Synthesis of 2,3-disubstituted pyrrolidines and piperidines via one-pot oxidative decarboxylation-beta-iodination of amino acids

A new synthesis of 2,3-disubstituted pyrrolidines and piperidines is descri bed. This mild procedure is based on the one-pot oxidative decarboxylation- beta -iodination of alpha -amino acid carbamates or amides. The iodine is i ntroduced at the previously unfunctionalized 3-position. Different substitu ents can be introduced at C-2, e.g., hydroxy, alkoxy, allyl, alkyl, etc. A trans relationship between the C-2 and C-3 substituents is exclusively obta ined. The influence of the solvent and the ring size of the starting amino acid are studied, as well as the nature of the protecting group on the nitr ogen. The stereoselectivity of the reaction was also studied using chiral m ethyl (2S,4S)-4-acetyloxyproline-1-carboxylate (8). The products obtained c an be manipulated to give bicyclic systems present in many natural products . By using the tandem decarboxylation-iodination-alkylation reaction, 2-sub stituted-3-iodopyrrolidines are formed, which are precursors of 2-substitut ed-2,5-dihydropyrrols.