantiopurity (Scheme 4b ).…”

Redox-neutral carbon–heteroatom bond formation under photoredox catalysis

“…In 2022, Feng and co-workers 33 demonstrated the photoredox catalyzed C(sp 3 )–heteroatom bond formation reaction via ring opening functionalization of electronically unbiased aryl cyclopropanes 23a . After irradiating several photocatalysts in the presence of a blue LED, the acridinium photocatalyst ( E 1/2 (Acr*/Acr − ) = +2.08 V vs. SCE) proved to be the best to offer product 23c in up to 95% yield (Scheme 23).…”

Synthesis of α-Difluoromethylene Ethers via Photoredox-Induced Hyperconjugative Ring Opening of gem-Difluorocyclopropanes

“…During the past few decades, many gem -difluorocyclopropanation approaches via the difluorocarbene process have been developed, enabling their further transformations . In this regard, Feng and co-workers have developed a series of photoredox-catalyzed carbon–carbon (C–C) bond cleavage-functionalization of cyclopropanes . Although the transition-metal-catalyzed ring opening of gem -difluorocyclopropane generally afforded defluorinated products − (Scheme c), the photoredox-induced C–C bond cleavage of gem -difluorocyclopropane in the presence of Et 3 N·3HF furnished trifluoromethylated products (Scheme d).…”