Transition metal-free approach for late-stage benzylic C(sp³)–H etherifications and esterifications

Abstract

Herein, we report a transition metal-free approach for the regioselective functionalisation of benzylic C(sp3)-H bonds using alcohols and carboxylic acids as the nucleophiles. This approach provides a straightforward route for...

Transition-metal-free access to benzyl ethers via aerobic cross-dehydrogenative coupling of benzylic C(sp3)–H bonds with alcohols

“…2 Furthermore, a majority of synthetic strategies in this field have been established to construct benzylic C–O bonds. 3 Recently, Yoon's group reported a photoredox and Cu-mediated site-selective alkoxylation of an electron-rich benzylic C–H bond by cross-coupling of benzylic C–H with alcohols (Scheme 1a). 4 Almost at the same time, Stahl's group disclosed a radical relay method exploiting Cu catalysts in combination with N -fluorobenzenesulfonimide (NFSI) to realize benzylic C–H etherification with excellent functional group compatibility via benzylic C–H cross-coupling reactions (Scheme 1b).…”

Visible-Light-Driven Organocatalytic Alkoxylation of Benzylic C–H Bonds

“…In 2021, Liu and co-workers developed a photoredox/nickel dual-catalytic protocol for synthesis of benzyl ethers through benzylic C–H alkoxylation (Scheme f) . Very recently, an important advancement for the metal-free strategy in alkoxylation of benzylic C–H bonds was achieved by Das and co-workers (Scheme g) …”

“…34 Very recently, an important advancement for the metalfree strategy in alkoxylation of benzylic C−H bonds was achieved by Das and co-workers (Scheme 1g). 35 Although many methods for direct alkoxylation of benzyl have been reported, the metal-free catalytic system is rarely reported. It is highly desirable for the development of a metalfree benzyl alkoxylation method as an alternative strategy because metal-free methods have the advantages of avoiding metal contaminants.…”

“…Ethylbenzene as a basic scaffold widely exists in drug molecules and is also a common synthon in organic synthesis. − The direct functionalization of the sp 3 C–H bond at the benzyl position is one of the most straightforward and effective methods for last-stage structural modification of molecules containing ethylbenzene skeletons. , In recent years, a wide range of functionalization reactions at benzyl sites have been developed, such as arylation, cyanation, halogenation, − and other functionalizations of benzyl. − Among them, alkoxylation is a powerful and atom-economical tool for the introduction of the C–O bond to the benzylic position. In view of the importance of benzyl ether in drug synthesis, − different strategies for direct alkoxylation of the benzylic C–H bond, including conventional chemical methods, − electrocatalytic methods, − and photocatalytic methods, − have been developed. In 2016, Fu’s group reported the coupling reaction of γ-aryl alkynoates with alcohols catalyzed by chiral phosphine (Scheme a) .…”

Recyclable Mesoporous Graphitic Carbon Nitride Catalysts for the Sustainable Photoredox Catalyzed Synthesis of Carbonyl Compounds

“…The development of transition-metal-free protocols for synthesizing value-added products from abundant feedstock supplies is a central topic in organic synthesis. − Alkanes, alkenes, and carboxylic acids are abundantly available in nature, petrochemical, and pharmaceutical industries. − Converting these materials into high-value carbonyl compounds is a desirable and cost-effective approach. − However, most reported methods for this transformation rely on transition-metal-based catalysts or require harsher reaction conditions or toxic oxidants. − ,− , Visible-light photoredox catalysis has emerged as a powerful tool for sustainable organic synthesis. ,,, Initially, expensive transition-metal photocatalysts (such as Ir or Ru complexes) or photounstable organic dyes were often employed for catalytic conversions. − In recent years, heterogeneous photocatalytic systems have gained significant interest in organic synthesis and energy storage applications. − Notably, mesoporous graphitic carbon nitride (mpg-CN) has attracted attention in the field of photochemistry due to its stability, large surface area, and recyclability. ,− With a band gap of 2.7 eV, mpg-CN possesses similar properties to many homogeneous photocatalysts . Thus, the direct utilization of mpg-CN catalysts for converting readily available feedstock materials into value-added functional groups under low-energy visible light irradiation is highly desirable yet relatively unexplored.…”