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Winter 2004 Crooks Group Research Highlight

The Stille Reaction Catalyzed by Dendrimer-Encapsulated Pd Nanoparticles

One of the many interesting structural features of dendrimers are their internal cavities. For example, we previously demonstrated that highly monodisperse monometallic, bimetallic, and semiconductor nanoparticles can be prepared within these cavities (Crooks R.M. et al., J. Phys. Chem. B, 2005 109, 692-704). This synthetic strategy involves two steps. First, the interior of the dendrimer is loaded with the metal ions. Second, the metal ion/dendrimer composite is chemically reduced by using BH₄^-. These two steps result in formation of highly monodisperse DENs having sizes up to ~3 nm in diameter. Here, we used this methodology to prepare Pd DENs within the interior of a fourth-generation, hydroxyl-terminated PAMAM dendrimer (G4-OH(Pd₄₀)). These materials, which have an average diameter of 1.7 ± 0.4 nm, are catalytically active for the Stille reaction.

The Stille reaction belongs to a family of cross-coupling transformations that are widely used in synthetic organic chemistry. It is defined as a reaction of an organometallic reagent with an electrophile catalyzed by a complex of transition metal like Pd or Ni (Farina, V.; Krishnamurthy, V.; Scott, W. J. The Stille Reaction. John Wiley & Sons: N. Y., 1998.). Research group members Raphael Lezutekong and Dr. Joaquin C. Garcia-Martinez have demonstrated that Pd DENs can catalyze the Stille reaction. This is an important result for two reasons. First, it expands the scope of DENs as catalysts for carbon-coupling reactions, which has previously included only the Heck and Suzuki reactions. Second, Pd DENs catalyze the Stille reaction at room temperature in water, and this results in extended catalyst life and reduced likelihood of byproduct formation.

The DEN-catalyzed Stille reaction was carried out by mixing 0.50 mmol of the aryl halide and 2.00 mmol of phenyltin trichloride in 6.00 mL of 3.0 M aqueous KOH and 2.00 mL of deionized water. Next, 5.00 mL of a 2.50 µM G4-OH(Pd₄₀) DEN catalyst solution was added to the reactant mixture (Scheme 1), which was then stirred for 15 h at room temperature. Figure 1 shows the ¹H-NMR spectrum of a mixture of 4-iodobenzoic acid and phenyltin trichloride dissolved in CDCl₃ prior to addition of the DEN catalyst (Figure 1a) and the crude reaction product (Figure 1b). Only one compound is represented in the spectrum, and it corresponds to the anticipated Stille coupling product of biphenyl-4-carboxylic acid.

Scheme 1

Figure 1. (a) Physical mixture of the starting material with PhSnCl₃ with no catalyst.
(b) Reaction product with no further purification

In addition to 4-iodobenzoic acid, a number of other aryl halide substrates were tested to evaluate the generality of the DEN-catalyzed Stille reaction. Table 1 lists these reactants and the corresponding yields calculated from NMR and GC-MS data (Table 1). All the halides selected for evaluation were either acids or phenols because they are soluble in KOH solutions. For example, the first two entries in Table 1 are the two iodobenzoic acid isomers. Like 4-iodobenzoic acid, the yield for 3-iodobenzoic acid is 100%. Bromide derivatives of the acid and phenol (Table 1, Entries 3, 4, and 5, respectively) also undergo Pd DEN-catalyzed Stille reactions. However, a higher concentration of the G4-OH(Pd₄₀) catalyst was required to couple the bromides as compared to the iodides (25.0 µM versus 2.50 µM, respectively) because of the lower reactivity of the bromide. The reaction yields are good in both cases, but there is a significant contribution from the homocoupling byproduct for the phenol.

The DEN catalysts were evaluated by transmission electron microscopy (TEM) before and after the Stille reaction (Figure 2). Prior to reaction the metal core of the G4-OH(Pd₄₀) catalyst had an average diameter of 1.7 ± 0.4 nm, but after reaction, the average diameter increased to 2.7 ± 1.1 nm indicating a modest amount of aggregation. To confirm that this aggregation was a consequence of the catalytic reaction, rather than just exposure to the solvent, a G4-OH(Pd₄₀) solution identical to that used for the catalytic reaction was stirred overnight. The particle size before and after exposure to only the solvent resulted in a just a small change in the particle diameter from 1.7 ± 0.4 to 1.9 ± 0.6 nm.

Figure 2. HRTEM micrographs and size-distribution histograms for G4-OH(Pd₄₀)
(a) before and (b) after the Stille reaction carried out in water at 23 ^oC.

To summarize, we have shown that Pd nanoparticles encapsulated within the interior of PAMAM dendrimers are catalytically active for the Stille reaction. Moreover, the reaction takes place under very mild conditions (water, room temperature) and with good yields. Finally, the Stille reaction is the third class of carbon-coupling reactions that DENs have been demonstrated to catalyze, and therefore there is a reason to believe these catalysts are generally useful for organic transformations. This is interesting, because it is somewhat surprising that two such large reactants could find their way into the restricted volume of the dendrimer interior, encounter the catalyst, and react.