Hafnium-Catalyzed Direct Amide Formation at Room Temperature

Abstract

Herein, the first example of a metal-catalyzed protocol for direct amidation of nonactivated carboxylic acids at ambient temperature (26 °C) is presented. The mild reaction conditions give rise to high yields of a range of amides in reaction times as short as 90 min, employing a commercial hafnium complex, [Hf(Cp) 2 Cl 2 ], as catalyst. Amino acids are transformed into their corresponding amides without racemization, and the catalyst displays full selectivity for the amidation of carboxylic acids over esters. Electronic properties of the carboxylic acids were found to have a strong influence on the rate of the amidation reaction, and the need for a balanced amount of molecular sieves was observed to be highly important for optimal reaction outcome.

Direct synthesis of macrodiolides via hafnium(iv) catalysis

“…Low yields of 3 were also observed with other catalysts such as Sc(OTf) 3 (34%), Sm(OTf) 3 (0%) and Yb(OTf) 3 (17%), Dy(OTf) 3 (18%) and La(OTf) 3 (29%). 20 The Lewis acidity of the Hf(OTf) 4 complex 21 is well documented and both Hf(OTf) 4 as well as other hafnium complexes 22 have been demonstrated to promote direct amidation, suggesting a mechanism proceeding by activation of the carboxylic acid. Finally, extending the reaction time to 48 h provided a slight increase in the yield of 3 to 92%.…”

Protecting‐Group‐Free Amidation of Amino Acids using Lewis Acid Catalysts

“…We have also attempted the reaction to synthesise 1a under similar conditions with av ariety of group (IV) metal salts (Table 4), as these types of species have been reported to be active catalysts for amide bond formation in recent years. [16,17] While reactions employing zirconium-based reagents solidified and produced only minor quantities of amide 1a,T i(OiPr) 4 was identified as as uitable alternative amidation reagent. The reactions were also attempted in the presence of molecular sieves but the resulting yields were slightly lower.As electiono f amino amides were synthesised using 1equiv of Ti(OiPr) 4 ( Figure 1).…”

Amide Synthesis by Nickel/Photoredox‐Catalyzed Direct Carbamoylation of (Hetero)Aryl Bromides

“…[8] Catalytic methods for amide synthesis have the potential to minimize waste,i mprove the environmental burden, and lower costs of the process. [5] Some recent key advances include the use of group IV metal salts [9] or boron compounds [10] as catalysts and the development of Pd-catalyzed aminocarbonylation-the three-component coupling of an aryl halide with an amine and carbon monoxide. [11] However, the need for toxic gaseous CO and copious amounts of molecular sieves as drying agents complicates the use of these catalytic methods.I na ddition, most of the protocols require severe reaction conditions and elevated temperatures,w hich limit the tolerance for substrates with sensitive functional groups.T herefore,t here is still an eed for catalytic amide synthesis approaches that operate at room temperature,offer ab road substrate scope,a nd avoid the use of excess drying agents.…”