Amination of Aryl Bromides and Chlorides

Nolan and coworkers have also recently developed an amination of aryl bromides and chlorides with morpholine using 5 mol % of the well-defined CpNi(NHC)Cl catalyst [61]. The catalyst can be easily prepared by refluxing the NHC - HC1 in a THF solution of nickelocene (Eq. 26). The well-defined catalyst has the advantage of not having to generate the free carbene, which can sometimes be problematic depending on the stability of the carbene. 

Hartwig, J.F. Kawatsura, M. Hauck, S.I. Shaughnessy, K.H. Alcazar-Roman, L.M. Room-temperature palladium-catalyzed amination of aryl bromides and chlorides and extended scope of aromatic C-N bond formation with a commercial ligand. J. Org. Chem. 1999, 64, 5575. 

The application of transition metal catalysis for aryl amination was reported and developed primarily by the groups of Buchwald and Hartwig in the late 1990s and presented a mild and broadly applicable method for amination of aryl bromides and chlorides by use of palladium(II) and BINAP, tol-BINAP, or... 

Despite the great success of the BINAP (1) ligand in the arylation of anilines, the amination of aryl chlorides required high reaction temperatures and high catalyst loadings. In contrast, the Q-Phos ligand (24) in combination with [Pd(dba)2] was capable of promoting the amination of aryl bromides and chlorides at room temperature or at 100°C, respectively (Scheme 13.64) [95]. 

Solid-supported versions of the Buchwald-Hartwig reaction are known too. In 2012, Al-Amin et al. [42] reported a stable heterogeneous sulfur-modified gold-supported palladium material (SAPd), which was used for the amination of aryl bromides and chlorides. The catalyst was employed at a loading of about 0.2 mol%, and can be used for a minimum of 10 reaction cycles without loss of catalytic activity, affording very good yields for a large cross-section of substrates. 

Table 7.4. Reactions of aryl bromides and chlorides with amines catalyzed by Pd(0)/P(f-Bu)3...

As by-product, diynes R C=C C=C R were formed [93]. (4) Finally, the animation of aryl bromides and chlorides with aliphatic and aromatic amines turned out to be possible in toluene/aq. KOH with Pd(Pt[ Bu)3]2) and CTABr at 90°C [94],... 

On the other hand, true ligand acceleration (type 3 processes) shows preference for solvents of low polarity and lower Lewis basicity (toluene, dioxane and THF) with soluble tertiary amines as bases. In this respect, these Mizoroki-Heck reactions resemble cross-coupling processes, which also display strong preference for these solvents. Reactions in nonpolar solvents (toluene or xylene) have been known since Heck s seminal articles [8]. The halide remains a crucial subject of concern in reactions catalysed by phosphine complexes of palladium, aryl iodides prefer triarylphosphines and polar solvents, whereas reactions of aryl bromides and chlorides indeed prefer electron-rich trialkylphosphines and nonpolar solvents [63-65]. 

Complex /c -C,N-[Pd(dmba)Cl(PTA)] (52, dmba = dimethylbenzylamine. Scheme 7.12) and Pd(OAc)2/PTA (1 3 molar ratio) were tested for catalytic Sonogashira cross-coupling reactions of aryl bromides and chlorides with terminal alkynes without the need of added copper or amines (Scheme 7.13) [55]. 

Multiple arylations of polybromobenzenes have been conducted to generate electron-rich arylamines. Tribromotriphenylamine and 1,3,5-tribromobenzene all react cleanly with A-aryl piperazines using either P(o-tolyl)3 or BINAP-ligated catalysts to form hexamine products [107]. Reactions of other polyhalogenated arenes have also been reported [108]. Competition between aryl bromides and iodides or aryl bromides and chlorides has been investigated for the formation of aryl ethers [109], and presumably similar selectivity is observed for the amination. In this case bro-mo, chloroarenes reacted preferentially at the aryl bromide position. This selectivity results from the faster oxidative addition of aryl bromides and is a common selectivity observed in cross-coupling. Sowa showed complete selectivity for amination of the aryl chloro, bromo, or iodo over aryl-fluoro linkages [110]. This chemistry produces fluoroanilines, whereas the uncatalyzed chemistry typically leads to substitution for fluoride. 

Until recently, alkylphosphines had been used less often than arylphosphines in crosscoupling chemistry. However, several studies pointed to the potential of such ligands in the palladium-catalyzed amination of aryl halides. Alkylphosphines in combination with palladium catalyst precursors have now been shown to allow milder conditions for the amination of aryl bromides, to improve yields with acyclic secondary amines, to give high turnover numbers, and to induce mild aminations of inexpensive aryl chlorides and tosylates. 

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