Leaving Groups in Metal‐Free Arylations: Make Your Choice!

Abstract

Cleavage of an Aryl–Leaving Group bond (Ar–LG) is the key step in most arylation processes for the synthesis of highly functionalized (hetero)arenes. In metal‐free arylations, depending on the nature of the starting substrates, different thermal and photochemical approaches can be adopted: Single Electron Transfer (SET) and homolysis/heterolysis of an Ar–LG bond to afford an aryl radical (Ar·) or an aryl cation (Ar+), respectively. Accordingly, the nature of LG plays a key‐role in determining the mechanism and efficiency of the process.

Non-innocent Radical Ion Intermediates in Photoredox Catalysis: Parallel Reduction Modes Enable Coupling of Diverse Aryl Chlorides

“…Aryl radicals are reactive intermediates that engage in a myriad of synthetically valuable transformations. − Classically, aryl radical intermediates are generated from aryl diazonium salts, iodides, or bromides. − Aryl chlorides are rarely used as radical precursors despite the fact they comprise over two-thirds of commercially available aryl halides (Figure B). − This is a consequence of their resistance to reductive activation, and high C­(sp 2 )–Cl BDE. , König recently pioneered an elegant strategy, termed consecutive photoinduced electron transfer (conPET), wherein a photochemically generated radical anion is subsequently excited. , This approach primes the photocatalyst with an electron prior to excitation and, in principle, can generate much deeper reduction potentials through E 1/2 (PC/PC •–* ). Indeed, later implementations of this conPET strategy unlocked exceptionally challenging reductions. , However, all recent advances in visible light photoredox methods that reduce electronically diverse chloroarenes have been limited to proteodefunctionalization and borylation reactions. ,− Recent electrophotocatalytic − approaches have directly generated these electron-primed photocatalysts cathodically. , While this strategy has begun to expand the range of radical coupling reactions that engage aryl chlorides, a general approach to leverage the expansive pool of aryl chloride substrates in radical couplings has remained elusive and the need for electrochemical equipment remains a barrier in some settings. , In particular, net-reductive radical coupling processes, such as alkene hydroarylation, − have remained elusive for aryl chloride substrates for all modern methods.…”

Photo-Induced Thiolate Catalytic Activation of Inert Caryl-Hetero Bonds for Radical Borylation

“…These results are particularly noteworthy considering the fact that thiolate anions are rarely used as leaving groups in radical arylation reactions and sulfides possess more negative reduction potentials, which are caused by the electrondonating property of SR groups. 8,58 Table 2. Leaving group scope for photo-induced ipso-borylation of substituted arenes a (2.0 eq.…”

Photo-Induced Thiolate Catalytic Activation of Inert Caryl-Hetero Bonds for Radical Borylation

“…These results are particularly noteworthy considering the fact that thiolate anions are rarely used as leaving groups in radical arylation reactions and sulfides possess more negative reduction potentials, which are caused by the electrondonating property of SR groups. 8,58 After surveying the scope of phenyl radical precursors, we next sought to study the preparative scope of our reaction utilizing substituted aryl fluorides, O-Boc protected phenols as well as organosulfur compounds. We were pleased to see a wide variety of aryl fluorides bearing para-(3b-3o), ortho-(3p and 3q) and meta-(3r-3u) substituents reacting smoothly to afford the corresponding boronic esters.…”