Metal-Free Intermolecular Oxidative C–N Bond Formation via Tandem C–H and N–H Bond Functionalization

Abstract

The development of a novel intermolecular oxidative amination reaction, a synthetic transformation that involves the simultaneous functionalization of both an N-H and C-H bond, is described. The process, which is mediated by an I(III) oxidant and contains no metal catalysts, provides a rapid and green method for synthesizing protected anilines from simple arenes and phthalimide. Mechanistic investigations indicate that the reaction proceeds via nucleophilic attack of the phthalimide on an aromatic radical cation, as opposed to the electrophilic aromatic amination that has been reported for other I(III) amination reactions. The application of this new reaction to the synthesis of a variety of substituted aniline derivatives is demonstrated.

Metal-Catalyzed and Metal-Free Intermolecular Amination of Light Alkanes and Benzenes

“…Noteworthy are analogous efforts by Antonchick and co-workers, 74 who at about the same time as the Cho-Chang 13 and DeBoef 72 reports, disclosed amidations of simple arenes (2 equiv.) by acetanilides in the presence of PhI(OAc) 2 (1.5 equiv.)…”

“…Almost contemporaneously with the Cho-Chang contribution, DeBoef and co-workers 72 disclosed an almost identical system for the imidation of aromatics by several cyclic imides, although only phthalimide and succinimide provide good yields (Scheme 24). Notably, the substrate can be present as solvent (4.0 mL), but also in small excess (1.5 equiv.)…”

“…Indeed, the authors favor a standard electrophilic aromatic metallation by Au(III), which is electronically ortho / para directed, but due to the bulk of the metal, auration of the para position is preferred (Scheme 31(b)). A certain degree of meta activation is also observed, presumably owing to the intervention of low-level, metal-free imidation (as noted in DeBoef’s contribution 72 noted above), especially with electron-deficient arenes, for which electrophilic auration tends to be slow. The role of PhI(OAc) 2 is considered to be dual, first by enabling the oxidation of Au(I) to Au(III), and further by engaging in transmetallation of the PhthN- moiety from a preformed PhthN-I(OAc)Ph to Au(III) (albeit in a redox unbalanced step).…”

Hypervalent Iodine(III) in Direct Carbon–Hydrogen Bond Functionalization

“…Independently, DeBoef's group developed the PIDA-mediated intermolecular imidation of simple arenes using phthalimide. 12 High temperature was required in this case too. A broad scope of the reaction was demonstrated.…”

Oxidative Heterocycle Formation Using Hypervalent Iodine(III) Reagents

“…The final products were obtained with high regioselectivity and are amenable for further amination as was demonstrated by the successful amination of 146 by benzoxazinone 147 (Scheme 36 (2)). Simultaneously, Chang's [101] and DeBoef's group [102] independently reported an intermolecular oxidative amination of simple arenes using PIDA as a stoichiometric oxidant (Scheme 37). The authors were able to arylate several heterocycles to form new C-N bonds under the respective reaction conditions.…”