Radical Deoxyfunctionalisation Strategies**

Abstract

Due to their abundance and readily available synthesis, alcohols provide ideal handles for the selective derivatisation of organic molecules. Radical chemistry offers versatile strategies for the conversion of Csp3−O bonds into a wide range of Csp3−C, Csp3−H, or Csp3−heteroatom bonds. In these reactions, alcohols are readily derivatised with an activator group which can undergo facile mesolysis to generate a primary, secondary, or tertiary open‐shell species that can engage in further transformations. These strategies are particularly effective at overcoming steric limitations associated with nucleophilic substitution pathways. Despite their potential, the use of radical deoxyfunctionalisation reactions as a general strategy for the synthesis of useful and complex molecules remains underutilised. In this Review, we highlight recent advancements in this exciting field in which photocatalysis, transition metal catalysis or electrochemistry are used to initiate the radical processes.

Photocatalytic Late-Stage C–H Functionalization

“…Actinometric quantum yield measurements (Φ = 90) speak in favor of a radical chain process, with persulfate anion acting as chain carrier (Scheme 10B). 71 Overman and coworkers reported a conceptually related double decarboxylative Minisci reaction of heteroarenes (10.1) with alkyl oxalates (10.7) 72 (Scheme 10C). 70 [Ir-1], in combination with (NH 4 ) 2 S 2 O 8 as terminal oxidant, could generate densely substituted tertiary radicals from the corresponding oxalates (E 1/2 ox = −1.22 V vs SCE) via reductive quenching.…”

“…Actinometric quantum yield measurements (Φ = 90) speak in favor of a radical chain process, with persulfate anion acting as chain carrier (Scheme B) . Overman and co-workers reported a conceptually related double decarboxylative Minisci reaction of heteroarenes ( 10.1 ) with alkyl oxalates ( 10.7 ) (Scheme C) …”

Practical and General Alcohol Deoxygenation Protocol

“… [16] While Barton‐McCombie variants designed to reduce or eliminate trialkyl tin reagents have been developed, these approaches remain limited in scope and still require unstable thiocarbonyl activating groups, which can also be difficult to install. As a result, the development of alternative deoxygenation methods continues to be an area of considerable synthetic interest [17–37] . Specifically, mechanistically distinct polar S N 1 and S N 2‐type substitution processes that exploit silane hydride sources are increasingly favored alternatives [38–40] .…”

Visible-Light-Driven Photocatalyst-Free Deoxygenative Radical Transformation of Alcohols to Oxime Ethers

“…Within the past decade, the development of visible-light photoredox chemistry provides a preeminent handle for deoxygenative radical functionalization of alcohols. Numerous photoredox catalytic methods have emerged to activate alcohols for homolytic cleavage of C­(sp 3 )–O bonds . However, the developed approaches are either not amenable to primary alcohols for generation of nonstabilized alkyl radicals or require noble metal photocatalysts .…”

“…Numerous photoredox catalytic methods have emerged to activate alcohols for homolytic cleavage of C­(sp 3 )–O bonds . However, the developed approaches are either not amenable to primary alcohols for generation of nonstabilized alkyl radicals or require noble metal photocatalysts . Very recently, we revealed that a xanthate anion can be directly excited by visible light and exhibits strong reducing ability in its excited state (* E 1/2 red < −2.4 V vs SCE) .…”