Nucleophilic Trifluoromethoxylation of Acyl Chlorides: A Direct Route to Trifluoromethyl Esters

A one‐pot two‐step nucleophilic trifluoromethoxylation of versatile acyl chlorides was developed, offering a straightforward access to high added‐value trifluoromethyl carboxylic esters. By harnessing the reactivity of acyl chlorides with the in situ‐generated AgOCF 3 from the readily available trifluoromethyl para ‐toluenesulfonate and commercially available AgF, a large panel of aromatic and aliphatic trifluoromethyl carboxylic esters was synthesized (28 examples, up to 69% yields). The transformation was tolerant of carbamates and olefins, and the synthetic utility of the approach was further illustrated by the functionalization of complex molecules such as fatty acids, steroids, and amino acids. This study represents the first synthetically useful path to access trifluoromethyl esters by direct trifluoromethoxylation, employing readily available reagents. Beyond enabling access to trifluoromethyl esters, this study examines their stability under various reaction conditions and explores the reactivity of this unique class of activated esters toward common reagents, such as reducing agents and nucleophiles, both of which remain largely underexplored.