Gammaarylation

Gammaarylation is a class of chemical transformations that install an aryl group at the gamma position of a carbon framework relative to a functional group, typically a carbonyl or a directing group. The gamma position is defined as the carbon three atoms away from the reference functionality. This type of arylation enables direct construction of gamma-aryl carbonyl compounds and related motifs, expanding routes to complex molecules.

Most developed gamma-arylation methods rely on modern C–H activation or difunctionalization strategies. In directing-group–assisted approaches, a suitable tether or substituent guides metal catalysts (commonly palladium or nickel) to the gamma C–H bond of ketones, aldehydes, amides, or esters, allowing installation of an aryl moiety via cross-coupling or oxidative coupling steps. Radical and photoredox pathways provide complementary routes, in which aryl radicals or aryl-activated species add to substrates to generate a gamma-centered intermediate that is subsequently transformed into the gamma-aryl product. Gamma-arylation can also occur in carbon–carbon–bond-forming difunctionalizations of alkenes and enones, where an aryl unit is introduced at the gamma position during sequential radical or ionic steps.

Applications of gamma-arylation include the efficient synthesis of gamma-aryl ketones, esters, and related derivatives, which are valuable motifs in pharmaceuticals, agrochemicals, and natural-product synthesis. Ongoing work focuses on improving regioselectivity, expanding substrate scope, and enabling enantioselective variants.

See also: arylation, C–H activation, radical arylation, difunctionalization.