Regioselective ring-opening cyclization of spirocyclopropanes with NaSH proceeded smoothly, and subsequent addition of an acid afforded tetrahydrobenzo[b]thiophen-4-ones that could be converted into the 4-hydroxybenzo[b]thiophenes. This protocol provides an alternative synthetic method to access benzo[b]thiophenes without using multisubstituted benzenes as starting materials, which are often difficult to prepare.

Abstract

A novel approach for the construction of the benzo[b]thiophene skeleton has been developed. Regioselective ring-opening cyclization of cyclohexane-1,3-dione-2-spirocyclopropanes using sodium hydrosulfide as a sulfur-transfer reagent proceeded smoothly and subsequent addition of an acid afforded the corresponding tetrahydrobenzo[b]thiophen-4-one derivatives in good to excellent yields. Cycloheptane-1,3-dione-2-spirocyclopropanes could be also applied to the present protocol. In contrast, the reaction of monocyclic 1,1-diacetyl-2-phenylcyclopropane with sodium hydrosulfide and subsequent addition of an acid gave decomposition products instead of the desired product. This result suggests that the spiro structure is crucial for successful ring-opening cyclization. One of the products obtained from cyclohexane-1,3-dione-2-spirocyclopropanes could be converted into the 2-substituted 4-hydroxybenzo[b]thiophene derivative while avoiding oxidation of the sulfide to sulfoxide or sulfone. This protocol provides an alternative synthetic method to access benzo[b]thiophenes without using multisubstituted benzenes as starting materials, which are often difficult to prepare. To our knowledge, this is the first report of the synthesis of benzo[b]thiophenes from cyclopropanes.