Reductive elimination Buchwald-Hartwig amination

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. 

The generally accepted catalytic cycle for the Buchwald-Hartwig amination mirrors that of other palladium catalyzed cross-coupling reactions.10 11 irThere is an oxidative addition (A to B), followed by an exchange on palladium (B to C), and finally a reductive elimination (C to D and A). The main difference involves the exchange step. In a Suzuki, or Stille, reaction this step proceeds through a discrete transmetallation event, whereas... 

The transition-metal catalyzed cross-coupling reaction of (hetero)aryl hahdes and triflates with primary and secondary amines or (hetero)aryl amines is know as the Buchwald-Hartwig reaction [144]. Mechanistically, this reaction is related to the crosscoupling reactions outlined thus far (Fig. 4.6). The modification arises at the point of transmetalation. This step in the process is substituted with the coordination of the amine reactant. Deprotonation of the amine nitrogen now precedes the reductive elimination step to generate the aryl amine product. This reaction has foimd utility in the academic setting, for use in natural product total synthesis, and in industry, for the preparation of materials up to the multi-hundred kilogram scale. 

An amine can be coupled with an aryl bromide, iodide or triflate in the presence of a palladium catalyst, a base, typically KOBu or CSCO3, and a ligand such as the bidentate phosphine BINAP. These reactions are known as Buchwald or Buchwald-Hartwig reactions (Scheme 10.24). A catalytic cycle is again involved, with the amine displacing X from Ar-Pd -X to form Ar-Pd -NHR2. Abstraction of a proton by the base produces Ar-Pd -NRj, which undergoes a reductive elimination. 

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. 

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). 

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