Sulfinamide Crossover Reaction

Abstract

This study unveils a new catalytic crossover reaction of sulfinamides. Leveraging mild acid catalysis, the reaction demonstrates a high tolerance to structural variations, yielding equimolar products across diverse sulfinamide substrates. Notably, small sulfinamide libraries can be selectively oxidized to sulfonamides, providing a new platform for ligand optimization and discovery in medicinal chemistry. This crossover chemotype provides a new tool for high-throughput experimentation in discovery chemistry.

Figure 1

Schematic depiction of a crossover reaction in biology (A) and chemistry (B).

Figure 2

(A) Selected examples of crossover (exchange) reactions utilized in dynamic combinatorial chemistry. (B) Crossover of sulfinamides presented in this article.

Figure 3

Development of the first acid-catalyzed sulfinamide crossover reaction.

Figure 4

Substrate scope of the crossover reaction. Molar ratios of products and their yields were determined by HPLC. ^a 40 mol % TFA was used in the reaction. ^b The reaction time was 24 h.

Figure 5

Summary of the crossover of three different sulfinamides. (A) Structures of all sulfinamides utilized in the experiments. (B) HPLC trace of an equimolar amount of sulfinamide substrates/products. (C) HPLC traces of six different crossover reactions leading to the mixture of the same products. Conditions of the reaction: 200 mM sulfinamides and 6.6 mM TFA in DMSO, 40 °C, 24 h.