Assessment of Complementary Catalysts in an Uncharted Enantioselective Reaction of Sulfondiimines

Traditionally, many chemists turn to “privileged” catalyst scaffolds, which often demonstrate appreciable performance for a broad range of transformations. However, these structures can be challenging to modify, so complementary catalysts, such as peptides, are of interest. We simultaneously explored both peptidic and privileged cinchona catalysts for the asymmetric trifluoroacetylation of sulfondiimines (SDIs), an unexplored enantioselective reaction. The resultant acylated SDIs can enable access to a broad range of enantioenriched sulfur(VI) products for potential applications as bioisosteres. A significant challenge facing the establishment of an enantioselective variant of this reaction is that the background reaction has a high rate of reactivity, achieving 70% conversion in just 1 h at −78 °C. Nonetheless, we identified both a peptide and a cinchona alkaloid featuring kinetic profiles that outcompete this extremely fast background reactivity by an order of magnitude. Substrate scope was profiled using an algorithmic strategy followed by a comparison of statistical models relating substrate molecular descriptors and ΔΔG^‡ to reveal the contrasting nature of each catalyst’s performance.