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Heterogeneous catalysis in organic chemistry Part 8.
Journal M2313
of Molecular
Catalysis,
72 (1992)
229-242
229
Heterogeneous catalysis in organic chemistry Part 8*. The use of supported palladium catalysts for the Heck arylation Robert L. Augustine** and Shaun T. O’Leary Departmat
of Chemistry,
Seton Hall University, South 0range,
NJ 07079, CUSA)
(fteceived August 8, 1991; revised October 16, 1991)
Abstract It has been found that the Heck arylation proceeds smoothly over supported Pd catalysts to give the same reaction products as are obtained with the more commonIy used homogeneous catalysts. The effect of reaction variables on the regioselectivity of the process is about the same for both the homogeneous and heterogeneously catalyzed reactions, so the use of the supported metal catalyst in such reactions appears to be straightforward. Such materials should be considered as viable alternatives for the commordy used homogeneous catalytic species.
Introduction The use of metal complex promoted reactions in organic synthesis is well documented. However, the presence of such catalytically active species in a reaction mixture can present problems associated with the separation, recovery and regeneration of the metal complex. Such problems can be obviated by the use of heterogeneous catalysts for these reactions. While polymer- or oxide-supported complexes can provide some advantages in this regard 12-41, such materials can dissociate, resulting in the potential incorporation of metallic species and/or ligands into the reaction mixture. One possible solution to this potential problem is the use of a supported metal catalyst to promote synthetically useful C-C bond-forming reactions. While such catalysts are commonly used synthetically for functional group hydrogenations [5-7] and occasionally for hydroformylations [8, 91 or alcohol oxidations [lo], only a few reports have been published on the use of such materials to promote the formation of C-C bonds other than in hydroformylations. It has been shown that Pd/C in the presence of triphenylphosphine will promote the allylation of aniline with ally1 acetate, but it was considered that this reaction may have been catalyzed by a soluble palladium complex, formed by dissolution of the supported palladium by the phosphine Ill]. Another report stated that Pd/C will promote the Heck arylation [ 12-141 *For Part 7 see [l]. **Author to whom correspondence should be addressed.
0304-5102/92/$5.00
8 1992 - Elsevier Sequoia. All rights reserved
230
between p-nitrobenzoyl chloride and n-butyl vinyl ether, but the heterogeneously-promoted reaction data was limited to only a few entries in a table [I5, 161. In view of recent reports of the use of homogeneously catalyzed Heck arylations in the synthesis of a variety of compounds [17-201, it was felt that a more complete investigation of the usefulness of supported metals as catalysts for this reaction would be worthwhile and should lead to a better appreciation of the use of heterogeneous catalysts by synthetic chemists.
Experimental Mass spectra were obtained on a F’innigan 4021 (Data System Incas 2100) gas chromatograph-mass spectrometer, operating at 70 eV. Infrared spectra were obtained on a Mattson Cygnus 25B Fl!-IR and a Perkin-Elmer 567 grating IR. ‘H and r3C NMR spectra were recorded in deuterochloroform on a General Electric QE-300 spectrometer. Chemical shifts are given relative to the solvent lock. The gas chromatographic analyses were run on a HewlettPackard 5890 with F’ID interfaced with an H/P 3392A integrator using a 15 mX0.53 mm J&W Scientific fused silica megabore column with a 1.5 DB-1 stationary phase film thickness. Materials Palladium acetate was purchased from Aldrich Chemicals. Triphenylphosphine, obtained from Aldrich Chemical, and 1,3diphenylphosphinopropane (DPPP), obtained from Strem Chemical, were used without further purification. The 5% Pd/C catalyst was a standard commercial material obtained from Englehard Corp. The 5% Pd/@la03 catalysts were supplied by Precious Metals Corp. (#104-lot 30002; #153-lot 30021). All other catalysts were prepared as outlined in the following section. The butyl vinyl ether was purchased from Aldrich and distilled immediately before use at 92-94 “C using a short-path apparatus. The aroyl chloride, la, and aryl iodide, lb, were purchased from Aldrich Chemical and were puritied using Kugelrohr distillation at reduced pressure. N-ethylmorpholine, triethylamine and N,N-dimethylbenzylamine were purchased from Aldrich and were distilled and stored over 3A molecular sieves. The internal standard, dodecane, was spectroquality from Matheson, Coleman & Bell. It was washed with concentrated HaSO until the acid layer was clear and then distilled. The solvents were all HPLC grade and were purihed using standard procedures. Catalyst Preparation The procedures used for the preparation of 1.22% Pd/SiOa, 5% Pt/yA1203, and 2.29% Rhly-AlaO, catalysts have been previously reported [21]. The 6.06% Pdly-AlaO was prepared by shrrrying 15.0 g of 100-120 mesh -y-AlaO in 500 ml of triple-distilled (td) deionized water in a three-necked flask equipped with a stirring motor, dropping funnel and septum. Using a
232
Hz pretreatment eflect on reaction (Table 4) The reactions were run in a dry 50 ml three-necked fiask fitted with a magnetic stirring bar, condenser, thermometer and septum. The catalyst, 5% Pdly-AlzOs (0.25 mol% of Pd based on starting 4nitrobenzoyl chloride), dodecane as internal standard (33.3 mol% of starting aryl compound), and 10.0 ml of dioxane were added to the flask. The reactor was purged five tunes with nitrogen and twice with hydrogen. The solution was stirred and hydrogen was bubbled through the catalyst solvent mixture for the indicated time. After the prescribed hydrogen purging time, the reaction flask was purged twice with nitrogen and a positive pressure of nitrogen was maintained during the reaction. A mixture of the 4nitrobenzoyl chloride (2.5 mmol), n-butyl vinyl ether (2 equivalents relative to starting aryl halide) and N-ethyl morpholine (120 mol% of starting aryl compound) in 10 ml of solvent (total solvent amount equals 20 ml) were added to the flask by cannma under nitrogen. The reaction was brought to 100 “C with vigorous stirring. The reaction was monitored by gas chromatography of samples drawn after a 10 s pause in stirring for the catalyst to settle. Sealed tube arylations (Tables 3 and 6) The sealed tube experiments were performed in Pyrex screw top test tubes. The catalyst (Pd, 1 mol% of starting aryl compound) and magnetic stirring bar were placed in the tube and it was sealed using a septum and wire. The tubes were placed in an oil bath and purged with argon. The solvent (5 ml), vinyl ether (2 equivalents), amine (150 mol% of starting aryl compound) and internal standard (25 mol% of starting aryl compound) were added under argon and the reaction mixture brought to 100 “C. The aryl or aroyl halide (0.5 mmol) was added under nitrogen and this was taken to be time zero. The reaction was monitored by gas chromatography with a pause in stirring for lo-15 s to allow the catalyst to settle before samples were taken. Preparative ar2/lution reacticms The (butoxyethenyl)-4nitrobenzenes (2 and 3) were isolated from a reaction run in a dry 100 ml two-necked flask fitted with a magnetic stirring bar, condenser and septum. A solution of Pd(OAc& (0.09 g, 0.4 mmol) and N-ethylmorpholine (6.1 ml, 48 mmol) in 40 ml of toluene was stirred until an orange homogeneous mixture was obtained. To this solution was added n-butyl vinyl ether (10.3 ml, 80 mmol) and la (40 mmol). The mixture was heated with stirring to reflux. During the reaction the solution grew dark black and palladium black particles could be seen in suspension. After 8 h, the solution was cooled and then added, with stirring, to 100 ml of ether. The precipitated amine hydrochloride was removed by filtration and the solution was treated with two 20 ml portions of 5% HCl and the aqueous phases were extracted with 20 ml of ether. The combined organic phases were washed with two 25 ml portions of saturated sodium bicarbonate solutions, followed by one 25 ml portion of saturatedsodium chloride solution.
233
The organic solution was dried using MgS04 and concentrated under reduced pressure. The crude oil was subjected to flash chromatography on a 5 mm X 15 mm silica column using pentane/chIoroform or pentane/ethyl acetate as eluent. (RN: 97826-85-2): clear oil; eluent, pentane/chIoroform, 2/l; ‘H NMR (CDCla) 6 (ppm) 8.14 (d, 2H, aryl), 7.66 (d, 2H, aryl), 6.40 (d, lH, OCHWAr), 5.26 (d, lH, ArCHCHO), 4.02 (t, 2H, OC&CH,), 1.74 (m, 2H, OCH&E&CHa), 1.46 (m, 2H, CH,CH,CH,), 0.95 (t, 3H, CH,CH,); i3C NMR (CD&J 6 (ppm) 14.7 (CH&I-13), 20.1 (CH&‘H&H3), 29.2 (CH&‘I-I&H2), 32.8 (OCI-IaCH,), 75.4 (OCHCH), 105.3 (aryl), 125.1 (aryl), 129.2 (aryl), 145.1 (aryl), 152.3 (ArCHCH); mass spectrum, m/e 221 (M’), 165, 57, 41; IR (CH,C12): 1649 (olefin-aryl), 1098 (ether), 856 @-aryl) cm-‘. Coincides with literature values [16l. (Ej-I-(2-butoxyethenyl)-4-nitrobenzene (SE) (RN: 97826-86-3): light yellow oil; eluent, pentane/chIoroform, 2/l; ‘H NMR (CDC&) S 8.1-7.3 (m, 4H, a@), 7.18 (d, lH, OCHCEUr), 5.84 (d, lH, ArCHCNO), 3.90 (t, 2H, OC&CH,), 1.71 (m, 2H, OCH&&CHa), 1.46 (m, 2H, CH,CH,CHs), 0.97 (t, 3H, CHaCH,); i3C NMR (CDCb) 6 @pm) 14.7 (CH,CH,), 20.1 (CH&H&H3), 29.2 (CH&‘I-12CH2), 32.0 (OCH,CH,), 71.5 (OCHCH), 104.6 (aryl), 125.6 (axyl), 129.2 (a@), 145.1 (aryl), 151.7 (ArCHCH); mass spectrum, m/e 221 (M+), 165, 57, 41; IR (CHaCl,): 1639 (olefin-aryl), 1164 (ether), 845 (p-aryl) cm-‘. Coincides with literature values 1161. I-(l-~~~~ethenyl)-4-nitrob~~ (2’ (RN: 109125-23-7): mass spectrum, m/e 222 (M+ 1), 221 @I+), 206, 166,56,41; IR (CH&l,) 1647 (zu, olefin-aryl), 1351 (Ar-N02), 1122 (ether), 856 o>-aryl) cm- ‘. Coincides with literature values [ 161. 1- (4-Nitropheny lJ -3-butozy-2-propen-l -one (61 This compound was prepared using reaction conditions identical to those for the preparation of 2 and 3 with the following exceptions. The reaction flask was not equipped with a condenser but was stoppered and heated to 50 “C for 8 h. 6 was obtained as a light yellow oil in 44% yield. (RN: 114657-09-9): Distillation gave a colorless oil; eluent, pentane/EtAc, 3/l; ‘H NMR (CDCl,) 6 @pm) 8.4-8.0 (m, 4H, aryl), 7.82 (d, 2H, OCCHCH), 6.30 (d, 2H, OCCHCHO), 4.03 (t, 2H, OCH,CH,), 1.69 (m, 2H, CH&H,CH,), 1.47 (m, 2H, CH&&CHa), 0.98 (t, 3H, CHaCH,); mass spectrum, m/e 249 @!I+), 220, 206, 194, 176; IR (CH,Cl,): 1750 (ketone), 1645 (zu, olefin-aryl), 1280 (C-O), 848 (p-aryl) cm-‘. Coincides with literature values [20]. Butyl 4-nitrobenzoate (5) The ester was prepared using standard Schotten-Baumann techniques and isolated as Iight yellow crystals in approximately 95% yield. (RN: 120-
234
48-9): ‘H NMR (CDCla) 6 (ppm) 8.2 (q, 4H, aryl), 4.4 (t, 2H, OW&Ha), 1.8 (m, 2H, OCH,CH,CH,), 1.5 (m, 2H, CH&&CH3), 0.98 (t, 3H, CH,cW,); 13C NMR (CDCl,) 6 (ppm) 14.1 (CH&‘Ha), 20.0 (CH&H&Ha), 30.9 (CH&H&Ha), 67.0 (OCH,CH,), 124.5 (aryl), 131.0 (a@), 137.2 (aryl), 151.2 (aryl), 165.4 (ArOCO); mass spectrum, m/e 224 (M+l), 208, 194, 138, 120; IR (toluene): 1744 (ester), 1270 (C-O), 859 @-a.@) cm-‘. Coincides with literature values [22]. 1,l -LMn4..toxyethane(4) (RN: 871-22-7): IR (CHaCl,): 2900 (s, C-H stretch), 1100 (C-O acetal); mass spectrum, m/e 160, 159, 101, 57, 45, 41. Coincides with literature values [23].
Results
and discussion
The initial stage of this study involved the repetition of the reported reaction of p-nitrobenzoyl chloride and n-butyi vinyl ether run over a 5% Pd/C catalyst in toluene containing the base, triethylamine [ 151. Initially, the reaction proceeded rapidly but, with time, the activity decreased significantly. In the Heck reaction, the amine is added to remove the hydrogen halide from the palladium and, thus, regenerate the catalytically active species. In homogeneous systems, the formation of the amine salt can be useful in visually following the extent of the reaction, but in the heterogeneously catalyzed reaction this insoluble salt formation is detrimental, since it deposits on the catalyst surface and thus decreases catalytic activity. To overcome this problem, dioxane was used as the solvent to keep the triethylammonium hydrochloride in solution. With the dioxane solvent the Pd/C-catalyzed reaction TABLE 1 Product composition from heterogeneously catalyzed Heck arylatious’ Catalyst
5% Pd/Cb 5% Pd/C Pd(OAc)ab 6.06% Pd/AlaOa 1.22% Pd/SiOa 6.06% Pd/Ala03 5% Pt/Alaos 2.2% Rh/Alaoa=
Reaction time Q
Percent formed a (2)
B (3)
acetal (4)
ester (6)
6.6 7.0 1.0 6.6 4.5 5.6 0 0
65.2 70.1 56.4 64.7 46.1 66.9 0 0
1.8 9.4 38.0 7.6 8.0 0 21.7 32.2
1.2 6.6 1.7 10.7 7.8 4.3 7.4 21.1
‘40&l chloride:Pd ratio using the small scale arylation reaction conditions described in the Experimental. blOO:l chloride:Pd ratio. Reaction time was extended to 10 h with no signScant increase in product ratios.
235
proceeded smoothly to completion. The product composition is listed in Table 1. The products were the expected p-aryl vinyl ethers, E- and Z-l(2-butoxyethenyl)-4nitrobenzene, 3a and b, and the (Yisomer, l-(l-butoxyethenyl)-4nitrobenzene, 2. Also found in the reaction mixture were the ester, n-butyl 4-nitrobenzoate (6) and the acetal, l,l-di-n-butoxyethane (4). Also found in some reaction mixtures was E-3-n-butoxy-1-phenyl-2-propen-l-one (6), the aroylated species resulting from incomplete decarbonylation of the acid chloride, la. The amount of this material present depended on the reaction temperature used, but was always under 5% and most generally present only in trace amounts.
3E @YI
Pd 6B”
OZN
,-;
O,N
1
2 02N
a, X =COCI b,X=l
4
6
6
It was initially thought that the butyl ester, 6, was formed by reaction of the acid chloride with some butanol produced by the hydrolysis of the butyl vinyl ether with some water in the reaction mixture. However, when care was taken to exclude all water from the reaction, ester formation was still observed. An alternative explanation for the presence of the butanol needed for the formation of both 4 and 6 involves the cleavage of the vinyl oxygen bond of the butyl vinyl ether on the palladium surface to give an adsorbed butoxy species, which could then react either with the acid chloride to give 6 or with butyl vinyl ether to give the acetal, 4. The source of the hydrogens needed to complete these reactions is not clear, but they could orignate from some trace amounts of water still present, metal-promoted dehydrogenation of some solvent molecules, surface -OH groups on the catalyst support and/or residual hydrogen remaining in the catalyst from the reduction procedure used in its preparation. The enhancement of acetal formation on hydrogen-presaturated catalysts, as discussed later, indicates that the latter possibility may prevail. Further support for the proposed bond cleavage comes from the observation of trace amounts of 4nitrostyrene in many of these reactions. This material has been produced by the reaction of 4nitrobenzoyl chloride with ethylene under Heck arylation conditions [24].
236
The acid chloride:Pd ratio in this reaction was lOO:l, as is commonly used in homogeneously catalyzed reactions of this type. The heterogeneous catalyst, though, was more active on a weight of metal basis than was a Pd(OAc)a. catalyst. Decreasing the amount of Pd/C to give a 4OO:l acid chloride:Pd ratio resulted in the reaction proceeding at approximately the same rate as the Pd(OAc)a-promoted reaction run using a 1OO:l ratio. Since the active surface atoms on supported catalysts comprise only a small fraction of the total Pd content [2 11, these heterogeneous catalysts are significantly more reactive. As shown by the data in Table 1, a decrease in the amount of Pd present in the heterogeneously catalyzed reaction mixture increases slightly the amount of product enol ether formed but has virtually no effect on the cr//? (2/3) ratio. However, more of the ester 6 and the acetal 4 are formed in the reaction promoted by the smaller amount of Pd. Since in this reaction, enol ether formation is slower than is observed with the larger amount of Pd, there is more time for the cleavage of the butyl vinyl ether to take place, resulting in the formation of more side products. Since it was shown that this reaction did, indeed, proceed as reported [ 15, 161, the next step was to determine whether Pd/C was the only viable catalyst or if other supported metals could also be used. It was found that both Pd/SiOa and Pd/A1203 promoted the reaction, with Pd/AlaO, having about the same degree of activity as observed with Pd/C, while Pd/SiOa was somewhat less active. The amounts of ester 5 and acetal 4 produced with these catalysts were also about the same as that found with Pd/C (Table 1). Catalysis of the reaction, however, was restricted to Pd since the use of either Pt/A1203 or Rh/AlaOa gave as products only the ester 6 and acetal 4. The similarity between the heterogeneously catalyzed reaction data and that obtained using a Pd(OAc)a catalyst might suggest that the catalyst for these reactions is a dissolved Pd species. To test this, the reaction was run over a Pd/AlaOa catalyst to N lo-20% completion in a two-section Schlenk tube with a fritted disc between the two sections. The reaction liquid was then separated from the solid catalyst by filtration through the fiit and its composition determined by gas chromatography. The liquid was then heated for an additional 2 h, sufllcient time for further reaction to occur if a soluble catalyst were present, and the composition again determined. There was no detectable difference in the liquid composition after this time, showing that there was no soluble catalyst in the reaction system. In a related evaluation, the reaction was run in the presence of the soluble catalyst, Pd(OAc)a. As has been reported in other studies [25], the reaction mixture grew turbid as the catalyst system became active. This has been attributed to a reduction of the Pd(II) to Pd(0) [ 25 1. After the reaction proceeded to N 20% completion, the product composition was determined and a small amount of elemental mercury was added to the reaction mixture. This mixture was then heated for an additional 72 h with no detectable change observed in the product composition. Since mercury will poison heterogeneous metal catalysts but has no effect on homogeneous systems
237
[26-281, this loss of activity shows that, contrary to popular opinion, the Pd(OAc),-catalyzed Heck arylation is not homogeneously promoted but rather, that the catalyst is apparently some form of palladium black. Attempts to use the recovered Pd black catalyst for further arylation reactions failed, possibly due to an agglomeration of the most active line metal particles into large clumps during the isolation process. These larger agglomerates would be expected to lack the activity of the smaller crystallites [25]. A further comparison can be made with homogeneously catalyzed arylation reactions by considering the effect which the nature of the reaction solvent has on the a@ product ratio. It has been reported that in homogeneously catalyzed reactions the use of non-coordinating aromatic solvents leads to predominant p-isomer formation, while the more coordinating dioxane would be expected to give more of the a-isomer [29]. As the data in Table 2 show, however, there is little difference in the cr//3 product ratios produced from Pd(OAc& catalyzed reactions run in toluene and dioxane. The major difference is the formation of somewhat more of the B-isomer, 3, in dioxane, which is contrary to expectation, and the rather large amount of acetal formation also observed in dioxane. That the solvent coordination was in some way responsible for the acetal formation can be seen by the increase in the amount of 4 formed when either triphenylphosphine or diphenyl-n-propylphosphine was added to the dioxane reaction mixture. The large amount of phosphine added in these reactions has been known to decrease the extent of product enol ether formation [ 161. Solvent comparison in Pd/Al,O,-catalyzed reactions, however, is more difllcult because of the catalyst deactivation brought about by the amine hydrochloride precipitation from the reaction mixture in toluene. If one allows the reaction to proceed long enough, however, the reaction can be made to go almost to completion even with the amine hydrochloride deactivation. The results of the Pd/Al,O,-catalyzed TABLE 2 Solvent effect in Heck aryJationa“ Catalyst
Pd(OAc),b Pd(OAc),b Pd(OAc),b Pd(OAc)zb Pd/AlzOs PdlA1,0s
Solvent
toluene dioxane dioxane= dioxaned toluene dioxaue
Reaction time Q
Percent formed Q (2)
P (3)
acetal (4)
ester (5)
4 4 4 4 8 4
Cl.0 1.0 1.3 2.6 6.0 6.5
42.9 66.4 6.7 18.4 80.3 64.7
4.0 38.0 71.6 52.3 6.4 7.6
1.7 1.7 7.6 25.9 3.8 10.7
a400:1 chloride:Pd ratio using the small scale arylation reaction conditions described in the Experimental. blOO:l chloride:Pd ratio. =2 mol% of triphenylphosphine added. dl .1 mol% of diphenyl-n-propylphosphine added.
238
reaction run in both toluene and dioxane are also shown in Table 2. With this catalyst the expected decrease in p-isomer formation with increasing coordination ability of the solvent was observed. A slight increase in acetal formation and a more pronounced increase in ester formation was also found. The nature of the amine used to regenerate the active catalyst species can also play a role in catalyst activity and selectivity, particularly in the formation of the ester and acetal side products. Earlier results have suggested that iV-benzyldimethylamine would give the most satisfactory results for the production of the arylation products 2 and 3 [ 301. Other amines have also been used and it has been concluded that the base should be a tertiary amine having a pK, between 7.5 and 11. Weaker bases tend to give slower reaction rates, and stronger bases may react with the other components of the reaction medium. As the data in Table 3 show, there is no valid comparison between the amine pK, and the amounts of 2 and 3 formed over a Pd/A1203 catalyst. However, the lower the pK, of the amine, the greater the extent of acetal formation. The reason for this enhanced acetal formation with increasing pK, on these heterogeneous Pd catalysts is not apparent at this time. The palladium catalysts used in this work had been stored in air for various periods of time. Since it has been established that this reaction takes place over Pd(0) species [25], it was felt that it might be of some advantage to treat the catalyst with hydrogen immediately before the reaction to reduce any surface oxides which might be present, and thus increase the amount of Pd(0) present on the surface. In this way it was envisioned that the reaction might proceed even more rapidly. To check this possibility hydrogen was bubbled through the catalyst-amine-solvent mixture for various times before the reactants were added and the reaction initiated. The results of these experiments are listed in Table 4. Instead of increasing the formation of the desired products 2 and 3, the amount of these materials produced decreased significantly with increasing hydrogen pretreatment. On the other hand, the amount of the side products 4 and 6 increased with increasing hydrogen pretreatment. Nishimura and coworkers [31] have reported that TABLE 3 Amine effect in heterogeneously catalyzed Heck arylationsa Amine
NJZMb BDAC TEAd
Plz
7.80 9.03 10.06
Reaction time Q
Percent formed a (2)
B (3)
acetal (4)
ester (6)
1 1 1
5.3 1.5 8.0
14.9 2.9 11.7
21.0 13.0 4.0
1.2 1.7 2.1
healed tube arylation reaction conditions described in the Experimental. “N-ethylmorpholine. cBenzyldimethylamine. Wethylamine.
239
TABLE 4 Effect of hydrogen pretreatment of the catalyst in heterogeneously catalyzed Heck arylations’ Hz Treatment time Q
Percent formed ff (2)
P (3)
acetal (4)
ester (6)
0
5.6 2.0 0 1.7
56.9 12.9 4.6 6.6
0 25.4 29.2 50.9
4.3 7.0 8.6 17.7
0.25 1 6
SuaU scale arylation reaction conditions described in the Experimental.
acetal formation in the metal-catalyzed hydrogenation of ketones in alcohol solvents is associated with the presence of adsorbed hydrogen, probably in an ionized state, and is dependent on the nature of the catalyst metal, with Pd the most effective. Thus, the formation of 4 and 6 is probably due to an increase in the number of acidic surface sites brought about by the hydrogen pretreatment of the PdL41203 catalyst. The decrease in 2 and 3 formation may be due to the presence of hydrogen adsorbed on the active sites on the metal, which could either block the formation of the surface intermediates required for the Heck arylation or react with these intermediates to prevent the formation of 2 and 3. The initial goal of this research was the development of methods for the production of aryl vinyl ethers, specifically the synthetically useful paryl systems, using supported metal catalysts. Earlier work has found that an electron- withdrawing group such as a 4-nitro substituent on the aryl ring exerts a strong directing force in coupling with the P-carbon of the n-butyl vinyl ether (321. Another factor in dete rmining the regioselectivity of the reaction was the nature of the halide on the aromatic ring 1291. In this work the trend for greater P-selectivity increased in the order Cl > Br> I, which agrees with the relative bond strength of the Pdn-X bond, I > Br > Cl [29]. However, the formation of the arylpalladium reagent is slow for a bromobenzene and almost nonexistent for a chlorobenzene. The arylpalladium chloride could be formed indirectly, however, by decarbonylation of the corresponding substituted benzoyl chloride, thus allowing for facile halogen selection in the control of reaction regioselectivity (301. The difference in regioselectivity between these benzoyl chloride reactions and those involving aryl bromides or iodides has been attributed solely to the halide ion and not to the presence on the metal surface of adsorbed carbon monoxide, a byproduct of the decarbonylation reaction [ 331. To ascertain whether these effects also occur with supported metal catalysts, the reaction of 4nitroiodobenzene, lb, over Pd(OAc)a, Pd/AlaOa and Pd/SiOa was also investigated. The results of these reactions along with the corresponding data from the 4nitrobenzoyl chloride reactions are listed in Table 5. Interestingly, there appears to be no halide ion effect on the
240 TABLE 5 Halide effect in heterogeneously catalyzed Heck arylationsp
Aryl
Catalyst
reactant
la la la lb lb lb
Pd(OAc)ab 6.06% Pd/AlaOa 1.22 % Pd/SiOz Pd(OAc)ab 6.06% Pd/AlaOs 1.22% Pd/SiOa
Reaction time Q
Percent formed a (2)
B (3)
EIZ
acetal (4)
ester (6)
1 1 1 4 4 4
6.3 5.8 4.5
77.5 58.5 46.1 25.3 30.1 11.8
1.86 2.75 1.99 0.68 0.98 0.74
12.0 5.4 7.6 38.0 39.3 43.2
3.2 4.4 7.8 ’ c ’
‘small scale arylation reaction conditions described iu the Experimental. blOO:l halide:Pd ratio. CEster formation not possible.
regioselectivily of the reaction, @isomer formation being markedly predominant in all cases. If anything, p-isomer formation appears to be even more selective with the iodobenzene lb than with the benzoyl chloride la. The rate of reaction is, however, slower with the iodo compound but its use did preclude any formation of ester as a byproduct. Acetal formation however was considerably enhanced in the iodobenzene reactions, probably because of the longer reaction times required with this material. One other interesting comparison between the products formed from these two reagents is in the ratio of the 3E and 32 isomers. With reactions run using the benzoyl chloride la, the E/Z ratios were generally two or greater while with the iodobenzene lb, the E/Z ratios are less than one. This correlates well with a previous report [29]. The size of the E/Z ratio has been ascribed to the effect of (a) the electron density of the aryl moiety, (b) the availability of ligands or (c) the nature of the halide ion present [29]. In these present reactions the electron density of the aryl moiety and the availability of ligands should be constant, even though there is the possibility of a carbon monoxide ligand being present on the metal surface in the benzoyl chloride reactions. It would seem, then, that the nature of the halide is the most critical factor in the determination of the E/Z ratio, providing, of course, that this ratio is indicative of the true product stereochemistry and not the result of some secondary isomerizations. To check this, a 1:l mixture of the E and 2 isomers, 3E and 32, was added to the normal reactants in an amount equal to the expected p-product yield. The final product composition showed twice the amount of p-isomer formation, indicating that no &isomer degradation had occurred. Further, after subtracting the amount of E and 2 isomers normally formed in this reaction, the initially-added 1:l E:Z ratio resulted, showing that there was no isomerization between these stereoisomers. In a further experiment, the 1: 1 ES mixture was treated with y-A1203 in dioxane under normal reaction conditions. No isomerization was observed.
241 TABLE 6 Effect of amine concentration on product enol ether stereochemist+ Concentrationb
E/Z ratio
80 110 120 150
0.76 0.81 0.98 0.99
healed tube axylation reaction conditions described in the Experimental. bMolar percent of amine.
It appears, then, that the results listed in Table 5 are those of the primary reactions with no subsequent isomerization taking place. The more extensive formation of the 2 isomer in the iodobenzene reaction may be related to the increased size of the iodide ion adsorbed on the active site, as compared to the smaller chloride ion. The more crowded the active site in the reaction, the less favorable the formation of the more sterically demanding tram or E isomer. An indication of the steric requirements for isomer formation can be seen in the results listed in Table 6, showing the effect the amount of base added to the reaction mixture has on the enol ether stereochemistry. In all cases the 2 isomer predominated, but the ratio decreased as more amine was added to the reaction mixture. With higher amine concentrations, the amount of the tramsor more sterically demanding isomer increased because of the more rapid removal the halide ions from the active sites by reaction with the amine and formation of the amine hydrohahde. While these results show that isomerization does not occur readily during the reaction, the isomerization of the 2 isomer to an E/Z mixture does take place slowly on standing. This isomerization has been followed over several months, using changes in the NMR of a sample kept in an NMR tube in deuterochloroform.
Conclusions
These results show that supported metals can be used in place of soluble organometallic catalysts for promoting synthetically useful reactions such as the Heck arylation. The effect of reaction variables on the regioselectivity of the process is about the same for both the homogeneous and heterogeneously catalyzed reactions. Thus use of the supported metal catalyst in such reactions appears to be straightforward and such materials should be considered asviable alternatives for the commonly used homogeneous catalytic species.
242
Acknowledgement This research was supported by Grant DE-FG02-84ER45120 from the U.S. Department of Energy, Office of Basic Energy Science. The metal salts were obtained through the Johnson-Matthey Precious Metal Loan Program. References 1 R. L. Augustine and F. [email protected], J. Org. Churn., 52 (1987) 1862. 2 Y. I. Ermakov and L. N. Arzamaskova,Stud. Sue Sci. Catal., (Catalytic Hydrogenation) 27 (1986) 459. 3 Y. I. Ermakov, Pure Appl. Chem., 52 (1980) 2075. 4 F. R. Hartley, Supported Metal Complexes: a New Generation of Catalysts, Reidel, Dordrecht, 1985. 5 R. L. Augustine, Catalytic Hydrogenationz Techniques and AppLications in Organic Chemistry, Marcel Dekker, New York, 1965. 6 P. N. Rylander, Catalytic Hydrogenation over Platinum Metals, Academic Press, New York, 1967. 7 P. N. Rylander, Catalytic Hydrogen&on in Ch-ganic Synthesis, Academic Press, New York, 1979. 8 J. Kijenski, M. GIinski and K. Bielawski,Stud. Suz$ Sci. CataL, (Heterogeneous Catalysis of Fine Chemicals), 41 (1988) 379. 9 C. Botteghi, R. Ganzerla, M. Lenaida and G. Moretti, J. Mol. Cat&., 40 (1987) 129. 10 K. Heyns and H. Paulsen, Newer Methods of Preparative 0rganic Chemistry, Vol. II, Interscience, New York, 1963, p. 303. 11 D. E. Bergbreiter and B. Chen, J. Chem. Sot., Chem. Commun., (1983) 1238. 12 -R. F. Heck, Act. Cha. Res., 12 (1979) 146. 13 R. F. Heck, Chem. Ind., Catalysis in Organic Synth.esis, Vol. 27, Marcel Dekker, New York, 1982, p. 345. 14 R. F. Heck, Pauadium Reagents in Organic Syzthesis, Academic Press, New York, 1985. 15 A. Hailberg, L. Westfelt and C.-M. Andersson, Synth. Commun, 15 (1985) 1131. 16 A. Hallberg and C.-M. Andersson, J. Org. Chem., 54 (1989) 1502. 17 R. C. Larock and W. H. Gong, .Z. Org. Chem., 55 (1990) 407. 18 F. Ozawa, A. Kubo and T. Hayashi, J. Am. Chem. Sot., 113 (1991) 1417. 19 A.-S. Carlstrom and T. Frejd, J. Org. Cha., 56 (1991) 1289. 20 A. HaIlberg and C.-M. Andersson, J. Org. Chcm., 53 (1988) 4257. 21 R. L. Augustine, D. R. Baum, K. G. High, L. S. Szivos and S. T. O’Leary, J. C&al., 127 (1991) 675. 22 N. Xavier and S. J. Arulrsj, Tetrahedron, 42 (1985) 2876. 23 R. R. Gallucci and R. C. Going, J. Org. C&m., 47 (1982) 3517. 24 A. Spencer, J. Organometall. Chem., 247 (1983) 117. 25 A. HaIlberg, C.-M. Andersson and K. Karabelas, J. Org. &em., 50 (1985) 3891. 26 R. H. Crabtree, P. C. Demou, D. Eden, J. M. Mehelcic, C. A. ParneIl, J. M. Quirk and G. E. Morris, J. Am. Chem. Sot., 104 (1982) 6994. 27 R. H. Crabtree, M. F. MeIlea, J. M. Mihelcic and J. M. Quirk, J. Am. Cha Sot., 104 (1982) 107. 28 G. M. Whitesides, M. Hackett, R. L. Brainard, J.-P. P. M. Lavalleye, A. F. Sowinskl, A. N. Isurd, S. S. Moore, D. W. Brown and E. M. Staudt, &-ganometaUics, 4 (1985) 1819. 29 G. D. Daves, C.-M. Andersson and A. HaIIberg, J. &g. them, 52 (1987) 3529. 30 A. Spencer and H.-U. Blaser, J. OrganometaU. t3em, 233 (1982) 267. 31 S. Nishimura, S. Iwafune, T. Nagura, Y. Akimoto and M. Uda, Chem. I&t., (1985) 1276. 32 B. Hahn, L. Westfelt and A. Hallberg, J. Org. Chem., 46 (1981) 5414. 33 A. Hallberg and C.-M. Andersson, J. Org. Chem., 53 (1986) 235.
of Molecular
Catalysis,
72 (1992)
229-242
229
Heterogeneous catalysis in organic chemistry Part 8*. The use of supported palladium catalysts for the Heck arylation Robert L. Augustine** and Shaun T. O’Leary Departmat
of Chemistry,
Seton Hall University, South 0range,
NJ 07079, CUSA)
(fteceived August 8, 1991; revised October 16, 1991)
Abstract It has been found that the Heck arylation proceeds smoothly over supported Pd catalysts to give the same reaction products as are obtained with the more commonIy used homogeneous catalysts. The effect of reaction variables on the regioselectivity of the process is about the same for both the homogeneous and heterogeneously catalyzed reactions, so the use of the supported metal catalyst in such reactions appears to be straightforward. Such materials should be considered as viable alternatives for the commordy used homogeneous catalytic species.
Introduction The use of metal complex promoted reactions in organic synthesis is well documented. However, the presence of such catalytically active species in a reaction mixture can present problems associated with the separation, recovery and regeneration of the metal complex. Such problems can be obviated by the use of heterogeneous catalysts for these reactions. While polymer- or oxide-supported complexes can provide some advantages in this regard 12-41, such materials can dissociate, resulting in the potential incorporation of metallic species and/or ligands into the reaction mixture. One possible solution to this potential problem is the use of a supported metal catalyst to promote synthetically useful C-C bond-forming reactions. While such catalysts are commonly used synthetically for functional group hydrogenations [5-7] and occasionally for hydroformylations [8, 91 or alcohol oxidations [lo], only a few reports have been published on the use of such materials to promote the formation of C-C bonds other than in hydroformylations. It has been shown that Pd/C in the presence of triphenylphosphine will promote the allylation of aniline with ally1 acetate, but it was considered that this reaction may have been catalyzed by a soluble palladium complex, formed by dissolution of the supported palladium by the phosphine Ill]. Another report stated that Pd/C will promote the Heck arylation [ 12-141 *For Part 7 see [l]. **Author to whom correspondence should be addressed.
0304-5102/92/$5.00
8 1992 - Elsevier Sequoia. All rights reserved
230
between p-nitrobenzoyl chloride and n-butyl vinyl ether, but the heterogeneously-promoted reaction data was limited to only a few entries in a table [I5, 161. In view of recent reports of the use of homogeneously catalyzed Heck arylations in the synthesis of a variety of compounds [17-201, it was felt that a more complete investigation of the usefulness of supported metals as catalysts for this reaction would be worthwhile and should lead to a better appreciation of the use of heterogeneous catalysts by synthetic chemists.
Experimental Mass spectra were obtained on a F’innigan 4021 (Data System Incas 2100) gas chromatograph-mass spectrometer, operating at 70 eV. Infrared spectra were obtained on a Mattson Cygnus 25B Fl!-IR and a Perkin-Elmer 567 grating IR. ‘H and r3C NMR spectra were recorded in deuterochloroform on a General Electric QE-300 spectrometer. Chemical shifts are given relative to the solvent lock. The gas chromatographic analyses were run on a HewlettPackard 5890 with F’ID interfaced with an H/P 3392A integrator using a 15 mX0.53 mm J&W Scientific fused silica megabore column with a 1.5 DB-1 stationary phase film thickness. Materials Palladium acetate was purchased from Aldrich Chemicals. Triphenylphosphine, obtained from Aldrich Chemical, and 1,3diphenylphosphinopropane (DPPP), obtained from Strem Chemical, were used without further purification. The 5% Pd/C catalyst was a standard commercial material obtained from Englehard Corp. The 5% Pd/@la03 catalysts were supplied by Precious Metals Corp. (#104-lot 30002; #153-lot 30021). All other catalysts were prepared as outlined in the following section. The butyl vinyl ether was purchased from Aldrich and distilled immediately before use at 92-94 “C using a short-path apparatus. The aroyl chloride, la, and aryl iodide, lb, were purchased from Aldrich Chemical and were puritied using Kugelrohr distillation at reduced pressure. N-ethylmorpholine, triethylamine and N,N-dimethylbenzylamine were purchased from Aldrich and were distilled and stored over 3A molecular sieves. The internal standard, dodecane, was spectroquality from Matheson, Coleman & Bell. It was washed with concentrated HaSO until the acid layer was clear and then distilled. The solvents were all HPLC grade and were purihed using standard procedures. Catalyst Preparation The procedures used for the preparation of 1.22% Pd/SiOa, 5% Pt/yA1203, and 2.29% Rhly-AlaO, catalysts have been previously reported [21]. The 6.06% Pdly-AlaO was prepared by shrrrying 15.0 g of 100-120 mesh -y-AlaO in 500 ml of triple-distilled (td) deionized water in a three-necked flask equipped with a stirring motor, dropping funnel and septum. Using a
232
Hz pretreatment eflect on reaction (Table 4) The reactions were run in a dry 50 ml three-necked fiask fitted with a magnetic stirring bar, condenser, thermometer and septum. The catalyst, 5% Pdly-AlzOs (0.25 mol% of Pd based on starting 4nitrobenzoyl chloride), dodecane as internal standard (33.3 mol% of starting aryl compound), and 10.0 ml of dioxane were added to the flask. The reactor was purged five tunes with nitrogen and twice with hydrogen. The solution was stirred and hydrogen was bubbled through the catalyst solvent mixture for the indicated time. After the prescribed hydrogen purging time, the reaction flask was purged twice with nitrogen and a positive pressure of nitrogen was maintained during the reaction. A mixture of the 4nitrobenzoyl chloride (2.5 mmol), n-butyl vinyl ether (2 equivalents relative to starting aryl halide) and N-ethyl morpholine (120 mol% of starting aryl compound) in 10 ml of solvent (total solvent amount equals 20 ml) were added to the flask by cannma under nitrogen. The reaction was brought to 100 “C with vigorous stirring. The reaction was monitored by gas chromatography of samples drawn after a 10 s pause in stirring for the catalyst to settle. Sealed tube arylations (Tables 3 and 6) The sealed tube experiments were performed in Pyrex screw top test tubes. The catalyst (Pd, 1 mol% of starting aryl compound) and magnetic stirring bar were placed in the tube and it was sealed using a septum and wire. The tubes were placed in an oil bath and purged with argon. The solvent (5 ml), vinyl ether (2 equivalents), amine (150 mol% of starting aryl compound) and internal standard (25 mol% of starting aryl compound) were added under argon and the reaction mixture brought to 100 “C. The aryl or aroyl halide (0.5 mmol) was added under nitrogen and this was taken to be time zero. The reaction was monitored by gas chromatography with a pause in stirring for lo-15 s to allow the catalyst to settle before samples were taken. Preparative ar2/lution reacticms The (butoxyethenyl)-4nitrobenzenes (2 and 3) were isolated from a reaction run in a dry 100 ml two-necked flask fitted with a magnetic stirring bar, condenser and septum. A solution of Pd(OAc& (0.09 g, 0.4 mmol) and N-ethylmorpholine (6.1 ml, 48 mmol) in 40 ml of toluene was stirred until an orange homogeneous mixture was obtained. To this solution was added n-butyl vinyl ether (10.3 ml, 80 mmol) and la (40 mmol). The mixture was heated with stirring to reflux. During the reaction the solution grew dark black and palladium black particles could be seen in suspension. After 8 h, the solution was cooled and then added, with stirring, to 100 ml of ether. The precipitated amine hydrochloride was removed by filtration and the solution was treated with two 20 ml portions of 5% HCl and the aqueous phases were extracted with 20 ml of ether. The combined organic phases were washed with two 25 ml portions of saturated sodium bicarbonate solutions, followed by one 25 ml portion of saturatedsodium chloride solution.
233
The organic solution was dried using MgS04 and concentrated under reduced pressure. The crude oil was subjected to flash chromatography on a 5 mm X 15 mm silica column using pentane/chIoroform or pentane/ethyl acetate as eluent. (RN: 97826-85-2): clear oil; eluent, pentane/chIoroform, 2/l; ‘H NMR (CDCla) 6 (ppm) 8.14 (d, 2H, aryl), 7.66 (d, 2H, aryl), 6.40 (d, lH, OCHWAr), 5.26 (d, lH, ArCHCHO), 4.02 (t, 2H, OC&CH,), 1.74 (m, 2H, OCH&E&CHa), 1.46 (m, 2H, CH,CH,CH,), 0.95 (t, 3H, CH,CH,); i3C NMR (CD&J 6 (ppm) 14.7 (CH&I-13), 20.1 (CH&‘H&H3), 29.2 (CH&‘I-I&H2), 32.8 (OCI-IaCH,), 75.4 (OCHCH), 105.3 (aryl), 125.1 (aryl), 129.2 (aryl), 145.1 (aryl), 152.3 (ArCHCH); mass spectrum, m/e 221 (M’), 165, 57, 41; IR (CH,C12): 1649 (olefin-aryl), 1098 (ether), 856 @-aryl) cm-‘. Coincides with literature values [16l. (Ej-I-(2-butoxyethenyl)-4-nitrobenzene (SE) (RN: 97826-86-3): light yellow oil; eluent, pentane/chIoroform, 2/l; ‘H NMR (CDC&) S 8.1-7.3 (m, 4H, a@), 7.18 (d, lH, OCHCEUr), 5.84 (d, lH, ArCHCNO), 3.90 (t, 2H, OC&CH,), 1.71 (m, 2H, OCH&&CHa), 1.46 (m, 2H, CH,CH,CHs), 0.97 (t, 3H, CHaCH,); i3C NMR (CDCb) 6 @pm) 14.7 (CH,CH,), 20.1 (CH&H&H3), 29.2 (CH&‘I-12CH2), 32.0 (OCH,CH,), 71.5 (OCHCH), 104.6 (aryl), 125.6 (axyl), 129.2 (a@), 145.1 (aryl), 151.7 (ArCHCH); mass spectrum, m/e 221 (M+), 165, 57, 41; IR (CHaCl,): 1639 (olefin-aryl), 1164 (ether), 845 (p-aryl) cm-‘. Coincides with literature values 1161. I-(l-~~~~ethenyl)-4-nitrob~~ (2’ (RN: 109125-23-7): mass spectrum, m/e 222 (M+ 1), 221 @I+), 206, 166,56,41; IR (CH&l,) 1647 (zu, olefin-aryl), 1351 (Ar-N02), 1122 (ether), 856 o>-aryl) cm- ‘. Coincides with literature values [ 161. 1- (4-Nitropheny lJ -3-butozy-2-propen-l -one (61 This compound was prepared using reaction conditions identical to those for the preparation of 2 and 3 with the following exceptions. The reaction flask was not equipped with a condenser but was stoppered and heated to 50 “C for 8 h. 6 was obtained as a light yellow oil in 44% yield. (RN: 114657-09-9): Distillation gave a colorless oil; eluent, pentane/EtAc, 3/l; ‘H NMR (CDCl,) 6 @pm) 8.4-8.0 (m, 4H, aryl), 7.82 (d, 2H, OCCHCH), 6.30 (d, 2H, OCCHCHO), 4.03 (t, 2H, OCH,CH,), 1.69 (m, 2H, CH&H,CH,), 1.47 (m, 2H, CH&&CHa), 0.98 (t, 3H, CHaCH,); mass spectrum, m/e 249 @!I+), 220, 206, 194, 176; IR (CH,Cl,): 1750 (ketone), 1645 (zu, olefin-aryl), 1280 (C-O), 848 (p-aryl) cm-‘. Coincides with literature values [20]. Butyl 4-nitrobenzoate (5) The ester was prepared using standard Schotten-Baumann techniques and isolated as Iight yellow crystals in approximately 95% yield. (RN: 120-
234
48-9): ‘H NMR (CDCla) 6 (ppm) 8.2 (q, 4H, aryl), 4.4 (t, 2H, OW&Ha), 1.8 (m, 2H, OCH,CH,CH,), 1.5 (m, 2H, CH&&CH3), 0.98 (t, 3H, CH,cW,); 13C NMR (CDCl,) 6 (ppm) 14.1 (CH&‘Ha), 20.0 (CH&H&Ha), 30.9 (CH&H&Ha), 67.0 (OCH,CH,), 124.5 (aryl), 131.0 (a@), 137.2 (aryl), 151.2 (aryl), 165.4 (ArOCO); mass spectrum, m/e 224 (M+l), 208, 194, 138, 120; IR (toluene): 1744 (ester), 1270 (C-O), 859 @-a.@) cm-‘. Coincides with literature values [22]. 1,l -LMn4..toxyethane(4) (RN: 871-22-7): IR (CHaCl,): 2900 (s, C-H stretch), 1100 (C-O acetal); mass spectrum, m/e 160, 159, 101, 57, 45, 41. Coincides with literature values [23].
Results
and discussion
The initial stage of this study involved the repetition of the reported reaction of p-nitrobenzoyl chloride and n-butyi vinyl ether run over a 5% Pd/C catalyst in toluene containing the base, triethylamine [ 151. Initially, the reaction proceeded rapidly but, with time, the activity decreased significantly. In the Heck reaction, the amine is added to remove the hydrogen halide from the palladium and, thus, regenerate the catalytically active species. In homogeneous systems, the formation of the amine salt can be useful in visually following the extent of the reaction, but in the heterogeneously catalyzed reaction this insoluble salt formation is detrimental, since it deposits on the catalyst surface and thus decreases catalytic activity. To overcome this problem, dioxane was used as the solvent to keep the triethylammonium hydrochloride in solution. With the dioxane solvent the Pd/C-catalyzed reaction TABLE 1 Product composition from heterogeneously catalyzed Heck arylatious’ Catalyst
5% Pd/Cb 5% Pd/C Pd(OAc)ab 6.06% Pd/AlaOa 1.22% Pd/SiOa 6.06% Pd/Ala03 5% Pt/Alaos 2.2% Rh/Alaoa=
Reaction time Q
Percent formed a (2)
B (3)
acetal (4)
ester (6)
6.6 7.0 1.0 6.6 4.5 5.6 0 0
65.2 70.1 56.4 64.7 46.1 66.9 0 0
1.8 9.4 38.0 7.6 8.0 0 21.7 32.2
1.2 6.6 1.7 10.7 7.8 4.3 7.4 21.1
‘40&l chloride:Pd ratio using the small scale arylation reaction conditions described in the Experimental. blOO:l chloride:Pd ratio. Reaction time was extended to 10 h with no signScant increase in product ratios.
235
proceeded smoothly to completion. The product composition is listed in Table 1. The products were the expected p-aryl vinyl ethers, E- and Z-l(2-butoxyethenyl)-4nitrobenzene, 3a and b, and the (Yisomer, l-(l-butoxyethenyl)-4nitrobenzene, 2. Also found in the reaction mixture were the ester, n-butyl 4-nitrobenzoate (6) and the acetal, l,l-di-n-butoxyethane (4). Also found in some reaction mixtures was E-3-n-butoxy-1-phenyl-2-propen-l-one (6), the aroylated species resulting from incomplete decarbonylation of the acid chloride, la. The amount of this material present depended on the reaction temperature used, but was always under 5% and most generally present only in trace amounts.
3E @YI
Pd 6B”
OZN
,-;
O,N
1
2 02N
a, X =COCI b,X=l
4
6
6
It was initially thought that the butyl ester, 6, was formed by reaction of the acid chloride with some butanol produced by the hydrolysis of the butyl vinyl ether with some water in the reaction mixture. However, when care was taken to exclude all water from the reaction, ester formation was still observed. An alternative explanation for the presence of the butanol needed for the formation of both 4 and 6 involves the cleavage of the vinyl oxygen bond of the butyl vinyl ether on the palladium surface to give an adsorbed butoxy species, which could then react either with the acid chloride to give 6 or with butyl vinyl ether to give the acetal, 4. The source of the hydrogens needed to complete these reactions is not clear, but they could orignate from some trace amounts of water still present, metal-promoted dehydrogenation of some solvent molecules, surface -OH groups on the catalyst support and/or residual hydrogen remaining in the catalyst from the reduction procedure used in its preparation. The enhancement of acetal formation on hydrogen-presaturated catalysts, as discussed later, indicates that the latter possibility may prevail. Further support for the proposed bond cleavage comes from the observation of trace amounts of 4nitrostyrene in many of these reactions. This material has been produced by the reaction of 4nitrobenzoyl chloride with ethylene under Heck arylation conditions [24].
236
The acid chloride:Pd ratio in this reaction was lOO:l, as is commonly used in homogeneously catalyzed reactions of this type. The heterogeneous catalyst, though, was more active on a weight of metal basis than was a Pd(OAc)a. catalyst. Decreasing the amount of Pd/C to give a 4OO:l acid chloride:Pd ratio resulted in the reaction proceeding at approximately the same rate as the Pd(OAc)a-promoted reaction run using a 1OO:l ratio. Since the active surface atoms on supported catalysts comprise only a small fraction of the total Pd content [2 11, these heterogeneous catalysts are significantly more reactive. As shown by the data in Table 1, a decrease in the amount of Pd present in the heterogeneously catalyzed reaction mixture increases slightly the amount of product enol ether formed but has virtually no effect on the cr//? (2/3) ratio. However, more of the ester 6 and the acetal 4 are formed in the reaction promoted by the smaller amount of Pd. Since in this reaction, enol ether formation is slower than is observed with the larger amount of Pd, there is more time for the cleavage of the butyl vinyl ether to take place, resulting in the formation of more side products. Since it was shown that this reaction did, indeed, proceed as reported [ 15, 161, the next step was to determine whether Pd/C was the only viable catalyst or if other supported metals could also be used. It was found that both Pd/SiOa and Pd/A1203 promoted the reaction, with Pd/AlaO, having about the same degree of activity as observed with Pd/C, while Pd/SiOa was somewhat less active. The amounts of ester 5 and acetal 4 produced with these catalysts were also about the same as that found with Pd/C (Table 1). Catalysis of the reaction, however, was restricted to Pd since the use of either Pt/A1203 or Rh/AlaOa gave as products only the ester 6 and acetal 4. The similarity between the heterogeneously catalyzed reaction data and that obtained using a Pd(OAc)a catalyst might suggest that the catalyst for these reactions is a dissolved Pd species. To test this, the reaction was run over a Pd/AlaOa catalyst to N lo-20% completion in a two-section Schlenk tube with a fritted disc between the two sections. The reaction liquid was then separated from the solid catalyst by filtration through the fiit and its composition determined by gas chromatography. The liquid was then heated for an additional 2 h, sufllcient time for further reaction to occur if a soluble catalyst were present, and the composition again determined. There was no detectable difference in the liquid composition after this time, showing that there was no soluble catalyst in the reaction system. In a related evaluation, the reaction was run in the presence of the soluble catalyst, Pd(OAc)a. As has been reported in other studies [25], the reaction mixture grew turbid as the catalyst system became active. This has been attributed to a reduction of the Pd(II) to Pd(0) [ 25 1. After the reaction proceeded to N 20% completion, the product composition was determined and a small amount of elemental mercury was added to the reaction mixture. This mixture was then heated for an additional 72 h with no detectable change observed in the product composition. Since mercury will poison heterogeneous metal catalysts but has no effect on homogeneous systems
237
[26-281, this loss of activity shows that, contrary to popular opinion, the Pd(OAc),-catalyzed Heck arylation is not homogeneously promoted but rather, that the catalyst is apparently some form of palladium black. Attempts to use the recovered Pd black catalyst for further arylation reactions failed, possibly due to an agglomeration of the most active line metal particles into large clumps during the isolation process. These larger agglomerates would be expected to lack the activity of the smaller crystallites [25]. A further comparison can be made with homogeneously catalyzed arylation reactions by considering the effect which the nature of the reaction solvent has on the a@ product ratio. It has been reported that in homogeneously catalyzed reactions the use of non-coordinating aromatic solvents leads to predominant p-isomer formation, while the more coordinating dioxane would be expected to give more of the a-isomer [29]. As the data in Table 2 show, however, there is little difference in the cr//3 product ratios produced from Pd(OAc& catalyzed reactions run in toluene and dioxane. The major difference is the formation of somewhat more of the B-isomer, 3, in dioxane, which is contrary to expectation, and the rather large amount of acetal formation also observed in dioxane. That the solvent coordination was in some way responsible for the acetal formation can be seen by the increase in the amount of 4 formed when either triphenylphosphine or diphenyl-n-propylphosphine was added to the dioxane reaction mixture. The large amount of phosphine added in these reactions has been known to decrease the extent of product enol ether formation [ 161. Solvent comparison in Pd/Al,O,-catalyzed reactions, however, is more difllcult because of the catalyst deactivation brought about by the amine hydrochloride precipitation from the reaction mixture in toluene. If one allows the reaction to proceed long enough, however, the reaction can be made to go almost to completion even with the amine hydrochloride deactivation. The results of the Pd/Al,O,-catalyzed TABLE 2 Solvent effect in Heck aryJationa“ Catalyst
Pd(OAc),b Pd(OAc),b Pd(OAc),b Pd(OAc)zb Pd/AlzOs PdlA1,0s
Solvent
toluene dioxane dioxane= dioxaned toluene dioxaue
Reaction time Q
Percent formed Q (2)
P (3)
acetal (4)
ester (5)
4 4 4 4 8 4
Cl.0 1.0 1.3 2.6 6.0 6.5
42.9 66.4 6.7 18.4 80.3 64.7
4.0 38.0 71.6 52.3 6.4 7.6
1.7 1.7 7.6 25.9 3.8 10.7
a400:1 chloride:Pd ratio using the small scale arylation reaction conditions described in the Experimental. blOO:l chloride:Pd ratio. =2 mol% of triphenylphosphine added. dl .1 mol% of diphenyl-n-propylphosphine added.
238
reaction run in both toluene and dioxane are also shown in Table 2. With this catalyst the expected decrease in p-isomer formation with increasing coordination ability of the solvent was observed. A slight increase in acetal formation and a more pronounced increase in ester formation was also found. The nature of the amine used to regenerate the active catalyst species can also play a role in catalyst activity and selectivity, particularly in the formation of the ester and acetal side products. Earlier results have suggested that iV-benzyldimethylamine would give the most satisfactory results for the production of the arylation products 2 and 3 [ 301. Other amines have also been used and it has been concluded that the base should be a tertiary amine having a pK, between 7.5 and 11. Weaker bases tend to give slower reaction rates, and stronger bases may react with the other components of the reaction medium. As the data in Table 3 show, there is no valid comparison between the amine pK, and the amounts of 2 and 3 formed over a Pd/A1203 catalyst. However, the lower the pK, of the amine, the greater the extent of acetal formation. The reason for this enhanced acetal formation with increasing pK, on these heterogeneous Pd catalysts is not apparent at this time. The palladium catalysts used in this work had been stored in air for various periods of time. Since it has been established that this reaction takes place over Pd(0) species [25], it was felt that it might be of some advantage to treat the catalyst with hydrogen immediately before the reaction to reduce any surface oxides which might be present, and thus increase the amount of Pd(0) present on the surface. In this way it was envisioned that the reaction might proceed even more rapidly. To check this possibility hydrogen was bubbled through the catalyst-amine-solvent mixture for various times before the reactants were added and the reaction initiated. The results of these experiments are listed in Table 4. Instead of increasing the formation of the desired products 2 and 3, the amount of these materials produced decreased significantly with increasing hydrogen pretreatment. On the other hand, the amount of the side products 4 and 6 increased with increasing hydrogen pretreatment. Nishimura and coworkers [31] have reported that TABLE 3 Amine effect in heterogeneously catalyzed Heck arylationsa Amine
NJZMb BDAC TEAd
Plz
7.80 9.03 10.06
Reaction time Q
Percent formed a (2)
B (3)
acetal (4)
ester (6)
1 1 1
5.3 1.5 8.0
14.9 2.9 11.7
21.0 13.0 4.0
1.2 1.7 2.1
healed tube arylation reaction conditions described in the Experimental. “N-ethylmorpholine. cBenzyldimethylamine. Wethylamine.
239
TABLE 4 Effect of hydrogen pretreatment of the catalyst in heterogeneously catalyzed Heck arylations’ Hz Treatment time Q
Percent formed ff (2)
P (3)
acetal (4)
ester (6)
0
5.6 2.0 0 1.7
56.9 12.9 4.6 6.6
0 25.4 29.2 50.9
4.3 7.0 8.6 17.7
0.25 1 6
SuaU scale arylation reaction conditions described in the Experimental.
acetal formation in the metal-catalyzed hydrogenation of ketones in alcohol solvents is associated with the presence of adsorbed hydrogen, probably in an ionized state, and is dependent on the nature of the catalyst metal, with Pd the most effective. Thus, the formation of 4 and 6 is probably due to an increase in the number of acidic surface sites brought about by the hydrogen pretreatment of the PdL41203 catalyst. The decrease in 2 and 3 formation may be due to the presence of hydrogen adsorbed on the active sites on the metal, which could either block the formation of the surface intermediates required for the Heck arylation or react with these intermediates to prevent the formation of 2 and 3. The initial goal of this research was the development of methods for the production of aryl vinyl ethers, specifically the synthetically useful paryl systems, using supported metal catalysts. Earlier work has found that an electron- withdrawing group such as a 4-nitro substituent on the aryl ring exerts a strong directing force in coupling with the P-carbon of the n-butyl vinyl ether (321. Another factor in dete rmining the regioselectivity of the reaction was the nature of the halide on the aromatic ring 1291. In this work the trend for greater P-selectivity increased in the order Cl > Br> I, which agrees with the relative bond strength of the Pdn-X bond, I > Br > Cl [29]. However, the formation of the arylpalladium reagent is slow for a bromobenzene and almost nonexistent for a chlorobenzene. The arylpalladium chloride could be formed indirectly, however, by decarbonylation of the corresponding substituted benzoyl chloride, thus allowing for facile halogen selection in the control of reaction regioselectivity (301. The difference in regioselectivity between these benzoyl chloride reactions and those involving aryl bromides or iodides has been attributed solely to the halide ion and not to the presence on the metal surface of adsorbed carbon monoxide, a byproduct of the decarbonylation reaction [ 331. To ascertain whether these effects also occur with supported metal catalysts, the reaction of 4nitroiodobenzene, lb, over Pd(OAc)a, Pd/AlaOa and Pd/SiOa was also investigated. The results of these reactions along with the corresponding data from the 4nitrobenzoyl chloride reactions are listed in Table 5. Interestingly, there appears to be no halide ion effect on the
240 TABLE 5 Halide effect in heterogeneously catalyzed Heck arylationsp
Aryl
Catalyst
reactant
la la la lb lb lb
Pd(OAc)ab 6.06% Pd/AlaOa 1.22 % Pd/SiOz Pd(OAc)ab 6.06% Pd/AlaOs 1.22% Pd/SiOa
Reaction time Q
Percent formed a (2)
B (3)
EIZ
acetal (4)
ester (6)
1 1 1 4 4 4
6.3 5.8 4.5
77.5 58.5 46.1 25.3 30.1 11.8
1.86 2.75 1.99 0.68 0.98 0.74
12.0 5.4 7.6 38.0 39.3 43.2
3.2 4.4 7.8 ’ c ’
‘small scale arylation reaction conditions described iu the Experimental. blOO:l halide:Pd ratio. CEster formation not possible.
regioselectivily of the reaction, @isomer formation being markedly predominant in all cases. If anything, p-isomer formation appears to be even more selective with the iodobenzene lb than with the benzoyl chloride la. The rate of reaction is, however, slower with the iodo compound but its use did preclude any formation of ester as a byproduct. Acetal formation however was considerably enhanced in the iodobenzene reactions, probably because of the longer reaction times required with this material. One other interesting comparison between the products formed from these two reagents is in the ratio of the 3E and 32 isomers. With reactions run using the benzoyl chloride la, the E/Z ratios were generally two or greater while with the iodobenzene lb, the E/Z ratios are less than one. This correlates well with a previous report [29]. The size of the E/Z ratio has been ascribed to the effect of (a) the electron density of the aryl moiety, (b) the availability of ligands or (c) the nature of the halide ion present [29]. In these present reactions the electron density of the aryl moiety and the availability of ligands should be constant, even though there is the possibility of a carbon monoxide ligand being present on the metal surface in the benzoyl chloride reactions. It would seem, then, that the nature of the halide is the most critical factor in the determination of the E/Z ratio, providing, of course, that this ratio is indicative of the true product stereochemistry and not the result of some secondary isomerizations. To check this, a 1:l mixture of the E and 2 isomers, 3E and 32, was added to the normal reactants in an amount equal to the expected p-product yield. The final product composition showed twice the amount of p-isomer formation, indicating that no &isomer degradation had occurred. Further, after subtracting the amount of E and 2 isomers normally formed in this reaction, the initially-added 1:l E:Z ratio resulted, showing that there was no isomerization between these stereoisomers. In a further experiment, the 1: 1 ES mixture was treated with y-A1203 in dioxane under normal reaction conditions. No isomerization was observed.
241 TABLE 6 Effect of amine concentration on product enol ether stereochemist+ Concentrationb
E/Z ratio
80 110 120 150
0.76 0.81 0.98 0.99
healed tube axylation reaction conditions described in the Experimental. bMolar percent of amine.
It appears, then, that the results listed in Table 5 are those of the primary reactions with no subsequent isomerization taking place. The more extensive formation of the 2 isomer in the iodobenzene reaction may be related to the increased size of the iodide ion adsorbed on the active site, as compared to the smaller chloride ion. The more crowded the active site in the reaction, the less favorable the formation of the more sterically demanding tram or E isomer. An indication of the steric requirements for isomer formation can be seen in the results listed in Table 6, showing the effect the amount of base added to the reaction mixture has on the enol ether stereochemistry. In all cases the 2 isomer predominated, but the ratio decreased as more amine was added to the reaction mixture. With higher amine concentrations, the amount of the tramsor more sterically demanding isomer increased because of the more rapid removal the halide ions from the active sites by reaction with the amine and formation of the amine hydrohahde. While these results show that isomerization does not occur readily during the reaction, the isomerization of the 2 isomer to an E/Z mixture does take place slowly on standing. This isomerization has been followed over several months, using changes in the NMR of a sample kept in an NMR tube in deuterochloroform.
Conclusions
These results show that supported metals can be used in place of soluble organometallic catalysts for promoting synthetically useful reactions such as the Heck arylation. The effect of reaction variables on the regioselectivity of the process is about the same for both the homogeneous and heterogeneously catalyzed reactions. Thus use of the supported metal catalyst in such reactions appears to be straightforward and such materials should be considered asviable alternatives for the commonly used homogeneous catalytic species.
242
Acknowledgement This research was supported by Grant DE-FG02-84ER45120 from the U.S. Department of Energy, Office of Basic Energy Science. The metal salts were obtained through the Johnson-Matthey Precious Metal Loan Program. References 1 R. L. Augustine and F. [email protected], J. Org. Churn., 52 (1987) 1862. 2 Y. I. Ermakov and L. N. Arzamaskova,Stud. Sue Sci. Catal., (Catalytic Hydrogenation) 27 (1986) 459. 3 Y. I. Ermakov, Pure Appl. Chem., 52 (1980) 2075. 4 F. R. Hartley, Supported Metal Complexes: a New Generation of Catalysts, Reidel, Dordrecht, 1985. 5 R. L. Augustine, Catalytic Hydrogenationz Techniques and AppLications in Organic Chemistry, Marcel Dekker, New York, 1965. 6 P. N. Rylander, Catalytic Hydrogenation over Platinum Metals, Academic Press, New York, 1967. 7 P. N. Rylander, Catalytic Hydrogen&on in Ch-ganic Synthesis, Academic Press, New York, 1979. 8 J. Kijenski, M. GIinski and K. Bielawski,Stud. Suz$ Sci. CataL, (Heterogeneous Catalysis of Fine Chemicals), 41 (1988) 379. 9 C. Botteghi, R. Ganzerla, M. Lenaida and G. Moretti, J. Mol. Cat&., 40 (1987) 129. 10 K. Heyns and H. Paulsen, Newer Methods of Preparative 0rganic Chemistry, Vol. II, Interscience, New York, 1963, p. 303. 11 D. E. Bergbreiter and B. Chen, J. Chem. Sot., Chem. Commun., (1983) 1238. 12 -R. F. Heck, Act. Cha. Res., 12 (1979) 146. 13 R. F. Heck, Chem. Ind., Catalysis in Organic Synth.esis, Vol. 27, Marcel Dekker, New York, 1982, p. 345. 14 R. F. Heck, Pauadium Reagents in Organic Syzthesis, Academic Press, New York, 1985. 15 A. Hailberg, L. Westfelt and C.-M. Andersson, Synth. Commun, 15 (1985) 1131. 16 A. Hallberg and C.-M. Andersson, J. Org. Chem., 54 (1989) 1502. 17 R. C. Larock and W. H. Gong, .Z. Org. Chem., 55 (1990) 407. 18 F. Ozawa, A. Kubo and T. Hayashi, J. Am. Chem. Sot., 113 (1991) 1417. 19 A.-S. Carlstrom and T. Frejd, J. Org. Cha., 56 (1991) 1289. 20 A. HaIlberg and C.-M. Andersson, J. Org. Chcm., 53 (1988) 4257. 21 R. L. Augustine, D. R. Baum, K. G. High, L. S. Szivos and S. T. O’Leary, J. C&al., 127 (1991) 675. 22 N. Xavier and S. J. Arulrsj, Tetrahedron, 42 (1985) 2876. 23 R. R. Gallucci and R. C. Going, J. Org. C&m., 47 (1982) 3517. 24 A. Spencer, J. Organometall. Chem., 247 (1983) 117. 25 A. HaIlberg, C.-M. Andersson and K. Karabelas, J. Org. &em., 50 (1985) 3891. 26 R. H. Crabtree, P. C. Demou, D. Eden, J. M. Mehelcic, C. A. ParneIl, J. M. Quirk and G. E. Morris, J. Am. Chem. Sot., 104 (1982) 6994. 27 R. H. Crabtree, M. F. MeIlea, J. M. Mihelcic and J. M. Quirk, J. Am. Cha Sot., 104 (1982) 107. 28 G. M. Whitesides, M. Hackett, R. L. Brainard, J.-P. P. M. Lavalleye, A. F. Sowinskl, A. N. Isurd, S. S. Moore, D. W. Brown and E. M. Staudt, &-ganometaUics, 4 (1985) 1819. 29 G. D. Daves, C.-M. Andersson and A. HaIIberg, J. &g. them, 52 (1987) 3529. 30 A. Spencer and H.-U. Blaser, J. OrganometaU. t3em, 233 (1982) 267. 31 S. Nishimura, S. Iwafune, T. Nagura, Y. Akimoto and M. Uda, Chem. I&t., (1985) 1276. 32 B. Hahn, L. Westfelt and A. Hallberg, J. Org. Chem., 46 (1981) 5414. 33 A. Hallberg and C.-M. Andersson, J. Org. Chem., 53 (1986) 235.