Polymer Supported Metal-Salen Catalysts in Mediated Electrohydrocyclization Reactions

Abstract

The electrohydrocyclization (EHC) reactions have both been used extensively as the key step in the synthesis of several anti-cancer compounds and natural products.1 Metal-salen compounds can serve as excellent electrochemical mediators in these reactions, resulting in a chemoselective process due to the reaction being run at a more positive potential than unmediated reactions.2 In addition, since only a catalytic amount of mediator is needed, the resultant chemical waste is greatly reduced, resulting in a more environmentally friendly reaction. Previous work in our group studied these catalytic reactions experimentally and computationally.3 This poster will focus upon our efforts to develop a polymer supported metal-salen compound that can serve as a catalyst in EHC reactions. Synthesis of a metal-salen compound that could be anchored to a polystyrene resin was accomplished using a modified procedure from Jacobsen.4 Several catalysts were studied and one example is shown in Figure 1. The primary benefit of this heterogeneous catalyst is the improvement upon reaction workup and purification. The solid phase metal-salen compounds were studied by cyclic voltammetry to establish their conductive properties. Infrared spectroscopy and atomic absorption were used to characterize the polymer supported catalysts. Cyclic voltammetry (Figure 2) showed that 5 mM Ni-salen 1 gives a reversible wave at -1.6 V (vs Ag/AgCl). When 50 mM EHC substrate 3 was added to the Ni-salen solution, the existence of a catalytic current was found to exist. The cyclic voltammograms were run using a glassy carbon working electrode, platinum wire counter electrode, and a Ag/AgCl reference electrode. The experiment was run in dimethylformamide (DMF) solvent using 0.1 M tetrabutylammonium hexafluorophosphate as the supporting electrolyte at a scan rate of 0.2 V/sec. Compound 1 exhibited catalytic activity towards electrohydrocyclization (Scheme 1). Controlled potential electrolysis using 10 mol % mediator, dimethyl malonate as proton donor, 0.1 M tetrabutylammonium hexafluorophosphate as supporting electrolyte in dimethylformamide gave cyclized products cis (4) and trans (5). The reaction proceeded with >95% product conversion after 2 hours and yielded a cis:trans ratio of 38:62. These results showed an improvement over previous metal-salen mediated electrohydrocyclizations with higher yields and faster reaction times. We also investigated several other compounds, all of which exhibited catalytic activity as well. We ran the cyclization reaction using non-polymer supported catalysts first, and then compared the results to the polymer supported catalyst. ACKNOWLEDGEMENTS We are grateful to the Sacramento State University (College of Natural Science and Mathematics and Associated Students, Inc.) for their support of this research. We are also grateful to the Associated Students, Inc. for supplying an Instructionally Related Activities grant to support our research. REFERENCES L. Moens, M.M. Baizer, R.D. Little. J. Org. Chem., 51, 4497 (1986).J. A. Miranda, C.J. Wade, R.D. Little. J. Org. Chem., 70, 8017 (2005).J.M. Yates, J.S. Fell, J.A. Miranda, B.F. Gherman. J. Electrochem. Soc., 160, G3080 (2013).D.A. Allen, E.N. Jacobsen J. Am. Chem. Soc., 121, 4147 (1999). Figure 1