Synthesis cyclization of alpha-(trifluoromethyl)pyrrolidines by of N-tosyl-alpha-(trifluoromethyl)homoallylamine derivatives

Treatment of N-tosyl-alpha-(trifluoromethyl)homoallylamines (4), obtained b y the ene type reaction of N-(2,2,2-trifluoro-1-ethoxyethyl)tosylamide (3), with a protic acid afforded N-tosyl-a-(trifluoromethyl)pyrrolidine derivat ives (5 and 6). For example, 4-phenyl-N-tosyl-1-(trifluoromethyl)-3-butenyl amine (4a) gave cis- and trans-2-phenyl-N-tosyl-5-(trifluoromethyl (5a and de). Interestingly, 6a was a major product in a moderate reaction condition , while 5a was a major product in more drastic conditions. The mechanism of these reactions is speculated. Treatment of 4a with iodine in the presence of sodium hydrogencarbonate brought about iodocyclization to give 3-iodo-2 -phenyl-5-(trifluoromethyl)-N-tosylpyrrolidines (7 and 8).