Sustainable Synthesis of Diverse Privileged Heterocycles by Palladium‐Catalyzed Aerobic Oxidative Isocyanide Insertion

Abstract

O(2) in, H(2)O out: Various diamines and related bisnucleophiles readily undergo oxidative isocyanide insertion with Pd(OAc)(2) (1 mol %) as the catalyst and O(2) as the terminal oxidant to give a diverse array of medicinally relevant N heterocycles. The utility of this highly sustainable method is demonstrated by a formal synthesis of the antihistamines astemizole and norastemizole.

Recent advancements on the use of 2-methyltetrahydrofuran in organometallic chemistry

“…Maes et al developed a novel palladium-catalyzed aerobic oxidation to access guanidine-containing and related heterocycles from bisnucleophiles and aliphatic isocyanides in 2-MeTHF [79] (Scheme 17). The protocol is highly versatile, thus enabling a fast access to a plethora of pharmaceutically relevant heterocyclic systems (e.g., astemizole and norastemizole).…”

One-Pot Palladium-Catalyzed Ligand- and Metal-Oxidant-Free Aerobic Oxidative Isocyanide Insertion Leading to 2-Amino-substituted-4(3H)-quinazolinones

“…[13] At first, a dinucleophile (3) is formed from isatoic anhydride (1) and amine (2). Complex (a) is formed by coordination of isocyanide to palladium acetate, which reacts with the dinucleophile to form intermediate I.…”

“…A few of them include (a) solid-phase synthesis of 2-amino-substituted-4(3H)-quinazolinones, [9] (b) palladium-catalyzed cyclocarbonylation of o-iodoanilines with heterocumulenes, [10] (c) efficient synthesis by tandem palladium-catalyzed addition= cyclocarbonylation, [11] (d) molybdenum-mediated synthesis of quinazolin-4(3H)-ones via cyclocarbonylation using microwave irradiation, [12] and (e) synthesis of 2-aminobenzimidazoles starting from o-phenylenediamines. [13] However, these methodologies require either the use of strong base, expensive ligand, hazardous CO gas, or preparation of starting material.…”

Palladiumkatalysierte migratorische Insertion von Isocyaniden: eine neue Methode für die Kreuzkupplungschemie

“…[60] Isocyanide (9) und o-Phenylendiamine (163, X = NH oder NR 3 ) werden unter oxidativen Bedingungen problemlos gekuppelt und führen zu 2-Aminobenzimidazolen in ausgezeichneten Ausbeuten. [60] Isocyanide (9) und o-Phenylendiamine (163, X = NH oder NR 3 ) werden unter oxidativen Bedingungen problemlos gekuppelt und führen zu 2-Aminobenzimidazolen in ausgezeichneten Ausbeuten.…”