Carbenes palladium chloride

Scheme 78) [89]. Aryl chlorides with activating as well as deactivating substituents could also be coupled under the same conditions in high yields, ranging from 60% to 95%, within 30-60 min of microwave irradiation. The process does not require an inert atmosphere. The increased conversion observed with the addition of the ionic liquid reveals that it might have an additional function besides simply acting as a molecular irradiator . It cannot be excluded for instance that carbene palladium complexes are formed in situ and implicated in the catalytic cycle. 

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. 

The Heck reaction was the first catalytic application examined for palla-dium/NHC complexes. A high degree of efficiency was observed for chelating bis-carbene/palladium complexes in this transformation. The reactions involving butyl acrylate with aryl halides were efficiently mediated by such complexes at catalyst loadings as low as 10" mol%. Unactivated chlorides required, however, a catalyst loading up to 1 mol%. The impressive stability of the catalytic system under harsh reaction conditions and its reactivity profile were described as quite impressive [32,56]. 

Finally, the acyclic amino(aryl)carbene palladium complex 26 (see Figure 5.7) gave high conversions in the coupling of aryl bromides with morpholine at ambient temperature. For pyridyl chloride substrates, higher temperatures (70 °C) were required in order to achieve an appreciable 73% yield. ... 

A closely related yet distinct group of NHC adducts are imidazolium hydro-gencarbonate salts. These can be prepared by reaetion of potassium hydro-gencarbonate with the corresponding imidazolium chloride loss of water can lead to the formation of the carboxylate adduct, or loss of water and carbon dioxide liberates the free carbene. Palladium and gold complexes were... 

In pyridinium chloride ionic liquids and in l,2-dimethyl-3-hexylimida2olium chloride ([HMMIMjCl), where the C(2) position is protected by a methyl group, only [PdClJ was observed, whereas in [HMIMjCl, the EXAFS showed the formation of a bis-carbene complex. In the presence of triphenylphosphine, Pd-P coordination was observed in all ionic liquids except where the carbene complex was formed. During the Heck reaction, the formation of palladium was found to be quicker than in the absence of reagents. Overall, the EXAFS showed the presence of small palladium clusters of approximately 1 nm diameter formed in solution. 

Independently, Caddick et al. reported microwave-assisted amination of aryl chlorides using a palladium-N-heterocyclic carbene complex as the catalyst (Scheme 99) [lOlj. Initial experiments in a domestic microwave oven (reflux conditions) revealed that the solvent is crucial for the reaction. The Pd source also proved very important, since Pd(OAc)2 at high power in DMF gave extensive catalyst decomposition and using it at medium and low power gave no reaction at all. Pd(dba)2/imidazohum salt (1 mol% catalyst loading) in DME with the addition of some DMF was found to be suitable. Oil bath experiments indicated that only thermal effects are governing the amination reactions. 

In 2003, Sigman et al. reported the use of a chiral carbene ligand in conjunction with the chiral base (-)-sparteine in the palladium(II) catalyzed oxidative kinetic resolution of secondary alcohols [26]. The dimeric palladium complexes 51a-b used in this reaction were obtained in two steps from N,N -diaryl chiral imidazolinium salts derived from (S, S) or (R,R) diphenylethane diamine (Scheme 28). The carbenes were generated by deprotonation of the salts with t-BuOK in THF and reacted in situ with dimeric palladium al-lyl chloride. The intermediate NHC - Pd(allyl)Cl complexes 52 are air-stable and were isolated in 92-95% yield after silica gel chromatography. Two diaster corners in a ratio of approximately 2 1 are present in solution (CDCI3). 

Utilizing more reactive discrete palladium-N-heterocyclic carbene (NHC) complexes (for example, Pd(carb)2) or in situ generated palladium/imidazolium salt complexes (1 mol% ligand A), Caddick and coworkers were able to extend the rapid amination protocols described above to electron-rich aryl chlorides (Scheme 6.61) [128],... 

The synthesis of this salt started with the enantiomerically pure 1,2-diamine 106, that was converted into the corresponding thiourea derivative 107 (Scheme 12). Exposure of the thiourea 107 to oxalyl chloride in toluene at 60 °C cleanly afforded the desired imidazolinium chloride 108. These two salts were used to produce new palladium and nickel carbene complexes. The structure of both palladium carbene complexes 96a and 96b has been elucidated by X-ray diffraction <2005CEJ1833>. 

The push-spectator stabilization system enables one to employ various alkyl groups with different types of steric environment, which differentiate amino(alkyl) carbenes dramatically from the NHCs as ligands. Taking advantage of their steric and electronic properties, Bertrand et al. nicely demonstrated the utility of CAACs as ligands in the palladium catalyzed a-arylation of ketones. Depending on the nature of the aryl chloride used, dramatic differences were observed in the catalytic activity of Pd-complexes with CAACs featuring different types of steric environment [36]. 

In early studies, it was observed that when the NHG was already attached to the metal center, reaction times were shortened since the time for the deprotonation of the salt and coordination to the metal center was no longer required. The use of well-defined systems also allows for a better understanding of the actual amount of stabilized palladium available in the system. Herrmann reported on two similar Pd(0) complexes bearing two carbenes, 37 and 38. The latter was used in 2002 as the first example of coupling of aryl chlorides (activated and unactivated) with arylboronic acids at room temperature, in high yields, and reaction times between 2 and 24 h in the presence of GsF as base. 

The same year, Herrmann and co-workers prepared a series of mixed palladium(ii) complexes bearing A -heterocyclic carbenes and alkyl or arylphosphines. Complex 59 was identified as the most active catalyst for the coupling of aryl bromides, but failed in the case of aryl chlorides. 

Chromium carbene complexes, 82 Palladium(II) chloride, 234 Tetralins... 

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. 

In a related transformation, a palladium-benzothiazole carbene complex has been reported to efficiently catalyze the arylation of allylic alcohols [79]. Carrying the reaction in an ionic liquid, the authors could couple aryl bromides and activated aryl chlorides with terminal allylic alcohols with remarkable regioselectivity (Scheme 10). The interest of this methodology was also highlighted by its application to the synthesis of three intermediates in the synthesis of medicinal products [80-82],... 

Note The palladium(II) complex in Figure 3.73 shows no Pd-0 coordination despite the existence of a free coordination site owing to chloride abstraction by the silver carbene complex. Coordination of the weak donor acetonitrile is preferred. 

The more popular routes towards transition metal phosphino functionalised carbene complexes avoid the formation of the free carbene and apply one of several in situ methods. Lee et al. reacted the phosphino functionalised imidazolium salt with palladium(II) chloride in the presence of sodium acetate as base [241,281] resulting in the expected paUadium(II) chelate complex. 

Switching from palladium to rhodium, we encounter some very interesting chemistry. Zeng et al. [302] reacted the tiidentate PCP phosphino functionalised imidazolium salt with silver(I) oxide and subsequently transferred the carbene to rhodium(I) (see Figure 3.100). Careful selection of the rhodium precursor complex and reaction conditions enables tetrahedral, square bipyramidal and octahedral rhodium(I) and rhodium(III) complexes to be formed. As the authors explained, the activation of the C-Cl bond in methylene chloride in an oxidative addition reaction on rhodium(I) resulting in a rhodium(in) complex requires an electron rich rhodium(I) complex. The presence of a NHC ligand is advantageous in this respect. 

A totally different approach to bis-carbene ligands on a cyclic scaffold comes from Burgess and coworkers [351], They start from AA -dimethyl-l,2-diaminocyclohexane and acetylate this compound with chloroacetic acid chloride. Addition of an N-substituted imidazole yields the chiral bis-imidazolium salt (see Figure 3.110). Reaction with silver(I) oxide and carbene transfer to palladium(II) completes the reaction sequence. 

The palladium(II) pincer carbene complex showed good activity in standard Heck cou-phng reactions using activated aryl bromides, but was less effective with chlorides. 

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