Zinc and Nickel-Salophen Catalysts in Mediated Electrohydrocyclization Reactions
Authors: Miranda James A , Zepeda Nancy , Littell Lauren , Clendenin Brittanie 
Published: February 2020

Electrohydrocyclization (EHC) refers to those processes which undergo an electrochemically promoted reductive cyclization leading to the formation of a new sigma bond between the beta-carbons of alpha, beta-unsaturated esters or nitriles. Moens, Baizer, and Little reported the use of an EHC reaction as the key step in the total synthesis of the natural product 1-sterpurene.1 Nickel-salen compounds have been shown as effective electron transfer agents in mediated electrohydrocyclization reactions.2 Experimental and computational methods have provided evidence that electron transfer occurs primarily through an inner-sphere process, implying the existence of a ligand-centered radical anion as the electron transfer agent.3

Our current study has focused upon changing the identity of the metal and changing the structure of the ligand in hopes of stabilizing the radical anion intermediate, resulting in a more efficient inner sphere electron transfer. The compounds we studied are shown in Figure 1.

Figure 2 cyclic voltammetry showed that Zn-salophen 1 gives an irreversible wave at -1.70 V (vs Ag/AgCl) and Ni-salophen 2 gives a reversible wave at -1.60 V (vs Ag/AgCl). 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.

Both compounds 1 and 2 exhibited catalytic activity towards mediated EHC (Scheme 1). Controlled potential electrolysis using 5 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 reactions proceeded with >95% product conversion after 2 hours and yielded similar cis:trans ratios for both catalysts. The cis: trans ratio using Zinc-salophen (1) was 35:65 and for Nickel-salophen (2) was 32:68. These results showed an improvement over previous metal-salen mediated EHC reactions with higher yields and faster reaction times.

Future work includes the investigation of other metal-salophens (different metals and varying the ligand structure) to further stabilize the radical anion intermediate. We also wish to develop a solid-phase version of mediated EHC using polymer supported metal-salen catalysts that utilize Merrifield resin or possibly zeolite frameworks for heterogeneous catalysis.

References

L. Moens, M.M. Baizer, and R.D. Little. J. Org. Chem.,
51, 4497 (1986).

J. A. Miranda, C.J. Wade, and 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).

Acknowledgments

We gratefully acknowledge Sacramento State University for their support of this research through the Instructionally Related Activities Grant (ASI), Russell-Forkey Summer Research Award (Chemistry Department), and Faculty Endowment for Student Scholarship Award. We also thank the Sacramento State College of Natural Science and Mathematics for funding this research.

Figure 1