Hybrid Synthetic and Computational Study of an Optimized, Solvent-Free Approach to Curcuminoids

Valeria A Stepanova; Andres Guerrero; Cullen Schull; Joshua Christensen; Claire Trudeau; Joshua Cook; Kyle Wolmutt; Jordan Blochwitz; Abdelrahman Ismail; Joseph K West; Amelia M Wheaton; Ilia A Guzei; Bin Yao; Alena Kubatova

doi:10.1021/acsomega.1c07006

Hybrid Synthetic and Computational Study of an Optimized, Solvent-Free Approach to Curcuminoids

ACS Omega. 2022 Feb 21;7(8):7257-7277. doi: 10.1021/acsomega.1c07006. eCollection 2022 Mar 1.

Affiliations

¹ Department of Chemistry and Biochemistry, University of Wisconsin La Crosse, 1725 State Street, La Crosse, Wisconsin 54601, United States.
² Department of Chemistry, Winona State University, 175 West Mark Street, Winona, Minnesota 55987, United States.
³ Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, Wisconsin 53706, United States.
⁴ Department of Chemistry, University of North Dakota, 151 Cornell Street, Grand Forks, North Dakota 58202, United States.

Abstract

A green and optimized protocol has been developed for the preparation of symmetric 1,7-bis(aryl)-1,6-heptadiene-3,5-diones and asymmetric 2-aryl-6-arylidenecyclohexanones with modified substrate scope and good functional group tolerance. Syntheses proceed smoothly under solvent-free conditions, providing moderate to excellent product yields with a minimal workup procedure. Control experiments, spectroscopic, and computational studies support a mechanism involving the boron-assisted in situ generation of imine intermediates. Crystal structures of three curcuminoids and isolated mechanistic intermediates are reported. The data provide insight for the further development of solvent-free protocols toward diverse curcumin derivatives in the fields of pharmaceutical and synthetic chemistries.