Synthetic approaches to (+)-retronecine

Abstract

We have investigated a new synthetic voute to (+)-retronecine and its analogs, which exhibit various pharmacological and biological activities. Stereoselective iodoamination of allylic imidate was employed as a key step for their syntheses. Iodocyclization of allylic imidate of 68 was carried out using iodine as electrophile to furnish oxazoline 71. The strategy applied to allylic alcohol 68 was unsuccessful due to poor stereo-selectivity of the iodocyclization and the failure to secure the bicyclic pyrrolizidine. Iodocyclization of allylic imidates from 93 and 95 with iodine mono-bromide showed excellent stereoselectivities to yield trans-oxazolines 96 and 97 exclusively. A synthesis of bicyclic pyrrolizidine skeleton 157 was attempted in overall 9 steps from osazoline 96.