Synthesis of Physiologically Active Compounds by Using Cyclization of Carbamoylmethyl Radicals

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We have found that the carbamoylmethyl radicals (=NCO-CH-) generated from alpha-cholroacetamides undergo cyclizations with intramolecular alkenes in regio- and stereo-selective manner to give a variety of lactams.1. The N-allyl-alpha-chloroacetamides, upon tratment with Bu_3SnH and azoisobutyronitrile (AIBN) in refluxing benzene, gave fie-membered lactams. This reaction was applied for the synthesis of (-)-trachelanthamidine, a kainoid analog, ((〕SY.+-.〔))-mesembranol, and ((〕SY.+-.〔))-elwesine.2. Similar treatment of omicron-alkenylphenyl-alpha, alpha-dichloroacetamides gave six- to eight-membered lactams in regioselective manner.3. The N-vinylic alpha-haloacetamides also cyclized to give either four- or five-membered lactams, depending upon the substituents which can stabilize the adical intermediates formed after cyclizations. This cyclixation was applied for the synthesis of ((〕SY.+-.〔))-cotinine, a metabolite of nicotine, and beta-lactams such as (+)-PS-5 and (+)-thienamycin.4. When N-allylic alpha-chloro-alpha-methelthioacetamides were heated with RuCl_2(PPh_3)_2 in benzene at 140ﾟC in a sealed tube, atom-transfer type cyclizations took place to give fic-membered rings. This cyclization was applied to the synthesis of (-)-trachlanthamidine and ((〕SY.+-.〔))-pretazettine.