Rhodium-Catalyzed Cycloisomerization of <i>N</i>-Propargyl Enamine Derivatives

2006-05-17T00:00:00Z (GMT) by Hahn Kim Chulbom Lee
A novel rhodium-catalyzed cycloisomerization has been developed which converts <i>N</i>-propargyl enamine derivatives to their isomeric six-membered azacycles in good yields under mild reaction conditions. The [Rh(C<sub>2</sub>H<sub>2</sub>)<sub>2</sub>Cl]<sub>2</sub>/P(4-F−C<sub>6</sub>H<sub>4</sub>)<sub>3</sub> catalyst, in combination with DABCO as a base and DMF as a solvent, was found to be effective in promoting the cyclization process. The reaction is proposed to proceed through an intramolecular nucleophilic attack of the enamine to the rhodium vinylidene followed by a base-mediated proton-shunting process. The base was found to play a crucial role in the transformation, indicating the proton migration to be an integral component of the catalytic cycle. An aprotic polar solvent was required for high conversion, which points to the intermediacy of a zwitterionic intermediate. The present reaction should prove useful for the efficient synthesis of various six-membered azacycles that are important structural motifs of many natural isolates and medicinal agents.