Functionalized oxetanes and azetidines are promising bioisosteres, yet their inclusion in agrochemical and pharmaceutical candidate screening remains limited due to a lack of viable synthetic methods. Herein, we utilize XtalFluor-E® to prepare 3,3-arylamino oxetanes and 3,3-arylamino azetidines in moderate-to-high yields (30–97%) using a mild, one-step deoxyamination strategy. This work establishes a direct deoxyamination using suflur (IV) fluoride reagents. We coupled experimental screening with multivariate linear regression (MLR) analysis to gain greater insight regarding factors that influence the reaction scope. Furthermore, experiments paired with density functional theory (DFT) calculations provided key mechanistic insight into the nucleophilic substitution reactions at the sulfur(IV) center. The simplicity and short reaction times of our protocol facilitates the library syntheses of these key bioisosteres. Functionalized oxetanes and azetidines hold potential as bioisosteres, but their use in agrochemical and pharmaceutical screenings is hindered by synthetic challenges. Here, the authors employ XtalFluor-E® for a mild one-step deoxyamination, achieving 30–97% yields in one hour or less, and provide mechanistic insights through multivariate linear regression and density functional theory, enhancing their synthetic accessibility.
Thomson et al. (Fri,) studied this question.