Current Green Chemistry   Mukund Ghavre a,b,d,* , Brid Quilty c and Nicholas Gathergood b,e,* a School of Chemical Sciences and National Institute of Cellular Biotechnology, Dublin City University, Glasnevin, Dub- lin 9, Ireland; b SFI SRC in Solar Energy Conversion, UCD School of Chemical & Bioprocess Engineering, Engineering & Materials Science Centre, UCD Dublin, Belfield, Dublin 4, Ireland; c School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland; d Department of Chemistry, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, L2S 3A1 ON, Canada; e Department of Chemistry, Chair of Green Chemistry, Tallinn University of Technology, Aka- deemia tee 15, Tallinn, Estonia A R T I C L E H I S T O R Y Received: August 11, 2015 Revised: June 14, 2016 Accepted: June 15, 2016 DOI: 10.2174/221334610366616072811 5628 Abstract: Background: Low toxicity ionic liquids (ILs) have shown a wide range of applications in material chemistry, synthetic chemistry, and green chemistry. They can be considered as 'green' alternatives to the conventional solvents, as their unique properties can offer additional benefits. In our previous reports, we have shown that such ILs can be used as reaction media in hydrogenation, carbonyl-ene reactions, and Brønsted acid catalyzed reactions. Methods: Low toxicity ILs are prepared by a short synthesis. The palladium based catalyst bearing an asymmetric ligand is immobilized in these ILs. This ‘green’ cata- lytic system is employed for enantioselective Tsuji-Trost reactions. For comparison, several reactions are run in conventional solvents. Results: The reactions in ILs provide good to excellent enantiomeric excess, however, low yields are obtained compared to the conventional solvents. The catalytic system is recyclable. Conclusion: Conventional solvent (DMSO) is proved to be superior to our ILs, however, the results in our ILs are an improvement over [bmim] ILs. The low yields are attributed to high viscosity of the ILs, and we propose can be resolved by tuning the viscosity of the IL by anion exchange. Keywords: Enantioselectivity, ionic liquids, Pd-catalysis, recyclable, Tsuji-Trost reaction. 1. INTRODUCTION The Tsuji-Trost reaction is one of the classical coupling methods to form C-C bonds using transition metal catalysts. A unique feature of this reaction is replacement of a leaving group on an allylic carbon with a range of suitable nucleo- philes. The Tsuji-Trost reaction is an important methodology in the preparation of allyl substituted organic molecules [1]. Asymmetric Tsuji-Trost reactions have been developed for the synthesis of enantiopure drug molecules [2]. Ionic liquids (ILs) have been investigated as reaction media in transition metal catalysis for over a decade. This is mainly because of their properties, such as low vapor pres- sure [3], non-flammability, high boiling point, and high di- electric constant. There are many examples demonstrating the use of ILs in hydrogenation [4], Heck [5], Suzuki [6], carbonyl-ene [7] and Diels-Alder reactions [8]. A number of investigations have been made to apply ILs in Tsuji-Trost *Address correspondence to these authors at the Department of Chemistry, Chair of Green Chemistry, Tallinn University of Technology, Akadeemia tee 15, Tallinn, Estonia; Tel: +372-620-4381; E-mail: Nicholas.Gathergood@ttu.ee; and Department of Chemistry, Brock University, 1812 Sir Isaac Brock Way, St. Catharines, L2S 3A1 ON, Canada; Tel: 905-688-5550 (4174); E-mail: mghavre2@brocku.ca reactions [9-15] as well as reactions with chitosan supported catalysts [16], microwave assisted reactions [17], and reac- tions in ILs-organic solvent biphasic media [18]. Toma et al. [19, 20] reported enantioselective Tsuji-Trost reactions in [bmim][PF 6 ] (1-butyl-3-methyl-imidazolium hexafluoro- phosphate) using a range of homochiral ferrocenyl phosphine ligands. ILs, may be considered 'green' alternatives to conven- tional solvents and can offer a number of benefits in chemi- cal processes. They can solubilize a wide range of inorganic and organic compounds, including immobilizing reagents and catalysts in one phase. ILs can also be utilized in high vacuum systems due to low vapor pressure, and can be recy- clable [21]. Additionally, low toxicity and biodegradable ILs have potential to be less harmful to ecosystem than the con- ventional solvents [22]. Reported data on the toxicity of [bmim] based ILs show that some examples are less toxic than conventional solvents [e.g. toluene, acetonitrile, DCM (dichloromethane) and DMSO (dimethyl sulfoxide)] [23]. The toxicity of [Rmim] (1-alkyl-3-methylimidazolium) ILs with a long hydrocarbon side chain (R = C 6 -C 10 ) have been determined to exhibit higher antimicrobial activity than shorter alkyl groups (e.g. R = C 1 -C 4 ) [24]. Hence, we chose to incorporate heteroatoms into the alkyl side chains, predict- 2213-347X/16 $58.00+.00 © 2016 Bentham Science Publishers Send Orders for Reprints to reprints@benthamscience.ae Current Green Chemistry, 2016, 3, 181-189 181 RESEARCH ARTICLE Enantioselective Tsuji-Trost Reactions in Low Toxicity Ionic Liquids