Direct Amide Coupling of Non-activated Carboxylic Acids and Amines Catalysed by Zirconium(IV) Chloride

Helena Lundberg; Fredrik Tinnis; Hans Adolfsson

doi:10.1002/chem.201104055

Substrate selective amide coupling driven by encapsulation of a coupling agent within a self-assembled hexameric capsule

Chemical Communications ◽

10.1039/c4cc08833f ◽

2015 ◽

Vol 51 (9) ◽

pp. 1658-1661 ◽

Cited By ~ 29

Author(s):

Sonia Giust ◽

Giorgio La Sorella ◽

Laura Sperni ◽

Giorgio Strukul ◽

Alessandro Scarso

Keyword(s):

Carboxylic Acids ◽

Coupling Agent ◽

Primary Amines ◽

Substrate Selectivity ◽

Synthesis Reaction ◽

Amide Synthesis ◽

Amide Coupling ◽

Self Assembled

Encapsulation of a cationic carbodiimide condensing agent within a self-assembled hexameric capsule made of resorcin[4]arene units provides a nano-environment that efficiently steers the substrate selectivity in the amide synthesis reaction between carboxylic acids and primary amines.

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Rapid Mechanochemical Synthesis of Amides with Uronium-Based Coupling Reagents, a Method for Hexa-amidation of Biotin[6]uril

10.26434/chemrxiv.12735377.v1 ◽

2020 ◽

Author(s):

Tatsiana Dalidovich ◽

Kamini A. Mishra ◽

Tatsiana Shalima ◽

Marina Kudrjašova ◽

Dzmitry Kananovich ◽

...

Keyword(s):

Carboxylic Acids ◽

Reaction Rates ◽

Solid State Reactions ◽

Sustainable Chemistry ◽

Fast Reaction ◽

Amide Bonds ◽

Amide Coupling ◽

Phosphate Species ◽

Acyl Phosphate ◽

Phenylalanine Methyl Ester

Solid-state reactions using mechanochemical activation have emerged as solvent-free atom-efficient strategies for sustainable chemistry. Herein we report a new mechanochemical approach for the amide coupling of carboxylic acids and amines, mediated by combination of (1-сyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (COMU) or N,N,N′,N′-tetramethylchloroformamidinium hexafluorophosphate (TCFH) and K2HPO4. The method delivers a range of amides in high 70–96% yields and fast reaction rates. The reaction protocol is mild, maintains the integrity of the adjacent to carbonyl stereocenters, and streamlines isolation procedure for solid amide products. Minimal waste is generated due to the absence of bulk solvent. We show that K2HPO4 plays a dual role, acting as a base and a precursor of reactive acyl phosphate species. Amide bonds from hindered carboxylic acids and low-nucleophilic amines can be assembled within 90 min by using TCFH in combination with K2HPO4 or N-methylimidazole. The developed mechanochemical liquid-assisted amidation protocols were successfully applied to the challenging couplings of all six carboxylate functions of biotin[6]uril macrocycle with phenylalanine methyl ester, resulting in an 80% yield of highly pure hexa-amide-biotin[6]uril. In addition, fast and high-yielding synthesis of peptides and versatile amide compounds can be performed in a safe and environmentally benign manner, as verified by green metrics.

Download Full-text

Rapid Mechanochemical Synthesis of Amides with Uronium-Based Coupling Reagents, a Method for Hexa-amidation of Biotin[6]uril

10.26434/chemrxiv.12735377 ◽

2020 ◽

Author(s):

Tatsiana Dalidovich ◽

Kamini A. Mishra ◽

Tatsiana Shalima ◽

Marina Kudrjašova ◽

Dzmitry Kananovich ◽

...

Keyword(s):

Carboxylic Acids ◽

Reaction Rates ◽

Solid State Reactions ◽

Sustainable Chemistry ◽

Fast Reaction ◽

Amide Bonds ◽

Amide Coupling ◽

Phosphate Species ◽

Acyl Phosphate ◽

Phenylalanine Methyl Ester

Solid-state reactions using mechanochemical activation have emerged as solvent-free atom-efficient strategies for sustainable chemistry. Herein we report a new mechanochemical approach for the amide coupling of carboxylic acids and amines, mediated by combination of (1-сyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate (COMU) or N,N,N′,N′-tetramethylchloroformamidinium hexafluorophosphate (TCFH) and K2HPO4. The method delivers a range of amides in high 70–96% yields and fast reaction rates. The reaction protocol is mild, maintains the integrity of the adjacent to carbonyl stereocenters, and streamlines isolation procedure for solid amide products. Minimal waste is generated due to the absence of bulk solvent. We show that K2HPO4 plays a dual role, acting as a base and a precursor of reactive acyl phosphate species. Amide bonds from hindered carboxylic acids and low-nucleophilic amines can be assembled within 90 min by using TCFH in combination with K2HPO4 or N-methylimidazole. The developed mechanochemical liquid-assisted amidation protocols were successfully applied to the challenging couplings of all six carboxylate functions of biotin[6]uril macrocycle with phenylalanine methyl ester, resulting in an 80% yield of highly pure hexa-amide-biotin[6]uril. In addition, fast and high-yielding synthesis of peptides and versatile amide compounds can be performed in a safe and environmentally benign manner, as verified by green metrics.

Download Full-text