Transition Metal‐Controlled Direct Regioselective Intermolecular Amidation of C−H Bonds with Azodicarboxylates: Scope, Mechanistic Studies, and Applications

Abstract

A simple and efficient transition metal-catalyzed CÀH amidation with azodicarboxylates has been developed. Under silver catalysis, the amide substrates undergo regioselective CÀH amidation at C5-position of the quinoline. Conversely, with palladium as the catalyst, the reaction gave b-C(sp 3 )ÀH amidation products via the activation of methylene C(sp 3 )ÀH bonds. Mechanistic studies suggested that the single-electrontransfer and organometallic mechanism pathways gave rise to these surprising and distinct outcomes. Based on the mechanistic analysis, we designed a palladium-catalyzed/silver-promoted direct intermolecular b-C(sp 3 )ÀH amidation to activate the methylene C(sp 3 )ÀH bonds of 5-chloro-8-aminoquinoline (CQ)-protected aliphatic amides with azodicarboxylates. Both catalytic protocols provide alternative, convenient, and simple strategies for efficiently accessing structurally unique CÀN bond-containing compounds in a regioselective manner.

Asymmetric Organocatalytic Synthesis of 2,3-Allenamides from Hydrogen-Bond-Stabilized Enynamides

“…The enynamide might be stabilized by the regulation of its molecular conformation and increased the barrier to rotation of the C–C bond a , so that the nucleophilic attack of the oxygen atom was unfavored. Based on our previous research about the N -quinolone amide, this hypothesis might be achieved with N -quinolone enynamides as the substrate due to the interaction of its intramolecular H-bonds (Scheme , eq 3) . This assumption was indeed supported by the H-bonds (N–H···N and C–H···O) and approximately plane conformation of enyamide 1m observed in the X-ray crystal structure (see SI), in which the oxygen and alkynyl group were on the opposite side of the C–C single bond a .…”

How the Conformational Movement of the Substrate Drives the Regioselective C–N Bond Formation in P450 TleB: Insights from Molecular Dynamics Simulations and Quantum Mechanical/Molecular Mechanical Calculations

“…Among these types of reactions catalyzed by P450, the biosynthesis of the C–N bond is particularly attractive, ,− since nitrogen heterocycles constitute one of the most prevalent motifs in drugs . Unlike many chemical approaches, the recently characterized P450 TleB can catalyze the intramolecular C–H aminations in benign conditions. , P450 TleB from Streptomyces blastmyceticus was found to catalyze the biosynthesis of indolactam V ( 2 ) from the dipeptide N -methyl- l -valyl- l -tryptophanol (NMVT, 1 ) via forming the C4–N13 bond of indolactam (Scheme ).…”

Supramolecular synthon hierarchy in cyclopropyl-containing peptide-derived compounds

“…Consequently, 33 crystal structures consisting of cyclopropyl were extracted. The CSD refcodes of these entries are as follows: ADELOM, ADELUS, ADEMAZ, ADEMED, 119 APOFOD, 120 BUTCIE, 121 CARYAY, 122 CATWEA, 123 CEGVUH, 124 CERQUM, 125 EDIWIZ, 126 FIJDIO, 127 GENYUU, 128 HILXIM, 129 HORZEU, 130 IHUFEY, 131 JAWLAU, 132 KEZNEJ, 133 KUDZIS, 134 LIKFIX, 135 MENHIW, 136 MOYSEB, 137 PEDWOM, 138 ROPQUL, 139 VEHDIY, 140 VETKEL, 141 WICMIH, 142 WOVXAG, 143 XICRAC, 144 ZAMJEF, ZAMJOP, 145 ZEGGEZ, 146 and ZUQBIY. 147 The molecular views and basic crystallographic data for the literature ‘hits’ are summarized in Tables S2 and S3,† respectively.…”