Synthesis. Previously, preparation of polyfluorinated oxetanes has been performed via formal [2+2] cycloaddition, intramolecular radical cyclization, or base-promoted reaction of fluorinated enolates and carbonyl compounds; all these methods are hardly extendable to the synthesis of 3,3difluorooxetanes. Construction of the target 3,3-difluoroxetane core could be achieved by the intramolecular nucleophilic substitution in 2,2-difluoro-3-haloalcohols of type 6 (Scheme 1); a few precedents of this transformation has been mentioned in the literature for the non-functionalized substrates. This retrosynthetic disconnection is easily telescoped to ketones 5 that can be obtained via the difluorocyclopropanation of silyl enolates according to the reported method. Aiming at the multigram preparation of building blocks suitable for further functionalization by common chemical transformations, we synthesized -bromoketones 5a-e bearing an N-Boc-protected amine or aryl bromide moieties. Reduction of compounds 5a-e with NaBH4 cleanly produced alcohols 6a-e in good to excellent yields (73-98%). After evaluating several reaction conditions for the key cyclization step, we have found that t-BuOK in THF gave the best results (Table ). In this way, N-Boc protected derivatives 4a-d and aryl bromide 4e were synthesized in 40-72% yield over two steps. Compounds 4a-d were treated with TFA in CH2Cl2 giving target amine building blocks 7a-d as trifluoroacetates in 74-95% yield. Expectedly, both compounds 4b and 4d were synthesized as ca. 1:1 mixtures of diastereomers. While their bulk separation appeared to be difficult, we were able to isolate individual (R*,S*) and (S*,S*) isomers on a subgram scale after the column chromatography. The relative configuration of each product was established by 2D NMR spectroscopy and, in the case of (S*,S*)-4d, by X-Ray diffraction studies. [a] Conditions: 6c (1 mmol), base (1.5 mmol), THF Pd-catalyzed carbonylation of aryl bromide 4e followed by alkaline saponification of the ester formed produced carboxylic acid 9 in 63% overall yield (Scheme 1, C). Buchwald-Hartwig amination of compound 4e with BocNH2 cleanly afforded N-Boc-protected aniline 10 in 88% yield. Unfortunately, all attempts to cleave the carbamate moiety in the molecule of 10 were accompanied by oxetane ring opening, so the corresponding aniline derivative could not be obtained. Acidity/basicity. The pKa values of synthesized amine 7c (trifluoroacetate) and carboxylic acid 9, as well as their analogs 11a-n and 12a-n, respectively, were measured by standard acidbase titration (Figure , Table in the Supporting Information).