Direct Copper-Catalyzed Three-Component Synthesis of Sulfonamides

First introduced into medicines in the 1930s, the sulfonamide functional group continues to be present in a wide range of contemporary pharmaceuticals and agrochemicals. Despite their popularity in the design of modern bioactive molecules, the underpinning methods for sulfonamide synthesis are essentially unchanged since their introduction, and rely on the use of starting materials with preinstalled sulfur-functionality. Herein we report a direct single-step synthesis of sulfonamides that combines two of the largest monomer sets available in discovery chemistry, (hetero)­aryl boronic acids and amines, along with sulfur dioxide, using a Cu­(II) catalyst, to deliver a broad range of sulfonamides. Sulfur dioxide is provided by the surrogate reagent DABSO. The reaction tolerates broad variation in both coupling partners, including aryl, heteroaryl and alkenyl boronic acids, as well as cyclic and acyclic alkyl secondary amines, and primary anilines. We validate the method by showing that a variety of drugs, and drug-fragments, can be incorporated into the process

Expedient Preparation of Nazlinine and a Small Library of Indole Alkaloids Using Flow Electrochemistry as an Enabling Technology

An expedient synthesis of the indole alkaloid nazlinine is reported. Judicious choice of flow electrochemistry as an enabling technology has permitted the rapid generation of a small library of unnatural relatives of this biologically active molecule. Furthermore, by conducting the key electrochemical Shono oxidation in a flow cell, the loading of electrolyte can be significantly reduced to 20 mol % while maintaining a stable, broadly applicable process