Next Article in Journal
Label-Free Exosomal Detection and Classification in Rapid Discriminating Different Cancer Types Based on Specific Raman Phenotypes and Multivariate Statistical Analysis
Previous Article in Journal
The Profile of Secondary Metabolites and Other Bioactive Compounds in Cucurbita pepo L. and Cucurbita moschata Pumpkin Cultivars
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Molecules
Volume 24
Issue 16
10.3390/molecules24162946
molecules-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Communication

Remarkable Effect of [Li(G4)]TFSI Solvate Ionic Liquid (SIL) on the Regio- and Stereoselective Ring Opening of α-Gluco Carbasugar 1,2-Epoxides

by
Sebastiano Di Pietro
1,
Vittorio Bordoni
1,2,
Andrea Mezzetta
1,
Cinzia Chiappe
1,†,
Giovanni Signore
3,
Lorenzo Guazzelli
1,* and
Valeria Di Bussolo
4,*
1
Dipartimento di Farmacia, Università di Pisa, Via Bonanno 33, 56126 Pisa, Italy
2
Present address: Max Planck Institute of Colloids and Interfaces, Am Mühlen- berg 1, 14476 Potsdam, Germany
3
Fondazione Pisana per la Scienza, via F. Giovannini 13, San Giuliano Terme (PI), 56017 Pisa, Italy
4
Dipartimento di Chimica e Chimica Industriale, Università di Pisa, Via G. Moruzzi 3, 56124 Pisa, Italy
*
Authors to whom correspondence should be addressed.
†
In beloved memory.
Molecules 2019, 24(16), 2946; https://doi.org/10.3390/molecules24162946
Submission received: 31 July 2019 / Revised: 9 August 2019 / Accepted: 13 August 2019 / Published: 14 August 2019
(This article belongs to the Section Organic Chemistry)
Browse Figures
Versions Notes

Abstract

:
Carba analogues of biologically relevant natural carbohydrates are promising structures for the development of future drugs endowed with enhanced hydrolytic stability. An open synthetic challenge in this field is the optimization of new methodologies for the stereo- and regioselective opening of α-gluco carbasugar 1,2-epoxides that allow for the preparation of pseudo mono- and disaccharides of great interest. Therefore, we investigated the effect of Lewis acids and solvate ionic liquids (SILs) on the epoxide ring opening of a model substrate. Of particular interest was the complete stereo- and regioselectivity, albeit limited to simple nucleophiles, toward the desired C(1) isomer that was observed using LiClO4. The results obtained with SILs were also remarkable. In particular, Li[NTf2]/tetraglyme ([Li(G4)]TFSI) was able to function as a Lewis acid and to direct the attack of the nucleophile preferentially at the pseudo anomeric position, even with a more complex and synthetically interesting nucleophile. The regioselectivity observed for LiClO4 and [Li(G4)]TFSI was tentatively ascribed to the formation of a bidentate chelating system, which changed the conformational equilibrium and ultimately permitted a trans-diaxial attack on C(1). To the best of our knowledge, we report here the first case in which SILs were successfully employed in a ring-opening process of epoxides.

Graphical Abstract

1. Introduction

Ionic liquids (ILs) are salts with low melting temperatures that have gained significant research attention as pure compounds, in their mono- or dicationic forms [1,2,3], as well as mixtures [4,5] for a wide variety of applications spanning from materials science [6,7,8,9] to analytical chemistry [10,11] and biological science [12].
The favorable characteristics of ILs also make them extremely interesting for carrying out reactions in carbohydrate chemistry [13,14,15].
Recently, a range of novel solvate ionic liquids (SILs) have been identified [16,17,18,19,20,21,22,23,24]. SILs are a sub-class of ILs, consisting of a metal salt and a stoichiometric amount of a coordinating ligand that form stable one-to-one mixtures of complexed cations and counter ions [25]. The most widely investigated SILs are probably based on oligoethers (glymes) and metal salts. The equimolar mixtures of glymes and certain lithium salts are indeed liquids at room temperature and, similar to many ILs, are endowed with low volatility, high ionic conductivities and high electrochemical stability, thus justifying the proposed name (solvate ionic liquids).
The potential use of SILs as new electrolytes for lithium-based batteries [26,27,28] or as electrolytes for thermoelectrochemical cells [29] has been studied in depth, while only very few applications in organic transformations have been reported [30]. Recently, some significant examples have focused on the use of SILs in Diels Alder reactions [30], as organo-catalysts in aldol reactions with (S)-proline [31], in the [2 + 2] cycloaddition formation of dienes [30], and in the preparation of α-aminophosphonates [32]. Although ILs have been employed as media for the ring opening of epoxides [33,34,35,36], no data are available for SILs.
Herein, we report an unexplored attractive application of these SILs as solvents/Lewis acids that are able to efficiently promote the ring opening of epoxides due to the coordination between the substrate and the cationic species present into the glyme [37]. In particular, in the context of a research program concerning the discovery of new methodologies for the synthesis of carbasugars [38,39,40,41,42], the Li[NTf2]/tetraglyme ([Li(G4)]TFSI) system was found to promote a highly regio- and stereoselective ring opening of carbapyranoses 1,2-epoxides with an α-gluco configuration, such as those represented in Scheme 1. These substrates can be used as a pseudo glucosyl donor for the synthesis of C(1)-carbasugars featuring the challenging pseudo β-glucosidic bond.

2. Results and Discussion

As has been extensively reported [43,44,45], carbapyranose 1,2-epoxides with a β-manno configuration can be opened successfully by O- and N-nucleophiles with excellent regio- and stereoselectivity through a sterically and electronically favored 1,2-trans-diaxial process. Conversely, carbapyranose 1,2-epoxides with an α-gluco configuration do not give such a good result both in terms of regioselectivity and yields. Indeed, in saturated-α-1,2-epoxides, both positions C(1) and C(2) present conflicting features for the smooth running of the reaction. An attack at C(1) is sterically and electronically favoured because the C(1) carbon is flanked by a small and relativity electron-rich methylene group, but leads to an unfavourable trans-diequatorial ring-opening (Scheme 2, route a), while attack at C(2), which could lead to a Fürst–Plattner favoured trans-diaxial ring-opening (Scheme 2, route b) is sterically hindered and electronically unfavourable. Nevertheless, a carbapyranose 1,2-epoxide with an α-gluco configuration turns out to be an effective β-carbaglucosyl donor for the synthesis of attractive pseudosaccharides and pseudodisaccharides, with a pseudo-gluco configuration of the carbapyranose unit [46].
Our study started with the synthesis of the model substrate 4α (Scheme 3) with the aim of investigating the possible effects of the Lewis acid partner on the regioselectivity of the ring opening reaction. Carbocyclic system 1 was built by the known Claisen rearrangement developed by Sudha and Nagarajan, starting from tri-O-acetyl glucal [47,48]. The primary hydroxyl group was then removed by means of a tosylation and a subsequent reduction with LiAlH4 in Et2O, to afford the desired methyl compound 3. The latter was then subjected to epoxidation by means of m-chloroperoxybenzoic acid, to give the two diastereoisomeric epoxides 4α and 4β, characterized by α-gluco and β-manno configurations, respectively, in a 60:40 ratio due to the presence of the bulky benzylic ether on the C3 position.
Epoxide 4α represents the model carbaglycosylating agent that was subjected to the ring opening reaction with either methanol or diacetone-D-galactose as nucleophiles in CH2Cl2, in the presence of a catalytic amount of Cu(OTf)2 as the Lewis acid catalyst (Table 1) [49].
As expected, no regioselectivity was observed in either case (Table 1, entry 1 and 2) and an almost 1:1 ratio of the products of the anti attack on C(1) and C(2) were isolated (a subsequent acetylation reaction afforded 5Ac–8Ac, which allowed for the full characterization of the diastereoisomeric compounds).
Next, we employed LiClO4 as the Lewis acid and methanol in the dual role of solvent and nucleophile (Table 1, entry 3) [50].
The reaction proceeded quite slowly (7 days, 80 °C), but, surprisigly, only one of the two possible regiosomeric products was isolated at the end of the reaction. It was possible to ascertain that only the C(1) attack occurred with complete regioselectivity. A working hypothesis to rationalise this result involves the presence of an ion with strong chelating properties, such as Li+, that is able to shift its ground state towards the less stable conformation 4α’’-Li, in which the -OBn group on C(3) and the oxirane oxygen form a bidentate chelating system for the Li+ cation (Figure 1). This species can then undergo the favoured trans-diaxial ring-opening process with nucleophilic attack at C(1) to afford compound 5 as the only reaction product.
Although this was an astonishing result, it was very frustrating to verify that the reaction scope was limited to the use of nucleophiles in large excess, which clearly precludes the synthesis of complex structures. In addition, from a safety perspective, the use of the potentially explosive LiClO4 needs to be minimised.
Hence, having the experimental evidence that lithium salts can dramatically affect the regiochemical outcome of this reaction in hand, we searched the literature for alternatives. As mentioned above, SILs containing lithium salts, which are relatively polar solvents with Lewis acid characteristics, have been recently developed. Therefore, Li[NTf2], in either tri- or tetra-glyme form, [Li(G3)]TFSI or [Li(G4)]TFSI, respectively, were investigated.
In Table 2, the results of the ring-opening reaction of epoxide 4α, using different SILs and methanol or diacetone-D-galactose as nucleophiles, are summarized.
All of the reactions were performed in an argon atmosphere after stirring the SILs under a high vacuum at 70 °C for at least 24 h, in order to remove traces of water that would have a detrimental effect on the reaction. In addition, the reaction temperature was set to 70 °C, which allowed for a decreased viscosity of the SILs and thus facilitated the reaction.
It was interesting to note that no conversion was observed with [Li(G3)]TFSI and methanol (20 equivalents) even after 3 days (entry 1), while in the case of [Li(G4)]TFSI, the epoxide-opening reaction did occur in 24 h under the same reaction conditions, even using 5 equivalents of methanol (entry 2). Indeed, the two SILs are characterized by a different size and slightly different hydrogen bond-donating ability (Kamlet–Taft α-values) [51], which could account for the results obtained. It is also worth mentioning that it is not unusual to observe a diverse outcome when these two SILs are employed under identical reaction conditions [25]. However, the number of reports concerning their use in synthesis is still limited and it is not possible yet to draw any general conclusion.
If this latter reaction is instead compared to the previous reaction with LiClO4 (Table 1, entry 3), two main aspects are to be highlighted: the shorter reaction time for the reaction to go to completion (24 h versus 8 days), and the lower regioselectivity, although it was still in favor of the C(1) attack (the regioisomeric α-methoxy alcohols 5 and 6 were found to be formed in a 60:40 ratio according to 1H-NMR on the crude versus complete regioselection). The effect on the reaction rate could be related to the higher amount of lithium, which is part of the solvent system, when SIL was employed. Concerning the second aspect, it has to be considered that Li+ in the SIL is already chelated by the glyme, which will result in a less coordinating cation than in the case of LiClO4. Therefore, it can be speculated that the bidentate chelate system will have a lower stability, and thus, a lower regioselectivity.
To further ascertain whether the presence of non-chelated lithium could enhance the regioselectivity, a new reaction was performed by adding additional LiTf2N (0.2 equivalents) to [Li(G4)]TFSI under otherwise identical conditions (entry 3). In this case, the only noticeable effect was a decrease in the reaction rate, while 5 and 6 were again obtained in a 60:40 ratio.
As a last attempt, we wanted to verify the reaction potential with a more synthetically useful nucleophile, an option that is ruled out when using LiClO4, as mentioned above. Therefore, the synthesis of a pseudodisaccharide was attempted, employing diacetone-D-galactose as the nucleophile (3.0 equivalents, entry 4). To our delight, after 24 h, we observed a high degree of regioselectivity with the attack of the more complex nucleophile having taken place at C1 (80:20) under the (partially) chelating conditions in [Li(G4)]TFSI. The regioselectivity was evaluated by HPLC-MS after acetylation of the crude mixture using compounds 7Ac and 8Ac, obtained in the copper catalyzed process, as standards. The HPLC chromatogram showed a regioisomeric ratio of 80:20 in favor of the C1 adduct 7Ac (please refer to the ESI).
The increased regioselectivity that was observed, if compared with entry 2, seems to suggest that other features, beside the bidentate chelate system, are potentially involved in determining the stereo- and regiochemical outcome of the reaction. For instance, the steric hindrance of the nucleophile could play a major role in these outcomes.
Further studies are currently ongoing and aim to shed light on the optimal experimental conditions required to maximize the regioselectivity and elucidate the mechanism involved in the reaction. The results will be presented in due course.

3. Materials and Methods

All solvents and chemicals were used as purchased without further purification. SIL [Li(G3)]TFSI and [Li(G3)]TFSI were prepared following a previously reported procedure [30]. Chromatographic separations were performed on silica gel columns by flash (Kieselgel 40, 0.040–0.063 mm; Merck, Darmstadt, Germany) or by automated chromatography with Isolera® Biotage, Uppsala, Sweden. Reactions were followed by thin-layer chromatography (TLC) on Merck aluminum silica gel (60 F254) sheets that were visualized under a UV lamp. Evaporation was performed in vacuo (rotating evaporator). Sodium sulfate was always used as the drying agent. Melting points were determined with a Kofler hot-stage apparatus and are uncorrected. Optical rotations were measured with a ATAGO AP-300 Automatic Polarimeter (Tokyo, Japan) at 25 °C. 1H- and 13C-NMR spectra were recorded with a Bruker Avance 250 MHz spectrometer (Billerica, MA, USA) using the indicated deuterated solvents. Chemical shifts are given in parts per million (ppm) (δ relative to the residual solvent peak for 1H and 13C). FTIR spectra were obtained with an IR Cary 600 FTIR (Agilent Technologies, Santa Clara, CA, USA). Yields refer to isolated and purified products. LC-MS evaluation and identification of the products was performed using a Shimadzu Nexera UHPLC chromatograph (Kyoto, Japan) equipped with a diode array detector and interfaced with an ABSciex API 3200 QTRAP mass spectrometer (Milan, Italy), using the following parameters. LC conditions: Column: Phenomenex Kinetex C18 EVO 3 × 150 mm, particle size 5 µm, flow 0.5 mL/min. Mobile phase A: ammonium formate 20 mM (pH 4.8) Mobile phase B: acetonitrile. Gradient: 95% A (1 min), then linear gradient to 100% B in 12 min, followed by a 3 min wash step at 100% B. MS conditions: Ionization mode: ESI. Curtain gas 10 mL/min; ion spray voltage: 5500 V; temperature: not used; declustering potential: 75 V; entrance potential: 10 V; collision energy: 50 eV; collision energy potential: 43 V. Elemental analyses were obtained using an Elementar Vario MICRO cube (Langenselbold, Germany). All the detailed experimental procedures, NMR and HPLC-MS spectra are given in the Supplementary Materials.

4. Conclusions

In this work, we synthetized epoxide 4α as a model of carbapyranose 1,2-epoxide with α-gluco configuration and we studied the corresponding nucleophilic ring-opening reaction under standard (Nu-H/CH2Cl2/Cu(OTf)2) or chelating conditions. It can be speculated that, when employing a Lewis acid such as LiClO4 in MeOH or, even more interestingly, when using an appropriate solvent such as [Li(G4)]TFSI containing an available Li+ cation, the conformational equilibrium of the starting epoxide can be altered, thus allowing for a highly (complete in the case of LiClO4) stereo- and C(1)-selective ring-opening process.
In brief, by using SIL [Li(G4)]TFSI, a new and efficient protocol for the synthesis of carbasaccharides or pseudodisaccharides with β-gluco configuration was revealed.

Supplementary Materials

The following are available online, all the detailed experimental procedures, NMR and HPLC-MS spectra.

Author Contributions

C.C., V.D.B., L.G. conceived the study. S.D.P., V.B., A.M. and G.S. performed the experiments. V.D.B. and L.G. wrote the main text. All authors reviewed the manuscript.

Funding

L. Guazzelli acknowledges University of Pisa (Progetti di Ricerca di Ateneo, PRA_2018_18).

Conflicts of Interest

The authors declare no competing interests.

References

  1. Welton, T. Ionic liquid: A brief history. Biophys. Rev. 2018, 10, 691–706. [Google Scholar] [CrossRef] [PubMed]
  2. Han, X.; Armstrong, D.W. Using geminal dicationic ionic liquids as solvents for high-temperature organic reactions. Org. Lett. 2005, 7, 4205–4208. [Google Scholar] [CrossRef] [PubMed]
  3. Guglielmero, L.; Mezzetta, A.; Guazzelli, L.; Pomelli, C.S.; D’Andrea, F.; Chiappe, C. Systematic synthesis and properties evaluation of dicationic ionic liquids, and a glance into a potential new field. Front. Chem. 2018, 6, 612. [Google Scholar] [CrossRef] [PubMed]
  4. Niedermeyer, H.; Hallett, J.P.; Villar-Garcia, I.J.; Hunt, P.A.; Welton, T. Mixtures of ionic liquids. Chem. Soc. Rev. 2012, 41, 7780–7802. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  5. Mezzetta, A.; Douton, M.J.R.; Guazzelli, L.; Pomelli, C.S.; Chiappe, C. Microheterogeneity in ionic liquids mixtures: Hydrogen bonding, dispersed ions, and dispersed ion cluster. Aust. J. Chem. 2019, 72, 106–111. [Google Scholar] [CrossRef]
  6. Zhang, S.; Zhang, Q.; Zhang, Y.; Chen, Z.; Watanabe, M.; Deng, Y. Beyond solvents and electrolytes: Ionic liquids-based advanced functional materials. Prog. Mater. Sci. 2016, 77, 80–124. [Google Scholar] [CrossRef] [Green Version]
  7. Chiappe, C.; Douton, M.J.R.; Mezzetta, A.; Guazzelli, L.; Pomelli, C.S.; Assanelli, G.; De Angelis, A.R. Exploring and exploiting different catalytic systems for the direct conversion of cellulose into levulinic acid. N. J. Chem. 2018, 42, 1845–1852. [Google Scholar] [CrossRef]
  8. Palazzo, I.; Mezzetta, A.; Guazzelli, L.; Sartini, S.; Pomelli, C.S.; Parker, W.O., Jr.; Chiappe, C. Chiral ionic liquids supported on natural sporopollenin microcapsules. RSC Adv. 2018, 8, 21174–21183. [Google Scholar] [CrossRef] [Green Version]
  9. Chiappe, C.; Demontis, G.C.; Di Bussolo, V.; Rodriguez Douton, M.J.; Rossella, F.; Pomelli, C.S.; Sartini, S.; Caporali, S. From pollen grains to functionalized microcapsules: A facile chemical route using ioni liquids. Green Chem. 2017, 19, 1028–1033. [Google Scholar] [CrossRef]
  10. Ghorbanizamani, F.; Timur, S. Ionic liquids from biocompatibility and electrochemical aspects towards applying in biosensing devices. Anal. Chem. 2018, 90, 640–648. [Google Scholar] [CrossRef]
  11. Longhi, M.; Arnaboldi, S.; Husanu, E.; Grecchi, S.; Buzzi, I.F.; Cirilli, R.; Rizzo, S.; Chiappe, C.; Mussini, P.R.; Guazzelli, L. A family of chiral ionic liquids from the natural pool: Relationships between structure and functional properties and electrochemical enantiodiscrimination tests. Electrochim. Acta 2019, 298, 194–209. [Google Scholar] [CrossRef]
  12. Egorova, K.S.; Gordeev, E.G.; Ananikov, V.P. Biological activity of ionic liquids and their application in pharmaceutics and medicine. Chem. Rev. 2017, 117, 7132–7189. [Google Scholar] [CrossRef] [PubMed]
  13. Galan, M.C.; Jones, R.A.; Tran, A.T. Recent developments of ionic liquids in oligosaccharide synthesis: The sweet side of ionic liquids, Carbohydr. Res. 2013, 375, 35–46. [Google Scholar] [CrossRef] [PubMed]
  14. El Seoud, O.A.; Koschella, A.; Fidale, L.C.; Dorn, S.; Heinze, T. Applications of Ionic Liquids in Carbohydrate Chemistry: A Window of Opportunities. Biomacromolecules 2007, 8, 2629–2647. [Google Scholar] [CrossRef] [PubMed]
  15. Zhang, Z.C. Catalytic transformation of carbohydrates and lignin in ionic liquids. WIREs Energy Environ. 2013, 2, 655–672. [Google Scholar] [CrossRef]
  16. Ueno, K.; Yoshida, K.; Tsuchiya, M.; Tachikawa, N.; Dokko, K.; Watanabe, M. Glyme−Lithium salt equimolar molten mixtures: Moncentrated solutions or solvate ionic liquids? J. Phys. Chem. B 2012, 116, 11323–11331. [Google Scholar] [CrossRef] [PubMed]
  17. Kitazawa, Y.; Iwata, K.; Imaizumi, S.; Ahn, H.; Kim, S.Y.; Ueno, K.; Park, M.J.; Watanabe, M. Gelation of solvate ionic liquid by self-assembly of block copolymer and characterization as polymer electrolyte. Macromolecules 2014, 47, 6009–6016. [Google Scholar] [CrossRef]
  18. Mandai, T.; Yoshida, K.; Ueno, K.; Dokko, K.; Watanabe, M. Criteria for solvate ionic liquids. Phys. Chem. Chem. Phys. 2014, 16, 8761–8772. [Google Scholar] [CrossRef]
  19. Moon, H.; Tatara, R.; Mandai, T.; Ueno, K.; Yo-Shida, K.; Tachikawa, N.; Yasuda, T.; Dokko, K.; Watanabe, M. Mechanism of Li Ion Desolvation at the Interface of Graphite Electrode and Glyme–Li Salt Solvate Ionic Liquids. J. Phys. Chem. C 2014, 118, 20246–20256. [Google Scholar] [CrossRef]
  20. Terada, S.; Mandai, T.; Nozawa, R.; Yoshida, K.; Ueno, K.; Tsuzuki, S.; Dokko, K.; Watanabe, M. Physicochemical properties of pentaglyme–sodium bis (trifluoromethanesulfonyl) amide solvate ionic liquid. Phys. Chem. Chem. Phys. 2014, 16, 11737–11746. [Google Scholar] [CrossRef]
  21. Tsuzuki, S.; Shinoda, W.; Matsugami, M.; Ume-Bayashi, Y.; Ueno, K.; Mandai, T.; Seki, S.; Dokko, K.; Watanabe, M. Structures of [Li(glyme)]+ complexes and their interactions with anions in equimolar mixtures of glymes and Li[TFSA]: Analysis by molecular dynamics simulations. Phys. Chem. Chem. Phys. 2015, 17, 126–129. [Google Scholar] [CrossRef]
  22. Ueno, K.; Tatara, R.; Tsuzuki, S.; Saito, S.; Doi, H.; Yoshida, K.; Mandai, T.; Matsugami, M.; Umebayashi, Y.; Dokko, K. Li+ solvation in glyme-Li salt solvate ionic liquids. Phys. Chem. Chem. Phys. 2015, 17, 8248–8257. [Google Scholar] [CrossRef]
  23. Zhang, C.; Ueno, K.; Yamazaki, A.; Yoshida, K.; Moon, H.; Mandai, T.; Umebayashi, Y.; Dokko, K.; Watanabe, M. Chelate effects in glyme/lithium bis(trifluoromethanesulfonyl)amide solvate ionic liquids. I. stability of solvate cations and correlation with electrolyte properties. J. Phys. Chem. B 2014, 118, 5144–5153. [Google Scholar] [CrossRef]
  24. Zhang, A.C.; Yamazaki, J.; Murai, J.-W.; Park, T.; Mandai, K.; Ueno, K.; Dokko, M. Watanabe, Chelate Effects in Glyme/Lithium Bis (trifluoromethanesulfonyl) amide Solvate Ionic Liquids, Part 2: Importance of Solvate-Structure Stability for Electrolytes of Lithium Batteries. J. Phys. Chem. C 2014, 118, 17362–17373. [Google Scholar] [CrossRef]
  25. Eyckens, D.J.; Henderson, L.C. A review of solvate ionic liquids: Physical parameters and synthetic applications. Front. Chem. 2019, 7, 263. [Google Scholar] [CrossRef]
  26. Carbone, L.; Gobet, M.; Peng, J.; Devany, M.; Scrosati, B.; Greenbaum, S.; Hassoun, J. Comparative Study of Ether-Based Electrolytes for Application in Lithium–Sulfur Battery. ACS Appl. Mater. Interfaces 2015, 7, 13859–13865. [Google Scholar] [CrossRef]
  27. Ueno, K.; Park, J.W.; Yamazaki, A.; Mandai, T.; Tachikawa, N.; Dokko, K.; Watanabe, M. Anionic Effects on Solvate Ionic Liquid Electrolytes in Rechargeable Lithium–Sulfur Batteries. J. Phys. Chem. C 2013, 117, 20509–20516. [Google Scholar] [CrossRef]
  28. Yoshida, K.; Tsuchiya, M.; Tachikawa, N.; Dokko, K.; Watanabe, M. Correlation between Battery Performance and Lithium Ion Diffusion in Glyme–Lithium Bis (trifluoromethanesulfonyl) amide Equimolar Complexes. J. Electrochem. Soc. 2012, 159, A1005–A1012. [Google Scholar] [CrossRef]
  29. Black, J.J.; Murphy, T.; Atkin, R.; Dolan, A.; Aldous, L. The thermoelectrochemistry of lithium–glyme solvate ionic liquids: Towards waste heat harvesting. Phys. Chem. Chem. Phys. 2016, 18, 20768–20777. [Google Scholar] [CrossRef]
  30. Eyckens, D.J.; Champion, M.E.; Fox, B.L.; Yoganantharajah, P.; Gibert, Y.; Welton, T.; Henderson, L.C. Solvate Ionic Liquids as Reaction Media for Electrocyclic Transformations. Eur. J. Org. Chem. 2016, 5, 913–917. [Google Scholar] [CrossRef]
  31. Obregon-Zuniga, A.; Milàn, M.; Juaristi, E. Improving the catalytic performance of (S)-proline as organocatalyst in asymmetric aldol reactions in the presence of solvate ionic liquids, involvement of a supramolecular aggregate. Org. Lett. 2017, 19, 1108–1111. [Google Scholar] [CrossRef]
  32. Eyckens, D.J.; Henderson, L.C. Synthesis of α-aminophosphonates using solvate ionic liquids. RSC Adv. 2017, 7, 27900–27904. [Google Scholar] [CrossRef]
  33. Yadav, J.S.; Reddy, B.V.S.; Jyothirmai, B.; Murty, M.S.R. Ionic Liquids/H2O Systems for the Reaction of Epoxides with NaN3: A New Protocol for the Synthesis of 2-Azidoalcohols. Tetrahedron Lett. 2005, 46, 6559–6562. [Google Scholar] [CrossRef]
  34. Chen, J.; Wu, H.; Jin, C.; Zhang, X.; Xie, Y.; Su, W. Highly regioselective ring-opening of epoxides with thiophenols in ionic liquids without the use of any catalyst. Green Chem. 2006, 8, 330–332. [Google Scholar] [CrossRef]
  35. Yang, M.-H.; Yan, G.-B.; Zheng, Y.-F. Regioselective ring-opening reactions of 1, 2-epoxides with thiols and arylselenols directly promoted by [Bmim] BF4. Tetrahedron Lett. 2008, 49, 6471–6474. [Google Scholar] [CrossRef]
  36. Rad, M.N.S.; Behrouz, S. The base-free chemoselective ring opening of epoxides with carboxylic acid using [Bmim] Br: A rapid entry into 1, 2-diol mono-esters synthesis. Mol. Divers. 2013, 17, 9–18. [Google Scholar] [CrossRef]
  37. Terada, S.; Ikeda, K.; Ueno, K.; Dokko, K.; Watanabe, M. Liquid Structures and Transport Properties of Lithium Bis (fluorosulfonyl) amide/Glyme Solvate Ionic Liquids for Lithium Batteries. Aust. J. Chem. 2019, 72, 70–80. [Google Scholar] [CrossRef]
  38. Arjona, O.; Gómez, A.M.; López, J.C.; Plumet, J. Synthesis and Conformational and Biological Aspects of Carbasugars. Chem. Rev. 2007, 107, 1919–2036. [Google Scholar] [CrossRef]
  39. Marco-Contelles, J.; Molina, M.T.; Anjum, S. Naturally Occurring Cyclohexane Epoxides: Sources, Biological Activities, and Synthesis. Chem. Rev. 2004, 104, 2857–2900. [Google Scholar] [CrossRef]
  40. Cumpstey, I. Synthesis of carbasugar-containing non-glycosidically linked pseudodisaccharides and higher pseudooligosaccharides Carbohydr. Res. 2009, 344, 2285–2310. [Google Scholar] [CrossRef]
  41. Di Bussolo, V.; Frau, I.; Checchia, L.; Favero, L.; Pineschi, M.; Uccello-Barretta, G.; Balzano, F.; Roselli, G.; Renzi, G.; Crotti, P. Synthesis of carba analogs of 6-O-(benzyl)-D-allal-and-D-galactal-derived allyl epoxides and evaluation of the regio-and stereoselective behavior in nucleophilic addition reactions. Tetrahedron 2011, 67, 4696–4709. [Google Scholar] [CrossRef]
  42. Di Bussolo, V.; Frau, I.; Favero, L.; Bordoni, V.; Crotti, S.; Barretta, G.U.; Balzano, F.; Crotti, P. Carba-D, L-allal-and-D, L-galactal-derived vinyl N-nosyl aziridines as useful tools for the synthesis of 4-deoxy-4-(N-nosylamino)-2, 3-unsaturated-5a-carbasugars. Tetrahedron 2017, 73, 6677–6695. [Google Scholar] [CrossRef]
  43. Ogawa, S.; Sasaki, S.; Tsunoda, H. Convenient Synthesis of Oxo-Linked 5a-Carba-di- and tri-saccharides of Biological Interests. Chem. Lett. 1993, 9, 1587–1590. [Google Scholar] [CrossRef]
  44. Frigell, J.; Cumpstey, I. Carbasugar analogues of galactofuranosides: α-O-linked derivatives. Beilstein J. Org. Chem. 2010, 6, 1127–1131. [Google Scholar] [CrossRef]
  45. Bordoni, V.; Porkolab, V.; Sattin, S.; Thépaut, M.; Frau, I.; Favero, L.; Crotti, P.; Bernardi, A.; Fieschi, F.; Di Bussolo, V. Stereoselective innovative synthesis and biological evaluation of new real carba analogues of minimal epitope Manα (1,2) Man as DC-SIGN inhibitors. RSC Adv. 2016, 6, 89578–89584. [Google Scholar] [CrossRef]
  46. Roscales, S.; Plumet, J. Biosynthesis and Biological Activity of Carbasugars. Int. J. Carbohydr. Chem 2016, 2016, 4760548. [Google Scholar] [CrossRef]
  47. Sudha, A.V.R.L.; Nagarajan, M. Biosynthesis and Biological Activity of CarbasugarsCarbohydrates to carbocycles: An expedient synthesis of pseudo-sugars. Chem Comm. 1998, 29, 925–926. [Google Scholar] [CrossRef]
  48. Frau, I.; Di Bussolo, V.; Favero, L.; Pineschi, M.; Crotti, P. Stereodivergent Synthesis of Diastereoisomeric Carba Analogs of Glycal-Derived Vinyl Epoxides: A New Access to Carbasugars. Chirality 2011, 23, 820–826. [Google Scholar] [CrossRef]
  49. Bernardi, A.; Arosio, D.; Manzoni, L.; Micheli, F.; Pasquarello, A.; Seneci, P. Stereoselective Synthesis of Conformationally Constrained Cyclohexanediols: A Set of Molecular Scaffolds for the Synthesis of Glycomimetics. J. Org. Chem. 2001, 66, 6209–6216. [Google Scholar] [CrossRef]
  50. Colombini, M.; Crotti, P.; Di Bussolo, V.; Favero, L.; Gardelli, C.; Macchia, F.; Pineschi, M. Regiochemical control of the ring opening of 1, 2-epoxides by means of chelating processes.9. Synthesis and ring opening reactions of cis- and trans-oxides derived from 3-(benzyloxymethyl) cyclopentene and methyl 2-cyclopenten-1-carboxylate 1. Tetrahedron 1995, 51, 8089–8112. [Google Scholar] [CrossRef]
  51. Eyckens, D.J.; Demir, B.; Walsh, T.R.; Welton, T.; Henderson, L.C. Determination of Kamlet-Taft parameters for selected solvate ionic liquids. Phys. Chem. Chem. Phys. 2016, 18, 13153–13157. [Google Scholar] [CrossRef]
Molecules 24 02946 sch001 550
Scheme 1. Regio- and stereoselective addition of a generic nucleophile in [Li(G4)]TFSI to a carbapyranose-α-1,2-epoxide.
Scheme 1. Regio- and stereoselective addition of a generic nucleophile in [Li(G4)]TFSI to a carbapyranose-α-1,2-epoxide.
Molecules 24 02946 sch001
Molecules 24 02946 sch002 550
Scheme 2. Possible nucleophilic addition pathways.
Scheme 2. Possible nucleophilic addition pathways.
Molecules 24 02946 sch002
Molecules 24 02946 sch003 550
Scheme 3. Preparation of α-gluco carbasugar 1,2-epoxides.
Scheme 3. Preparation of α-gluco carbasugar 1,2-epoxides.
Molecules 24 02946 sch003
Molecules 24 02946 g001 550
Figure 1. Conformational equilibrium shift due to the lithium coordination.
Figure 1. Conformational equilibrium shift due to the lithium coordination.
Molecules 24 02946 g001
Table
Table 1. Lewis acid (L.A.)-mediated ring-opening addition of alcohol nucleophile (Nu-H) to epoxide 4α.
Table 1. Lewis acid (L.A.)-mediated ring-opening addition of alcohol nucleophile (Nu-H) to epoxide 4α.
Molecules 24 02946 i001
EntryAlcohol Nucleophile (Nu-H)L.A.SolventTime Temp.NuC(1) Adduct1 (%)C(2) Adduct1 (%)Isolated Yield2
1MeOHCu(OTf)2CH2Cl212 h
r.t.		OMe5 (50)6 (50)C1: 32%
C2: 32%
21,2:3,4-di-O-isopropylidene-d-galactopyranoseCu(OTf)2CH2Cl212 h
r.t.		 Molecules 24 02946 i0027 (55)8 (45)C1: 35%
C2: 28%
3MeOHLiClO4MeOH7 days
80°C		OMe5 (>99)/C1: 55%
1 regioselectivity estimated by 1H-NMR of the crude reaction product. 2 yields calculated on the corresponding acetyl derivatives 5Ac–8Ac that were easily separable.
Table
Table 2. Results for the ring-opening addition of alcohol nucleophiles to epoxide 4α in various SILs and different conditions.
Table 2. Results for the ring-opening addition of alcohol nucleophiles to epoxide 4α in various SILs and different conditions.
Molecules 24 02946 i003
EntryAlcohol Nucleophile (Nu-H)SILConditionsNuC(1) Adduct (%)C(2) Adduct (%)
1MeOH Molecules 24 02946 i004
[Li(G3)]TFSI		i) IL dried
ii) 70 °C
3 days		OMe//
2MeOH Molecules 24 02946 i005
[Li(G4)]TFSI		i) IL dried
ii) 70 °C
24 h		OMe5 (60)16 (40)1
3MeOH[Li(G4)]TFSIi) IL dried
ii) 70 °C
LiTf2N excess
3 days		OMe5 (60)16 (40)1
41,2:3,4-di-O-isopropylidene-d-galactopyranose [Li(G4)]TFSIi) IL dried
ii) 70 °C
24 h		 Molecules 24 02946 i0067Ac (80)2 8Ac (20)2
1 regioselectivity estimated by 1H-NMR of the crude reaction product. 2 regioselectivity assessed by HPLC-MS of the acetylation crude, using 7Ac and 8Ac previously isolated as standards.

Share and Cite

MDPI and ACS Style

Di Pietro, S.; Bordoni, V.; Mezzetta, A.; Chiappe, C.; Signore, G.; Guazzelli, L.; Di Bussolo, V. Remarkable Effect of [Li(G4)]TFSI Solvate Ionic Liquid (SIL) on the Regio- and Stereoselective Ring Opening of α-Gluco Carbasugar 1,2-Epoxides. Molecules 2019, 24, 2946. https://doi.org/10.3390/molecules24162946

AMA Style

Di Pietro S, Bordoni V, Mezzetta A, Chiappe C, Signore G, Guazzelli L, Di Bussolo V. Remarkable Effect of [Li(G4)]TFSI Solvate Ionic Liquid (SIL) on the Regio- and Stereoselective Ring Opening of α-Gluco Carbasugar 1,2-Epoxides. Molecules. 2019; 24(16):2946. https://doi.org/10.3390/molecules24162946

Chicago/Turabian Style

Di Pietro, Sebastiano, Vittorio Bordoni, Andrea Mezzetta, Cinzia Chiappe, Giovanni Signore, Lorenzo Guazzelli, and Valeria Di Bussolo. 2019. "Remarkable Effect of [Li(G4)]TFSI Solvate Ionic Liquid (SIL) on the Regio- and Stereoselective Ring Opening of α-Gluco Carbasugar 1,2-Epoxides" Molecules 24, no. 16: 2946. https://doi.org/10.3390/molecules24162946

Article Metrics

Back to TopTop