Convenient and flexible syntheses of gem-dimethyl carboxylic triggers via mono-selective β-C(sp3)–H arylation of pivalic acid with ortho-substituted aryl iodides

Abstract

This work presents a palladium(II)-catalyzed mono-selective C(sp³)–H arylation of pivalic acid for rapid construction of an important library of 3-aryl-2,2-dimethylpropanoic acids, especially ortho-substituted-aryl compounds. The strategy greatly streamlines access to a series of trimethyl-lock-type triggers – arylated gem-dimethyl carboxylic acids bearing ortho-activatable substituents, which can be used as a self-immolative spacer for selective chemical release initiated under specific conditions. Flexible transformation and derivatization of these activatable carboxylic triggers are also showcased.