Gold-catalyzed reaction of oxabicyclic alkenes with electron-deficient terminal alkynes to produce acrylate derivatives

Abstract

Oxabicyclic alkenes can react with electron-deficient terminal alkynes in the presence of a gold catalyst under mild conditions, affording the corresponding addition products in moderate yields. When using alkynyl esters as substrates, the (Z)-acrylate derivatives are obtained. Using but-3-yn-2-one (ethynyl ketone) as a substrate, the corresponding addition product is obtained with (E)-configuration. The proposed mechanism of these reactions is also discussed.

Introduction

Oxabicyclic alkenes are common intermediates in organic synthesis since these compounds can be easily prepared and have a high reactivity for further transformations [1–8]. For example, they are often used to construct substituted tetrahydronaphthalene skeletons in the presence of metal catalysts such as Pd [9–10], Ir [11–15], Rh [16–21] and Cu [22]. However, their reactivity in the presence of gold catalysts has been rarely reported [23]. It is well known that gold catalysts have different catalytic abilities compared with other transition metals [24]. Moreover, gold-catalyzed chemical transformations have made significant progress during the last 5 years [25–56]. Many gold complexes have been proved to be efficient catalysts in C–C [33–48] bond or C–X (X = heteroatom) [49–56] bond forming reactions. Our group has a long-standing interest in gold-catalyzed C–C [57–61] or C–X bond [62–67] formation reactions. So far, we have reported a variety of gold-catalyzed intramolecular rearrangements with highly strained small rings for C–C or C–X bond formations [57–59,62–68]. Based on these previous findings, we envisaged that oxabicyclic alkenes could also react with electron-deficient alkynes in the presence of gold catalysts to generate a new C–C or C–O bond thereby releasing the oxabicyclic alkenes of their ring strain. In this paper, we report the formation of (Z)-acrylate derivatives in the gold catalyzed intermolecular reaction of oxabicyclic alkenes with electron-deficient terminal alkynes under mild conditions [69–76] (Scheme 1).

Scheme 1.

Gold-catalyzed reactions of oxabicyclic alkenes with electron-deficient terminal alkynes.

Results and Discussion

To generate a new C–O bond in the reaction of oxabicyclic alkene 1a with electron-deficient terminal alkyne 2a, we first used PPh₃AuCl as a catalyst, AgSbF₆ as an additive, and toluene as a solvent to examine the reaction outcome. Acrylate derivative 3a was formed with (Z)-configuration in 11% yield (Table 1, entry 1). In this reaction, naphthalen-1-ol was also obtained with 44% yield as the major product. The usage of IPrAuCl, dppb(AuCl)₂, (p-FC₆H₄)₃PAuCl, DPE-phos(AuCl)₂, Me₃PAuCl and Cy₃PAuCl as gold catalysts did not significantly improve the yield of 3a (Table 1, entries 2–7). In these cases, the maximum yield of 3a was 34% when the gold complex Cy₃PAuCl coordinated by an electron-rich phosphine ligand was used as a catalyst (Table 1, entry 7). In order to further improve the yield of 3a, we employed gold complex 6 (Figure 1) coordinated by a sterically bulky and electron-rich biaryl phosphine-type ligand as a catalyst, affording 3a in 40% yield (Table 1, entry 8). In the absence of AgSbF₆, no reaction occurred (Table 1, entry 9). The usage of AgSbF₆ as a catalyst produced naphthalen-1-ol (5) as the major product (Table 1, entry 10). Next, we further screened the reaction conditions with gold complex 6 as a catalyst. When using AgOTs or CF₃CO₂Ag as a silver additive, we did not obtain any of the desired products (Table 1, entries 12 and 13), whereas the usage of AgNTf₂ as a silver additive afforded 3a in 32% yield (Table 1, entry 11). AgOTf was not an effective silver additive, giving 3a in 20% yield (Table 1, entry 14). Utilization of the already prepared electrophilic cationic phosphinogold(I) complexes XPhosAuNTf₂ and XPhosAu(MeCN)SbF₆ as gold catalysts slightly increased the yield of 3a to 33% and 45% yields, respectively (Table 1, entries 15 and 16). The examination of solvent effects revealed that toluene was the best solvent (Table 1, entries 17–22). Adding 4 Å MS into the reaction system, 3a was obtained in only 10% yield (Table 1, entry 23).

Table 1.

Initial screening of the reaction conditions.

Entrya	Au cat.	Ag salt	Solvent	Yieldb (%) 3a
1c	Ph3PAuCl	AgSbF6	toluene	11
2	IPrAuCl	AgSbF6	toluene	19
3	dppb(AuCl)2	AgSbF6	toluene	trace
4	(p-FC6H4)3PAuCl	AgSbF6	toluene	26
5	DPE-phos(AuCl)2	AgSbF6	toluene	N.R.
6	Me3PAuCl	AgSbF6	toluene	N.R.
7	Cy3PAuCl	AgSbF6	toluene	34
8	6	AgSbF6	toluene	40
9	6	–	toluene	N.R.
10c	None	AgSbF6	toluene	trace
11	6	AgNTf2	toluene	32
12	6	AgOTs	toluene	N.R.
13	6	CF3COOAg	toluene	N.R.
14	6	AgOTf	toluene	20
15	XPhosAuNTf2	–	toluene	33
16	XPhosAu(MeCN)SbF6	–	toluene	45
17	XPhosAu(MeCN)SbF6	–	CH3CN	trace
18	XPhosAu(MeCN)SbF6	–	CH3NO2	N.R.
19	XPhosAu(MeCN)SbF6	–	Et2O	N.R.
20	XPhosAu(MeCN)SbF6	–	THF	complex
21	XPhosAu(MeCN)SbF6	–	DCM	25
22	XPhosAu(MeCN)SbF6	–	DCE	28
23d	XPhosAu(MeCN)SbF6	–	toluene	10

^aThe reaction was carried out on a 0.2 mmol scale in solvent (1.0 mL). The ratio of 1a/2a was 1:2. ^bYield determined by ¹H NMR by using 1-iodo-2-methoxybenzene (4) as an internal standard. ^cNaphthalen-1-ol (5) was the major product. ^d50 mg of 4 Å MS was added to the reaction system.

Figure 1.

Gold complexes used in this reaction.

Since the yield of 3a was still low, we next tried to improve the yield of 3a by deploying different ligands, Ag salts, solvents and temperature. The results are summarized in Table 2. At first, we examined many other gold(I) phosphane complexes with dialkylbiarylphosphane ligands (Figure 1) by using AgSbF₆ as an additive and toluene as a solvent. No reaction occurred when gold(I) phosphane complexes 8–10 (Figure 1) were used as catalysts under identical conditions (Table 2, entries 2–4). Furthermore, the usage of gold(I) phosphane complexes 7, 11, 13 and 14 (Figure 1) as catalysts gave 3a in 10–29% yields (Table 2, entries 1, 5, 7 and 8). Gold complex 12 (Figure 1) with an electron-rich biphenylphosphine ligand was identified as the best catalyst, giving 3a in 67% yield (Table 2, entry 6). We attempted to further optimize the reaction conditions by using SPhosAuCl 12 as a catalyst and AgNTf₂ or AgSbF₆ as an additive and obtained 3a in 66% and 67% yields, respectively (Table 2, entries 6 and 9). However, the use of AgOTf or AgBF₄ as an additive afforded 3a in 37% and 11% yields, respectively (Table 2, entries 10 and 11). Employment of the prepared electrophilic cationic phosphinogold(I) complex SPhosAu(MeCN)SbF₆ as a catalyst gave 3a in 78% NMR based yield and 67% isolated yield (Table 2, entry 12). The phosphinogold(I) complex SPhosAuNTf₂ produced 3a in 53% yield under the standard conditions (Table 2, entry 13). The examination of solvent effects disclosed that toluene was the best solvent (Table 2, entries 14–16). Either increasing or decreasing the reaction temperature did not further improve the reaction outcome (Table 2, entries 17–20). Careful screening of the reaction conditions led to the conclusion that the reaction should be carried out in toluene at room temperature with SPhosAu(MeCN)SbF₆ as the catalyst (Table 2, entry 12).

Table 2.

Further screening of the reaction conditions.

entrya	Au cat.	Ag salt	solvent	T (°C)	Yieldb (%) 3a
1c	7	AgSbF6	toluene	rt	11
2	8	AgSbF6	toluene	rt	N.R.
3	9	AgSbF6	toluene	rt	trace
4	10	AgSbF6	toluene	rt	N.R.
5	11	AgSbF6	toluene	rt	10
6	12	AgSbF6	toluene	rt	67
7	13	AgSbF6	toluene	rt	20
8	14	AgSbF6	toluene	rt	29
9	12	AgNTf2	toluene	rt	66 (59)c
10	12	AgOTf	toluene	rt	37
11	12	AgBF4	toluene	rt	11
12	SPhosAu(MeCN)SbF6	–	toluene	rt	78 (67)c
13	SPhosAuNTf2	–	toluene	rt	53
14	SPhosAu(MeCN)SbF6	–	DCM	rt	49
15	SPhosAu(MeCN)SbF6	–	DCE	rt	55
16	SPhosAu(MeCN)SbF6	–	CHCl3	rt	45
17d	SPhosAu(MeCN)SbF6	–	toluene	0	50
18	SPhosAu(MeCN)SbF6	–	toluene	40	45
19	SPhosAu(MeCN)SbF6	–	toluene	10	59
20	SPhosAu(MeCN)SbF6	–	toluene	30	70

^aThe reaction was carried out on a 0.2 mmol scale in solvent (1.0 mL) and the ratio of 1a/2a was 1/2. ^bYield determined by ¹H NMR by using 1-iodo-2-methoxybenzene 4 as an internal standard. ^cIsolated yield in parentheses.

Having identified the optimal conditions, we next examined the substrate scope of this reaction. We found that only the usage of ethynylbenzene and dimethyl but-2-ynedioate as substrates did not afford any of the desired products (Table 3, entries 6 and 9). In all other cases, the reactions proceeded smoothly to give the desired products in moderate to good yields (Table 2, entries 1–5, 7 and 8). The introduction of electron-donating substituents on the benzene ring impaired the reaction outcome (Table 3, entries 1 and 7). Increasing the steric hindrance of the ester group improved the yields of 3 (Table 3, entries 4 and 5). The usage of but-3-yne-2-one (terminal alkyne ketone) 2i as a substrate gave the corresponding 3i with (E)-configuration in 48% yield (Scheme 2).

Table 3.

Substrate scope of the reactions with SPhosAu(MeCN)SbF₆ as a catalyst.

entrya	R1	R2, R3	Yieldb (%) 3
1	Me	COOMe, H	3b, 42
2	F	COOMe, H	3c, 66
3	Br	COOMe, H	3d, 76
4	H	COOEt, H	3e, 54
5	H	COOt-Bu, H	3f, 84
6	H	Ph, H	trace
7	Me	COOt-Bu, H	3g, 58
8	Br	COOt-Bu, H	3h, 72
9	H	COOMe, COOMe	N.R.

^aThe reaction was carried out on a 0.2 mmol scale in solvent (1.0 mL). The ratio of 1/2 was 1/2. ^bIsolated yield.

Scheme 2.

The reaction with terminal alkyne 2i as a substrate.

Since naphthalene-1-ol (5) was obtained in this reaction, we used naphthalene-1-ol (5) as a substrate and carried out the reaction under the optimal conditions to clarify whether the reaction proceeded through naphthalene-1-ol. The formation of 3a could not be observed, suggesting that naphthalene-1-ol is not the intermediate in this reaction (Scheme 3).

Scheme 3.

The reaction with naphthalen-1-ol (5) as a substrate.

Based on the previously established mechanistic model [23,77], we propose the following pathway for the formation of acrylate derivatives 3a and 3i (Scheme 4). In the presence of cationic phosphinogold(I) complex, a cationic intermediate A is formed by a regioselective opening of the oxygen bridge in substrate 1a. Intermediate A releases a proton to afford intermediate B. Intermediate B attacks methyl propiolate, which is activated by the gold catalyst, to generate gold vinyl complex C. In intermediate C, the ester group and the naphthalene ring are on the same side, yielding the final product 3a with (Z)-configuration via protodeauration. The alkyne ketone 3i is more electron-deficient and more reactive than methyl propiolate and it is more difficult to coordinate by the gold complex. Therefore, with alkyne ketone 2i as a substrate, intermediate B attacks non-coordinated alkyne ketone 2i in a cis-addition manner to generate gold vinyl complex D. In intermediate D, the carbonyl group and the naphthalene ring are on opposite sides, affording product 3i with (E)-configuration by protodeauration.

Scheme 4.

The proposed mechanism for Au(I)-catalyzed reaction.

Conclusion

In summary, we have developed a novel method to synthesize acrylate derivatives from oxabicyclic alkenes and electron-deficient terminal alkynes in toluene in moderate to good yields in the presence of the gold catalyst SPhosAu(MeCN)SbF₆ under mild conditions. Efforts are in progress to elucidate the mechanistic details of this reaction and to disclose its scope and limitations.

Experimental

General remarks

Dichloromethane was freshly distilled from calcium hydride; THF and toluene were distilled from sodium under an argon atmosphere. ¹H NMR, ¹³C NMR and ¹⁹F NMR spectra were recorded on a Bruker AM-400 spectrometer. Infrared spectra were recorded on a Perkin-Elmer PE-983 spectrometer with absorption in cm⁻¹. Flash column chromatography was performed by using 300–400 mesh silica gel. For thin-layer chromatography (TLC), silica gel plates (Huanghai GF254) were used. Mass spectra were recorded by ESI, and HRMS were measured on a HP-5989 instrument.

General procedure for the reaction catalyzed by Au(I) catalysts

Into an oven-dried reaction flask under Ar gas protection was added oxabicyclic alkene (0.2 mmol), Au catalyst (0.001 mmol), methyl propiolate (0.4 mmol) and toluene (1.0 mL). The reaction mixture was stirred at room temperature normally overnight. After complete consumption of the starting materials, monitored by TLC, the solvent was removed under reduced pressure and the residue was purified by flash column chromatography.

Supporting Information

File 1

Experimental procedures and characterization data of compounds.

This article is part of the Thematic Series "Gold catalysis for organic synthesis II".