Synthesis of highly substituted 3-formylfurans by a gold(I)-catalyzed oxidation/1,2-alkynyl migration/cyclization cascade

Abstract

3-Formylfuran derivatives are core structures of a variety of bioactive natural products. However, procedures for their preparation are still rare and generally inefficient in terms of atom economy: These methods require multiple steps or harsh reaction conditions and show selectivity problems. An efficient gold(I)-catalyzed cascade reaction that leads to 3-formylfurans from easily accessible starting materials is now described. A wide variety of 3-formylfurans were obtained from the corresponding symmetric and unsymmetric 1,4-diyn-3-ols in the presence of an N-oxide in good to excellent yields. Isotope-labeling experiments as well as DFT calculations support a mechanism in which, after an initial oxygen transfer, a 1,2-alkynyl migration is favored over a hydride shift; a cyclization ensues to afford the desired functionalized furan core. Blazing a new trail: 3-Formylfurans were prepared by a gold(I)-catalyzed cascade reaction that involves oxidation, 1,2-alkynyl migration, and cyclization from simple, easily available 1,4-diyn-3-ols. Isotope-labeling experiments and DFT calculations were carried out to elucidate the reaction mechanism. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.