An unusual reaction mode of 1-phenylpyrazolidinones toward diazonaphthalen-2(1H)-ones featuring cascade C(sp2)-H and C(sp3)-H bond cleavage

Herein, a novel synthesis of pyrazolidinone fused 1,3-benzooxazepine derivatives via a formal [4 + 3] annulation reaction of 1-phenylpyrazolidinones with diazonaphthalen-2(1H)-ones is presented. Mechanistically, the formation of products involves an unprecedented reaction mode of 1-phenylpyrazolidinone featuring cascade C-alkylation/C-annulation through C(sp(2))-H/C(sp(3))-H bond cleavage instead of C-alkylation/N-annulation via C(sp(2))-H/N-H bond cleavage as reported in previous studies on the reaction of 1-phenylpyrazolidinone. In this cascade process, the pyrazolidinone unit firstly acts as an embedded directing group to assist in the alkylation and subsequently it is transformed into a cyclic iminium species to undergo an intramolecular nucleophilic addition with the in situ formed naphthol unit to give the polycyclic product. Compared with literature methods for the preparation of N-fused 1,3-oxazepines, the protocol developed herein has advantages such as easily accessible starting materials, structurally complex and biologically attractive products, a unique mechanistic pathway, and excellent chemo/regioselectivity.

Automated summary

A novel synthesis of pyrazolidinone fused 1,3-benzooxazepine derivatives via a formal [4 + 3] annulation reaction of 1-phenylpyrazolidinones with diazonaphthalen-2(1H)-ones is presented. The mechanism involves an unprecedented reaction mode of 1-phenylpyrazolidinone, featuring cascade C-alkylation/C-annulation through C(sp(2))-H/C(sp(3))-H bond cleavage. Compared with literature methods, this protocol offers advantages such as easily accessible starting materials, structurally complex and biologically attractive products, a unique mechanistic pathway, and excellent chemo/regioselectivity.