Selective Friedel–Crafts Acylation of N ‐Tosylindoles Enabling a Concise Total Synthesis of Breitfussin B

ABSTRACT

Breitfussin B is a halogen‐rich dipeptide natural product isolated from the Arctic invertebrate Thuiaria breitfussi . We report a concise total synthesis of Breitfussin B enabled by a practical SnCl ₄ ‐mediated Friedel–Crafts acylation of N ‐tosylindoles. The acylation proceeds regioselectively at C3 and provides a series of 3‐acylindoles in good to excellent yields using aliphatic, aromatic, and α,β‐unsaturated acyl chlorides. This strategy streamlines access to key intermediates and supports an efficient synthesis of Breitfussin B.