Pd–PEPPSI: a general Pd–NHC precatalyst for Buchwald–Hartwig cross-coupling of esters and amides (transamidation) under the same reaction conditions

Abstract

Amides are of fundamental interest in many fields of chemistry involving organic synthesis, chemical biology and biochemistry. Here, we report the first catalytic Buchwald-Hartwig coupling of both common esters and amides by highly selective C(acyl)-X (X = O, N) cleavage to rapidly access aryl amide functionality via a cross-coupling strategy. Reactions are promoted by versatile, easily prepared, well-defined Pd-PEPPSI type precatalysts, and proceed in good to excellent yields and with excellent chemoselectivity for the acyl bond cleavage. The method is user friendly because it employs commercially-available, moisture- and air-stable precatalysts. Notably, for the first time we demonstrate selective C(acyl)-N and C(acyl)-O cleavage/Buchwald-Hartwig amination under the same reaction conditions, which allows for streamlining amide synthesis by avoiding restriction to a particular acyl metal precursor. Of broad interest, this study opens the door to using a family of well-defined Pd(ii)-NHC precatalysts bearing pyridine "throw-away" ligands for the selective C(acyl)-amination of bench-stable carboxylic acid derivatives.

SingaCycleTM‐A1‐Catalyzed Successive Suzuki‐Miyaura and Buchwald Couplings for the Synthesis of Various New Pyridine Analogues

“…M. A. Topichy and his co‐workers explained solvent free Buchwald coupling reaction utilizing expanded ring NHC−Pd complexes . Buchwald‐Hartwig transamidation with pyridine bearing Pd‐NHC (Pd‐PEPPSI) catalyst was reported by S. Shi and M. Sczostak . Methyl indazole and methyl pyrazole complexed Pd‐NHCs were synthesized and applied for C−N coupling of aryl chlorides and amines by X.…”

Catalytic Isofunctional Reactions—Expanding the Repertoire of Shuttle and Metathesis Reactions

“…Theacidic NH proton in secondary amides also poses problems,a nd early reports used stoichiometric quantities of Lewis acids to promote the reaction. [109] More recently,t he groups of Garg [110] and Szostak [111] described Ni-or Pd-catalyzed transamidations of activated Boc-protected amides,although these reactions are not isofunctional. [107] This has instigated the development of several other transamidation processes,f rom both the Gellman and Stahl groups [108] and others,t ypically using Lewis acid catalysts.…”

Katalytische, isofunktionelle Reaktionen – Erweiterung des Repertoires an Shuttle‐ und Metathesereaktionen

“…Das acide NH-Proton von sekundären Amiden stellt ein weiteres Problem dar, weshalb in den ersten Berichten stçchiometrische Mengen von Lewis-Säuren verwendet wurden, um die Reaktion voranzutreiben. [109] Vork ürzerer Zeit beschrieben die Gruppen von Garg [110] und Szostak [111] Ni-oder Pd-katalysierte Umamidierungen von aktivierten, Boc-geschützten Amiden, wobei diese Reaktionen nicht isofunktionell sind. [107] Dies gab den Anstoss zur Entwicklung weiterer Umamidierungsprozesse von der Gellman-wie auch der Stahl-Gruppe [108] und anderen, die typischerweise Lewis-Säurekatalyse nutzen.…”

“…[107] Dies gab den Anstoss zur Entwicklung weiterer Umamidierungsprozesse von der Gellman-wie auch der Stahl-Gruppe [108] und anderen, die typischerweise Lewis-Säurekatalyse nutzen. [109] Vork ürzerer Zeit beschrieben die Gruppen von Garg [110] und Szostak [111] Ni-oder Pd-katalysierte Umamidierungen von aktivierten, Boc-geschützten Amiden, wobei diese Reaktionen nicht isofunktionell sind.…”