PhI?OCOCF₃?₂-Mediated Construction Of A 2-Spiropseudoindoxyl Skeleton Via Cascade Annulation Of 2-Sulfonamido-N-phenylpropiolamide Derivatives

The spiropseudoindoxyl skeleton,one of the key heterocyclic structures,is abundant in many indole alkaloids.It has been found that many potent antiviral agents that exhibit promising anticancer properties or potent opioid agonistic activities are alkaloids bearing a spiropseudoindoxyl core.Literature survey showed that a handful of synthetic methods have been reported for the construction of2-spiropseudoindoxyls by now.However,most ring-constructing reactions so far established involve transition-metal reagents such as organopalladium and gold-complex.³ There is still a demand for methodology research in formulating novel cascade annulation reactions that are adapted for metal-free conditions.Westartedoutourinvestigation,choosingcompound2-sulfonamido-N-phenylpropiolamide 116a,a relatively easily prepared product from commercially available propargylic acid and N-methylaniline in a straight forward three-step process,as the model substrate.After a series of conditions screening,we prepared 2-spiropseudoindoxyl product by using PIFA as oxidant in DCE under ice bath.So in this paper we developed a new method for the synthesis of additional2-spiropseudoindoxyl derivatives 117.To verify the substrate adaptability which PIFA-mediated C?sp²?-C?sp?and C?sp?-N bond formation,we also prepared a series of amides substrates.Experimental results show that eighteen 2-spiropseudoindoxyl derivatives have been synthesized under optimal conditions.Both the substrates and products have been well characterized by melting point,¹H NMR,¹³C NMR.In addition,they were also confirmed by HRMS.What'more,they are undoubtedly characterized through X-ray crystallography.According to these control experimental results as well as our previous studies,we propose two plausible mechanistic pathways for this newly discovered PIFA-mediated tandem oxidation reaction.