One “Click” to controlled bifunctional supported catalysts for the Cu/TEMPO-catalyzed aerobic oxidation of alcohols

Abstract

A simple and reliable methodology is described for the preparation of heterogeneous bifunctional catalysts with a high control over surface composition. The strategy relies on the grafting of a mix of catalytic components from an azide-functionalized silica platform using the CuAAC reaction. The resulting finely engineered supported catalysts are employed in the model Cu/TEMPO-catalyzed aerobic oxidation of benzylic alcohol.

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Most catalytic systems in homogeneous catalysis rely on the interactions between multiple components such as ligands, metal salts, bases and other additives that, properly combined, afford the desired chemicals with optimal yield and selectivity within a minimal period of time. Nature itself has developed some of the most efficient and complex catalytic systems that essentially depend on the cooperative action of a set of amino acid residues within a tailored catalytic pocket, resulting in dramatic rate enhancement and selectivity. Developing robust and controlled ways to arrange multiple catalytic components on a surface is thus critical to understanding and creating new catalysts with enhanced activity. However, although ubiquitous in nature, examples of multifunctional heterogeneous cooperative catalysts¹ are limited in part because it remains difficult to find suitable ligation chemistries allowing the grafting of complex homogeneous catalytic systems with acceptable synthetic efforts. The immobilization of cooperative catalytic components on porous silica surfaces has however brought significant improvement over single site homogeneous or heterogeneous catalysts.²

The strategy generally employed for the preparation of catalytic bifunctional silica surfaces relies on a pre-functionalization step with two different silanes either by co-condensation or post-grafting.^{1d,2a–c,e,f,h,3} This approach subsequently requires orthogonal and sequential chemistries to match the mixed bifunctional support and the catalytic species in case of complex catalytic systems.^3e–g We reasoned that reducing the complexity of such approach to a single, efficient, modular and functional group-tolerant chemical step would significantly facilitate the preparation and study of advanced multifunctional catalytic surfaces. One potential solution could be using “click” chemistries,⁴ and more specifically the quintessential Cu-catalyzed azide–alkyne cycloaddition (CuAAC).⁵

One important example involving a complex but very efficient catalytic system is the Cu/TEMPO-catalyzed⁶ aerobic oxidation of alcohols recently developed by Stahl and coworkers⁷ that commonly comprises 2,2′-bipyridine, Cu(CH₃CN)₄OTf and 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO). Several approaches have been described to heterogenize either the ligand/Cu⁸ or the TEMPO⁹ catalysts. We anticipated that immobilizing both ligand/Cu and TEMPO on the same support could afford noticeable benefits through synergistic effects (Scheme 1).

Scheme 1 “Click” bifunctional Cu/TEMPO heterogeneous catalyst.

Although the use of CuAAC chemistry for the immobilization of homogeneous catalysts is well documented,¹⁰ and the synchronous¹¹ or successive¹² CuAAC-grafting of different functional groups has been recently reported, the demonstration of a modular strategy applied to the preparation and operation of heterogeneous multifunctional catalysts remains elusive.

Here, we report a robust, simple and general methodology to easily access such multifunctional catalytic platforms. We surmised that a single azide-functionalized mesoporous silica platform 1 could serve to anchor simultaneously each component, preliminary derivatized into their corresponding terminal alkynes, using the CuAAC ligation (Scheme 2). We further took advantage of the CuAAC strategy to directly generate¹³ the bipyridine motif on surface using 2-ethynylpyridine 2 that forms a pyridyltriazol (pyta) ligand.^3f,14 Assumingly, precise control of surface composition could be attained using varying proportions of alkynes 2 and 3^9b–e in the grafting solution.

Scheme 2 Synthesis of mono- and bifunctional heterogeneous catalysts.

The azide-functionalized platform 1 (0.30 mmol g⁻¹) was prepared easily by silanation of mesoporous spherical silica particles with 3-azidopropyl trimethoxysilane followed by end-capping with hexamethyldisilazane to avoid unselective Cu adsorption. The CuAAC ligation was first optimized separately with 2-ethynylpyridine 2 and TEMPO derivative 3 (Scheme 2). Both 2 and 3 could be coupled to the azide platform 1 under identical CuAAC conditions employing CuI (10 mol%), Et₃N (5 equiv.) in DMF at 50 °C to give 4 and 5, respectively. Indeed, FT-IR indicated disappearance of the characteristic azide band at ca. 2100 cm⁻¹ in both cases, while thermogravimetric analysis (TGA) provided loadings of 0.26 and 0.27 mmol g⁻¹ for 4 and 5, respectively, corresponding to a ca. 90% grafting (see ESI†). Copious washing with Na₂EDTA followed by Soxhlet extraction with CH₃CN ensured total removal of residual Cu as determined by atomic absorption spectroscopy (AAS) (Cu < 0.002 mmol g⁻¹).

Likewise, bifunctional catalyst precursors 6a–e were prepared using varying proportions of 2 and 3 in the “click” solution (Scheme 2). FT-IR monitoring again confirmed the disappearance of the typical azide peak (see ESI†). 4 and 6a–e were then complexed with Cu(CH₃CN)₄OTf in CH₃CN to give 4.Cu and 6a–e.Cu (Scheme 2).

X-ray photoelectron spectroscopy (XPS) confirmed the appearance of Cu and F peaks after complexation (Fig. 1a and b and ESI†) while the Cu content was determined by AAS (Fig. 1d). The Cu 2p3/2 and 2p1/2 peaks could be fitted to a single component with a binding energy centered at 932.9 eV and 952.7 eV, respectively, corresponding to Cu^I (Fig. 1b).¹⁵

Fig. 1 (a) XPS survey scan and (b) high-resolution Cu 2p region of 6c.Cu. (c) TEMPO content (as determined by EPR) as a function of the percentage of 3 used in the preparation of supported catalysts 5 and 6a–e.Cu. (d) Cu content (as determined by AAS) and deduced pyta content as a function of the percentage of 2 used in the preparation of supported catalysts 4.Cu and 6a–e.Cu.

Interestingly, the Cu content was found not to scale linearly with the fraction of 2 used in the grafting solution but tended toward a limit value of half of the pyta loading (Fig. 1d);^14a for higher pyta density, a 2 : 1 ligand/Cu complex is more likely formed on surface.¹⁶ In parallel, EPR spectroscopy allowed to quantify the concentration of TEMPO radicals in 6a–e (Fig. 1c) and to deduce the complementary pyta content for each catalyst. Remarkably, the surface concentration of TEMPO sites reflected particularly well the composition of the grafting solution and nicely aligned with what can be expected given a ca. 90% grafting efficiency (correlating also pretty well with TGA measurement for TEMPO catalyst 5, i.e. 100% of 3).

The activity of 6a–e.Cu was tested in the model aerobic oxidation of benzyl alcohol (0.26 mmol) in toluene (0.2 M) at 80 °C under O₂ bubbling (5.5 mL min⁻¹), maintaining in each case a 5 mol% Cu loading (Fig. 2). In both cases, the reaction rates (see ESI†) increased linearly with decreasing the fraction of 2 (Fig. 2b), until a threshold upon which the activity significantly dropped most probably because, for extreme binary compositions, one component started to become missing. Comparatively, combining 4.Cu (5 mol%) and 5 (5 mol%) only gave trace amounts (<5%) of the aldehyde. Remarkably, combining 4.Cu and free TEMPO (5 mol%) only gave 11% of benzaldehyde after 5 hours (Fig. 2a). These results indicate that immobilization of both active sites on silica, with engineered relative distribution, is crucial for enabling high catalytic activity.

Fig. 2 (a) Catalytic activity of 4.Cu, 5 and 6a–e.Cu in the aerobic oxidation of benzylic alcohol. (b) Activity of 6a–e.Cu as a function of the percentage of 2 used for their preparation. (c) Recycling of 6c.Cu. Conditions: BnOH (0.26 mmol) in toluene (0.2 M), O₂ bubbling (5.5 mL min⁻¹), 80 °C. Reactions are performed at a loading of 5 mol% in Cu.

The recycling of 6c.Cu was finally investigated (Fig. 2c). A significant decrease of activity was observed after each run. AAS analysis of the used catalyst (after 3 runs) showed a minor Cu loss of ca. 10%. These observations, together with the fact that limited activity is observed when using 4.Cu/5 or 4.Cu/TEMPO, preclude Cu leaching as being responsible for catalytic activity and deactivation. Further investigations are underway to elucidate the mechanism of deactivation of our catalysts.

In conclusion, we have developed a simple and reliable strategy for the controlled assembly of bifunctional heterogeneous catalysts and demonstrated the influence of surface composition on catalytic activity. The key feature of our approach relies in immobilizing a set of active ingredients from a single azide-functionalized mesoporous silica platform using mixtures of alkynes in one “click” CuAAC reaction. Modifying the relative proportion of the different alkyne derivatives in the grafting solution allows achieving an accurate control on surface composition and cooperative catalytic properties. Noticeably, this strategy significantly limits the synthetic efforts towards the preparation of multifunctional supported catalysts often associated with the combination of orthogonal and sequential chemistries both on supports and substrates. The bifunctional heterogeneous catalysts exhibited remarkable activity compared to their monofunctional counterparts as a result of the synergistic interactions between the two supported active sites.

Given the scope of CuAAC, and the relative ease of preparation of azide functionalized supports and ethynylated partners, we anticipate that this method will find application in the development of advanced multifunctional surfaces for application in catalysis and beyond.

Acknowledgements

The authors acknowledge the F.R.S.-FNRS (A.E.F.), Wallonie-Bruxelles International (A.E.F.), the Belgian Federal Science Policy (IAP P7/05) and Novartis for financial support. A.E.F. is a Chargé de Recherches of the F.R.S.-FNRS.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra05026c

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