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

Abstract

Seit der Entdeckung der Ugi‐Reaktion und ähnlicher Isocyanid‐ basierter Mehrkomponentenreaktionen sind Isocyanide wichtige Bausteine für die organische Synthese. In den letzten zehn Jahren fanden Isocyanide als vielseitige C1‐Bausteine in der Palladiumkatalyse eine neue Anwendung. Palladiumkatalysierte Reaktionen, die unter Isocyanidinsertion ablaufen, bieten ein enormes Potenzial für die Synthese stickstoffhaltiger Feinchemikalien. In diesem Kurzaufsatz werden alle erzielten Erfolge auf diesem neu entstehenden Gebiet diskutiert.

Silver‐Catalyzed Three‐Component 1,1‐Aminoacylation of Homopropargylamines: α‐Additions for Both Terminal Alkynes and Isocyanides

“…To channel the reaction towards the planned pathway,c ompetitive insertion of 4a into the NÀHb ond of 3a,l eading to amidine,h as to be avoided. [10] While many transition metals promote this transformation efficiently, [11] we have recently shown that as ilver salt, because of its high alkynophilicity,p referred to coordinate to the triple bond of the propargylamine,t herefore inhibiting the N À Hi nsertion process. [12] To our delight, reaction of 3a and 4a in toluene in the presence of AgOTf indeed afforded the proline amide 5a (16 %) resulting from aformal 1,1-gem difunctionalization of the terminal alkyne.Systematic survey of reaction conditions [*] Dr.S .T ong, […”

Synthesis of Diverse Azolo[c]quinazolines by Palladium(II)‐ Catalyzed Aerobic Oxidative Insertion of Isocyanides

“…We have no explanation for this surprising result. Various electron-withdrawing and electron-donating groups are tolerated at the R 1 position and afford the corresponding products in good yields (Table 2, entries [5][6][7][8][9][10]. The use of sterically more congested substrates is tolerated and does not deteriorate the yield or rate of the reaction (entries 8 and 9).…”

“…This is quite remarkable considering that the isocyanide scope is often limited in imidoylative palladium catalysis and in many reactions only tertbutyl isocyanide works well. [5] A less reactive triazole possessing a phenyl group at the R 1 position also reacted with various isocyanides under the standard conditions (entries 18-21). We chose to use 10 mol% PdA C H T U N G T R E N N U N G (OAc) 2 as catalyst with a long reaction time (72 h) as standard conditions for the reactions with secondary isocyanides for convenience and to illustrate generality.…”

“…[5] Most of the developments have focused on imidoylative cross-coupling of aryl halides with nucleophiles to furnish amidines, amides or imidates, [6] while applications to other reaction types have been scarce. [7] We recently introduced the oxidative coupling of bisnucleophiles and isocyanides to afford cyclic guanidines as a new reaction type to address this limitation.…”

Silver‐Catalyzed Three‐Component 1,1‐Aminoacylation of Homopropargylamines: α‐Additions for Both Terminal Alkynes and Isocyanides

“…Theproline derivatives 5/8 are useful building blocks for the synthesis of conformationally constrained peptidomimetics [8] and are key structural units of anumber of pharmaceuticals. [10] While many transition metals promote this transformation efficiently, [11] we have recently shown that as ilver salt, because of its high alkynophilicity,p referred to coordinate to the triple bond of the propargylamine,t herefore inhibiting the N À Hi nsertion process. To channel the reaction towards the planned pathway,c ompetitive insertion of 4a into the NÀHb ond of 3a,l eading to amidine,h as to be avoided.…”