Catalytic Asymmetric[4+1]Spiroannulation ofα-Bromo-βNaphthols with Azoalkenes by an Electrophilic Dearomatization/S_(RN)1-Debromination Approach

An enantioselective[4+1]spiroannulation ofαbromo-β-naphthols with azoalkenes has been developed for the one-step construction of a new class of pyrazoline-based spirocyclic molecules.Using chiral Cu(II)/Box catalysts,asymmetric induction was achieved with high levels of enantioselectivity[up to 99:1 enantiomeric ratio(er)].Notably,α-chloroandα-iodo-substitutedβ-naphthols were also tolerated by this reaction.Mechanistic studies disclosed that this process was triggered by electrophilefacilitated dearomatization ofα-bromo-β-naphthols and followed by the debromination via SRN 1-subsitution with in situ-formed N-nucleophile.The chiral copper(II)-species,bound with azoalkene moiety,was assumed to control the enantiodiscrimination over the naphthoxy C-radical that was generated from the debromination step.Moreover,the potential utility of this protocol was greatly amplified by the derivatization of spirocyclic products through oxidative dearomatization of the other aromatic ring in the naphthyl fragment,providing a rather attractive route for the rapid generation of synthetically more valuable doubly dearomatized architectures.