Experimental study demonstrates a direct route to trifluoromethyl esters via acyl chloride trifluoromethoxylation, highlighting synthetic utility for complex molecules.
Key Points
Develop a practical one-pot method for direct nucleophilic trifluoromethoxylation of acyl chlorides to synthesize trifluoromethyl carboxylic esters.
Generated silver trifluoromethoxide (AgOCF3) in situ from trifluoromethyl para-toluenesulfonate and commercially available silver fluoride.
Coupled the in situ-generated reagent with diverse aromatic and aliphatic acyl chlorides across a one-pot, two-step sequence.
Evaluated substrate tolerance across 28 targets—including steroids, fatty acids, and amino acids—and probed ester stability against nucleophiles and reducing agents.
Successfully produced 28 aromatic and aliphatic trifluoromethyl carboxylic esters with isolated yields up to 69%.
Demonstrated functional group compatibility with sensitive carbamates and olefins, facilitating late-stage diversification of complex biomolecules.
Mapped the chemical stability and reactivity profiles of the synthesized trifluoromethyl esters toward routine nucleophiles and reducing reagents.