4H,5H,6H-cyclopenta(b)thiophen-6-one → 2-(4H-cyclopenta[b]thiophen-6-yl)benzaldehyde

Participants

Reaction Steps

This scheme can be summarized as follows: 2-(2-bromophenyl)-1,3-dioxolane (A) is treated with 2 equivalents of tert-butyl lithium to effect halogen-methyl exchange. The 2-(2-lithiophenyl)-1,3-dioxolane (B) is then reacted in situ with 4,5-dihydro-6H-cyclopenta[b]thiophen-6-one. After aqueous acid workup, 2-(4H-cyclopenta[b]thiophen-6-yl)benzaldehyde (C) is isolated by flash chromatography. This is treated with a Grignard reagent (R4MgBr) to provide the 6-[2-(1-hydroxyalkyl)phenyl]-4H-cyclopenta[b]thiophene (D) which is subsequently oxidized to the 6-[2-(alkylcarbonyl)phenyl]-4H-cyclopenta[b]thiophene (E). Reductive amination of E should then provide compounds of structure III.

Provenance & Evidence