Aryl halides, amination

With the exception of intramolecular amination reactions, all of the early aryl halide aminations were catalyzed by palladium complexes containing the sterically hindered P(o-tol)3. In papers published back-to-back in 1996, amination chemistry catalyzed by palladium complexes of DPPF and BINAP was reported.36,37 These catalysts allowed for the coupling of aryl bromides and iodides with primary alkyl amines, cyclic secondary amines, and anilines. 

In 1978 and 1980 the coupling of aryl bromides and iodides with both aliphatic and aromatic thiols was first reported in the presence of NaO-t-Bu and Pd(PPh3)4 (Equation (35)).118,119 In contrast to aryl halide aminations and etherifications, the thiation reactions did not require unusual catalysts. Yet, reactions that form aryl alkyl sulfides from alkyl thiols occurred in modest yields in many cases ... 

Aryl chlorothioformates, 23 628 Aryl complexes, zirconium, 26 655 Aryl ethers, uses for, 70 581 2-Arylglycine esters, 72 166 Aryl halide amination, 9 278 Aryl halides, reaction with carbon monoxide, 5 11 Arylhydrazines, 9 270 Arylmethane dyes, 9 503... 

Scheme 9. Overall mechanism for aryl halide amination catalyzed by P(o-C6H4Me)3-ligated palladium complexes.

Studies of aryl halide amination with secondary aminostannanes and palladium catalysts bearing P(o-C6H4Me)3 ligands are summarized in Scheme 7. These studies revealed four... 

Representative for the Palladium-Catalyzed Arylation of Amines with Aryl Chlorides using (f-BuljP/Pd (Reproduced with permission from [50]. 1999 American Chemical Society) In a dry box, aryl halide, amine, Pd(dba)j, (t-BuljP, and sodium fert-butoxide were weighed directly into a screw cap vial. A stir bar was added followed by 1.0-2.0 ml of toluene to give a purple mixture. The vial was removed from the dry box, and the mixture was stirred at room temperature. After 5.5 h, the reaction mixture was adsorbed onto sihca gel and chromatographed with 50% toluene/hexanes to give 242 mg (90%) of N-(4-cyano-phenyl)diphenylamine as a white solid. 

The mechanism of palladium/aryl halide amination is very closely related to that of cross coupling, with displacement of the halide on palladium (or copper or nickel) by an amine or A-anion instead of the trans-metallation step. In the case of Cu and Ni catalysis, it may proceed through M(0)-M(11) or M(l)-M(lll) cycles. 

Some of the optimized procedures for Stille and Sonogashira reactions involve the addition of copper cocatalysts to accelerate the cross-coupling procedures. A word of caution should be provided on the role of these additives in Pd-catalyzed amination procedures. Beletskaya and Davydov have reported the arylation of benzotriazole and of diary-lamines in polar organic or aqueous organic solvents using a combination of palladium and copper as catalyst.The arylation of amino acids has been reported under similar conditions.However, these reaction conditions are similar to classic Ullmann procedures for the synthesis of arylamines, except for the addition of palladium to the reaction mixture. In one case, subsequent work showed that the palladium species was not an essential component and that copper alone was the true catalyst in their reactions. An unusual accelerating effect of amino acid coordination to copper was used to explain the low-temperature Ullmann conditions. Beletskaya, however, showed that lower yields and a mixture of N1 and N2 arylation products were observed from the reactions of benzotriazole in the absence of copper and no reaction was observed in the absence of palladium. The conditions for this chemistry are, however, distinct enough from those of the majority of the aryl halide aminations to support the idea that a different mechanism may operate. 

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