Heptadecafluorooctanesulfonic acid catalyzed ring opening reactions of methylenecyclopropanes with aromatic amines, sulfonamides and alcohols in supercritical carbon dioxide

Abstract

The ring opening reactions of methylenecyclopropanes (MCPs) with ArNH₂, RSO₂NH₂ and alcohols can be carried out in scCO₂ in the presence of heptadecafluorooctanesulfonic acid which offer a way to synthesize homoallylic amines, sulfonamides and ethers in environmentally benign conditions.

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Green Context

Supercritical carbon dixide is now widely recognised as an environmentally benign solvent for chemical transformations and has now been proven in this context on an industrial scale. Many organic reactions require catalysis to enable the reaction to be carried out under moderate conditions or to give good product selectivity. Here a new catalyst–scCO₂ combination is described. Perfluorooctylsulfonic acid in scCO₂ is shown to be a good catalyst for the ring opening reactions of methyl cyclopropanes with various nucleophites.

JHC

Introduction

Chemistry has made a great contribution to the development of human society. The pollution and waste from chemical industries and laboratories, however, have deteriorated our environment. In order to achieve mutual societal, economic and environmental benefits, scientists have developed ‘green chemistry’ which is providing challenges and opportunities to those who practice chemistry in industry, education and research.^1–5 Presently the area of employing ‘novel’ solvent alternatives is receiving increasing attention. Among suitable alternatives such as ionic liquids,⁶ perfluorinated hydrocarbons⁷and water,⁸ supercritical carbon dioxide has been widely investigated and has been most attractive in green chemistry. Several of the advantages include that CO₂ is inexpensive, nonflammable, environmentally benign and readily separated from products.^9–11 Above the critical temperature and pressure, (T_c = 31 °C, P_c = 7.4 MPa) CO₂ has a gas-like viscosity and a liquid-like density. These moderate critical conditions allow for safe commercial and laboratory operating conditions. For example, in 1994 Noyori and coworkers,¹² reported one of the first synthetically useful homogeneous catalytic hydrogenetions catalyzed by an Ru(II) catalyst involving scCO₂ as both solvent and substrate. Tanko and coworkers,^10,11Wells and DeSimone,¹² Jessop et al.,¹³ and Beckman and coworkers¹⁴ reported radical reactions in scCO₂. In addition, many applications such as oxidation,¹⁵ hydroformylation,¹⁶ Diels–Alder cycloaddition,¹⁷ Mukaiyama aldol condensation¹⁸ and various metal-catalyzed¹⁹ reactions have been carried out in the presence of scCO₂.

Recently, we have reported that metal Lewis acid such as Sn(OTf)₂ or Yb(OTf)₃ catalyzed reactions of MCPs with ArNH₂ and alcohols in 1,2-dichloroethane (DCE).²⁰ However, is well known that halogenated solvents are environmentally hazardous materials. In addition, many metal catalysts are also pollution sources for the environment. In order to explore an environmentally benign condition for this process, we attempted to carry out this reaction in scCO₂ in the absence of metal catalyst. Herein, we wish to report the ring opening reactions of MCPs with aromatic amines, sulfonamides or alcohols catalyzed by the Brønsted acid R_fSO₃H in scCO₂ under mild conditions.

First of all, we chose various RSO₃H as Brønsted acid catalysts (10 mol%) to promote the reaction of diphenylmethylenecyclopropane 1a (0.45 mmol) with 3-(trifluoromethyl)aniline 2a (0.15 mmol) at 85 °C and 10 MPa in scCO₂. The results are listed in Table 1 (entry 1). The reaction proceeded smoothly to give two adducts: dialkylated product 3a (39%) and monoalkylated 4a (11%) in moderate yields in the presence of CF₃SO₃H (Table 1, entry 1). Using C₈F₁₇SO₃H as the catalyst under the same conditions the two adducts were obtained in very high yields (Table 1, entry 2).²¹ It should be noted that no reaction occurred when using p-toluenesulfonic acid as the Brønsted acid catalyst even with the addition of perfluorotoluene as a CO₂-philic additive (Table 1, entries 3 and 4). A long chain perfluorinated sulfonic acid should be used as a promoter for this novel ring opening reaction. This is because a long perfluorinated alkyl chain can allow the scCO₂ reaction system to become an effective homogenous phase. Viewing through the high pressure glass window placed in the scCO₂ reaction vessel, we confirmed that the C₈F₁₇SO₃H, 1a, and aniline are completely dissolved in scCO₂ to form a homogeneous system.

Table 1 The effects of various RSO₃H on the reactions of MCP 1a with 2a in scCO₂

			Yield^a (%)
Entry	RSO2H	Additive	3a	4a
a Isolated yields.
1	CF3SO3H	—	39	11
2	C8F17SO3H	—	52	47
3		—	—	—
4			—	—

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Further investigations were performed using various MCPs and ArNH₂ or RSO₂NH₂ to examine this reaction (Table 2). We chose different MCPs and RNH₂ or RSO₂NH₂ as substrates. As can be seen from Table 2, many of the reactions take place to give two adducts 3 and 4 in moderate to high yields catalyzed by C₈F₁₇SO₃H (10 mol%) in scCO₂. The ring opened products are obtained in higher yields when using aromatic amines which bear an electron-withdrawing group on the benzene ring.²⁰ For example, the reaction of 1a with 2b or 2c affords the corresponding adducts in high yields, respectively (Table 2, entries 1 and 2). For aniline 2d and aromatic amine 2e having an electron-donating group, the reactions also proceeded smoothly to give the two products in good yields (Table 2, entries 3 and 4). For MCP 1b having an electron-withdrawing group on the benzene ring and aliphatic MCP 1c, the reactions can take place as well. However, the ring opened products were obtained in lower yields (Table 2, entries 5 and 6). On the other hand, the yields can be improved dramatically using MCP 1d having an electron-donating group on the phenyl ring instead of aliphatic MCP 1c (Table 2, entry 7). Apart from aromatic amines, the reaction of 1a with various sulfonamides also can proceed smoothly to give 3 and 4 in the presence of C₈F₁₇SO₃H (10 mol%) in scCO₂. For example, the reactions of 1a with 2f and 2g give the two corresponding adducts 3i or 3j and 4i or 4j in high yields, respectively (Table 2, entries 8 and 9). However, using p-nitrobenzenesulfonamide 2h as a substrate to react with 1a under the same conditions led to no reaction owing to the insolubility of p-nitrobenzenesulfonamide 2h in scCO₂. Based on these results, we can conclude that C₈F₁₇SO₃H is an excellent Brønsted acid catalyst in scCO₂ and it is applicable to extensive ring opening reactions of MCPs with ArNH₂ or RSO₂NH₂.

Table 2 The reactions of MCPs with ArNH₂ or RSO₂NH₂ catalyzed by C₈F₁₇SO₃H (10 mol%) in scCO₂

					Yield^a (%)
Entry	MCP		ArNH2		3	4
a Isolated yield.
1		1a		2b	3b (65)	4b (21)
2		1a		2c	3c (95)
3		1a		2d	3d (42)	4d (18)
4		1a		2e	3e (37)	4e (20
5		1b		2a	3f (7)	4f (10)
6		1c		2a	3f (18)	4g (19)
7		1d		2a	3b (72)	4g (19)
8		1a		2f	3i (48)	4i (41)
9		1a	CH3SO2NH2	1g	3j (30)	4j (42)
10		1a		2h	—	—

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The ring opening reaction of MCPs (0.5 mmol) with ethanol (200 μL, 3.4 mmol) was also carried out in scCO₂ in the presence of C₈H₁₇SO₃H (15 mg, 10 mol%) to give the ring opened product 5a in very high yield (Table 3, entry 1). In general, it was found that the reactions proceed very well and the corresponding ring opened products 5 were obtained in excellent yields with complete conversions for various MCPs under the same conditions (Table 3). We believe that this is because the alcohols themselves can modify the physical properties of scCO₂ and subsequently enhance the solubilities of the reactants in scCO₂ and improve the reaction efficiency.

Table 3 The reactions of MCPs with alcohols catalyzed by C₈F₁₇SO₃H (10 mol%) in scCO₂

				Conv.^a (%)	Yield^a (%)
Entry	MCP		ROH	MCP	5
a Isolated yield.
1		1a	EtOH	100	5a (95)
2		1a	^iPrOH	100	5b (93)
3		1a	^iBuOH	100	5c (92)
4		1b	EtOH	100	5d (97)
5		1c	EtOH	100	5c (97)
6		1d	EtOH	100	5f (98)

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It should be emphasized here that the CO₂-philic catalyst C₈F₁₇SO₃H can be recovered from the reaction mixture by extraction with toluene. The catalyst C₈F₁₇SO₃H is insoluble in toluene whereas the products are soluble in toluene. The extracts can be subjected to column chromatography and the catalyst residue can be reused for the next reaction as a catalyst.

A plausible mechanism for the ring-opening reactions of MCPs with ArNH₂, NH₂SO₂R and ROH is shown in Scheme 1. The MCPs first give cation 6 which immediately rearranges to the ring-opened cation 7²¹ in the presence of Brønsted acid C₈F₁₇SO₃H. The subsequent nucleophilic attack of RNH₂, NH₂SO₂R or ROH to 7 affords the adduct 8. The final product is formed after proton elimination.

Scheme 1

In conclusion, serious environmental problems necessitate our rethinking of strategies toward organic synthesis. The ideal reaction would incorporate all of the atoms of the reactions. Major benefits that derive from atom-economic processes include more effective use of limited raw materials and decreased emissions and waste disposal. In this article, we have disclosed an atom-economical reaction of MCPs applied to scCO₂ catalyzed by the Brønsted acid C₈F₁₇SO₃H.²² This reaction offers an access to the formation of homoallylic amines, sulfonamides and ethers in environmentally benign conditions. By comparison of the reaction procedure in scCO₂ reported in this paper with those reported in previous papers,^20a it is very clear that when the reaction is carried out in scCO₂ by means of a CO₂-philic catalyst C₈F₁₇SO₃H, the use of the hazardous solvent 1,2-dichloroethane can be avoided and the very similar yields can be achieved. Especially, for the reactions of MCPs with alcohols in scCO₂, the reactions proceed completely and no chromatography is required. We also hope that this type of reaction is conducive to the development of green chemistry as well as new organic syntheses.

Experimental

Typical reaction procedure: 1a (93 mg, 0.45 mmol), 2a (24 mg, 0.15 mmol) and C₈F₁₇SO₃H (7.5 mg, 10 mol%)²² were placed in the scCO₂ reactor. The reaction proceeded at 85 °C at 10 MPa for 24 h. The residue was purified by flash chromatography (SiO₂) using EtOAc–hexane (1∶100) or CH₂Cl₂–hexane (1∶8) as the eluent to yield 3a (45 mg, 52%) as a colorless solid and 4a (26 mg, 47%) as an oil.

3a: mp 118–120 °C, IR (neat): ν 3052, 3028, 2925, 1609, 1495, 1454, 1322 cm⁻¹; ¹H NMR (300 MHz, CDCl₃, TMS), δ 2.30–2.38 (m, 4H, CH₂), 3.29 (t, 4H, J = 7.6 Hz, CH₂), 6.05 (t, 2H, J = 7.5 Hz, =CH), 6.40–6.43 (m, 1H, Ar), 6.69 (s, 1H, Ar), 6.81 (d, 1H, J = 8.0 Hz, Ar), 7.07–7.39 (m, 21H, Ar); MS (EI): m/z 573 (M⁺, 0.3), 380 (54), 167 (100), 129 (61), 91 (53%); Anal. Calc. for C₃₉H₃₄F₃N (%): C, 81.68; H, 5.93; N, 2.44. Found: C, 81.72; H, 6.09; N, 2.41.

4a: IR (neat): ν 3421, 3054, 2986, 1614, 1495, 1449, 1421, 1265 cm⁻¹; ¹H NMR (300 MHz, CDCl₃, TMS), δ 2.43–2.50 (m, 2H, CH₂), 3.24 (t, 2H, J = 6.8 Hz, CH₂), 3.81 (s, 1H, NH), 6.12 (t, 1H, J = 7.5 Hz, =CH), 6.64–6.67 (m, 1H, Ar), 6.74 (s, 1H, Ar), 6.90–6.92 (d, 1H, J = 7.5 Hz, Ar), 7.10–7.41 (m, 11H, Ar); ¹³C NMR (75 MHz, CDCl₃, TMS), δ 29.81, 43.89, 109.79, 111.49, 113.88, 123.75 (q, J = 271.4 Hz), 125.80, 127.27, 127.39, 127.45, 128.37, 128.58, 129.80, 129.94, 130.060 (q, J = 31.6 Hz), 139.87, 143.54, 145.98, 149.83; MS (EI): m/z 367 (M⁺, 1.8), 174 (100), 145 (9), 91 (6), 77 (3%); HRMS (EI): Calc. for C₂₃H₂₀F₃N 367.1548 (M⁺), Found: 367.1526.

The products 3i and 4i were isolated by column chromatography as colorless oily compounds (eluent: EtOAc–hexane (1∶10)).

3i: IR (neat): ν 3055, 2986, 1653, 1598, 1494, 1266 cm⁻¹; ¹H NMR (300 MHz, CDCl₃, TMS), δ 2.16–2.24 (m, 4H, CH₂), 2.35 (s, 3H, CH₃), 3.13 (t, 4H, J = 7.5 Hz, CH₂), 5.92 (t, 2H, J = 7.3 Hz, =CH), 7.03–7.59 (m, 24H, Ar); ¹³C NMR (75 MHz, CDCl₃, TMS), δ 21.78, 28.75, 47.38, 125.15, 127.18, 127.59, 128.36, 128.42, 128.58, 128.72, 129.87, 129.97, 137.38, 139.89, 142.33, 143.21, 144.18; MS (EI): m/z 583 (M⁺, 2.0), 390 (47), 193 (17), 155 (8), 167 (100), 91 (41%); HRMS (EI): Calc. for C₂₄H₂₄NSO₂ 391.1606 (M⁺ − C₁₅H₁₃⁺) (M⁺ = C₃₉H₅₇NSO₂). Found: 391.1570.

4i: IR (neat): ν 3283, 3056, 2928, 1638, 1598, 1494 cm⁻¹; ¹H NMR (300 MHz, CDCl₃, TMS), δ 2.24–2.31 (m, 2H, CH₂), 2.42 (s, 3H, CH₃), 3.02–3.08 (m, 2H, CH₂), 4.40 (t, 1H, J = 6.0 Hz, NH), 5.90 (t, 1H, J = 7.5 Hz, =CH), 7.08–7.71 (m, 14H, Ar); ¹³C NMR (75 MHz, CDCl₃, TMS), δ 21.79, 30.07, 43.29, 124.81, 127.25, 127.31, 127.32, 127.46, 127.52, 128.37, 128.62, 129.95, 137.02, 139.65, 142.21, 143.61, 144.82; MS (EI): m/z 193 (M⁺ − C₈H₁₀NSO₂, 44.0), 184 (16), 155 (18), 91 (28), 84 (100%); HRMS (EI): Calc. for C₂₃H₂₃NSO₂ 377.1449 (M⁺), Found: 377.1432.

The products 3j and 4j were isolated by column chromatography as colorless oily compounds (eluent: EtOAc–hexane (1∶4)).

3j: IR (neat): ν 3038, 2928, 1654, 1599, 1494, 1445 cm⁻¹; ¹H NMR (300 MHz, CDCl₃, TMS), δ 2.27–2.34 (m, 4H, CH₂), 2.69 (s, 3H, CH₃), 3.18 (t, 4H, J = 7.5 Hz, CH₂), 5.99 (t, 2H, J = 7.6 Hz, =CH), 7.11–7.39 (m, 20H, Ar); ¹³C NMR (75 MHz, CDCl₃, TMS), δ 28.97, 39.16, 47.05, 124.91, 127.44, 127.52, 127.55, 128.44, 128.61, 129.90, 139.81, 142.20, 144.42; MS (EI): m/z 507 (M⁺, 1.3), 314 (6), 193 (24), 167 (38), 105 (100), 91 (21), 84 (86), 77 (61%); HRMS (EI): Calc. for C₃₃H₃₃NSO₂ 507.2232 (M⁺), Found: 507.2214.

4j: IR (neat): ν 3291, 3028, 2939, 1653, 1599, 1494, 1444 cm⁻¹; ¹H NMR (300 MHz, CDCl₃, TMS), δ 2.35–2.42 (m, 2H, CH₂), 2.83 (s, 3H, CH₃), 3.17–3.24 (m, 2H, CH₂), 4.64 (t, 1H, J = 5.8 Hz, NH), 6.04 (t, 1H, J = 7.3 Hz, =CH), 7.14–7.41 (m, 10H, Ar); ¹³C NMR (75 MHz, CDCl₃, TMS), δ 30.65, 40.47, 43.34, 124.78, 127.50, 127.55, 127.62, 128.56, 128.67, 130.32, 139.74, 142.19, 145.0; MS (EI): m/z 301 (M⁺, 13.9), 206 (57), 193 (100), 165 (17), 115 (56), 91 (19%); HRMS (EI): Calc. for C₁₇H₁₉NSO₂ 301.1136 (M⁺), Found: 301.1143.

Acknowledgements

We thank the State Key Project of Basic Research (Project 973) (No. G2000048007), Shanghai Municipal Committee of Science and Technology, and the National Natural Science Foundation of China (20025206 and 20272069) for financial support.

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