Abstract
Electrohydrocyclization (EHC) reactions were introduced by Baizer in 1966 which ring closure was achieved through electrolytic reductive coupling of alpha-beta unsaturated double bonds. Baizer successfully demonstrated ring closure of 3, 5, and 6-membered rings. Building on this work in the 2000’s, Miranda, Wade, and Little investigated the use of a Ni(II)salen mediator to enhance yields and reduce by-products. Subsequent studies showed successful ring closure under various conditions but were limited to 6-membered rings. Medium-sized rings are often used pharmaceutically, may rely on long synthetic routes or isolation of natural products. The purpose of this work is to investigate the possibility of medium-sized ring synthesis via EHC. Cyclic voltammetry was performed to determine the electrochemical behavior of each sized substituents. It was determined that 7, 8, and 10-membered substrates showed strong potential for electrochemical reduction. Bulk electrolysis reactions were carried out at different working potentials on each substrate for ≥8 hours. Characterization data supports evidence of successful ring closure for each 7, 8, and 10-membered rings in the presence of by-products. The 6-membered ring diethyl 2,2’-(1,2-cyclohexanediyl)diacetate was successfully synthesized with a crude recovery after column chromatography of 21.4% and a cis/trans ratio of 1.4:1. The 7-membered ring diethyl 2,2’-(1,2-cycloheptanediyl)diacetate had a 102% crude recovery with a cis/trans ratio 7.08:1, the 8-membered ring diethyl 2,2’-(1,2-cycloocantedaiyl)diacetate had a 39.9% crude recovery with a cis/trans ratio 8.28:1, and the 10-membered ring diethyl 2,2’-(1,2-cyclodecanediyl)diacetate had a 53.0% crude recovery with a cis/trans ratio 25.4:1. Future work includes methods to increase reaction yields and reduce by-products.