Metallaphotocatalytic modular synthesis of masked arylaminomethyl trifluoromethyl ketones

Trifluoromethyl ketones (TFMKs) represent a crucial class of functional groups in organic synthesis and drug design. Carbo- and heteroatom-substituted methyl TFMKs have been developed extensively, leading to a broad array of structurally diverse trifluoromethylated compounds. However, aminomethyl TFMKs remain largely underexplored, likely due to the intrinsic incompatibility between amino and carbonyl groups. Here, we present a modular strategy for accessing aminomethyl TFMKs in a cyclic acetal-protected form. Using 2-(trifluoromethyl)-1,3-dioxolane-2-carboxylic acid as a masked trifluoroacetyl radical precursor, along with nitroarenes and tertiary alkylamines as readily available reaction components, we demonstrate the feasibility of assembling these compounds under metallaphotocatalytic conditions. This approach selectively yields a diverse array of N -(2-trifluoromethyl)dioxolanylmethyl aniline compounds, which act as inactivated forms of arylaminomethyl TFMKs and can be readily converted into arylaminomethyl TFMKs, various amine derivatives, and azaheterocycles. The structurally distinctive trifluoromethylated dioxolanylmethyl anilines and their downstream products hold significant potential for pharmaceutical and agrochemical development.