The synthesis of β-enamino esters from the thermal, catalyst-free ring opening of aminocyclopropenones

Abstract

In an attempt to react aminocyclopropenones with cyclic imines in order to synthesise amido-substituted pyrrolizidine natural products, we found that aminocyclopropenones undergo a previously unreported stereospecific and regiospecific catalyst-free, thermal ring-opening reaction with alcohols to yield β-enamino esters (also known as vinylogous carbamates or aminoacrylates). We report 21 examples in 45 to 97% isolated yield. The reaction occurs via nucleophilic attack at the cyclopropenone carbonyl followed by regiospecific ring opening of the cyclopropenone with retention of alkene geometry. Preliminary studies with colon cancer cell line HCT116 show that a sub-set of these β-enamino esters have promising activity.