Amide bond formation: beyond the myth of coupling reagents.

  title={Amide bond formation: beyond the myth of coupling reagents.},
  author={Eric Valeur and Mark Bradley},
  journal={Chemical Society reviews},
  volume={38 2},
Amide bond formation is a fundamentally important reaction in organic synthesis, and is typically mediated by one of a myriad of so-called coupling reagents. This critical review is focussed on the most recently developed coupling reagents with particular attention paid to the pros and cons of the plethora of "acronym" based reagents. It aims to demystify the process allowing the chemist to make a sensible and educated choice when carrying out an amide coupling reaction (179 references). 
A Cross-Coupling Approach to Amide Bond Formation from Esters
A palladium-catalyzed cross-coupling between aryl esters and anilines is reported, enabling access to diverse amides. The reaction takes place via activation of the C–O bond by oxidative additionExpand
Diphenylsilane as a coupling reagent for amide bond formation
A simple procedure for amide bond formation using diphenylsilane as a coupling reagent is described. This methodology enables the direct coupling of carboxylic acids with primary and secondaryExpand
Metal-catalysed approaches to amide bond formation.
In this tutorial review, highlights of the recent literature have been presented covering the key areas where metal catalysts have been used in amide bond formation. Expand
Transition-Metal-Free Activation of Amides by N-C Bond Cleavage.
This personal account highlights recent remarkable advances in transition-metal-free activation of amides by N-C bond cleavage, focusing on both mechanistic aspects of ground-state-destabilization of the amide bond enabling formation of tetrahedral intermediates directly from amides with unprecedented selectivity and synthetic utility of the developed transformations. Expand
Amide bond formation through iron-catalyzed oxidative amidation of tertiary amines with anhydrides.
Mechanistic studies indicated that the in situ-generated α-amino peroxide of tertiary amine and iminium ion act as key intermediates in this oxidative transformation. Expand
Phosphorus pentoxide for amide and peptide bond formation with minimal by-products
Abstract Phosphorus pentoxide and DMAP are used for amide bond formation from carboxylic acids and amines. Dipeptides and amides have been synthesized using this reagent in 42–77% yields and >99%Expand
Synthesis and properties of phenylogous amides
Abstract Vinylogy is a widely accepted principle involving the transfer of electronic chemical character through a double bond, and many reactions have been developed by applying this concept. InExpand
Iodine‐Catalyzed Formation of Amide bond: Efficient Strategy for the Synthesis of Aromatic Primary Amides
A practical and efficient methodology for the synthesis of aromatic primary amides by the reaction of benzylic alcohols and aqueous ammonia in the presence of I2/TBHP system in acetonitrile wasExpand
Metal free amide synthesis via carbon–carbon bond cleavage
Abstract A metal-free oxidative coupling of methyl ketones and primary amines to amides has been developed. The reaction tolerates a variety of functional groups, and is operationally simple. TheExpand
Application of NMI-TfCl-mediated amide bond formation in the synthesis of biologically relevant oxadiazole derivatives employing less basic (hetero)aryl amines.
The developed protocol using NMI-TfCl has been found to be effective and tolerant for the amide bond formation reaction of a series of electronically deactivating and sterically challenging amines. Expand


A new reagent for the mediation of amide bond formation in peptide synthesis.
Abstract The potential application of 1-oxo-1-chlorophospholane (5) as a novel reagent for the in situ activation of Nα -protected amino acids for use in peptide bond forming reactions has beenExpand
The myth of coupling reagents.
Coupling reagents have been proposed for peptide synthesis ever since the introduction of the method because of the convenience of the procedure, which consists of peptide bond formation by additionExpand
A low-epimerizing peptide coupling reagent based on the rearrangement of a carboxylic-sulfonic mixed anhydride
Abstract A series of peptides has been prepared using an o -hydroxybenzenesulfonyl chloride as the condensation reagent. Experimentally, the coupling is a one pot two-steps reaction: formation andExpand
Design and Synthesis of New Immonium‐Type Coupling Reagents
A new family of immonium-type coupling reagents is described here. The differences in the carbocation skeletons of these reagents can be correlated with differences in stability and thus reactivity.Expand
(Chloro-phenylthio-methylene)dimethylammonium chloride (CPMA): a new coupling reagent for the formation of ester and amide bond
CPMA is an efficient agent for the formation of esters and amides from carboxylic acids. It is compatible with substrates that are sensitive to basic conditions or oxophilic reagents. The reactionExpand
PS-IIDQ: a supported coupling reagent for efficient and general amide bond formation
Polystyrene-IIDQ, a polymer-supported coupling reagent, was synthesized in three steps from Merrifield resin in 86% overall conversion. This reagent efficiently coupled carboxylic acids to amines inExpand
Polymer-supported Mukaiyama reagent: a useful coupling reagent for the synthesis of esters and amides.
Polymer-supported N-alkyl-2-chloro pyridinium triflate was synthesized in one step from Wang resin. This reagent proved to be a very effective coupling reagent for the synthesis of esters or amidesExpand
A Facile Synthesis of Carboxamides by Dehydration Condensation Between Free Carboxylic Acids and Amines Using O,O'-Di(2-pyridyl) Thiocarbonate as a Coupling Reagent
Carboxamides are prepared in high yields by dehydration condensation between nearly equimolar amounts of free carboxylic acids and amines both of which involve secondary or tertiary alkyl substitutedExpand
HOBt and HOAt-derived immonium salts: new and highly efficient coupling reagents for peptide synthesis
Abstract Novel HOBt- and HOAt-derived immonium type coupling reagents BDMP, BPMP and AOMP were shown to be very efficient for peptide synthesis with high reactivity, low racemization and good yields.Expand
Direct Synthesis of Amides from Alcohols and Amines with Liberation of H2
A reaction in which primary amines are directly acylated by equimolar amounts of alcohols to produce amides and molecular hydrogen in high yields and high turnover numbers is reported. Expand