RUI: New approaches to the synthesis of 1-benzoxocanes

Western Washington University, Bellingham WA

Investigators

Abstract

This project addresses the development of general synthetic methods for the construction of 1-benzoxocanes. Several complementary strategies, involving both C-O and C-C bond-forming reactions, will be pursued. An 8-endo cyclization of a phenol nucleophile onto the more substituted position of an epoxide using bulky Lewis acid catalysts will be explored, with conformational constraints and electronic bias in the cyclization substrate favoring cyclization over epoxide rearrangement. Alternately, metal-catalyzed processes will be explored, including addition of a phenol nucleophile to a tethered alkene by Pd-catalyzed Wacker-type cyclization or by activating the alkene with electrophiles [PhSeX, Hg(II), I+, Ag(I), Au(I), Ru(III) and Ir(III)], intramolecular Pd-catalyzed etherification between an aryl triflate and a tertiary alkoxide, and intramolecular arylation of a tethered alkene [silane-terminated Heck reaction, Ru(III), I+], allene (Heck reaction), or epoxide [Au(III)]. With this RUI award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor James R. Vyvyan, of the Department of Chemistry at Western Washington University. Medium-sized ring compounds hold a special place in organic chemistry due to their presence in biologically active compounds and the challenge they present to the synthetic chemist. Professor Vyvyan and his students are exploring a variety of new strategies for the efficient synthesis of 1-benzoxocanes, 8-membered ring ethers fused to an oxygenated aromatic ring. The synthetic methods to be developed in this project will be valuable tools for the preparation of compounds that have potential as agrochemicals (heliannuols) and as drug leads (heliananes). The project is modular, using a few key cyclization substrates assembled by similar methods to test many different cyclization reagents and reaction conditions. This modular nature allows each student researcher to have their own project, and still make meaningful contributions to the long-range goal of synthesizing benzoxocane-containing natural products like the heliannuols and heliananes.