Hypoiodite-Catalyzed Oxidative Umpolung of Indoles for Enantioselective Dearomatization
Hiroki Tanaka, Naoya Ukegawa, Muhammet Uyanik, Kazuaki Ishihara
Abstract
Here we report the oxidative umpolung of 2,3-disubstituted indoles toward enantioselective dearomative aza-spirocyclization to give the corresponding spiroindolenines using chiral quaternary ammonium hypoiodite catalysis. Mechanistic studies revealed the umpolung reactivity of C3 of indoles by iodination of the indole nitrogen atom. Moreover, the introduction of pyrazole as an electron-withdrawing auxiliary group at C2 suppressed a competitive dissociative racemic pathway, and enantioselective spirocyclization proceeded to give not only spiropyrrolidines but also four-membered spiroazetidines that are otherwise difficult to access.
Topics & Concepts
UmpolungChemistryEnantioselective synthesisIndole testReactivity (psychology)CatalysisOxidative phosphorylationPyrazoleCombinatorial chemistryOrganocatalysisOrganic chemistryStereochemistryMedicineAlternative medicinePathologyNucleophileBiochemistryOxidative Organic Chemistry ReactionsCatalytic C–H Functionalization MethodsSynthesis and Catalytic Reactions