Mn(III)-mediated regioselective synthesis of (E)-vinyl sulfones from sodium sulfinates and nitro-olefins

Abstract

An efficient Mn(III)-mediated coupling reaction of sodium sulfinates with nitro-olefins has been developed, this reaction proceeds in mild and open-flask conditions to afford (E)-vinyl sulfones with high regioselectivities and in good to excellent yields. The control experiments revealed that this transformation could involve a radical process.

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Vinyl sulfones are important structural synthons in synthetic organic chemistry, which are good Michael acceptors and also easy to participate in cycloaddition reactions.¹ Nowadays, its derivatives have also shown wide ranging biological and pharmacological activities.² So far, many conventional approaches for the synthesis of vinyl sulfones have been established, including the oxidation of the corresponding sulfides,³ β-elimination of selenosulfones and halosulfones,⁴ and addition of sulfonyl chloride to alkynes/alkenes.⁵ In recent years, sodium sulfinate and sulfonyl hydrazine have been utilized to react with different partners for synthesis of vinyl sulfones, probably due to their good stability and ease of handling.⁶ The direct addition of sodium sulfinates to terminal aromatic alkynes⁷ and propiolic acid⁸ in the presence of Cu or Pd catalysts could give vinyl sulfones with high yields and regioselectivities. At the same time, alkenes are also good reaction partners to produce vinyl sulfones via oxidative coupling reactions with sodium sulfinates (Scheme 1).⁹ For instance, Nair's group reported one-pot synthesis of vinyl sulfones via CAN-mediated reaction of aryl sulfinates and alkenes.^9a Lately, KI/PhI(OAc)₂ (ref. 9b), KI/NaIO₄,^9c KI/TBHP^9d together with stoichiometric I₂ (ref. 9e) and other methods^9k–m have also been developed by different groups. The cinnamic acids can undergo decarboxylation in many reaction systems.¹⁰ Guo's group designed a copper-catalyzed aerobic oxidative decarboxylative sulfonylation reaction to synthesize vinyl sulfones by using cinnamic acids and sodium sulfinates as the starting materials.^10c Interestingly, Jiang and co-workers revealed a transition metal-free base-promoted variant, which made this transformation greener.^10d Nitro-olefins are relatively stable, simple to be obtained by Henry reaction from aldehyde and nitromethane, which have been widely used to synthesize useful organic molecules. In some cases, the nitro-olefins are equivalent to alkyne synthon by the elimination of HNO₂ or an oxidative dehydrogenation process. For example, nitro-olefins are good partners for the synthesis of NH-1,2,3-triazoles and NO₂-substituted 1,2,3-triazoles.¹¹

Scheme 1 Synthesis of vinyl sulfones from sodium sulfinates and alkenes.

In fact, Yadav's group reported a silver-catalyzed coupling reaction of nitro-olefins and sodium sulfinates in the presence of oxidant and under nitrogen atmosphere.¹² Encouraged by this work, we wanted to develop other methods, especially cheaper metal salts and simpler operation to make this transformation more applicable. Herein, we reported an efficient synthesis of (E)-vinyl sulfones by Mn(III)-mediated coupling reaction of nitro-olefins with sodium sulfinates under air.

Our studies began by examining the reaction between nitro-olefin (1a) and sodium benzenesulfinate (2a) in the presence of a stoichiomertic I₂ in DMF at room temperature under air (Table 1, entry 1), the corresponding product 3a was not observed at all, and KI/TBHP system gave the same result too (entry 2). However, TBHP, DTBP and K₂S₂O₈ could promote this reaction despite low yields (entries 3–5). Then, other metal salts oxidants such as Fe(NO₃)₃, FeCl₃, Mn(OAc)₃, and CuSO₄ were tested, Mn(OAc)₃ showed superior reactivity towards this coupling reaction and the yield of 3a increased to 38% (entries 6–9). By contrast with Yadav's protocol, AgNO₃ was also introduced into this reaction, but the product 3a was not observed at all, AgNO₃/K₂S₂O₈ system also gave the same result (entries 10 and 11), which revealed that the silver salt system could not work in this case. To further improve the yield of 3a, different reaction temperatures were set, the yield of the expected product 3a increased to 92% when the reaction temperature reached up to 100 °C (entries 12–16). Attempts to reduce the amount of Mn(OAc)₃ failed, and Mn(OAc)₃/K₂S₂O₈ system gave inferior result (entries 17–19). Meanwhile, various solvents were examined, which indicated that the reaction performed in DMF was significantly better than those in toluene, AcOH, EtOH, DMSO or H₂O (entries 20–24). Under argon atmosphere, the yield of 3a was similar to the open flask condition (entry 25).

Table 1 Optimization of the reaction conditions^a

Entry	Oxidant	Oxidant (equiv.)	Solvent	Temp (°C)	Yield^c (%)
a Reaction conditions: nitro-benzeneolefin (1a) (0.3 mmol), sodium benzenesulfinate (2a) (2 equiv., 0.6 mmol), solvent (5 mL), 8 h, air.b nd, not detected.c Isolated yield.d Argon atmosphere.
1	I2	2.5	DMF	rt	Trace
2	KI/TBHP	0.2/2.5	DMF	rt	Trace
3	TBHP	2.5	DMF	rt	16
4	DTBP	2.5	DMF	rt	19
5	K2S2O8	2.5	DMF	rt	14
6	Fe(NO3)3	2.5	DMF	rt	17
7	FeCl3	2.5	DMF	rt	13
8	CuSO4	2.5	DMF	rt	Trace
9	Mn(OAc)3	2.5	DMF	rt	38
10	AgNO3	2.5	DMF	rt	nd^b
11	AgNO3/K2S2O8	0.2/2.5	DMF	rt	nd
12	Mn(OAc)3	3	DMF	rt	46
13	Mn(OAc)3	3	DMF	40	59
14	Mn(OAc)3	3	DMF	60	65
15	Mn(OAc)3	3	DMF	80	77
16	Mn(OAc)3	3	DMF	100	92
17	Mn(OAc)3	0.2	DMF	100	33
18	Mn(OAc)3	2	DMF	100	84
19	Mn(OAc)3/K2S2O8	0.2/3	DMF	100	56
20	Mn(OAc)3	3	Toluene	100	nd
21	Mn(OAc)3	3	AcOH	100	47
22	Mn(OAc)3	3	EtOH	100	14
23	Mn(OAc)3	3	DMSO	100	45
24	Mn(OAc)3	3	H2O	100	37
25^d	Mn(OAc)3	3	DMF	100	90

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With the optimized protocol in hand, we further examined the scope and limitation of this coupling reaction between different nitro-olefins and sodium sulfinates, and the results are summarized in Table 2. Nitro-olefins with electron-donating functional group such as OMe, Me have higher yield than those with electron-drawing group such as Cl, Br. For instance, nitro-olefins with electron-donating functional group gave the corresponding product in 86–93% yields (3a–c, 3i–k, 3m–o, 3u–3v, 3w). Instead, nitro-olefins with electron-drawing group gave 73–81% yields of the products (3d–e, 3h, 3l, 3p–q). It is noteworthy that sodium sulfinates with electron-donating groups and withdrawing groups have no significant influence on the transformation (3v, 3t). Furthermore, acid-sensitive furanyl-substituted nitro-olefin was also suitable substrate to react with sodium sulfinate, the furanyl-substituted vinyl sulfone (3s) was obtained in 41% isolated yield. Unfortunately, nitro-olefins with NO₂ group couldn't give the corresponding products (3x–z).¹³

Table 2 Substrate scope for the synthesis of various vinyl sulfones^a

a Reaction conditions: nitroolefins (0.3 mmol), sodium sulfinates (0.6 mmol, 2 equiv.), Mn(OAc)₃ (0.9 mmol, 3 equiv.), DMF (5 mL), 100 °C, air.b Isolated yield.

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To gain insights into mechanism of the reaction, nitro-olefin (1a) and sodium benzenesulfinate (2a) reacted in the presence of 2,2,6,6-tetramethylpiperidinyloxy (TEMPO, 3 eq.) which is a radical scavenger under standard condition (Scheme 2). However, 3a was no detected, which implied that this reaction could involve a radical process. Under oxygen atmosphere, the reaction only gave the desired product 3a, while assumed oxidative product 4a was not detected, which showed that Mn(III) could not promote a metal-catalyzed oxidization process.¹⁴

Scheme 2 Control experiments.

Furthermore, in order to reveal the role of the nitro group in this reaction, we reconsidered the reaction between styrene and sodium sulfinates, most of which need I₂ or I⁻/oxidants, and Lei disclosed that I₂ system involve a HI elimination similar to the β-hydride elimination of transition metals process to achieve alkenylation for the formation of vinyl sulfones.^9h Then the reactions between styrene and sodium sulfinates in the presence of Mn(OAc)₃ were investigated. Under our standard condition, the reaction between styrene (5) and sodium sulfinates in the presence of three equivalent or catalytic amount of Mn(OAc)₃ induce the 100% conversion of styrene, however, the desired vinyl sulfone 3a was detected in less than 10% yield, most of styrene was polymerized. This result showed that Mn(III) could not react with the carbon radical, the successively β-hydride elimination process didn't exist. By contrast, a potential elimination of nitro radical should be involved during the coupling of nitro-olefins with sodium sulfinates.

On the basis of the results described above and previous literature reports,^12,15 a plausible mechanism was proposed in Scheme 3. Firstly, a radical A was initially formed through the oxidation of sodium sulfinate by Mn(III) under heating. Next, intermediate B was generated through the trans-addition of A to the nitro-olefin. Then, intermediate B eliminated a nitro radical to give product C. The nitro radical may be quenched by other radical species or Mn(OAc)₃, that's the reason why too much excess amount of Mn(OAc)₃ was needed.

Scheme 3 A plausible mechanism.

In summary, we have developed an efficient Mn(III)-mediated synthesis of (E)-vinyl sulfones through coupling reactions of sodium sulfinates with nitro-olefins. The synthetic method presented many advantages such as cheap metal, simple operation, easily available substrate, and good yields, which is promising for practical applications in relevant industry and manufacture in the future.

Acknowledgements

We are grateful to the National Natural Science Foundation of China (21002076), the Scientific Research Foundation for the Returned Overseas Chinese Scholars for financial support. We also thank No. CX2015151, supported by Graduate Innovative Fund of Wuhan Institute of Technology.

Notes and references

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Footnote

† Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ra17842a

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