Discovery of Active Catalyst and Optimization. A preliminary exploration of an asymmetric N-acylation was performed on a model benzenesulfonimidamide substrate 1a with commercially available 2,2,2-trifluoroethyl trifluoroacetate 2a as the electrophile. Cinchona-based organocatalysts emerged as a promising class for this transformation. Derivatives consisting of ester, amide, sulfonamide, urea, thiourea, squaramide, and phosphorus-based functional groups were evaluated via HTE (Figure ) (see SI for HTE details). Several of the cinchona derivatives demonstrated encouraging results to catalyze this enantioselective transformation. The lead catalyst, furnishing the desired product 4aa, was derived from a rarely utilized cinchona-phosphinate derivative. Notably, this catalyst displayed excellent chemoselectivity, with no detectable bis-acylated product 5aa observed. In contrast, bis-acylation was a competitive process for many of the other cinchona catalyst derivatives evaluated (up to 32% of 5aa observed in the crude reactions). Laboratory scale validation of catalyst 3a confirmed complete conversion of 1a with no detectable amount of bis-acylated product 5aa and high enantioselectivity of 4aa (95:5 er) (Fig-