The synthesis of 5-substituted proline derivatives and of 5-substituted pyrrole-2-carboxylates by 5-endo cyclisations featuring a method for effectively favouring these with respect to 5-exo cyclisations

Abstract

Overall 5-endo cyclisations of the C-allylic glycine sulfonamides 5 lead to usually excellent yields of the 2,5-cis- or 2,5-trans-pyrrolidine-2-carboxylates 11 and 12 respectively, depending upon whether base is absent or present. While reductions to the corresponding pyrrolidine-2-methanols 13 proved efficient, subsequent eliminations of the elements of hydrogen iodide gave mixtures of products 14–16. Suitably positioned hydroxy groups compete successfully with the sulfonamide via a 5-exo cyclisation mode. However, when such a substrate contains a furan ring attached to the alkene function (21), then cyclisation does occur at the sulfonamide, presumably by participation of the furan oxygen, to give an iodopyrrolidine-2-methanol 13a. Finally, base-induced elimination of both hydrogen iodide and toluene-p-sulfinic acid from the initial iodopyrrolidines 11 and 12 leads to 5-substituted pyrrole-2-carboxylates 26. Overall, this sequence is complementary to the Kenner pyrrole synthesis.