Copper-Catalyzed α‑Alkylation of Aryl Acetonitriles with Benzyl Alcohols

A highly efficient, in situ formed CuCl2/TMEDA catalytic system (TMEDA = N,N,N′,N′-tetramethylethylene-diamine) for the cross-coupling reaction of aryl acetonitriles with benzyl alcohols is reported. This user-friendly protocol, employing a low catalyst loading and a catalytic amount of base, leads...

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Veröffentlicht in:Journal of organic chemistry 2024-10, Vol.89 (19), p.14242-14254
Hauptverfasser: Danopoulou, Marianna, Zorba, Leandros P., Karantoni, Athanasia P., Tzeli, Demeter, Vougioukalakis, Georgios C.
Format: Artikel
Sprache:eng
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Zusammenfassung:A highly efficient, in situ formed CuCl2/TMEDA catalytic system (TMEDA = N,N,N′,N′-tetramethylethylene-diamine) for the cross-coupling reaction of aryl acetonitriles with benzyl alcohols is reported. This user-friendly protocol, employing a low catalyst loading and a catalytic amount of base, leads to the synthesis of α-alkylated nitriles in up to 99% yield. Experimental mechanistic investigations reveal that the key step of this transformation is the C­(sp3)–H functionalization of the alcohol, taking place via a hydrogen atom abstraction, with the simultaneous formation of copper-hydride species. Detailed density functional theory studies shed light on all reaction steps, confirming the catalytic pathway proposed on the basis of the experimental findings.
ISSN:0022-3263
1520-6904
1520-6904
DOI:10.1021/acs.joc.4c01662