Zirconium catalyzed amide formation without water scavenging

Abstract

A scalable homogeneous metal‐catalyzed protocol for direct amidation of carboxylic acids is presented. The use of 2–10 mol% of the commercially available Zr(Cp)2(OTf)2·THF results in high yields of amides at moderate temperature, using an operationally convenient reaction protocol that circumvents the use of water scavenging techniques.

Recent developments in catalytic amide bond formation

“…In a very recent report, the same group disclosed a water-tolerant zirconium system that does not require a dehydrating agent. [82] It was found that zirconium (IV) bis(cyclopentadieneyl)bistriflate was uniquely active compared to the corresponding hafnium or bischloride variant of this species.…”

“…Truong [96] ZrCl 4 THF 70 10 4 Å M.S. Adolfsson [81] ZrCp 2 (OTf) 2 THF 70 2 None Adolfsson [82] F I G U R E 1 0 Chelation promoted Tantalum catalyzed amidation of β-amino acids fromin-situgenerated silyl esters. R 1 = OAlkyl, Aryl.…”

En Route to a Heterogeneous Catalytic Direct Peptide Bond Formation by Zr-Based Metal–Organic Framework Catalysts

“…In these reactions, carboxylic acids usually require additional steps and/or reagents to facilitate NH 2 attack, substantially decreasing process efficiency by increasing waste generation and energy consumption. Catalysis has been explored as an alternative to streamline amide synthesis, resulting in amide bond formations directly from nonactivated carboxylic acids and amines catalyzed mainly by boron and group IV/V metal − catalysts . Notably, catalytic peptide bond formation remains underdeveloped, despite advancements featuring boron-, − metal-, , and organocatalysts reported recently.…”

Zirconium-catalysed direct substitution of alcohols: enhancing the selectivity by kinetic analysis

“…2,[16][17][18][19][20][21][22] In addition, the use of protic acids has been explored to a lesser extent [23][24][25][26][27] Tetravalent metal complexes with fluoroalkylsulfonate ligands constitute an interesting class of water-stable Lewis acidic catalysts for a variety of transformations. [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] Despite this, this catalyst class is hardly represented in the context of dehydrative substitution of alcohols in contrast to its trivalent (and bivalent) counterparts. [43][44][45][46][47][48][49][50][51][52][53][54][55][56][57][58][59][60] In direct etherification, two alcohols are joined with loss of water.…”