A Facile Access to Primary Alkylamines and Anilines via Ir(III)-Catalyzed C–H Amidation Using Azidoformates

Abstract

Described herein is the development of Ir­(III)-catalyzed direct C–H amidation using azidoformates as a readily deprotectable amino source. Substrates with unactivated methyl C­(sp3)–H and aromatic or olefinic C­(sp2)–H bonds were smoothly reacted by the iridium-based catalyst system to provide the corresponding primary alkylamines and anilines upon the subsequent removal of N-protecting groups, such as Boc, Fmoc, Cbz, pNZ, or Troc. A brief mechanistic study and synthetic applications are also presented.

Ligand-Promoted meta-C–H Amination and Alkynylation

“…9 Several transition metals, such as Ir, Ru, Rh, Pd, Fe, Co, and Cu, have been used for this purpose to afford amines and amides directly from C–H bonds. 10 However, direct C‒H amination at remote positions has not yet been reported. Based on the previous finding that 3-acetylamino-2-hydroxy pyridine based ligands can promote the meta -arylation of anilines with a broad substrate scope, we chose the aniline 1a as a model substrate to examine the feasibility of developing a meta -C–H amination reaction using norbornene as a transient mediator.…”

Quinolines from the cyclocondensation of isatoic anhydride with ethyl acetoacetate: preparation of ethyl 4-hydroxy-2-methylquinoline-3-carboxylate and derivatives

“…The anhydrides 9a – h were readily accessible by treatment of anthranilic acids AA with one equivalent of triphosgene in refluxing tetrahydrofuran at 0.36 molar concentration ( Scheme 3 ). This procedure is an alternative to the existing published protocol that relies on the use of toxic phosgene gas [ 23 ] as the acylating agent by replacing it with the non-volatile and weighable solid triphosgene [ 24 – 25 ]. After stirring for 12 hours, the reaction mixtures were quenched by pouring into approximately 30 volumes of water (1 volume = 10 mL of water per 1 gram of substrate) with subsequent stirring at room temperature for one hour.…”

Cu‐Catalyzed Directed C7−H Imidation of Indolines via Cross‐Dehydrogenative Coupling

“…documented almost simultaneously a very closely related work to Chang's report using same metal catalyst . In the quest of developing novel aminating sources, the Chang group further disclosed a protocol for the indoline C7 amidation using phosphoryl azides and azidoformates, albeit again via iridium catalysis . Dioxazolones and anthranils have also been explored as alternative aminating reagents for the indoline amidation.…”