INTRAMOLECULAR CYCLOADDITION OF ISOMUNCHNONE DIPOLES TO HETEROAROMATIC PI-SYSTEMS

A series of furanyl-, thienyl-, and indole-substituted diazo imides were prepared by treating the appropriate amides with diketene to give the N-acetoacylated imides. Exposure of the imides to standard diazo transfer conditions afforded the desired diazo imides. Treatment of these diazo imides bearing tethered heterocyclic rings with rhodium(II) acetate affords transient isomunchnone dipoles. The mesoionic dipoles are formed by cyclization of the rhodium carbenoid onto the neighboring amide carbonyl oxygen atom. The scope and limitations of the intramolecular 1,3-dipolar cycloaddition of the isomunchnones across a tethered furan and thiophene ring were studied. The facility of the internal cycloaddition is influenced by the length and nature of the tether connecting the dipole and dipolarophile functionalities. The reaction is critically dependent on conformational factors in the transition state. In addition, the first examples of intramolecular cycloaddition of isomunchnones to indole dipolarophiles are reported. Cycloadditions of this type generate highly functionalized polyheterocyclic systems with complete relative stereocontrol at the newly formed stereocenters.