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

The combination of catalytic aqueous hydrochloric acid (HCl) and -bromosuccinimide (NBS) generated electrophilic bromine monochloride (BrCl), which readily induced spiroannulation of 2-alkynolyl anilides ( = 1-3) to form -dibromospirocyclic benzo[][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[][1,3]oxazine, which was useful both as a pharmacophore and synthetic precursor. In addition, the current protocol allowed to effortlessly introduce the sp--dibromide carbon adjacent to the sterically demanding spiroketal center. These spiroheterocycles ( = 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 4-furo[3,2-]indoles. Additionally, the current protocol was flexible and adaptable to preparing the -dichloride variants.