MCC/S_NAr methodology. Part 1: Novel access to a range of heterocyclic cores

The novel solution-phase syntheses of arrays of biologically relevant indazolinones, benzazepines and benzoxazepines, utilizing multi-component condensation (MCC)/S_NAr methodology is reported. Reaction of commercially available 2-fluoro-5-nitrobenzoic acid with an aldehyde, isonitrile and a primary amine tethered to a Boc-protected internal amino or hydroxyl nucleophile, affords the Ugi product in good yield. Subsequent acid treatment followed by proton scavenging promotes cyclization of internal amino nucleophiles to a variety of ring sizes. Base treatment alone is sufficient to generate benzoxazepines. Interestingly, this communication also introduces a highly efficient two-step route to benzimidazoles.