Large yet Flexible N‐Heterocyclic Carbene Ligands for Palladium Catalysis

Abstract

A straightforward and scalable eight‐step synthesis of new N‐heterocyclic carbenes (NHCs) has been developed from inexpensive and readily available 2‐nitro‐m‐xylene. This process allows for the preparation of a novel class of NHCs coined ITent (“Tent” for “tentacular”) of which the well‐known IMes (N,N′‐bis(2,4,6‐trimethylphenyl)imidazol‐2‐ylidene), IPr (N,N′‐bis(2,6‐di(2‐propyl)phenyl)imidazol‐2‐ylidene) and IPent (N,N′‐bis(2,6‐di(3‐pentyl)phenyl)imidazol‐2‐ylidene) NHCs are the simplest and already known congeners. The synthetic route was successfully used for the preparation of three members of the ITent family: IPent (N,N′‐bis(2,6‐di(3‐pentyl)phenyl)imidazol‐2‐ylidene), IHept (N,N′‐bis(2,6‐di(4‐heptyl)phenyl)imidazol‐2‐ylidene) and INon (N,N′‐bis(2,6‐di(5‐nonyl)phenyl)imidazol‐2‐ylidene). The electronic and steric properties of each NHC were studied through the preparation of both nickel and palladium complexes. Finally the effect of these new ITent ligands in Pd‐catalyzed Suzuki–Miyaura and Buchwald–Hartwig cross‐couplings was investigated.

Synthesis and characterisation of an N-heterocyclic carbene with spatially-defined steric impact

“…Free carbenes tend to be at least somewhat airand moisture-sensitive, but there exist a variety of methods by which transition metal complexes can be prepared without the need to liberate and isolate these reactive species. 9 This theory has been put forward to explain the successful use in catalysis of various ligands such as the IBiox series of NHCs, 7,11 IPr* and derivatives, 9,[12][13][14] and IPent 8 and its analogues 15 (Figure 1). [7][8][9][10] Essentially, the theory is that an 'ideal' ligand should be bulky enough to protect and stabilise coordinatively unsaturated intermediate species -such as putative 'NHC-Pd 0 ' or 'NHC-Ni 0 ' complexes for cross-coupling -yet flexible enough to allow the coordination and reaction of substrates at the metal centre without impediment.…”

Synthesis and properties of heteroaromatic carbenes of the imidazole and triazole series and their fused analogues

“…50 The values for complexes of Mes and Dipp-substituted imidazol-2-ylidenes are significantly lower (36.5 and 44.5 %, respectively). New types of sterically complicated carbenes, ones that contain 2,6-dialkyl-4-methoxyphenyl substituents, are used frequently in catalytic studies, e.g., palladium complex catalysis of the Buchwald-Hartwіg 268,269 and Kumada reactions. 53 However, the individual carbenes have not yet been isolated.…”

A New Synthetic Route to p-Methoxy-2,6-disubstituted Anilines and their Conversion into N-Heterocyclic Carbene Precursors

“…The ITent NHC family, with 'Tent' standing for 'Tentacular', was very recently described by us as a new class of NHC bearing highly flexible bulk. 5 This class of NHC includes the well-known IPr, Organ's IPent, 6 and the IHept and INon more recently reported by us. 5 Their flexible bulk increases significantly as the size of the R alkyl groups become larger: IPr > IPent > IHept > INon.…”

“…This feature is considered as a key parameter for the stabilization of metal-NHC complexes and the ultimate optimization of their catalytic properties. 4,5 However, unlike the IPr* OMe which was easily accessed from the inexpensive and commercially available p-anisidine, 4 the synthesis of ITents OMe required the preparation of nonreadily available p-methoxyanilyl NHC precursors in a rapid and cost-effective manner. To our surprise, a literature search revealed a lack of reliable procedure to achieve the p-methoxylation of anilines.…”