Effect of substitution on the intramolecular 1,3-dipolar cycloaddition of alkene tethered münchnones.

A sequence of chemoselective activation of N-acylaminoacids, münchnone generation, intramolecular 1,3-dipolar cycloaddition, and ring opening efficiently generated functionalized polycyclic structures such as cyclopenta[b]pyrroles or zwitterionic bicyclo[4.3.0]nonane or bicyclo[3.3.0]octanes in one operation is given. These zwitterionic species were isolated for the first time and were subsequently reduced to bicyclic aminoalcohols. The effect of the substitution of both the dipolarophile and the münchnone on the intramolecular cycloaddition outcome was examined. It was found that either nonactivated or electron-poor alkenes can react with the münchnone if these alkenes are tethered at position 4 on the münchnone (2, R2 = alkene tether), whereas only an electron-poor alkene at position 2 (2, R3 = alkene tether) could undergo successful cycloaddition. Also, münchnones substituted at position 2 with a phenyl (2, R3 = Ph) showed a dramatic increase in reactivity, whereas a phenyl at position 4 (2, R2 = Ph) had a very limited effect.