Carbenes aryl halides

A number of Pd or Cu catalysts bearing NHC ligands have been prepared for carbonylation of aryl halides. Nacci and co-workers synthesised the benzothiazole carbene ligated Pd complex 32 (Fig. 9.6) and tested it for aryl halide carbonylation... 

Figure 2 Carbenes that have been used, in combination with palladium, for the amination of aryl halides.

This article presents the principles known so far for the synthesis of metal complexes containing stable carbenes, including the preparation of the relevant carbene precursors. The use of some of these compounds in transition-metal-catalyzed reactions is discussed mainly for ruthenium-catalyzed olefin metathesis and palladium-Znickel-catalyzed coupling reactions of aryl halides, but other reactions will be touched upon as well. Chapters about the properties of metal- carbene complexes, their applications in materials science and medicinal chemistry, and their role in bioinorganic chemistry round the survey off. The focus of this review is on ZV-heterocyclic carbenes, in the following abbreviated as NHC and NHCs, respectively. 

Aryl chlorides are more reluctant to participate in amination than most other aryl halides/pseudohalides. To tackle this problem, Caddick et al. examined the effect of palladium-N-heterocyclic carbenes as catalysts in rapid microwave-promoted reactions [87]. Para-tolyl and -anisyl chloride were reacted with aromatic and aliphatic amines in mostly good yields within 6 minutes of heating at 160 °C. Reactions using anisyl, tolyl or phenyl chlorides and aliphatic amines have also been reported by Maes et al. using a phosphine ligand and a strong base, which creates the desired products after 10 minutes of heating at 110-200 °C [88]. 

Nolan reported the use of the 2,6-diisopropylphenyl imidazolium carbene precursor, which contains an unsaturated backbone, for the reaction of aryl chlorides with a variety of amines at 100 °C [165, 166]. This temperature is lower than those conventionally used for reactions of aryl chlorides, but is higher than those used with P(tBu)3 or the 2-biphenylyl di-tert-butylphosphines. Reaction yields were high when 2 mol % palladium was used. Reactions of primary amines occurred in good yield, even when unhindered aryl halides were used. The monoarylamine was obtained in 86 % yield, and only a 5 % yield of the diaryl-amine by-product was isolated. Notably, reactions of both aryl bromides and iodides proceeded at room temperature. 

The cross-coupling of aryl halides and enolates is a powerful method to prepare a-arylated carbonyl compounds that are difficult to access through classic organic chemistry [29]. (NHC)Pd(allyl)Cl species [30] were the first NHC-bearing complexes used as pre-catalysts for the a-arylation of ketones [31,32]. More recently, novel (IPr)Pd(acac)Cl complexes have shown remarkable catalytic activity in this transformation [33]. From aryl chlorides, excellent yields were obtained after short reaction times at 60 °C, the lowest temperature reported to date with a carbene-based system (Table 1). 

N-Aryl amination, or the Buchwald-Hartwig reaction, has proven to be a useful and versatile method to obtain aryl amines, which are of great synthetical and industrial interest [145]. The first examples of carbene/palladium-catalyzed amination of aryl halides showed that in situ-generated catalyst could efficiently mediate the coupling of aryl halides with primary and secondary amines, imines and indoles [ 146-148]. Even if most of these reactions could be carried out at room temperature with aryl iodides and bromides, elevated temperatures were required in order to couple aryl chlorides. 

Examples of well-defined, highly active Ni/carbene complexes catalyzing the Suzuki reaction have also been reported. McGuinness and coworkers have shown that using as little as 0.03 mol % of Ni(tmiy)2l2 or Ni(tmiy)2(o-tolyl)Br (tmiy = l,3,4,5-tetramethylimidazol-2-ylidene) in the coupling of 4-bromoacetophenone with phenylboronic acid led to 19% (TON = 630) and 58% (TON = 1930) conversion of the aryl halide, respectively [55]. 

Having introduced the golden rule of phosphine chemistry to its carbene analogues we will proceed to break it several times in the following brief sununary of routes to synthesise phosphino functionalised carbenes. The best way to synthesise an imidazolium salt is to react an N-substituted imidazole with an alkyl or aryl halide [235], Thus, it is a good idea to utilise a functionalised alkyl halide. The functional group can then be used to introduce the phosphino group. 

Jafarpour, L., Grasa, G. A., Viciu, M. S., Hillier, A. C., Nolan, S. P. Convenient and efficient cross-coupling of aryl halides mediated by palladium/bulky nucleophilic carbenes and related ligands. Chimica Oggi200, 19,10-16. 

FIGURE 5. Sterically bulky, electronically rich, monodentate alkylphosphines and a carbene for a general reaction of acyclic secondary amines with aryl halides... 

Many types of palladacyclic complexes have been used as precursors to catalysts for a variety of coupling processes146,147. Mixtures of dimeric palladacycles containing bridging halide, acetate or trifluoroacetate ions and a phosphine or carbene ligand have been studied as catalysts for the animation of aryl halides. The isolated phosphine adducts can also be applied in catalysis. 

Extensive mechanistic studies have been conducted on the oxidative addition of aryl halides to Pd(0) complexes ligated by PPh3 in different media and with different additives175, 176. However, palladium complexes containing these ligands are not active catalysts for amination. Instead, one must consider the addition of aryl halides to palladium complexes bound by ligands relevant to amination. Studies of the mechanism of oxidative addition to palladium(O) complexes of P(tol-o)3, DPPF, BINAP, Q-phos, P(Bu-f)3 and an /V-heterocyclic carbene ligand have been reported. 

The order of reactivities observed in S Ar displacement reactions often parallels the order of reactivity of aryl halides in oxidative additions to Pd(0). Likewise, the ease with which the oxidative addition occurs for heteroaryl halides can often be predicted on the basis of S Ar reactivity of a given substrate. In addition, a- and y-chloroheteroarenes are sufficiently activated for use in Pd-catalyzed reactions with a variety of different catalysts, whereas Pd-catalyzed reactions of unactivated aryl chlorides (e.g. chlorobenzene) typically require large, electron-rich phosphine or 7V-heterocychc carbene ligands [4]. 

Later in 2010, Wu and co-workers developed a series of carbene adducts of cyclo-palladated ferrocenylimine (Figure 7) and evaluated their activity in the KTC reaction between aryl halides and aryl Grignard reagents. Palladacycle 68 was identified as the most active catalyst, generating a number of di- and tri-orf/io-substituted biaryls in good to excellent yield using 0.5 mol% catalyst loading and 2 equiv. of LiCl (Scheme 6). 

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