Buchwald-Hartwig amination mechanism

A plausible mechanism for the one-pot synthesis ofcarbazoles is shown in Scheme 5. It consists of two interlinked catalytic cycles. In the first cycle a classical Buchwald-Hartwig amination reaction occurs to generate an intermediate 5 which then enters the second cycle by oxidative addition to Pd(0). The resulting Pd(II) complex then undergoes intramolecular C-H activation to give a six-membered palladacycle which subsequently yields the carbazole by reductive elimination. 

Problem 6.22. Draw a mechanism for the following Buchwald-Hartwig amination. 

The mechanisms and catalysts used in this Buchwald-Hartwig chemistry mirror those of coupling reactions involving oxidative addition, transmetallation, and reductive elirruna-tion. The first step, as usual, is oxidative insertion of Pd(0) into the aryl-halogen bond. The Pd(ll) complex now adds the amine so that both coupling partners find themselves bonded to the same palladium atom. The base eliminates H—1 from the complex and reductive elimination forms the Ar—N bond. 

In 1995, Buchwald and Hartwig independently discovered the direct Pd-catalyzed C—N bond formation of aryl halides with amines in the presence of stoichiometric amount of base [93, 94], This field is becoming rapidly mature and many reviews covering the scope and limitations of this animation have been published since 1995 [95-102]. In the context of heteroaryl synthesis, one example is given to showcase the utility and mechanism of this reaction. Applications to individual heterocycles may be found in their respective chapters. 

Detailed kinetic studies have been carried out by the groups of Hartwig, Blackmond, and Buchwald under synthetically relevant conditions to study the mechanism of the amination of an aryl bromide with primary and secondary amines using Pd complexes of binap (2,2 -bis(diphenylphosphino)-l,l -binaphthyl), among others [393]. Different mechanisms were proposed for this reaction, and a final reevaluation of the mechanism was made in collaboration between the three aforementioned groups [393c[. 

The mechanism of the Hartwig-Buchwald amination involves three basic steps oxidative addition of the aryl halide to a palladium(O) species, coordination ofa nitrogen atom to the palladium or transmetaUation, and finally, reductive elimination (Scheme 13.1). 

D.v.a. Formation of C—N Bonds. Though Pd-catalyzed amination— the Hartwig-Buchwald reaction—is normally performed in anhydrous media in the presence of strong bases, no steps of the mechanism of this reaction strictly require the absence of water. Moreover, it has been shown that amido complexes of Pd, the key intermediates of this reaction, can easily form by ligand exchange of water or hydroxyl (Scheme 56). ... 

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