Dibrominative Spirocyclization of 2‑Butynolyl Anilides: Synthesis of gem-Dibromospirocyclic Benzo[d][1,3]oxazines and Their Application in the Synthesis of 4H‑Furo[3,2‑b]indoles

The combination of catalytic aqueous hydrochloric acid (HCl) and N-bromosuccinimide (NBS) generated electrophilic bromine monochloride (BrCl), which readily induced spiroannulation of 2-alkynolyl anilides (n = 1–3) to form gem-dibromospirocyclic benzo­[d]­[1,3]­oxazines in up to 92% yield. The reaction occurred under mild and metal-free conditions using EtOAc as a green solvent. The resulted spirocyclic products contained benzo­[d]­[1,3]­oxazine, which was useful both as a pharmacophore and synthetic precursor. In addition, the current protocol allowed to effortlessly introduce the sp3-gem-dibromide carbon adjacent to the sterically demanding spiroketal center. These spiroheterocycles (n = 1) were shown to be synthetically versatile and conveniently maneuvered. Base-promoted debrominative aromatization of these spirocycles unmasked rare and synthetically useful 2-aryl-3-bromofurans in mostly excellent yields. These 3-bromofurans were well-suited substrates for intramolecular Ullmann C–N bond coupling to construct difficult-to-prepare 4H-furo­[3,2-b]­indoles. Additionally, the current protocol was flexible and adaptable to preparing the gem-dichloride variants.