Ring-closing iodoamination of homoallylic amines for the synthesis of polysubstituted pyrrolidines: application to the asymmetric synthesis of (−)-codonopsinine

Ring-closing iodoamination of (E)-configured, N-α-methyl-p-methoxybenzyl protected homoallylic amines upon treatment with I2 and NaHCO3 in MeCN occurs with concomitant loss of the N-α-methyl-p-methoxybenzyl group to give 3-iodopyrrolidines in >99:1 dr. This transformation was used as one of the key steps in the total asymmetric synthesis of (−)-codonopsinine, which was achieved in seven steps (from commercially available tert-butyl crotonate) in 5% overall yield and >99:1 dr.

Graphical abstractThe asymmetric synthesis of (−)-codonopsinine was achieved via the ring-closing iodoamination of a functionalised homoallylic amine (which occurred with concomitant N-debenzylation) followed by functional group manipulation of the resultant 3-iodopyrrolidine.Figure optionsDownload full-size imageDownload as PowerPoint slide