Passerini reactions for the efficient synthesis of 3,3-disubstituted oxetanes

Three-component reactions of oxetan-3-ones with isocyanides and carboxylic acids produce 3,3-disubstituted oxetanes in good yields. Good levels of diastereocontrol (dr = 4:1) can be achieved in these Passerini reactions when the oxetane nucleus possesses a bulky cyclohexyl substituent at C–2. The (2S∗,3R∗)-stereochemistry of the major diastereomer was confirmed by X-ray crystallography after ester hydrolysis, and a possible mechanism to account for the diastereofacial selectivity is presented.