Synthesis and characterization of a cyclic vinylpalladium(II) complex: vinylpalladium species as the possible intermediate in the catalytic direct olefination reaction of enamide

Abstract

A six-membered cyclic vinylpalladium complex was synthesized via alkenyl C–H bond direct palladation, which was probed in detail by ¹H NMR spectroscopy and characterized by X-ray analysis. The cyclic vinylpalladium complex was propounded to be the intermediate during the olefination reaction of enamides. An efficient catalytic system for oxidative cross-coupling reaction of enamides with electron-deficient olefins catalyzed by palladium(II) acetate and 1 atm oxygen as sole oxidant was developed. The corresponding products were obtained in moderate to good yields under mild conditions.

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Introduction

During the last few decades, palladium-catalyzed coupling reaction has grown to become an attractive and powerful method for the formation of new C–C and C–heteroatom bonds.¹ Particularly, the atom economical merits conferred upon direct C–H bond functionalization catalyzed by palladium catalyst emerged in recent years, spurred intense development in this arena.² Among the various direct C–H bond functionalization examples, chelation-assisted sp² (aryl) and sp³ C–H bonds activation is one of the most well-studied (eqn (1)).^2l,3 Evidences of palladacyclic intermediate generated during coupling process have been disclosed.⁴ On the other hand, the formation of analogous vinylpalladium complex via alkenyl C–H bond direct functionalization lies in obscurity due to lack of detailed investigation.^4m,5 Recently our group presented a direct arylation of cyclic enamides at their β-position with aryl boronic acids or aryl silanes by using palladium(II) acetate as catalyst.⁶ A cyclic vinylpalladium intermediate was invoked in the catalytic cycle proposed for the coupling reaction (eqn (2)), although we were unfortunately not able to conclusively establish the vinylpalladium species at that moment. In this communication, we describe the independent synthesis, characterization, and reactivity studies of the vinylpalladium complex that is propounded to be the coupling intermediate in the above-said reaction.

Results and discussion

Initial studies and reaction optimization

A mixture of N-[1-(naphthalen-2-yl)vinyl]acetamide (1k) and palladium(II) acetate (1 equiv) in DMSO-d₆ was stirred in a round-bottom flask under an atmosphere of air for 12 h at 25 °C (or 10 min at 80 °C). Subsequent analysis by ¹H NMR revealed that the signal of one of the terminal alkenyl protons disappeared from the spectrum completely.⁷ The new complex was isolated as a solid via deposition with dry diethyl ether. A crystal suitable for X-ray analysis was prepared by recrystallization and a six-membered vinylpalladium cyclic intermediate (1k′) was unveiled. Next tert-butyl acrylate was introduced into the vinylpalladium solution and the mixture was heated at 80 °C for another 16 h. The desired product 3k was observed and isolated in 53% yield. (Scheme 1)⁸

Scheme 1 Formation of cyclic vinylpalladium complex and its reactivity study with tert-butyl acrylate.

Inspired by the observed results, our efforts were focused on the optimization of the reaction conditions and developing an efficient catalytic system for olefination of enamide. To this end, the reaction of N-(3H-inden-1-yl) enamide 1a and tert-butyl acrylate (2a) was screened under various reaction conditions using different palladium catalysts and oxidants. The results are shown in Table 1. When the reaction was carried out under the previously reported conditions, the desired product was obtained in 50% yield (Table 1, entry 1).^5b The reaction cannot proceed in DMSO solvent, wherein the starting material was recovered after 24 h (Table 1, entry 2). It was found that using acetic acid alone as solvent, with 10 mol% of palladium(II) acetate as catalyst, oxygen as the sole oxidant and with 1 equivalent of sodium acetate as additive under 80 °C, the desired product can be obtained in 80% yield (Table 1, entry 3). However, decreasing the catalyst loading to 5 mol% will lower the yield dramatically (Table 1, entry 4), while increasing the amount of NaOAc has no significant effect (Table 1, entry 5). Other palladium catalysts were also investigated in this reaction and Pd(TFA)₂, PdCl₂, Pd(CH₃)₂Cl₂ and Pd(PhCN)₂Cl₂ were all found to give the product in moderate yields (Table 1, entries 6, 8, 9 and 10); but no desired product was formed when Pd(PPh₃)₂Cl₂ was used as catalyst (Table 1, entry 7). We also observed that only 37% yield was achieved when the ratio of 1a and 2a was changed to 1 : 4, while no desired product was obtained in the absence of palladium catalyst. The absence of oxygen as the oxidant resulted in the rapid decomposition of the substrate and therefore trace amount of product formation (Table 1, entry 12).

Table 1 Direct cross-coupling reaction of 1a with tert-butyl acrylate.^a

Entry	Oxidant	Pd(II)/mol (%)	Solvent	Yield^b(%)
a Reaction conditions unless otherwise specified: 1a (2 equiv), 2a (1 equiv, 0.4 M) and Pd(II) (0.1equiv), oxygen (1 atm) at 80 °C in acetic acid. b Isolated yields. c without NaOAc as additive. d No reaction. e 4 equivalent of NaOAc was used. f The starting material decomposed. g Mole ratio 1a:2a = 1 : 4. HOAc: acetic acid; TFA: trifluoroacetate.
1^c	Cu(OAc)2 + O2	Pd(OAc)2/10	DMSO/AcOH (1 : 1)	50
2^d	O2	Pd(OAc)2/10	DMSO	-
3	O2	Pd(OAc)2/10	HOAc	80
4	O2	Pd(OAc)2/5	HOAc	55
5^e	O2	Pd(OAc)2/10	HOAc	81
6	O2	Pd(TFA)2/10	HOAc	58
7^f	O2	Pd(PPh3)2Cl2/10	HOAc	-
8	O2	PdCl2/10	HOAc	35
9	O2	Pd(PhCN)2Cl2/10	HOAc	73
10	O2	Pd(CH3)2Cl2/10	HOAc	51
11^g	O2	Pd(OAc)2/10	HOAc	37
12	—	Pd(OAc)2/10	HOAc	<10

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In addition to tert-butyl acrylate, different electron-deficient coupling partners were tested in this cross-coupling reaction using 10 mol% loading of Pd(OAc)₂. methyl acrylate, ethyl acrylate, n-butyl acrylate and phenyl acrylate all furnished the desired product in high yields. As for acrylonitrile, only 12% yield was obtained, while styrene afforded the corresponding desired product in 55% yield. Therefore tert-butyl acrylate was the best coupling partner in our system.⁹

Substrate scope

Next, a variety of enamide derivatives were screened with tert-butyl acrylate using 10 mol% Pd(OAc)₂ catalyst. The results are shown in Table 2. It can be seen that both cyclic enamides (Table 2, 3a–3i) and acyclic enamides (Table 2, 3j, 3k) can all generate the products in moderate to high yields. The effect of the substituents on the benzene ring was not obvious; an electron-donating group was well-tolerated (Table 2, 3c), while moderately electron-withdrawing groups slightly decreased the product yield (Table 2, 3g–3i). The presence of methyl group on the acyclic ring diminished the yield in acetic acid solvent (Table 2, 3b, 3h). Notably, halide substituents were tolerated, which is very useful for further transformation (Table 2, 3g–3i). The choice of solvent was found to be crucial for the success of this coupling reaction. For indanone- and tetralone-derived enamides, the desired products can be obtained in acetic acid solvent (Table 2, 3a–3e). On the other hand, 4-chromanone-derived enamide 1f completely decomposed in acetic acid, while a high yield of 76% can be achieved in DMSO. Substrates 1g and 1h can furnish the desired product in moderate yields either in acetic acid or in DMSO. Acyclic substrates were only compatible in DMSO, providing the corresponding products in moderate yields (Table 2, 3j, 3k).

Table 2 Direct cross-coupling of various enamides with tert-butyl acrylate catalyzed by Pd(OAc)₂

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Proposed mechanism

Based on the X-ray structure, a plausible mechanism is proposed in Scheme 2. The alkenyl C–H bond of enamide 1 is firstly activated by the Pd(II) complex to form the six-membered palladacycle intermediate 2 (a possible σ–C(sp³)–Pd intermediate 2′ cannot be ruled out in this step). Next, coordination of the acrylate to Pd followed by migratory insertion gives intermediate 5. The desired product 6 is finally obtained after β-hydride elimination. The Pd(0) that was generated is then recycled back to Pd²⁺ by the oxidant.

Scheme 2 Proposed catalytic cycle for direct cross-coupling reaction of olefins.

Conclusions

In summary, a mechanism of direct coupling reaction between enamide and acrylate was well-studied by ¹H NMR spectroscopy and X-ray analysis. A vinylpalladium cyclic complex was isolated and proved to be the possible coupling intermediate with acrylate. We also have developed the first successful catalytic olefination reaction of enamides with electron-poor alkenes catalyzed by Pd(OAc)₂ and 1 atm oxygen as sole oxidant. The corresponding products were obtained in moderate to high yields and with excellent regioselectivities. The use of oxygen as sole oxidant makes the method potentially appealing for the chemical industry in view of its environmental and economical advantages. This novel method produces highly functionalized, versatile compounds which can be converted to a wide variety of building blocks and complex molecules. Work along this line and detailed mechanistic studies are in progress.

Acknowledgements

We gratefully acknowledge the Nanyang Technological University and Singapore Ministry of Education Academic Research Fund Tier 2 (No. T207B1220RS) for the funding of this research. We thank Prof. K. Narasaka for his helpful discussions.

References

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7. See the detailed results in the supporting information.
8. The structure of 1k′ was identified by spectroscopic and X-ray crystallographic analysis. See the detailed results in the supporting information. CCDC 806122 (1k′) contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre viahttp://www.ccdc.cam.ac.uk./data_request/cif.
9. See Table 1 in the supporting information.

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Footnote

† Electronic supplementary information (ESI) available: Detailed experimental procedures and analytical data. CCDC reference numbers 806122–806123. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c1sc00262g

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