Efficient and accessible silane-mediated direct amide coupling of carboxylic acids and amines

Abstract

A highly practical method for the direct coupling of amines and unactivated carboxylic acids to form amides.

In situ silane activation enables catalytic reduction of carboxylic acids

“…This reaction design was predicated on previous observations that silyl esters function as activated carboxylic acids and that they are more potent reductants than phenylsilane. 34,35 Herein, we demonstrate that phenylsilane, in combination with substoichiometric N-methylmorpholine and Zn(OAc) 2 , effects the reduction of a range of carboxylic acids. This gives rise to a practical method for the reduction of carboxylic acids in standard laboratory glassware and demonstrates the principle of in situ silane activation of substrate and reductant.…”

Zirconium oxo clusters as discrete molecular catalysts for the direct amide bond formation

“…[18][19][20][21] In this context, we demonstrate herein that ZrOC can be developed into efficient catalysts by using the discrete dodecanuclear Zr-oxo cluster [Zr 6 IJOH) 4 O 4 IJOAcr) 12 ] 2 (OAcr = acrylate) (Zr 12 ) as a catalyst for the direct amide bond formations. [22][23][24][25][26][27] Catalytic amide bond formation [28][29][30][31][32][33][34][35][36][37] by direct condensation of non-activated carboxylic acids and amines is among the most relevant reactions enabled by Zr catalysts, [38][39][40][41] given their favorable atom economy compared to the amide coupling reagents, [42][43][44][45][46][47][48] and the ready availability of carboxylic acid and amine substrates. [22][23][24][49][50][51][52] However, recent promising advances in metal catalysts are still challenged by the catalyst overall stability, and its tolerance to the water formed as the reaction by-product.…”

Uniting Amide Synthesis and Activation by PIII/PV–Catalyzed Serial Condensation: Three-Component Assembly of 2-Amidopyridines

“…In practice, 93% yield of 5 (86% isolated yield on 0.5 mmol scale) was obtained with 15 mol % 1· [O], along with 2.2 equiv of diethyl­(methyl)­bromomalonate (DEMBM) as oxidant, 3.0 equiv of diphenylsilane as reductant, and 1.0 equiv of Hünig’s base at 40 °C in 1.0 M acetonitrile (Table , entry 1). The stoichiometry of oxidant and reductant required are in line with iterative P III /P V redox cycling to formally strip 2 equiv of H 2 O from the substrate molecules, whereas omitting 1· [O], DEMBM, or Ph 2 SiH 2 resulted in no product formation, indicating that P III /P V redox cycling is essential (see the Supporting Information for an expanded table) . Critically, this reaction allows for evaluation of the chemoselectivity of the organophosphorus redox catalyst for the intended amide condensation/activation manifold, as phosphonium electrophiles, such as peptide-coupling reagent PyBroP, are known to activate pyridine N -oxides for reaction with nucleophiles .…”