Photoredox Catalysis in Late-Stage Aryl C(sp3 )−H Functionalizations

The high prevalence of aromatics in natural products and potential drug candidates makes them intriguing candidates for continued development of C-H functionalization reactions that proceed with high positional selectivity. Achieving site-selectivity can be a steep challenge as when there is a lack of appropriate directing groups or substitution patterns, more than one product isomer is commonly produced. Therefore, the development of aromatic C-H functionalization by means of chemo and site-selective activation is of interest. 

The field of photoredox catalysis has continued to grow at a rapid rate due to the vast scope of synthetic transformations that are possible. Since the advent of photoredox catalysis, the development and application of light-induced reactions have brought about the creation of a variety of new bond constructions. In 1984, Cano-Yelo and Deronzier reported the first net oxidative photoredox-catalyzed reaction using aryldiazonium salts as the terminal oxidant for the conversion of benzylic alcohols to the corresponding aldehydes, shortly after this they disclosed the first redox-neutral transformation.¹ Several years after, the vast utility of alkyl radicals was realized during the pioneering work of Okada and co-workers, when they reported photosensitized decarboxylative Michael Addition through N-(acyloxy)phthalimides.² The field remained relatively inert until the late 2000s. In 2008, Yoon and co-workers disclosed a photoredox-catalyzed enone cycloadditon reaction, modulating the reactivity of enone substrate through use of a Lewis acid additive.³ Following this was the work done by MacMillan and co-workers using photoredox catalysis for the enantioselective alkylation of aldehydes.⁴ These reports underscored the applicability of photoredox catalysis as an efficient yet nontoxic means of activation. 

The merger of photoredox catalysis with other organocatalytic activation modes expanded the repertoire of C-C and C-H bond formations. Overall, the robust repertoire of photoredox catalysis as well as its application pertaining to aromatic C-H functionalizations will be discussed. 
 

References 

[1]Cano-Yelo, H., Deronzier, A. Tetrahedron Lett. 1984, 25, 5517-5520. 

[2]Okada, K,. et al. J. Am. Chem. 1991, 113, 9401-9402. 

[3]Yoon, Juana., et al. J. Am. Chem. 2008, 130, 12886-18887. 

[4]MacMillan, D., et al. Science. 2008, 322, 77-80.