Results and Discussion. Azetidine, pyrrolidine, and piperidine are among the most popular secondary amines in drug discovery. Scientists use these amines in almost every medicinal chemistry project. In addition, they are a part of more than one hundred drugs. Therefore, it is even hard to believe that in the 21 st century, the corresponding CF 3 -/CHF 2 -diazirines for replacing azetidine, pyrrolidine, and piperidine in bioactive compounds for subsequent photoaffinity studies, remain unknown. During the past years, we often received requests from pharmaceutical companies on those structures. Therefore, we needed to elaborate first on a general practical synthetic route to access them. 1) Synthesis. We started our synthetic efforts by trying to reach the simplest representative of this type -the derivative of azetidine (Scheme 1). Swern oxidation of the alcohol group in the commercially available compound 1a, followed by fluoridemediated nucleophilic addition of CF 3 TMS to the intermediate aldehyde gave the substituted trifluoroethanol 1b in 79% yield (Scheme 1). Oxidation of the latter gave ketone 1c that existed in the equilibrium with the corresponding hydrate. The obtained mixture of products was directly treated with hydroxylamine under heating to obtain oxime 1a in a 40% yield. O-Tosylation smoothly afforded product 1e in 85% yield. Reaction with liquid ammonia and oxidation of the crude intermediate with molecular iodine afforded the needed N-Boc substituted CF 3 -diazirine 1f in 70% yield. Finally, acidic cleavage of the N-Boc protecting group gave the desired amine hydrochloride 1g as a white crystalline solid. All synthetic steps were optimized, and we could subsequently synthesize amine 1g in a five-gram scale in a single run. The structure of 1g was confirmed by crystallographic analysis (Figure ). Following the elaborated strategy, a library of CF containing isomeric/homologous pyrrolidines piperidines 6g-11g was rapidly synthesized from the corresponding commercially available alcohols (please, see SI for details). Mesylation (3e-5e, 7e, 9e-11e) was shown to work equally well as O-tosylation (1e, 2e, 6e, 8e) and we used both methods allowing some flexibility. Structures of amines 4g and by crystallographic analysis (Figure ). In addition, we performed the synthesis of lin CF 3 -diazirine-substituted ethylamine and propylamine (Scheme 2). From the commercially available epoxide 12, the needed amine was obtained in nine steps. Alternatively, from fluoral was synthesized in ten steps.