A cross-dehydrogenative C(sp3)−H heteroarylation via photo-induced catalytic chlorine radical generation

Abstract

Hydrogen atom abstraction (HAT) from C(sp3)–H bonds of naturally abundant alkanes for alkyl radical generation represents a promising yet underexplored strategy in the alkylation reaction designs since involving stoichiometric oxidants, excessive alkane loading, and limited scope are common drawbacks. Here we report a photo-induced and chemical oxidant-free cross-dehydrogenative coupling (CDC) between alkanes and heteroarenes using catalytic chloride and cobalt catalyst. Couplings of strong C(sp3)–H bond-containing substrates and complex heteroarenes, have been achieved with satisfactory yields. This dual catalytic platform features the in situ engendered chlorine radical for alkyl radical generation and exploits the cobaloxime catalyst to enable the hydrogen evolution for catalytic turnover. The practical value of this protocol was demonstrated by the gram-scale synthesis of alkylated heteroarene with merely 3 equiv. alkane loading.

Development of a Quinolinium/Cobaloxime Dual Photocatalytic System for Oxidative C–C Cross-Couplings via H2 Release

“…Given the competence of photocatalysts in mediating redox steps, combining photoredox catalysis with Minisci reactions represents a fundamental advancement in various settings . However, their conditions often consist of costly photocatalysts and stoichiometric chemical oxidants that were either situated as exogenous additives or embedded in the reactants. ,,, In contrast, net-oxidation Minisci-type transformations that bypass these oxidizing components with their chemical equivalents, preferably in catalytic quantity, remain underexplored . Along this line, hydrogen evolution provides a paradigm-shifting alternative that could not only realize the redox adjustment but also drive the overall reaction progress.…”

Neutrally photoinduced MgCl2-catalyzed alkenylation and imidoylation of alkanes

“…Since the metal cation did not affect the occurrence of the reactions, the electron transfer between the chloride ion (Cl − ) and the existing π-system Π , probably involving the sulfone or solvent, under 390 nm light was proposed to be the initial step. 11–17 This single electron oxidation produces the chlorine radical (Cl˙) and Π˙ − . Then, the efficient hydrogen atom abstraction using the chlorine radical (Cl˙) with 2a produced the cyclohexyl radical Int-A and regenerated the chloride ion and proton.…”

“…10–17 Compared with the classic homolysis of Cl 2 , the direct single electron oxidation of the chloride ion (Cl − ) is an ideal method for the generation of the chlorine radical. 11–17 Particularly, the dramatic developments in photocatalysis over the past decade have shed light on such a process, and a few strategies have been explored (Scheme 1-ii): (a) photoinduced ligand-to-metal charge transfer coupling with metal reduction and chloride oxidation; typically, metals with strong oxidative ability, such as Ni( iii ), 4 a ,12 Ti( iv ), 13 Ce( iv ), 6 a , b Fe( iii ), 14 and Cu( ii ), 15 are required; (b) single electron transfer between a chloride and a stochiometric amount of an oxidant, such as I 2 , O 2 , and O-radical, under photothermal conditions; however, these reactions suffer from drawbacks, namely, the need for strong oxidants and typical acidic conditions; 16 and (c) chloride oxidation by robust photocatalysts, such as Mes-Acr + ClO 4 − , (N-heteroarene)H + , and [Ir(dF(CF 3 )ppy) 2 (dtbbpy)]Cl. 17 These pioneering examples have shown the advantages of chlorine radical formation using chloride; however, a mild catalytic system avoiding the use of strong acids, oxidants, and photocatalysts is still highly required.…”

“…11–17 Particularly, the dramatic developments in photocatalysis over the past decade have shed light on such a process, and a few strategies have been explored (Scheme 1-ii): (a) photoinduced ligand-to-metal charge transfer coupling with metal reduction and chloride oxidation; typically, metals with strong oxidative ability, such as Ni( iii ), 4 a ,12 Ti( iv ), 13 Ce( iv ), 6 a , b Fe( iii ), 14 and Cu( ii ), 15 are required; (b) single electron transfer between a chloride and a stochiometric amount of an oxidant, such as I 2 , O 2 , and O-radical, under photothermal conditions; however, these reactions suffer from drawbacks, namely, the need for strong oxidants and typical acidic conditions; 16 and (c) chloride oxidation by robust photocatalysts, such as Mes-Acr + ClO 4 − , (N-heteroarene)H + , and [Ir(dF(CF 3 )ppy) 2 (dtbbpy)]Cl. 17 These pioneering examples have shown the advantages of chlorine radical formation using chloride; however, a mild catalytic system avoiding the use of strong acids, oxidants, and photocatalysts is still highly required. Herein, we report a novel photocatalytic protocol utilizing magnesium chloride to generate chlorine radicals under redox-neutral and acid-free conditions, which enables C–H bond alkenylation and imidoylation of light alkanes with organic sulfones via efficient hydrogen atom abstraction (Scheme 1).…”

Synthetic Applications of Photocatalyzed Halogen‐Radical Mediated Hydrogen Atom Transfer for C−H Bond Functionalization

“…Similarly, we excluded those reports where the formation of the halogen atom does not depend on a photocatalyst, but is a consequence of photoinitiated and photochemical events [37–41] . Finally, we did not consider those cases where one of the substrates also works as the photocatalyst, [42] as these should be more properly referred to as photochemical approaches. It is worth mentioning that halogen radical‐mediated HAT has been also used to activate O−H bonds in alcohols and carboxylic acids [43,44] …”