Microwave promoted radical cyclization of trihaloacetamides

Pyrrolidines bearing bicyclic skeletons are components of various alkaloids or amino acid derivatives with important physiological activities. The efficient construction of the pyrrolidine ring is important in their synthesis. In the last years, most of the synthetic routes via radical cyclization of heteroatom-containing substrates, are based in generating an alkyl radical by treatment of haloalkanes with a radical initiator such as AIBN. One of the disadvantages of this methodology, which requires working with labile reagents, is the formation of a secondary product arising from the reduction of the halogen atom, on the contrary the copper (I) catalyzed radical atom transfer cyclization lack of this problem. We reported previously the synthesis1 of pyrrolizidines by homolysis of trichloroacetamides in the presence of a catalytic amount of Cu(I). These reactions are usually performed in a sealed tube and heating acetonitrile at temperatures around 150 C2. Although less harsh conditions are needed when TMEDA3and sometimes bipyridine 4 are used.