Chromenone‐Fused Pyrrolizines and Pyrrolizine Analogues of Lamellarins: Expanding the Lamellarin Family

Abstract

Several N‐ethoxycarbonylmethyl enaminones, prepared by Eschenmoser sulfide contraction between N‐(ethoxycarbonylmethyl)‐pyrrolidine‐2‐thione and various ortho‐oxygenated phenacyl halides, underwent cyclisation to give ethyl 6‐aryl‐2,3‐dihydro‐1H‐pyrrolizine‐5‐carboxylates upon microwave heating with silica gel in xylene. With enaminones made from ortho‐hydroxyphenacyl halides, not only did dihydropyrrolizine formation take place, but spontaneous lactonisation also occurred to give 9,10‐dihydrochromeno[4,3‐b]pyrrolizin‐6(8H)‐ones. Bromination and Suzuki–Miyaura arylation of these chromenopyrrolizines at the free C‐H site on the pyrrole ring afforded four analogues of the lamellarin alkaloids in which a pyrrolidine ring replaces the isoquinoline system in the fused polycyclic core. The product 11‐(3,4‐dimethoxyphenyl)‐2,3‐dimethoxy‐9,10‐dihydrochromeno[4,3‐b]pyrrolizin‐6(8H)‐one, in particular, is a congener of the well‐known lamellarin G trimethyl ether. Preliminary results pertaining to an extension to chromenone‐fused indolizines are also reported.