Synthesis of piperidin-4-ones starting from 2-(2-bromo-1,1-dimethylethyl)azetidines and 2-(2-mesyloxyethyl)azetidines through a ring expansion–oxidation protocol

cis-2-(2-Bromo-1,1-dimethylethyl)azetidines were transformed into novel 5,5-dimethylpiperidin-4-ones through a ring expansion–oxidation protocol upon heating in DMSO in the presence of Ag2CO3 or AgBF4. In addition, several 5,5-nor-dimethyl analogues of the latter piperidin-4-ones were synthesized in a selective way through a similar ring expansion–oxidation approach involving treatment of cis-2-(2-mesyloxyethyl)azetidines with K2CO3 in DMSO. Furthermore, both a diastereoselective and an enantioselective reduction of the carbonyl function in piperidin-4-ones were performed through a chemical and an enzymatic approach, respectively. Whereas the NaBH4-induced reduction proceeded with cis-diastereoselectivity, alcohol dehydrogenase-mediated reductions resulted in either an S- or R-enantioselectivity.