Facile Synthesis of Benzocyclohepta[1,2‐ c ]pyrazoles Starting from Morita–Baylis–Hillman Adducts Via an Intramolecular Friedel‐Crafts Alkenylation

Recently, we reported the synthesis of 1H-benzo[g]indazoles via a sequential propargyl-allenyl isomerization and 6πelectrocyclization protocol of the pyrazole 2a, as shown in Scheme 1. We also observed that an intramolecular Friedel-Crafts (IMFC) alkenylation of the pyrazole 2a could produce benzocyclohepta[1,2-c]pyrazole 3a in the presence of H2SO4 via the vinyl cation intermediate I. 1 The pyrazole 2a, bearing an arylpropargyl moiety at position 4, was prepared from Morita–Baylis–Hillman (MBH) adduct by sequential bromination, introduction of arylpropargyl moiety to formα,β-enone1a, and a one-pot synthesis of pyrazole2a by the reaction of 1a and phenylhydrazine. Various benzocyclohepta[1,2-c]pyrazole derivatives have been known as canabinoid-1 (CB1) antagonists, and most of the syntheses of these compounds used benzosuberones (benzocycloheptanones) as starting materials. To the best of our knowledge, the construction of seven-membered ring of benzocyclohepta[1,2-c]pyrazole by IMFC approach has not been reported. Thus, we decided to examine the synthesis of benzocyclohepta[1,2-c]pyrazoles from 4-phenylpropargyl-5-arylpyrazoles by IMFC approach under various conditions. Initially, we examined the feasibility for the synthesis of 3a from 2a under various conditions as summarized in Table 1. The use of p-TsOH, FeCl3, 6d,g,7c InCl3, 7a or InBr3 7a