Copper-catalyzed direct alkylation of 1,3-azoles with N-tosylhydrazones bearing a ferrocenyl group: a novel method for the synthesis of ferrocenyl-based ligands

Abstract

Copper-catalyzed cross-coupling of ferrocenyl ketone-derived N-tosylhydrazones with benzo[d]oxazole leads to the direct C-H bond functionalization by a secondary ferrocenyl alkyl group. This direct C-H bond alkylation of azoles with N-tosylhydrazones bearing a ferrocenyl group uses inexpensive CuBr as the catalyst without any ligand. The reaction is operationally simple and conducted under mild conditions, giving the corresponding ferrocenyl-based ligands in moderate to good yields. Furthermore, they were able to act as bidentate ligands, giving rise to the corresponding palladium chelated complex 6a-6c, which were obtained by reaction of 5a-5c with [PdCl2(MeCN)2].

Beyond Friedel and Crafts: Directed Alkylation of C−H Bonds in Arenes

“…In addition to the above-discussed transformations,which are all based on traditional alkylating agents,s everal additional reactions based on other types of reagents have been reported for the direct alkylation of azole derivatives.T hey include carboxylic acids, [78][79][80][81]130] peroxides, [127,131] aldehydes, [86,87] in situ generated iminium ions, [132] N-tosylhydrazones, [133][134][135] benzyl carbonates, [136] diarylmethyl carbonates and pivalates, [137] carboxylic xanthates, [97,98] and tertiary cycloalkanols. [99] Carboxylic acids have indeed been exploited for the alkylation of azoles and were shown to be both attractive and efficient alkylating agents.W hereas the use of photoredox catalysis only allowed the direct alkylation of some specific azoles, [78][79][80][81] Zhaoss ilver-promoted oxidative alkylation of azoles such as (benzo)thiazoles and benzoxazole with alkylcarboxylic acids was shown to be more general, affording the corresponding secondary and tertiary C2-alkylated products in good to excellent yields (Scheme 42).…”

“…Related copper-catalyzed processes for the direct benzylation and allylation, as well as for the introduction of ferrocenyl alkyl groups,o fv arious azoles have also been reported. [134,135] Some other more specific processes have also been reported for the direct alkylation of azoles:t hese include the palladium-catalyzed benzylation of azoles with benzyl carbonates, [136] the palladium-catalyzed cross-coupling between (benz)oxazoles and diarylmethyl carbonates and pivalates, [137] the metal-free oxidative radical methylation and related alkylations of azoles with carboxylic xanthates, [97,98] and the silver-catalyzed C2-alkylation of benzothiazoles and benzoxazoles with tertiary cycloalkanols. [99] As shown throughout this section, the direct alkylation of azole derivatives has been widely studied during the past few years and has led to the development of several efficient processes based upon the use of various alkylating agents, with alkenes being still the most commonly used ones.Some broadly applicable and very general processes,i nvolving transition-metal catalysis or based on the use of organic oxidants,have been reported and now permit the synthesis of aw ide range of alkylated azoles,w ith the C2-position being functionalized most frequently.F unctionalization at other positions requires the innate reactivity of these heterocycles to be overcome,w hich can be achieved by introducing adirecting group at the right position of the starting materials or by biasing the substrate through substitution of the C2position.…”

Beyond Friedel and Crafts: Innate Alkylation of C−H Bonds in Arenes

“…Overall, the secondary and tertiary alkylated products could be obtained in fair to good yields (Scheme ). Related copper‐catalyzed processes for the direct benzylation and allylation, as well as for the introduction of ferrocenyl alkyl groups, of various azoles have also been reported …”

Jenseits von Friedel und Crafts: dirigierte Alkylierung von C‐H‐Bindungen in Arenen

“…Zusätzlich bereits diskutierten Tr ansformationen mit etablierten Alkylierungsmitteln wurden weitere Reaktionen fürd ie direkte Alkylierung von Azolderivaten mit andersartigen Reagenzien beschrieben. Diese umfassen Carbonsäuren, [78][79][80][81]130] Peroxide, [127,131] Aldehyde, [86,87] in situ erzeugte Iminiumionen, [132] N-Tosylhydrazone, [133][134][135] Benzylcarbonate, [136] Diarylmethylcarbonate und -pivalate, [137] Xanthogenate [97,98] und tertiäre Cycloalkanole. [99] Carbonsäuren haben sich als attraktive und effiziente Reagenzien fürd ie Alkylierung von Azolen bewährt.…”

“…Eine andere elegante Strategie wurden von Va nder Eycken fürd ie kupferkatalysierte direkte Alkylierung von Azolen mit sekundären und tertiären Gruppen basierend auf der In-situ-Bildung von Iminiumionen aus Aminen und Aldehyden oder Ketonen bekanntgegeben. [132] Dieses Verfahren erlaubt die Synthese von a-aminomethylsubstituiertenH eteroarenen in ausreichenden bis guten Ausbeuten innerhalb einer Stunde [134,135] Darüber hinaus wurden einige speziellere Methoden für die direkte Alkylierung von Azolen beschrieben:d ie palladiumkatalysierte Benzylierung von Azolen mit Benzylcarbonaten, [136] die palladiumkatalysierte Kreuzkupplung zwischen (Benz)Oxazolen und Diarylmethylcarbonaten sowie -pivalaten, [137] die metallfreie oxidative radikalische Methylierung sowie verwandte Alkylierungen von Azolen mit Xanthogenaten [97,98] und die silberkatalysierte C2-Alkylierung von Benzothiazolen und Benzoxazolen mit tertiären Cycloalkanolen. [99] WieimLaufe dieses Abschnitts gezeigt, wurde die direkte Alkylierung von Azolderivaten während der vergangenen Jahre ausführlich untersucht, was zu der Entwicklung effizienter Verfahren mit diversen Alkylierungsreagenzien führte, wobei Alkene noch immer am häufigsten eingesetzt werden.…”