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

Recent advances in synthetic facets of immensely reactive azetidines

“…54 Piperidin-4-ones represent an important class of bioactive heterocycles due to their observed biological and pharmaceutical properties along with their use as intermediates in the synthesis of a variety of biologically active compounds such as functionalized piperidines through the reduction of the carbonyl moiety. De Kimpe et al 55 have recently explored the synthesis of functionalized piperidin-4-ones via ring expansionoxidation of corresponding azetidines. The key step in the synthesis involved the treatment of cis-2-(2-bromo-1,1dimethylethyl)azetidines 180a-e with silver salt in DMSO at 100 C for 18 h to afford the corresponding 5,5dimethylpiperidin-4-one 181a-e.…”

“…The abstraction of acidic proton at the oxygenated carbon atom resulted in the liberation of dimethylsulde via a-elimination affording the formation of corresponding piperidin-4-ones 181 (Scheme 43). 55 Couty and co-workers 56 have reported BTC (bistrichloromethylcarbonate, triphosgene) promoted selective bond cleavage of azetidine resulting in the formation of ve or six membered urea. The synthetic protocol involved regioselective C-2 cleavage of azetidine 182 with BTC to afford 183 and 184 in ratio of 1 : 2.…”