Catalytic cycle Buchwald-Hartwig amination

Carbon-carbon bond formation reactions and the CH activation of methane are another example where NHC complexes have been used successfully in catalytic applications. Palladium-catalysed reactions include Heck-type reactions, especially the Mizoroki-Heck reaction itself [171-175], and various cross-coupling reactions [176-182]. They have also been found useful for related reactions like the Sonogashira coupling [183-185] or the Buchwald-Hartwig amination [186-189]. The reactions are similar concerning the first step of the catalytic cycle, the oxidative addition of aryl halides to palladium(O) species. This is facilitated by electron-donating substituents and therefore the development of highly active catalysts has focussed on NHC complexes. 

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. 

Buchwald-Hartwig amination of p-bromotoluene with m-anisidine affords quantitatively the corresponding diarylamine. While oxidative cyclization using stoichiometric amounts of palladium(II) acetate provides only 36 % yield of 7-methoxy-3-methylcarbazole, up to 72 % yield is obtained using catalytic amounts of palladium(II). The highest turnover for the catalytic cycle is obtained with... 

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... 

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. 

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. 

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