Decarboxylative Ritter-Type Amination by Cooperative Iodine (I/III)-Boron Lewis Acid Catalysis

Recent years have witnessed important progress in synthetic strategies exploiting the reactivity of carbocations via photochemical or electrochemical methods. Yet, most of the developed methods are limited in their scope to certain stabilized positions in molecules. Herein, we report a metal-free system based on the iodine (I/III) catalytic manifold, which gives access to carbenium ion intermediates also on electronically disfavored benzylic positions. The unusually high reactivity of the system stems from a complexation of iodine (III) intermediates with BF3. The synthetic utility of our decarboxylative Ritter-type amination protocol has been demonstrated by the functionalization of benzylic as well as aliphatic carboxylic acids, including late-stage modification of different pharmaceutical molecules. Notably, the amination of ketoprofen was performed on a gram scale. Detailed mechanistic investigations by kinetic analysis and control experiments suggest two mechanistic pathways.

Automated summary

This study presents a metal-free system based on iodine (I/III) catalytic manifold that can generate carbenium ion intermediates at electronically disfavored positions. The system exhibits unusually high reactivity due to the complexation of iodine (III) intermediates with BF3. Detailed mechanistic investigations suggest two possible pathways for the decarboxylative Ritter-type amination protocol.