Palladium-catalyzed annulation of internal alkynes in aqueous medium†

Annulation of internal alkynes with functionalized aryl halides is a versatile and useful method for the synthesis of a wide variety of carboand heterocycles (Fig. 1). To date, many homogeneous transition metal-based catalytic systems have been developed for this transformation. Although homogeneous catalysis have many advantages, difficulties in separation and recovery of the catalyst and product contamination with traces of the heavy metal are common problems encountered which restrict their applications in the industries. To circumvent this problem, various annulation strategies involving heterogeneous catalysis have been developed. Heterogeneous catalysts can be separated from the reaction mixture in a straightforward manner, such as by ltration, but on the other hand, diffusion of the reactants to the solid catalyst occurs less readily, thus affecting the reaction rate. An alternative strategy is uorous catalysis which combines the advantages of homogenous catalysis for reactivity and heterogeneous catalysis for catalyst recovery. Since the seminal work by Horváth and Rábai, a selection of uorous ligands and catalysts have been developed for the catalysis of a variety of reactions. However to the best of our knowledge, there are no previous reports on the uorous catalysis of carboand heteroannulation of internal alkynes with functionalized aryl halides. Previously, we reported the synthesis of a chemically and thermally stable uorous, oxime-based palladacycle 1 (Fig. 2) and demonstrated its application as a precatalyst in a wide variety of C–C coupling reactions in aqueous and organic media under microwave irradiation. As palladacycle 1 is a “light uorous” compound, it can be easily recovered using reusable uorous silica gel eluted with common organic solvents. This avoids the use of peruorinated solvent which is persistent in the environment. The lower toxicity and persistence of “light uorous” compounds thus make it comparably more environmentally friendly than its “heavy uorous” counterpart. Analysis of the homogeneous and heterogeneous palladiumcatalyzed carboand heteroannulation of internal alkynes with functionalized aryl halides (Fig. 1) revealed that they were highly dependent on the choice of solvent, base, and additives. Herein we investigate the possibility of developing a uniform reaction condition suitable for all these annulation reactions. More importantly, we explore the application of palladacycle 1 as a recyclable precatalyst for carboand heteroannulation reactions in aqueous medium.