Synthesis of 4-Iodopiperidines via Aza-Prins Cyclization

Significance

Presented here is a one-step, three-component synthesis of 2-mono- and 2,6-disubstituted 4-iodopiperidines from homoallylic amines and aldehydes via aza-Prins cyclization using a catalytic amount of gallium(III) iodide and stoichiometric iodine. Excellent trans selectivity was observed for the formation of 2,4-disubstituted piperidines. Substituted homoallylic amines afforded 2,4,6-trisubstituted piperidines with all cis configuration. Other metal iodides (In, Al, Mg) with iodine (1 equiv) gave slightly lower yields. Catalytic FeCl₃ (10 mol%) with iodine (1 equiv) gave 4-iodopiperidines along with 4-chloropiperidine products.