Preparation of SRN1-Type Coupling Adducts from Aliphatic gem-Dinitro Compounds in Ionic Liquids

SRN1-type coupling adducts are readily prepared by the reaction between α-sulfonylesters or α-cyanosulfones and gem-dinitro compounds in ionic liquids. The reactions progress smoothly and recovered ionic liquids can be used for several iterations, as long as they are washed with water to remove alkali metallic salts. The reaction rate is slower than the corresponding SRN1 reaction in DMSO, but no acceleration on irradiation or no inhibition in the presence of m-DNB are observed.


Introduction
The S RN 1 reaction is a unique reaction that proceeds via a single electron transfer process [1][2][3]. The reaction usually starts with a single electron transfer that generates a radical anion species, which then gives a radical species via cleavage of the anion radical. Then, the radical reacts with a coupling partner to form products. The reaction is usually performed in either liquid ammonia or a dipolar aprotic solvent such as DMSO and HMPA. The reaction progresses through a radical chain mechanism and the reaction rate are significantly lowered by the presence of small amounts of a radical inhibitor such as p-dinitrobenzene. The S RN 1 reaction is frequently used to construct aromatic compounds [4][5][6][7][8][9][10][11][12][13][14][15]. The S RN 1 reaction between aliphatic compounds produces a new carbon-carbon or carbon-heteroatom bond between sterically hindered carbons in good yields. This type of bond formation is usually not easily achieved using any other reactions in organic synthesis. The adducts from an aliphatic S RN 1 OPEN ACCESS reaction are regarded as precursors for further palladium coupling materials [16] or tri-or tetrasubstituted alkenes [17][18][19][20][21][22].
Recently ionic liquids have attracted significant interest in organic synthesis because of their unique properties such as wide redox windows, high polarities and high solubilities [23][24][25][26][27][28]. During the course of our investigation on ionic liquid chemistry [29][30][31], it occurred to us that ionic liquids could become a new solvent system for a reaction via electron transfer such as S RN 1 reaction. To our best of knowledge, there have been no reports that employ ionic liquids for such reactions. In this paper, we demonstrate that the S RN 1-type coupling adducts are indeed readily obtained in the reaction in ionic liquids.

Results and Discussion
We first examined various ionic liquids for the S RN 1-type coupling reaction between gem-dinitro compounds and -sulfonylesters. gem-Dinitropropane 2a was added to a mixture of tert-BuOK and -sulfonyl propionic ester 1a in different ionic liquids under photoirradiation produced by a usual tungsten lamp, and the desired coupling product 3a was isolated (Scheme 1) [32]. Table 1 summarizes the results. Scheme 1. S RN 1-type coupling reactions between 1a and 2a.
Reagents and conditions: i, tert-BuOK (1.5 eq.), h, ionic liquids, rt. The coupling reaction between 1a and 2a took place smoothly in ionic liquids to give 3a in good yield. For example, the reaction in [bmim] [PF 6 ] resulted in the formation of the coupling product 3a in 58% yield (entry 1). The reaction was complete after 11 h at room temperature, but some amounts of the starting material 1a remained and were recovered from the reaction mixture. Although we have examined many bases such as Me 4 NOH, DBU and Et 3 N, none of these amine bases worked well in the reaction. Starting material 1a was recovered completely. Use of other ionic liquids that contained BF 4 and NTf 2 as a counter anion were examined (entries 2-6). The reaction progressed smoothly and the corresponding adduct 3a was isolated in good yield. Thus, ionic liquids were useful solvents for the coupling reaction. The reaction for other starting materials was explored next (Scheme 2). Table 2 summarizes the results. A mixture of 1b and 2,2-dinitropropane (2a) in [TMPA][NTf 2 ], for example, afforded coupling adduct 3b in 69% yield (entry 1). The reaction was complete within 8 to 24 h. Coupling with 2,2-dinitrobutane (2b) also gave the products in a 1:1 mixture of two possible diastereomers (entries 2 and 3). -Cyanosulfonyl compounds also underwent the reaction in ionic liquid, producing the corresponding coupling products 3e to 3h in moderate to good yields (entries 4-7). Thus, ionic liquids are useful solvents for promoting the coupling reaction effectively.   The recycling of the ionic liquids was performed in the following way: after the first reaction was completed, we performed a usual work-up. Thus, product 3a was isolated in 58% yield by direct extraction with ether from the ionic liquid and the remaining [bmim][PF 6 ] was used directly for the next reaction. The second run worked well and 3a was prepared in 62% yield. The third run, however, occurred sluggishly, and the desired product 3a was isolated in only 19% yield. We thought this might be due to accumulating side products such as sodium nitrite. Therefore, [bmim][PF 6 ] was washed with water to remove salts and other water-soluble impurities that had accumulated during the reaction. The ionic liquid was recovered without significant loss. After drying, we used the recovered [bmim][PF 6 ] for the reaction and obtained 3a in 51% yield. When we used it for the fifth time, [bmim][PF 6 ] worked well and product 3a was isolated in 50% yield. Thus, the present procedure allowed us to use the ionic liquid several times. We examined iterative use of ionic liquids [TMPA][NTf 2 ] for the reaction and successfully obtained 3a in good to moderate yields (Table 4). High yields of 3a were achieved until six times use, when 3a was obtained in 60%, after then the yields decreased to less than 40%. To explore the reaction profile, we examined the reaction kinetics. Figure 1 shows  was used for the kinetic measurements. We detected product 3a by HPLC analyses and estimated it using the curve fitting method. The reaction in DMSO progressed very fast to give 3a almost quantitatively within a minute, while the reaction in [TMPA][NTf 2 ] progressed much slowly, and the yield of 3a increased to greater than 80% after about 40 minutes. This difference in the reaction rate should arise from the difference in viscosity because ionic liquids usually possess greater viscosities than any other usual organic solvent [33]. It is noteworthy that the coupling reaction in ionic liquids showed no inhibition by additives or acceleration by photoirradiation. Scheme 4 summarizes the results in which the reaction progress was almost the same even on addition of m-dinitrobenzene or with irradiation from a tungsten lamp. These results are in sharp contrast with the conventional S RN 1 reaction in which inhibition by adding aromatic nitro compounds and acceleration with photo irradiation have been clearly observed [32].

General
All 1 H-and 13 C-NMR spectra were measured in CDCl 3 and recorded on a JEOL Lamda-500 spectrometer (at 500 MHz for 1 H and 126 MHz for 13 C). All reactions were performed under a nitrogen atmosphere unless otherwise mentioned. DMSO was dried over CaH 2 and distilled under reduced pressure before use. Ionic liquids, except for [DEME][NTf 2 ], were purchased from Kanto Chemical Co. Ltd. [DEME][NTf 2 ] was supplied by Nisshinbo Co. Ltd. Photoirradiation was carried out by a standard 40 W tungsten lamp. Elemental analyses and high-resolution mass spectra were measured at Tokiwa Instrumental Analysis Center, Yamaguchi University, Ube, Japan.

Conclusions
We have demonstrated the first examples of S RN 1-type coupling reactions in an ionic liquid, which not only possesses high polarity but is also regarded as a good solvent for promoting the electron transfer process. The ionic liquids [bmim] [PF 6 ] and [TMPA][NTf 2 ] were useful for the efficient progress of the reaction. Although amine base was not effective for the progress of the reaction, t-BuOK was a useful base to enhance the reactions. Although the reaction rate in the S RN 1 reaction was not as fast as that in the conventional S RN 1 reaction in DMSO, ionic liquids have an advantage over the conventional method because of the reusability of the solvent if it was washed with water; a simple manipulation that enabled the ionic liquid to be reused for another reaction. A notable contrast from the conventional S RN 1 reaction in DMSO was the fact that the reaction was not impeded by the presence of m-DNB, and the coupling products were obtained in a similar yield. The use of ionic liquids for other reactions is now under investigation in our laboratory.