Work

One-Pot Synthesis of Sulfonamides from Unactivated Acids and Amines via Aromatic Decarboxylative Halosulfonylation

Year: 2023

Type: article

Abstract: The coupling of carboxylic acids and amines to form amide linkages is the most commonly performed reaction in the pharmaceutical industry. Herein, we report a new strategy that merges these traditional amide coupling partners to generate sulfonamides, important amide bioisosteres. This method leverages copper ligand-to-metal charge transfer (LMCT) to convert aromatic acids to sulfonyl chlorides, followed by one-pot amination to form the corresponding sulfonamide. This process requires no prefunctionalization of the native acid or amine and extends to a diverse set of aryl, heteroaryl, and s -rich aliphatic substrates. Further, we extend this strategy to the synthesis of (hetero)aryl sulfonyl fluorides, which have found utility as “click” handles in chemical probes and programmable bifunctional reagents. Finally, we demonstrate the utility of these protocols in pharmaceutical analogue synthesis.

Source: Journal of the American Chemical Society

DOI: 10.1021/jacs.3c08218

Authors: P. Scott Pedersen, David C. Blakemore, Gary M. Chinigo, Thomas Knauber, David W. C. MacMillan

Institutions: Princeton University, Pfizer (United States)

Language: English

Topic: Sulfur-Based Synthesis Techniques

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green