The Efficient Copper(I) (Hexabenzyl)tren Catalyst and Dendritic Analogues for Green Click Reactions between Azides and Alkynes in Organic Solvent and in Water: Positive Dendritic Effects and Monometallic Mechanism

An easily synthesized, copper(I) (hexabenzyl)tren complex 1 is an efficient catalyst for the copper(I)-catalyzed Huisgen-type 1,3-cycloaddition between azides and alkynes (CuAAC) reaction in toluene. Alternatively, a convenient procedure involves mixing copper(I) bromide (CuBr) with hexabenzyltren and the substrates in toluene which gives, for instance, 100% yield of triazole in 10 min using 0.1 equiv. catalyst with phenylacetylene and benzyl azide at room temperature. The toluene-soluble catalyst 1 is recyclable and is applied, for example, to the CuAAC synthesis of an 81-branched dendrimer that previously required the use of a stoichiometric amount of copper(II) sulfate (CuSO4)+sodium ascorbate catalyst. Dendritic copper(I)-centered analogues 2 and 3 of the first and second generations (G1 and G2, respectively) containing respectively 18 and 54 branch termini, including a 54-branched water-soluble metallodendrimer 5, are also very efficient catalysts for the CuAAC reaction. With the metallodendritic Cu(I) derivatives 2 and 3, the dendritic frame brings about steric protection against the well-known inner-sphere aerobic oxidation of Cu(I) to bis(mu-oxo)-bis-Cu(II). The metallodendrimers 2 and 3 are also sometimes more efficient than the parent catalyst, as shown by kinetic studies. Catalysis in water without co-solvent of the CuAAC reactions of water-insoluble substrates was achieved under ambient conditions in good yields with the recyclable catalyst 5. Efficient catalysis of the CuAAC reaction by these bulky Cu(I) metallodendrimers emphasizes the monometallic mechanism. The difference of kinetic behavior between 1 and CuBr+hexabenzyltren suggests, however, that whereas a monometallic mechanism is working for 1, the mixture of CuBr+hexabenzyltren might involve the bimetallic mechanism proposed by Fokin and Finn.