Three-Component Domino Acylation/Trifluoromethylation of Bicyclic Amidines

Org Lett. 2023 Aug 4;25(30):5656-5660. doi: 10.1021/acs.orglett.3c02050. Epub 2023 Jul 21.

Abstract

We herein describe a three-component reaction involving bicyclic amidines such as DBN/DBU, acyl fluorides, and TMSCF3 for access to a novel class of N-acyl trifluoromethylated bicyclic aminals. Under mild and operationally simple conditions, bicyclic amidines can undergo difunctionalization (acylation/trifluoromethylation) using readily available reagents. Further Lewis acid-promoted nucleophilic ring-opening can lead to diverse products with quaternary carbon centers containing CF3. The corresponding pentafluoroethylation is also achieved by using TMSC2F5.