The construction of complex and diverse molecules from simple substrates by C-C bond forming reactions is a central theme in organic synthesis [1-3]. The traditional synthesis, mainly employing aryl (alkyl) halides as the coupling regent [4-6], suffers from low atom efficiency due to the large amount of mass loss with the leaving group of the alkylating agent and it also has toxic issues. Efforts have been devoted to developing efficient, mild, and straightforward approaches to achieve the C-C coupling reaction. Among these, the hydrogen auto-transfer strategy, which uses cheap, stable and readily available alcohols as the alkylation regent, has attracted increasing attention (Scheme 1(A)) [7]. In this protocol, alcohols undergo sequential dehydrogenation or aldol condensation or transfer hydrogenation to afford higher alcohols or ketones with H2O and/or H2 as the only byproduct. Various homogeneous catalysts [8, 9] and heterogeneous catalysts such as Pd/C [10], Ag/Al2O3[11] and Au-Pd/HT [12] have been used for this reaction. However, several drawbacks of these catalysts are: first, the homogeneous metal complex and ligands are difficult to recycle and are sensitive to moisture and air; second, due to the sluggish dehydrogenation of alcohols, harsh reaction conditions are employed (temperature usually above 115 ℃ and an organic solvent is used). For this reason, it is highly desirable to develop an efficient heterogeneous catalyst to accomplish the coupling reactions of alcohols under mild reaction conditions.
Gold and gold-containing bimetallic catalysts have attracted increasing attention for a broad array of organic reactions because of their unique activity and selectivity, as well as the mild conditions needed, especially for aerobic oxidative reactions [13-16]. Recently, our group developed a series of Au-based catalysts for the aerobic oxidation of alcohols and silanes, and the aerobic C-C cross-coupling of alcohols and amines [17-19]. With our ongoing interest in the aerobic oxidative reaction, we turned our attention to an alternative route: an aerobic oxidative strategy to accomplish the direct cross-coupling reactions of secondary and primary alcohols. To our delight, by employing an ion exchange resin supported Au-Pd alloy as catalyst, we succeeded in accomplishing the direct cross-coupling of secondary and primary alcohols to produce higher ketones (Scheme 1(B)) under mild reaction conditions under an O2 balloon atmosphere. A wide scope of substrates and functional groups can be used in the reaction system, and moderate to good yields of the products were obtained. Furthermore, the catalyst can be recovered and reused for at least 5 times without loss of activity.
HAuCl4·3H2O and PdCl2 were purchased from Shanghai Chemical Reagent Co., Ltd., and 717# ion exchange resin was provided by Sinopharm Chemical Reagent Co., Ltd. Other chemicals were purchased from Tianjin Kemiou Chemical Reagent Co., Ltd. All chemicals were analytical grade and used as received without further purification. The water used in this study was deionized by a milli-Q Plus system, having 18.2 MΩ electrical resistivity.
An aqueous solution of HAuCl4 with Au concentration of 9.56 mg/mL was prepared by dissolving 1.0 g of HAuCl4·3H2O in 50.0 mL milli-Q water. An aqueous solution of H2PdCl4 with Pd concentration of 12.00 mg/mL was prepared by dissolving 1.0 g of PdCl2 in 1.5 mL HCl (12 mol/L), and then diluted to 50.0 mL with milli-Q water. The 717# resin after anion exchange was washed with water several times until the filtrate became clean. After drying at 60 ℃, the resin was crushed with a ball mill at 250 r/min for 1 h and then sieved to 100-180 mesh for use as the catalyst support. The resin support was then soaked sequentially in NaOH (1.0 mol/L), HNO3(1.0 mol/L), and NaOH (1.0 mol/L) for 8 h, and finally in K2CO3 solution (2.0 mol/L) for 24 h. The resultant ion exchange resin was filtered and washed with water until the filtrate became neutral and then dried under vacuum at 60 ℃ for 12 h.
Monometallic Au/resin, Pd/resin and bimetallic Au-Pd/resin with different Au/Pd ratios were prepared with the ion exchange-NaBH4 reduction method reported in the literature [5]. With Au6Pd/resin as an example, 1.92 mL HAuCl4 solution (C(Au)=9.56 mg/mL) and 0.14 mL H2PdCl4 (C(Pd)=12.00 mg/mL) were mixed together in 200 mL H2O, followed by the addition of 1.0 g 717# resin and stirring for 2 h in dark. The recovered solid was re-dispersed in 30.0 mL water, followed by the addition of 15.0 mL NaBH4 solution (10.0 equiv.) and stirred for 0.5 h in dark to reduce the metal precursor. After filtration, washing, and drying at 60 ℃ for 8 h under vacuum, the catalyst was obtained and denoted as Au6Pd/resin. The other catalysts were prepared with the same method except for a different volume of the precursor solution. The total metal loading was controlled at 2.0 wt% for all the catalysts. All of the catalysts were stored in air before use.
X-ray powder diffraction (XRD) analysis was carried out on a PANalytical X’pert diffractometer using nickel-filtered Cu Kα radiation with a scanning angle (2θ) of 10°-80°, operated at 40 kV and 40 mA. High resolution transmission electron microscope (HRTEM) characterization was carried out with a Tecnai G2 Spirit (FEI) microscope operating at 200 kV. Prior to observation, a powder sample of the catalyst was ultrasonically dispersed in ethanol and a few droplets of the suspension were put on a copper grid covered with a holey carbon film and dried at room temperature.
X-ray absorption fine structure (XAFS) spectra at the Au LⅢ-edge and Pd K-edge were measured at the 14W beam line of Shanghai Synchrotron Radiation Facility (SSRF) and the insertion-device beamline 10-ID-B of the Materials Research Collaborative Access Team (MRCAT) at the Advanced Photon Source at Argonne National Laboratory. The X-ray absorption spectra were recorded at room temperature in the transmission mode. Au foil and Pd foil as references were measured simultaneously using the third ionization chamber so that the energy calibration could be performed scan-by-scan. The X-ray absorption data were processed by the Athena software package.
Unless otherwise noted, the reactions were carried out as follows. A mixture of primary alcohol (1.0 mmol), secondary alcohol (0.5 mmol), KOH (2.0 mmol) and catalyst (1.0-3.0 mol%) was added to 2 mL H2O in a test tube. The tube was sealed before evacuation and purging with O2 three times. The reaction mixture was vigorously stirred at 60 ℃ for 6 h under an oxygen balloon. After cooling down to room temperature, the catalyst was separated by filtration and the filtrate was extracted with ethyl acetate (2 × 20.0 mL). The organic layer was dried over anhydrous magnesium sulfate. After adding 100 μL n-dodecane as the internal standard, the organic mixture was submitted to GC analysis for conversion and yield determination. The crude product was purified by flash chromatography on a short silica gel (eluent: petroleum ether/ethyl acetate=10/1, 2/1).
The Au/resin, Pd/resin and Au-Pd/resin catalysts were prepared with the ion exchange-NaBH4 reduction method. STEM images (Fig. 1(a)-(c)) showed that nanoparticles with an average size of 2-3 nm were highly dispersed on the support. In agreement with the STEM images, the XRD patterns (Fig. 1(d)) showed broad peaks of the (111) reflection. The size of the nanoparticles in Au/resin and Au6Pd/resin samples calculated by the Scherrer equation was 2.5 nm, in good agreement with that estimated from the STEM images. On comparing with monometallic Au/resin and Pd/resin catalysts, the (111) reflection of the Au6Pd/resin was found to be positioned between them, suggesting the formation of a Au-Pd alloy in the Au6Pd/resin sample [20-22].
To evaluate the catalysts, aerobic C-C cross-coupling of benzyl alcohol and 1-phenylethanol was selected as the test reaction. The reaction was first conducted at 60 ℃ for 6 h under O2 atmosphere in aqueous media to have an environmentally benign process. As shown in Table 1, monometallic Au/resin and Pd/resin gave poor selectivity for the coupling reaction, giving the unsaturated chalcone with 18% and 11% yield, respectively. The main side products were benzoic acid and hypnone which came from the (over)oxidation of benzyl aldohol and 1-phenylethanol that did not undergo the cross-coupling reaction. In contrast, the bimetallic Au-Pd/resin catalysts gave a significantly increased yield of the product in comparison with the monometallic counterparts. For example, AuPd2/resin afforded a total yield of the coupling products of 39%, while Au6Pd/resin gave a total yield of 50%. The yield reached as high as 73% when the amount of catalyst was increased to 3.0 mol% under optimized reaction conditions, demonstrating a strong synergistic effect between Au and Pd.
After establishing the optimum reaction conditions, we addressed the issues of substrate scope and functional group tolerance of the catalytic system. As shown in Table 2, the Au-Pd/resin catalyst exhibited good tolerance for various substrates with different functional groups, and moderate to good yields were obtained. Notably, aliphatic alcohols, e.g., biomass derived 1-butanol that are usually slow to oxidize, was converted readily to the product although relatively low yields were obtained. More importantly, the Au-Pd/resin catalyst can be easily recovered from the reaction system by simple filtration. After washing and drying, the Au6Pd/resin catalyst was directly submitted to another cycle of reaction. As shown in Table 3, the catalyst could be reused for at least 5 times without significant decrease in product yield, demonstrating the high stability of the Au-Pd/resin catalyst.
It is interesting to note that the bimetallic Au-Pd/resin catalysts showed a distinct product distribution different from their monometallic counterparts. The main product over the Au-Pd/resin catalysts was the saturated ketones. It is widely accepted that in the coupling reactions of primary and secondary alcohols the substrates are first converted to the aldehyde and ketones, which then undergo aldol condensation reaction under basic conditions to yield the unsaturated ketones. When under inert or reduced conditions, this is followed by hydrogenation to yield the saturated products [12, 23]. Based on this reaction mechanism, we envision that in the case of the monometallic Au/resin and Pd/resin, the alcohols underwent sequential aerobic oxidation-aldol condensation to produce α, β-unsaturated ketone, whereas in the bimetallic Au-Pd/resin system, hydrogen auto-transfer occurred after the aldol condensation reaction, thus yielding the saturated product. To show the transfer reduction mechanism, control experiments of coupling of benzyl alcohol and chalcone under the same reaction conditions were conducted (Table 4). It can be seen that over the monometallic Au/resin and Pd/resin, the chalcone remained intact, whereas it was transformed to the corresponding saturated ketone over the bimetallic Au6Pd/resin catalyst. This confirmed that the hydrogen auto-transfered indeed occurred on the bimetallic Au-Pd/resin system.
To understand how the transferred hydrogenation occurred on the bimetallic Au-Pd/resin catalyst, we then performed XAFS characterizations to determine the valence state of Au and Pd in the catalyst. Fig. 2 shows the XANES spectra at the Pd K-edge of the Au-Pd/resin catalysts as well as of the reference samples. The E0 values of the catalysts, which usually increase with an increase of the oxidation state of Pd [24], followed the order of Pd foil < Au6Pd/resin < Au4Pd/resin < AuPd2/resin < Pd resin ≈ PdO (Fig. 2, inset and Fig. 3). This indicated that the Pd component in the Au6Pd catalyst was mainly in metallic state (Pd0). In other words, Pd became more resistant to oxidation when alloyed with Au, which was further demonstrated by the EXAFS fitting results. As shown in Table 5, Pd was totally oxidized to PdO in the Pd/resin sample when it was stored at ambient conditions for a long time. However, the proportion of Pd0 (coordination number of Pd-Au and Pd-Pd) increased in the bimetallic Au-Pd/resin samples with an increase of Au/Pd ratio. Based on these results, it was concluded that the forming of an alloy with Au prevented the oxidation of Pd and allowed Pd to keep its metallic state. Interestingly, in all of the samples investigated, Au always kept its metallic state. As mentioned before, the products over Au/resin was an unsaturated ketone. Therefore, we can exclude the possibility that the transferred reduction occurred on Au sites. Taken together, the metallic Pd sites on the Au-Pd/resin catalysts were believed to be responsible for the auto-transferred hydrogenation reaction.
It is well known that in the Pd catalysed oxidation reaction of alcohols, the abstraction of β-H, which is usually regarded as the rate determining step in the reaction, can directly occur on the Pd(0) catalyst [25]. Similarly, the Pd(0) sites in our Au6Pd/resin catalyst probably can abstract the β-C-H of alcohols to form a Pd-H species, which would be the source of hydrogen in the auto-transferred hydrogenation reaction. However, under our aerobic oxidative conditions, the super-oxo species activated on Au sites can also dissociate the β-C-H bond. Given the similar role of the super-oxo species and Pd(0) sites in the reaction, a contradiction would be: (1) if Pd(0) sites were responsible for the abstraction of the β-C-H of alcohols, the coupling reaction of primary and secondary alcohols would readily occur under inert atmosphere conditions, whereas our control experiment results showed that no any coupling products was detected; (2) if the super-oxo species contributed to the dissociation of β-C-H bond, then the auto-transfer hydrogenation reaction would not occur because of the transformation of the β-H to H2O.
To gain more insight into the reaction mechanism and discriminate between the role of the super-oxo species and Pd(0) sites in the reaction, another control experiment of Au6Pd/resin catalysed transformation of benzyl alcohol and 1-phenylethanol under an inert atmosphere condition was performed. Benzyl alcohol was smoothly converted to benzoic acid with a GC yield of 23.1% over Au6Pd/resin under Ar, whereas 1-phenylethanol remained intact. The results suggested that for primary alcohols that are usually easily oxidised, the Pd(0) sites in Au6Pd/resin can directly abstract the β-C-H without the assistance of oxygen, whereas for secondary alcohols which are more difficult to transform, oxygen is needed for the dissociation of the β-C-H bond.
Based on the control experiments and characterization results, a reaction mechanism of hydrogen auto-transfer in the coupling reactions of primary and secondary alcohols on the bimetallic Au6Pd/resin catalyst was proposed (Fig. 4). First, the metallic Pd sites on Au-Pd alloys abstract the β-H in the primary alcohols to from Pd-H species, and the alcohols are converted to the corresponding aldehydes. The super-oxo species on the Au sites readily dissociate the β-C-H bond in the secondary alcohols, and ketone is then produced. Second, the aldehyde and ketone undergo aldol condensation catalysed by KOH to yield the α, β-unsaturated ketone. Upon formation, the -C=C in the α, β-unsaturated ketone is hydrogenated by the hydride on Pd sites to give the saturated product.
We achieved the coupling of primary and secondary alcohols using Au6Pd/resin as catalyst and an aerobic oxidative route. The Au6Pd/resin catalyst showed good tolerance for many substrates and can be reused several times without significant decrease in yield. XAFS characterization results showed that Pd became more resistant to oxidation with an increase of Au/Pd ratio in the Au-Pd/resin and it kept its metallic state. Metallic Pd sites readily abstract the β-H in primary alcohols and transfer the hydride to the reaction intermediate α, β-unsaturated ketone, and were responsible for the transfered hydrogenation reaction. Our results provide an avenue to take advantage of hydrogen auto-transfer to synthesize fine chemicals under mild reaction conditions.
The authors are grateful to the National Science Foundation of China (21373206, 21202163, 21303194, 21476227, 21503219) for the financial supports. JTM was funded by the U.S. Department of Energy, Office of Basic Energy Sciences, Chemical Sciences under Contract DE-AC-02-06CH11357. Use of the Advanced Photon Source is supported by the U.S. Department of Energy, Office of Science, and Office of Basic Energy Sciences, under Contract DE-AC02-06CH11357. MRCAT operations are supported by the Department of Energy and the MRCAT member institutions. We also thank the BL 14W at the Shanghai Synchrotron Radiation Facility (SSRF) for the XAFS experiments.
2016,
Vol. 37 Issue (10): 1764-1770 
PDF
2016,
Vol. 37 Issue (10): 1764-1770 PDF