Synthesis of decahydropyrrolo[2,1,5-cd]indolizine derivatives through RuCl3/AgOTf induced alkene–alkene and alkene–arene double cycloisomerizations

In the presence of RuCl3/AgOTf, pyrrolizidine derivative with styrenyl substituents at the 3,5-positions undergo a 6-exo-trig cyclization and subsequent intramolecular Friedel–Crafts reactions to form decahydropyrrolo[2,1,5-cd]indolizine or decahydrocycl[3.2.2]azine derivatives. The cycloisomerization is highly stereoselective. Presence of electron donating groups on the styrenyl substituents inhibits the double cycloisomerization process and results in a trans to cis epimerization instead. No reaction takes place when electron withdrawing groups are present on the styrenyl substituents. Possible mechanisms are proposed for the observed reactions.