Modular Synthesis of Functionalisable Alkoxy-Tethered N-Heterocyclic Carbene Ligands and an Active Catalyst for Buchwald-Hartwig Aminations

• Published in: Advanced synthesis & catalysis Vol. 356; no. 2-3; pp. 460 - 474
• Main Authors: Krinsky, Jamin L., Martínez, Alberto, Godard, Cyril, Castillón, Sergio, Claver, Carmen
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 10.02.2014; WILEY‐VCH Verlag; Wiley
• Subjects: Accessibility; carbene ligands; Carbenes; Chemistry; Chemistry, Applied; Chemistry, Organic; Chlorides; CN cross-coupling; Derivatives; immobilisable catalysts; Joining; ligand design; Ligands; Modular; N-heterocyclic carbenes; NHCs; palladium; Physical Sciences; Science & Technology; Synthesis; ORTHO-SUBSTITUTED BIARYLS; ROOM-TEMPERATURE; OLEFIN METATHESIS CATALYSTS; PD-PEPPSI-IPENT; carbene ligands; SUZUKI-MIYAURA REACTION; NHCs; CROSS-COUPLING REACTIONS; NUCLEOPHILIC CARBENE; immobilisable catalysts; ligand design; CN cross-coupling; palladium; ARYL CHLORIDES; PALLADIUM CATALYSTS; IMIDAZOLIUM SALTS; N-heterocyclic carbenes
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.201300903

Modular syntheses of functionalised, alkoxy‐tethered 1,3‐bis(2,4,6‐trimethylphenyl)imidazolium (IMes⋅H+) and 1,3‐bis(2,6‐diisopropylphenyl)imidazolium (IPr⋅H+) derivatives 1,3‐bis(4‐alkyloxy‐2,4,6‐trimethylphenyl)imidazolium (IXyOR⋅H+) and 1,3‐bis(4‐alkyloxy‐2,6‐diisopropylphenyl)imidazolium (IPrOR⋅H+) are reported. A reliable synthesis of the key starting material 4‐amino‐3,5‐diisopropylphenol is also described. Etherification of hydroxy‐decorated ligand intermediates before formation of the imidazolium core and subsequent modification, or direct etherification of the versatile synthon IPrOH⋅HCl, allowed access to various linker types including triethoxysilyl, primary amino and norbornenyl, which are not accessible by other methods. An IPrOR–palladium(II) complex was prepared, and its catalytic activity was evaluated in challenging Buchwald–Hartwig aminations of aryl chlorides. This precatalyst displayed excellent activity and selectivity under mild reaction conditions, achieving in some cases a 10‐fold improvement in TOF relative to the IPr‐based version. An unexpected activity profile was observed wherein sterically demanding anilines were coupled more easily than those lacking ortho‐substitution.