By combining chemical intuition and high throughput experimentation (HTE), we have identified an enantioselective acylation of unprotected sulfonimidamides to access enantiomerically enriched N-trifluoroacetyl-sulfonimidamides via cinchona-phosphinate catalysis (Figure ). Applying this unique catalyst scaffold for an unreported reaction inspired a data science-informed evaluation of the substrate scope, which was leveraged to facilitate statistical modeling to drive traditional mechanistic studies. These investigations, which included reaction kinetics, catalyst structural studies, and density functional theory (DFT) transition state analysis, provided compelling evidence for turnover-limiting collapse of the tetrahedral intermediate and key insights into the origin of enantioselectivity.