Oxidation of Nonactivated Anilines to Generate N-Aryl Nitrenoids

Abstract

A low-temperature, protecting-group-free oxidation of 2-substituted anilines has been developed to generate an electrophilic N-aryl nitrenoid intermediate that can engage in C–NAr bond formation to construct functionalized N-heterocycles. The exposure of 2-substituted anilines to PIFA and trifluoroacetic acid or 10 mol % Sc­(OTf)3 triggers nitrenoid formation, followed by productive and selective C–NAr and C–C bond formation to yield spirocyclic- or bicyclic 3H-indoles or benzazepinones. Our experiments demonstrate the breadth of these oxidative processes, uncover underlying fundamental elements that control selectivity, and demonstrate how the distinct reactivity patterns embedded in N-aryl nitrenoid reactive intermediates can enable access to functionalized 3H-indoles or benzazepinones.

I(III)-Catalyzed Oxidative Cyclization–Migration Tandem Reactions of Unactivated Anilines

“…In contrast, catalytic reactions that construct C–NAr bonds employ an aryl azide or nitroarene as the N atom source require heat or superstoichiometric quantities of reductant to access the electrophilic N -aryl nitrogen intermediate. , Oxidative methods that generate the electrophilic N -aryl intermediate are less common and require an N -electron-withdrawing substituent on the aniline. We discovered that electrophilic N -aryl nitrenoids could be generated from I­(III)-mediated oxidation of unactivated 2-substituted anilines and trapped to afford benzazepinones or 3 H -indoles . At the conclusion of our study, we were curious if catalysis could be achieved by pairing iodobenzene with a superstoichiometric oxidant.…”

Recent discoveries on the structure of iodine(iii) reagents and their use in cross-nucleophile coupling

“… 19 Primary anilines on the other hand can be coupled intramolecularly to alkenes as the secondary nucleophiles ( Scheme 6c ). 90 After attack of the double bond onto the umpolung species, the alkyl substituent in intermediate 35 migrates preferentially. However, in other cases the phenyl has a larger migratory aptitude to shift onto the carbocationic position.…”

Recent Advances in the Development of Catalytic Methods that Construct Medium-Ring Lactams, Partially Saturated Benzazepines and Their Derivatives

“…Driver and co-workers reported in 2020 that benzazepinones 128 could be constructed from cyclobutanol-substituted anilines (Scheme 27). 51 The authors anticipated that the putative N-aryl nitrenoid intermediate might be accessed by a low-temperature oxidation of 136 and were curious to see whether it would exhibit similar reactivity to that of the rhodium N-aryl nitrene generated from the analogous aryl azide. After optimization, the authors determined that exposure of aniline 136 to 1.5 equivalents of PhI(O 2 CCF 3 ) 2 and 10 mol% of Sc(OTf) 3 in TFE at 0 °C to room temperature produced benzazepinone 128.…”