Regioselective Preparation of Benzo[b]furans from Phenols and α-Bromoketones

In this paper, a fully regiocontrolled synthesis of either 2- and 3-substituted benzo­[b]­furans is described. Direct reaction between phenols and α-bromoacetophenones in the presence of neutral alumina yields 2-substituted benzo­[b]­furans with complete regiocontrol. When a basic salt such as potassium carbonate is used, the corresponding 2-oxoether is obtained. Cyclization of these latter compounds promoted by neutral alumina yields the corresponding 3-substituted benzo­[b]­furans. Using the former method, Moracin M and other analogues can be obtained from commercial sources in two preparative steps. DFT calculations provide reasonable reaction paths to understand the formation of 2-substituted benzo­[b]­furans.