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 described. This mild procedure is based on the one-pot oxidative decarboxylation-beta-iodination of alpha-amino acid carbamates or amides. The iodine is introduced at the previously unfunctionalized 3-position. Different substituents 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 obtained. 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 nitrogen. The stereoselectivity of the reaction was also studied using chiral methyl (2S,4S)-4-acetyloxyproline-1-carboxylate (8). The products obtained can be manipulated to give bicyclic systems present in many natural products. By using the tandem decarboxylation-iodination-alkylation reaction, 2-substituted-3-iodopyrrolidines are formed, which are precursors of 2-substituted-2,5-dihydropyrrols.
Boto
A
A
Instituto de Productos Naturales y Agrobiología del C.S.I.C., Carretera de La Esperanza 3, 38206-La Laguna, Tenerife, Spain.
Hernández
R
R
de León
Y
Y
Suárez
E
E
D000596:Amino Acids / Q000737:chemistry*; D003653:Decarboxylation; D007455:Iodine / Q000737:chemistry*; D010084:Oxidation-Reduction; D010880:Piperidines / Q000737:chemistry*; D011759:Pyrrolidines / Q000737:chemistry*; D013237:Stereoisomerism
D000596:Amino Acids; D010880:Piperidines; D011759:Pyrrolidines; D007455:Iodine