Iodine(III)‐Mediated Oxidation of Anilines to Construct Dibenzazepines**

Abstract

The development of an efficient process that produces bioactive medium-sized N-heterocyclic scaffolds from 2-substituted anilines using either iodosobenzene or (bis(trifluoroacetoxy)iodo)-benzene is reported. The tether between the sulfonamide and the aryl group can be varied to access dihydroacridine-, dibenzazepine-, or dibenzazocine scaffolds. While substitution on the aniline portion is limited to electron-neutral-or electron-poor groups, a broader range of functional groups are tolerated on the ortho-aryl substituent and site selective CÀ NAr bond formation can be achieved. Preliminary mechanistic investigations suggest that mediumring formation occurs via radical reactive intermediates.

Iodine(III)-Catalyzed Oxidative Cyclization of Aryl Amines to Construct N-Alkylbenzimidazoles

“…We discovered that an electrophilic N-aryl iminoiodinane could be generated from I(III)-mediated oxidation of orthosubstituted anilines to afford dibenzazepines. 9 Our initial goal was to achieve benzylic C−H bond amination, yet exposure of 9 to the combination of stoichiometric amount of PhI-(O 2 CCF 3 ) 2 in the presence of MgO in HFIP preferentially formed dibenzazepine 12 where 2-phenylindoline 11 was not observed. At the conclusion of our study, we were curious if we could construct N-alkylbenzimidazoles from aryl amine 13 by generating a stronger iodine(III) reagent in situ using iodobenzene as the catalyst and selectfluor as the stoichio-metric terminal oxidant.…”

“…The substrate for our study was synthesized first by a S N Ar reaction using 1-fluoro-2-nitrobenzene and piperidine followed by a reduction using iron powder and ammonium chloride. The optimization process began by submitting 13a to iodosobenzene in HFIP with 4 Å molecular sieves as an additive to remove the water by-product because we found this combination of solvent and oxidant as an efficient method in facilitating iodine(III)oxidative cyclizations. , In contrast to our previous work, a moderate yield of 16a was observed (entry 1). Doubling the amount of oxidant successfully gave a quantitative yield and reduced the reaction time to 1 h (entry 2).…”

“…However, the reaction conditions were limited to the amination of activated aminomethylenes; when 2-(pyrrolidin-1-yl)­aniline 6 was subjected to their optimal reaction conditions benzimidazole 8 was not observed. We discovered that an electrophilic N -aryl iminoiodinane could be generated from I­(III)-mediated oxidation of ortho -substituted anilines to afford dibenzazepines . Our initial goal was to achieve benzylic C–H bond amination, yet exposure of 9 to the combination of stoichiometric amount of PhI­(O 2 CCF 3 ) 2 in the presence of MgO in HFIP preferentially formed dibenzazepine 12 where 2-phenylindoline 11 was not observed.…”