Modular synthesis of α-arylated carboxylic acids, esters and amides via photocatalyzed triple C-F bond cleavage of methyltrifluorides

alpha-Arylated carboxylic acids, esters and amides are widespread motifs in bioactive molecules and important building blocks in chemical synthesis. Thus, straightforward and rapid access to such structures is highly desirable. Here we report an organophotocatalytic multicomponent synthesis of alpha-arylated carboxylic acids, esters and amides from exhaustive defluorination of alpha-trifluoromethyl alkenes in the presence of alkyltrifluoroborates, water and nitrogen/oxygen nucleophiles. This operationally simple strategy features a unified access to functionally diverse alpha-arylated carboxylic acids, esters, and primary, secondary, and tertiary amides through backbone assembly from simple starting materials enabled by consecutive C-F bond functionalization at room temperature. Preliminary mechanistic investigations reveal that the reaction operates through a radical-triggered three-step cascade process, which involves distinct mechanisms for each defluorinative functionalization of the C-F bond.

Automated summary

This study reports an organophotocatalytic multicomponent synthesis method for the synthesis of alpha-arylated carboxylic acids, esters and amides from alpha-trifluoromethyl alkenes. The reaction involves a radical-triggered three-step cascade process and enables the functionalization of C-F bonds at room temperature, providing a straightforward access to a wide range of functionally diverse compounds.