Copper-mediated construction of benzothieno[3,2- b]benzofurans by intramolecular dehydrogenative C-O coupling reaction

Abstract

An efficient method to synthesize benzothieno[3,2-b]benzofurans via intramolecular dehydrogenative C-H/O-H coupling has been developed. Good to excellent yields (64-91%) could be obtained no matter if the substituted group is electron-donating or electron-withdrawing. Notably, three-to-six fused ring thienofuran compounds could be constructed using this method. A reaction mechanism study showed that 1,1-diphenylethylene can completely inhibit the reaction. Therefore, it is a radical pathway initiated by single electron transfer between the hydroxyl of the substrate and the copper catalyst.

Scheme 1. Synthetic strategies toward BTBFs.

Scheme 2. Reaction scope for the intramolecular dehydrogenative C–O coupling reaction under optimized conditions. ^a The yields in the parenthesis reported in our previous paper are shown for comparison with this work.

Fig. 1. Gram-scale synthesis.

Scheme 3. Kinetic isotope effect study. Reaction conditions: 1a and 1a-D (0.20 mmol), Cu catalyst (3 equiv., 0.6 mmol), base (1 equiv., 0.20 mmol), solvent (4 mL), 110 °C, 6 h under nitrogen.

Scheme 4. Free radical capture experiment.

Scheme 5. Proposed mechanism.