Palladium-catalyzed heck-type arylation of acrylate with diaryliodonium salts

Abstract

Highly effective palladium-catalyzed Heck-type arylation of acrylate with diaryliodonium salts has been developed, giving cinnamate in high yields without ligand and base.

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The formation of a carbon–carbon bond by palladium-catalyzed coupling of aryl or vinyl halides with olefins, known as the Heck reaction, has become a powerful tool in organic chemistry¹ and occupies a special place for its resourceful versatility.² Under its usual form, the Heck reaction involves the coupling of aryl, vinyl, benzyl, or allyl halides with olefins in the presence of a homogeneous or heterogeneous source of palladium as catalyst under basic conditions (Scheme 1). However, Pd(II)-precatalysts, such as Pd(OAc)₂, PdCl₂(PPh₃)₂ or PdCl₂CH₃CN are usually preferred in association with stabilizing ligands, such as phosphines or carbenes.³

Scheme 1 Arylation of acrylate.

The use of diaryliodonium salts has recently gained considerable attention in organic synthesis.⁴ Remarkable progress in both metal-catalyzed and metal-free direct arylations of indoles,⁵ pyrroles,⁶ phenols,⁷ carboxylic acids,⁸ aniline⁹ and carbonyls¹⁰ has been accomplished through the use of diaryliodonium salts as arylating reagents. In particular, the groups of Gaunt and Olofsson have conducted lots of work with the synthesis and applications of diaryliodonium salts.^11,12 Recently, Pd–Ag catalyzed and Pd catalyzed arylation of alkenes with PhI(OAc)₂ were reported by the groups of Magedov and Mao.¹³

As part of our ongoing interest in developing applications of diaryliodonium salts via transition metal catalysis, we herein wish to report a palladium-catalyzed Heck-type arylation of acrylate with diaryliodonium salts without ligand and base (Scheme 1). At the outset of our studies, a set of experiments was carried out using diphenyliodonium salt 1a and methacrylate 2a as model substrates. We tested various reaction conditions for the arylation of methacrylate (Table 1).

Table 1 Optimization of the model reaction^a

Entry	Catalyst	X	Solvent ^b	Yield (%)^c
a Diphenyliodonium salt (0.4 mmol) and methacrylate (2 equiv.) were mixed in solvent (1 mL) at r. t. before addition of Pd(OAc)2 and heating to 130 °C. b Solvent not dried. c Isolated yield.
1	—	OTs	toluene	—
2	Pd(OAc)2	OTs	toluene	23
3	Pd(OAc)2	OTs	DMF	83
3	Pd(OAc)2	OTs	DMSO	65
4	Pd(OAc)2	OTs	DMAC	74
5	Pd(OAc)2	OTs	NMP	21
6	Pd(OAc)2	OTs	DCE	61
7	PdCl2	OTs	DMF	77
8	Pd2(dba)3	OTs	DMF	73
9	Pd(OAc)2	BF4	DMF	85
10	Pd(OAc)2	PF6	DMF	81
11	Pd(OAc)2	Br	DMF	64
12	Pd(OAc)2	OTf	DMF	99
13	Pd(OAc)2(2% mol)	OTf	DMF	99
14	Pd(OAc)2(0.5% mol)	OTf	DMF	91

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First, these two coupling partners were reacted in DMF at 130 °C without the presence of Pd(OAc)₂, and no cinnamate product 3a was obtained (entry 1, Table 1). When 5% mol of Pd(OAc)₂ was employed, we are pleased to find that the reaction occurred to afford 3a in 23% yield (entry 2, Table 1), from GC-MS we find the major product was diphenyl from the coupling of diphenyl iodine 1a and toluene. So we change toluene into DMF which, gratifyingly, resulted in significant increase of the yield. Screening of solvents with Pd(OAc)₂ revealed that the yield of 3a was much higher in DMF than in DMSO, DMAC, NMP and DCE. After screening of various palladium catalysts, we found that Pd(OAc)₂ was the most effective catalyst than the other two palladium catalysts, such as PdCl₂ and Pd₂(dba)₃ (entries 7, 8, Table 1). Further studies were thus carried out about the influence of different diphenyliodonium anions, which showed that satisfactory results could be obtained with diaryliodonium tetrafluoroborates, hexafluorophosphates and bromide (entries 9–11, Table 1). Gratifyingly, significant improvement was achieved by the use of diphenyliodonium triflate resulting in clean formation of the product in 99% yield (entry 13). Moreover, decreasing the amount of Pd(OAc)₂ to 2% mol led to the same yield and 0.5% mol of catalyst led to the reduction of yields (entry 14, Table 1).

With optimized reaction conditions in hand, we probed the scope of methacrylate with different diaryliodonium triflate employing 2% mol of Pd(OAc)₂ in DMF at 130 °C. The results are summarized in Table 2.

Table 2 Arylation of methacrylate^a

Entry	Ar	Product 3	Yield (%)^b
a Diaryliodonium triflate salt (0.4 mmol) and Methacrylate (2 equiv.) were mixed in solvent (1 mL) at r.t. before addition of Pd(OAc)2 (2% equiv.) and heating to 130 °C. b Isolated yield.
1	C6H51a	3a	99
2	4-ClC6H41b	3b	93
3	4-FC6H41c	3c	92
4	4-NO2C6H41d	3d	96
5	4-EtOOCCOC6H41e	3e	91
6	4-PhC6H41f	3f	86
7	2-MeC6H41g	3g	93
8	3-BrC6H41h	3h	92
9	2-thiophen 1i	3i	76
10	2-pyridine 1j	3j	53

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The reaction scope was subsequently explored by using various asymmetrical diaryl iodonium salts 1 which were prepared with appropriate iodoarene and mesitylene.¹⁴ Excellent isolated yields of methyl cinnamate 3 were obtained with 2% mol of Pd(OAc)₂ in one hour. Substituted diphenyl iodoniumtriflate with electron-withdrawing substituents worked equally well as those with electron-donating substituents, giving cinnamates 1a–e in high yields (entries 1–6, Table 2). In particular, diaryl iodonium salts of p-nitrobenzene 1d resulted in higher yield of product 3d (entry 4). Likewise, ortho-substituted salts posed no problem in this reaction, as exemplified by o-methyl product 3g (entry 7). Steric bulk in the meta-position was very well tolerated, as demonstrated by arylation with salt 1h to yield high congested product 3h (entry 8). Furthermore, heterocyclics such as pyridine and thiophene, which are privileged scaffold, smoothly proceed to give 3i and 3j in good yield (entries 9, 10).¹⁵

The results encouraged us to extend our protocol to investigate this new Heck-type reaction. In this regard substrate acrylate 2 was surveyed under the optimized reaction conditions. To our delight, the results exceeded our expectations, and were somewhat better than those for the methacrylate. We found that this methodology was broadly applicable to a variety of acrylates, affording arylated products in synthetically valuable yields (Table 3). All of the substrates bearing either an ester group or an acid group formed the desired products. Generally, the reactions of substrates with more than two carbons of the ester bond afforded much better results than the methyl one (entries 3–5, Table 3). Excitingly, an extremely efficient reactions were observed in the case of 2c and 2e, products 3ac and 3ae being obtained in high yield after 1 h (97%, entries 3, 5). The substrates of acrylic acid also worked well and afforded products 3ab, 3ag in 81% and 92% yield, respectively (entries 2, 7).

Table 3 Phenylation of acrylate^a

Entry	2	Product 3	Yield (%)^b
a Diaryliodonium triflate salt (0.4 mmol) and methacrylate (2 equiv.) were mixed in solvent (1 mL) at r.t. before addition of Pd(OAc)2 (2% equiv.) and heating to 130 °C. b Isolated yield.
1	Methyl acrylate 2a	3a	99
2	Acrylic acid 2b	3ab	81
3	Ethyl acrylate 2c	3ac	97
4	Butyl acrylate 2d	3ad	96
5	2-Ethylhexyl acrylate 2e	3ae	97
6	2-Hydroxyethyl acrylate 2f	3af	85
7	Methacrylic acid 2g	3ag	92
8	Methyl methacrylate 2h	3ah	51

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It is interesting that the substrate of methyl methacrylate 2h exhibited a poor effect to yield product (entry 8). From GC-MS we found the major product was our expectation, but only 56% yield was afforded; the other side product was methyl-2-phenylacrylate which yields 23%, and the third one was cyclopropane product which yields 9% only. We hypothesize that the cyclopropane product was derived from the major product (Scheme 2). In order to prove our speculation, a reaction was carried out with allyl chloride which was easily transferred into cyclopropane. Rewardingly, the reaction furnished the desired product in 53% yield (Scheme 3).¹⁶

Scheme 2 Phenylation of methacrylate.

Scheme 3 Phenylation of allyl chloride.

Finally, in order to expand the use of the method, an additional attempt on styrene was developed without problem; diphenylethene was obtained in high yield (Scheme 4).

Scheme 4 Phenylation of styrene.

The plausible mechanism of this heck-type reaction is depicted in Scheme 5. At first, oxidative addition occurred of Pd(OAc)₂ with diaryliodonium salts in the reaction system to start the first catalytic cycle, which affording Pd-complex 4. The next step (4→5) is carbo-palladation followed by β-hydride elimination affording complex 6. Elimination of palladium hydride from intermediate 6 provides the product 3 and the Pd(OAc)₂, which is used for the next catalytic cycle.

Scheme 5 Possible mechanism of the arylation of acrylate reaction.

In conclusion, a fast and high regioselective Heck-type reaction has been developed with acrylate and diaryliodonium salts. Good to excellent yields are obtained without the use of ligand and base in this Palladium-Catalyzed system. Current studies are focused on further exploration of the substrate scope and synthetic utility of this catalyzed system.

Acknowledgements

Financial support from the Foundation of Chang Zhou University (No. ZMF1002130 & ZMF1002100), Changzhou Municipal Bureau of Science and Technology (No. KYZ1102100C) and the Priority Academic Program Development of Jiangsu Higher Education Institutions.

References

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16. 35% yield of 1, 2-Diphenylcyclopropane was obtained if the reaction temperature was 150 °C.

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Footnote

† Electronic supplementary information (ESI) available: Experimental details and the characterization data for all compounds. See DOI: 10.1039/c2ra20165h

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