Contemporary methods for generation of aryl radicals

Abstract

The synthetic utility of aryl radicals has been established in the last century, however, their broad applications were hampered by ineffective generation methods. It was in the last decade, that a rapid development of various redox systems took place, thus triggering a renaissance of aryl radical chemistry. This tutorial review focuses on the start-of-the-art methods for generation of aryl radicals. Primarily, various light-induced systems, including photoredox catalysis, visible light transition metal catalysis, and chemistry of electron donor-acceptor complexes, are reviewed. The main current precursors of aryl radicals are evaluated together with the selected examples of their modern applications.

Fig. 1

Generation and transformations of aryl radicals.

Figure 2

C–H bond-dissociation energy comparison.

Fig. 3

Generalized EDA complex formation.

Scheme 1

Sanford’s directed arylation using diazonium salts.

Scheme 2

König’s C–H arylation of heteroarenes.

Scheme 3

Proposed mechanism for König’s C–H arylation of heteroarenes.

Scheme 4

(a) Gevorgyan’s C–H amination reaction (b) Proposed mechanism.

Scheme 5

Hypothetical patways towards aryl radicals from diazonium salts.

Scheme 6

(a) Studer’s oxyarylation of alkenes (b) Proposed mechanism.

Scheme 7

(a) Mo’s electrochemical Sandmeyer reaction (b) Upscale synthesis.

Scheme 8

Proposed mechanism for Kubota’s and Ito’s C–H arylation and borylation reactions.

Scheme 9

Scope of Kubota’s and Ito’s C–H arylation and borylation reactions.

Scheme 10

Ryu’s mechanistic hypothesis.

Scheme 11

Ryu’s scope of photoinduced aminocarbonylation.

Scheme 12

Stephenson’s reduction of aryl iodides.

Scheme 13

Proposed mechanism to Stephenson’s reduction.

Scheme 14

König’s proposed mechanism of reduction.

Scheme 15

König’s aryl halide reduction.

Scheme 16

König’s arylation of pyrroles.

Scheme 17

General mechanistic concept for combined electrochemistry-photochemistry activation mode of aryl halides.

Scheme 18

Lambert’s and Lin’s borylation and stannylation scope.

Scheme 19

Scope of Wickens’ phosphorylation and arylation reactions.

Scheme 20

Proposed mechanistic patway for Gevorgyans desaturation reaction.

Scheme 21

Scope of Gevorgyan’s desaturation protocol.

Scheme 22

Radical clock experiment.

Scheme 23

Arndsten’s carbonylation protocol.

Scheme 24

(a) Scope of Xia’s oxyindole arylation (b) Proposed EDA complex.

Scheme 25

(a) Li’s proposed SET path for formation of aryl radical from aryl triflate.(b) Scope of borylation reaction.

Scheme 26

Scope of Li’s iodination of aryl triflates.

Scheme 27

Scope of Gevorgyan’s cyclization of aryl triflates.

Scheme 28

(a) Gevorgyan’s mechanistic proposal for cyclization of aryl triflates. (b) Labelling studies.

Scheme 29

Competetive reaction rates for reactions of benzoyl radical.

Scheme 30

Greaney’s radical protodecarboxylation.

Scheme 31

Glorious’ mechanistic hypothesis for formation of aryl radicals from benzoic acids.

Scheme 32

Scope of Glorious’ decarboxylative arylation.

Scheme 33

Yoshimi’s Meerwein arylation of Michael acceptors.

Scheme 34

Proposed mechanism for Yoshimi’s arylation of Michael acceptors.

Scheme 35

Scope of Xiao’s C–H arylation reaction.

Scheme 36

Proposed mechanism for Xiao’s C–H arylation reaction.

Scheme 37

Studer’s oxyarylation of alkenes using I(III) reagents.

Scheme 38

Studer’s proposed mechanism for formation of aryl radical.

Scheme 39

Mechanism of Ritter’s fluorination reaction.

Scheme 40

Scope of Ritter’s fluorination reaction.

Scheme 41

Scope Li’s tandem cyclization products.

Scheme 42

Proposed mechanism for Li’s tandem cyclization reaction.