INTRODUCTION

Trisubstituted alkenes attract interest as intermediate products for the preparation of pharmaceuticals and biologically active compounds, as well as semicon­ducting and emitting materials [1–4]. Such compounds can be obtained by arylation of alkenes with aryl halides, which is known as the Mizoroki–Heck reac­tion [5, 6]. In this case, the classical Mizoroki–Heck arylation utilizes disubstituted alkenes which, however, are significantly less reactive than monosubstituted analogs [3, 7]. An alternative way to obtain trisub­stituted alkenes by the catalytic Mizoroki–Heck reac­tion may be sequential double arylation of monosub­stituted alkenes. Numerous examples of such reactions have been reported, but most of them require palladium-based catalytic systems including expensive, often toxic, and moisture- and air-sensitive phosphine or nitrogen-containing ligands [1, 2, 8, 9], and the arylating agents are mainly aryl iodides that are more reactive but less accessible than the corresponding aryl bromides and aryl chlorides. There are examples of one-pot sequential double arylation with the use of so-called “ligand-free” palladium catalytic system and aryl iodides as arylating agents [3, 10], but long reac­tion times (12–30 h) and/or addition of toxic silver salts as a base [3] were necessary to achieve acceptable yields. A related alternative route to products of sequen­tial double arylation is the Heck–Matsuda reac­tion with arenediazonium salts [12]. In this work we demon­strated the possibility of obtaining trisubsti­tuted alkenes in high yields via one-pot sequential double arylation of monosubstituted alkenes in the pres­ence of a catalytic system based on simple palla­dium(II) salts containing no strong organic ligands.

RESULTS AND DISCUSSION

We tested the possibility of obtaining products of double arylation of monosubstituted terminal alkenes with aryl bromides and aryl chlorides that are less reactive but more accessible than aryl iodides under so-called “ligand-free” catalytic conditions. The arylations of styrene with bromobenzene and of butyl acrylate with 4-chloroacetophenone were selected as model reactions (Scheme 1). In fact, regardless of the reactant couple, the diarylated products were formed in a sequential manner, i.e., the consumption of monoarylated products began after the conversion of the initial alkene achieved 80–90%. Most probably, this reaction pattern is determined by the successive com­petition between the initial monosubstituted alkene and disubstituted alkene (monoarylated product) at the alkene activation step. According to the generally accepted views, this stage involves coordination and subsequent insertion of alkene in the Pd–C bond of the arylpalladium complex ArPdX formed as a result of oxidative addition of aryl halide to palladium [3, 7].

Scheme
scheme 1

1.

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The arylation of styrene with bromobenzene gave the only possible sequential double arylation product, triphenylethylene 1c (Scheme 1a). The yield of 1c reached 90% in 7 h, the initial alkene (styrene) was completely consumed, and the reaction mixture con­tained some amounts of the β- and α-arylation products, stilbene 1a and 1,1-diphenylethylene 1b (Table 1; entry nos. 1, 2). Reduction of the amounts of the palladium catalyst precursor and the arylating agent (bromo­benzene) resulted in some decrease in the yield of tri­phenylethylene; nevertheless, the conversion of styrene was complete (Table 1; entry nos. 3, 4).

Table 1. Mono- and diarylation of alkenes with aryl halides
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The arylation of butyl acrylate with 4-chloroaceto­phenone showed significantly higher selectivity of the first coupling at the β-position of the vinyl group than in the reaction of styrene with bromobenzene; GC/MS analysis of the reaction mixture revealed the formation of three different products of sequential double arylation (compounds 2c–2e; Scheme 1b). In all cases, the yield of β,β-coupling product 2c was much higher than the overall yield of α,β-coupling products 2d and 2e (Table 1; entry nos. 5, 6, 8), which is likely to be related to the higher reactivity of the β-carbon atom in the monoarylated product (2a) due to reduction of electron density on that atom [3]. As in the arylation of styrene with bromobenzene, in all experiments, including those with reduced loading of the palladium catalyst precursor, the initial alkene was completely consumed. The maximum yield of double arylation products 2c–2e was achieved using bis(acetylaceto­nato)palladium (II) (Table 1, entry no. 8). Thus, the use of palladium catalytic systems containing no strong organic ligands (such as phosphines, amines, carbenes, etc.) makes it possible to obtain products of sequential double arylation of terminal alkenes with low reactive aryl bromides and aryl chlorides within acceptable reaction times (2.5–7 h).

EXPERIMENTAL

Qualitative GC/MS analysis of the reaction mix­tures was performed using a Shimadzu GC-MS QP-2010 Ultra instrument (electron impact, 70 eV; GsBP-5MS column, 30 m×0.25 mm, film thickness 0.25 μm; carrier gas helium; oven temperature programming from 110 to 250°C; integer m/z values were scanned from 15 to 900 at a rate of 5000 amu/s). The obtained mass spectra were compared with reference ones from Wiley, NIST, and NIST05 libraries and those of authentic samples (Aldrich). Quantitative analysis of the reaction mixtures was carried out by GLC on a Chromatec Crystal 5000 chromatograph equipped with a flame ionization detector and an HP-5 column (15 m); carrier gas nitrogen, oven temperature prog­ramming from 110 to 250°C; the components were quantitated by the internal standard method (naph­thalene) using the experimental and calculated response factors determined for authentic samples and from the material balance equations, respectively.

Sequential double arylation of styrene with bromo­benzene. A mixture of bromobenzene (5 or 10 mmol), styrene (1.5 mmol), and naphthalene (internal standard for GLC, 0.5 mmol) in 5 mL of N,N-dimethylformamide (DMF) was introduced into a 15-mL round-bottom glass reactor equipped with a rubber septum and a magnetic stir bar and containing PdCl2 (0.01–0.04 mmol) and Bu4NOAc (base, 6.5 mmol). The reaction was initiated by placing the reactor in an oil bath preliminarily heated to 140°C with stirring at 480 rpm. The reaction time was 6–8 h. Samples of the reaction mixture (100 μL) were with­drawn periodically using a syringe with a metal needle and extracted with toluene–water (1:1), and the organic extract was analyzed by GLC.

Sequential double arylation of butyl acrylate with 4-chloroacetophenone. A mixture of 4-chloro­acetophenone (3.75 mmol), butyl acrylate (0.625 mmol), and naphthalene (internal standard for GLC, 1 mmol) in 2.5 mL of N-methylpyrrolidone (NMP) or DMF was introduced into a 15-mL round-bottom glass reactor equipped with a rubber septum and a magnetic stir bar and containing Pd(II) salt (0.0025 or 0.01 mmol), NaOAc (base, 3.25 mmol), and Bu4NBr (additive, 8 mmol). The reaction was initiated by placing the reactor in an oil bath preliminarily heated to 140°C with stirring at 480 rpm. The reaction time was 2–3 h. Samples of the reaction mixture (100 μL) were withdrawn periodically using a syringe with a metal needle and extracted with toluene–water (1:1), and the organic extract was analyzed by GLC.

The mass spectra of the single and double arylation products of styrene and butyl acrylate are given below.

(E)-1,2-Diphenylethene (1a). Mass spectrum, m/z (Irel, %): 180 (100) [M]+, 179 (89.57), 165 (48.26), 178 (47.67), 89 (44.01), 76 (25.16), 181 (13.06), 90 (10.25).

1,1-Diphenylethene (1b). Mass spectrum, m/z (Irel, %): 180 (100) [M]+, 165 (83.33), 179 (71.93), 178 (63.6), 89 (41.16), 76 (27.47), 77 (18.22), 181 (15.09), 166 (12.25), 152 (11.76), 51.1 (11.55), 176 (10.35).

1,1,2-Triphenylethene (1c). Mass spectrum, m/z (Irel, %): 256 (100) [M]+, 178 (34.22), 179 (25.49), 241 (23.24), 255 (22.22), 257 (20.72), 239 (20.5), 119 (16.66), 240 (15.43), 126 (15.41), 253 (15.17), 165 (14.46), 252 (13.37), 113 (11.58).

Butyl (E)-3-(4-acetylphenyl)prop-2-enoate (2a). Mass spectrum, m/z (Irel, %): 246 (23.47) [M]+, 175 (100), 43 (89.27), 231 (55.12), 190 (45.88), 131 (45.46), 102 (28.9), 173 (28.24), 29.1 (14.86), 91 (14.86), 41 (13.62), 147 (13.0), 191 (11.56), 76 (11.26), 56 (11.0).

Butyl 2-(4-acetylphenyl)prop-2-enoate (2b). Mass spectrum, m/z (Irel, %): 246 (14.58) [M]+, 175 (100), 43 (92.27), 231 (54.66), 131 (41.15), 190 (36.71), 102 (30.78), 173(23.73), 29 (19.63), 91 (16.65), 147 (15.04), 41 (13.42), 76 (12.88), 65 (12.82).

Butyl 3,3-bis(4-acetylphenyl)prop-2-enoate (2c). Mass spectrum, m/z (Irel, %): 364 (30.91) [M]+, 43 (100), 293 (81.26), 249 (33.76), 308 (29.41), 349 (21.01), 291 (18.71), 294 (15.46), 29 (12.12), 139 (9.81).

Butyl (Z)-2,3-bis(4-acetylphenyl)prop-2-enoate (2d). Mass spectrum, m/z (Irel, %): 364 (50.54) [M]+, 43 (100), 349 (37.74), 293 (35.74), 149 (26.25), 29 (18.37), 139 (13.79), 365(13.5), 263 (12.63), 308 (12.23), 205 (11.18), 41 (11.08).

Butyl (E)-2,3-bis(4-acetylphenyl)prop-2-enoate (2e). Mass spectrum, m/z (Irel, %): 364 (46.02) [M]+, 43 (100), 349 (35.03), 293 (33.59), 149 (22.56), 29 (15.62), 139 (15.49), 308 (13.29), 263 (12.3), 365 (11.31), 41 (10.83).

CONCLUSIONS

The possibility of obtaining products of sequential double arylation of monosubstituted terminal alkenes via the Mizoroki–Heck reaction using low-reactive aryl bromides and aryl chlorides and so-called “ligand-free” palladium catalytic systems without phosphine, nitro­gen-containing, or other stabilizing organic ligands has been demonstrated.