Directed ortho-Metalation-Halocyclization Route to Benzothiophenes

Significance

Reported is the synthesis of 2-aryl/alkyl-3-halo-7-oxygen functionalized benzothio­phenes starting from m-halophenyl-N,N-diethyl-O-carbamates. Directed ortho-metalation (DoM) of 1 followed by disulfide quench affords the 3-halo-2-sulfanyl carbamates 2 in good yields. Subsequent Sonogashira coupling furnishes the halocyclization precursors 3 also in good yields. Interestingly, the Sonogashira coupling failed for 2 (R^² = CH₂OH) providing only the phenol. The halocyclization step proceeds smoothly under mild conditions to afford the benzothiophenes poised for further functionalization. The cyclization fails for R^² = TIPS and E⁺ = NBS. Additionally, the selenophenes A were synthesized using the same methodology in good overall yields using Me₂Se₂ as the electrophile in the DoM reaction.