Palladium-NHC complexes

The direct arylation of heteroaryls is particularly attractive due to the fact that these moieties are present in many biologically active compounds [58], Recently, etinkaya and co-workers reported the direct arylation of benzoxazoles and ben-zothiazoles with aryl bromides catalysed by a bis-NHC-palladium complex [59], Also, Sames and co-workers have described the C-H arylation of different SEM-protected heteroarenes, catalysed by NHC-Pd complex 28 (Scheme 7.12, pathway a) [60],... 

It was originally reported that NHC-palladium complexes are unsuitable for nitrogen nucleophiles in these catalytic coupling reactions [262], but soon after, the reaction could be performed, albeit with a low activity [263] under anhydrous conditions. When biphasic conditions are employed, the amination reaction becomes reasonably active (reaction time... 

The lability of the NHC ligands is unexpected. However, few examples of NHC substitution have been reported in the literature. Caddick and Cloke described that phosphines and free carbenes can replace coordinated NHC ligands in palladium-based complexes to give mixed NHC-phosphines complexes (equations 27-29). Treatment of (185) with PCys at room temperature resulted in a quantitative conversion to the mixed complex (186). Similar behavior was observed with the more sterically hindered P(tol)3 with a lower conversion and requiring harsher reaction conditions. Ligand redistribution reaction between (188) and P(tol)s was also found to occur to give (189) in poor but isolable yield (equation 28). This same redistribution reaction was carried out with free F Bu instead of the phosphine and yielded, at room temperature, the two-coordinated mixed NHC-palladium complex (190). These experiments demonstrated that ligand... 

Figure 5 NHC-palladium complexes identified in [BMIM]Br/Pd(ll) systems.

Figure 15.2 Supported ionic liquid and NHC-palladium complex 8.

In 2001, Nolan reported that NHC-palladium complexes, in combination with a fluoride additive, catalyze the Stille crosselectron-deficient aryl chlorides (Equation 2.44) [80]. 

Orfho-disubstituted aryl iodides as representative examples of sterically hindered substrates are more challenging in palladium-catalyzed coupling reactions. In this respect it is interesting to note that Martin et al. reported a synthesis of sterically hindered aryl ketones by using the NHC palladium complex PEPPSI-iPr [34]. Several diaryl ketones were produced in moderate to good yields by this method (Scheme 4.18). 

An asymmetric version of the intramolecular hydroarylation of alkynes (286) to produce fused rings (287) has been developed. With the cationic Pd(II)/(5)-(285) catalyst, the resulting 4-aryl 2-quinolinones were obtained with <98% ee. Asymmetric addition of boronic acids R B(OH)2 to activated cumulenes R C=C=C=C(R )C02Et, catalysed by an NHC-palladium complex, has been shown to yield allenic products R C=C=C(R )CH(R )C02Et with moderate to good enantioselectivities. ... 

Well-defined palladium complexes are interesting from an academic point of view. In 2013, Shi, Cao and their co-workers prepared a well-defined fer-rocenyl functionalized NHC-palladium complex and applied it as an efficient catalyst for Larock heteroannulation. 2,3-Disubstituted indoles were isolated in good yields (69-90%) with high regioselectivity from the reactions between 2-iodoanilines or 2-bromoanilines and their derivatives with various internal alkynes (Scheme 2.98). The reactions occur in a broad scope and with a high tolerance of functional groups. NHC-palladium complexes could be excellent candidates to replace expensive palladium-phosphine complexes for Larock indole catalysis. 

A series of chiral NHC-palladium complexes was prepared from t-phenyl-alanine [38]. The catalytic activity of these complexes was tested in the Sonogashira coupling under copper-free conditions in air, showing that complex 27 was the most efficient for the coupling of aryl halides and phenylacetylene. 

Welton and co-workers reported a detailed study of the Suzuki reaction performed in imidazolium ionic liquids using palladium phosphine based catalysts, and found that mixed phosphine-NHC palladium complexes of the formula [(IBuMe)Pd(PPh3)2X] were formed. All catalytic conditions leading to formation of these complexes were successful in affecting the Suzuki reaction, and those conditions in which they could not be detected showed no conversion. This strongly suggests that [(NHC)Pd] complexes are relevant to reactions run in imidazolium-based ionic liquids. 

The increased donor ability of abnormally bound imidazolylidenes increased the nucleophilicity of the metal centre. Abnormal NHC-palladium complexes were thus shown reactive towards Lewis acids. When the abnormal NHC complex 15 was treated with AgBp4, the adduct 18 was formed while normal carbene complexes underwent the expected halide abstraction to form 17 (Scheme 5.5). Crystallographic analysis revealed short Ag- -Pd distances of 2.8701 A, suggesting a strong metal-metal interaction. Theoretical calculations indicated that the palladium centre acted as a Lewis base in this adduet, despite its formal dipositive charge. No such adduct formation was observed with analogous normal NHC-palladium complexes. 

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