Palladium oxidative cross-coupling reactions

Dipolar cycloaddition reaction of trimethylstannylacetylene with nitrile oxides yielded 3-substituted 5-(trimethylstannyl)isoxazoles 221. Similar reactions of (trimethylstannyl)phenylacetylene, l-(trimethylstannyl)-l-hexyne, and bis (trimethylsilyl)acetylene give the corresponding 3,5-disubstituted 4-(trimethyl-stannyl)isoxazoles 222, almost regioselectively (379). The 1,3-dipolar cycloaddition reaction of bis(tributylstannyl)acetylene with acetonitrile oxide, followed by treatment with aqueous ammonia in ethanol in a sealed tube, gives 3-methyl-4-(tributylstannyl)isoxazole 223. The palladium catalyzed cross coupling reaction of... 

It is assumed that the mechanism of the palladium-catalyzed cross-coupling reactions of iodonium salts involves the initial oxidative addition step, followed by ligand coupling at the iodine and then at the palladium centers analogously to the mechanism shown in Scheme 31 [63,66]. 

Halogen at ring positions of pyrazole 1-oxides can be activated by palladium toward cross-coupling reactions. However, no examples of nucleophilic displacement of such halogen have been reported. 

The mechanism of the Sonogashira reaction has not yet been established clearly. This statement, made in a 2004 publication by Amatore, Jutand and co-workers, certainly holds much truth [10], Nonetheless, the general outline of the mechanism is known, and involves a sequence of oxidative addition, transmetalation, and reductive elimination, which are common to palladium-catalyzed cross-coupling reactions [6b]. In-depth knowledge of the mechanism, however, is not yet available and, in particular, the precise role of the copper co-catalyst and the structure of the catalytically active species remain uncertain [11, 12], The mechanism displayed in Scheme 2 includes the catalytic cycle itself, the preactivation step and the copper mediated transfer of acetylide to the Pd complex and is based on proposals already made in the early publications of Sonogashira [6b]. 

The mechanism for this palladium-catalyzed cross-coupling reaction comprises the initial oxidative addition of the electrophile 37 to the palladium(O) catalyst followed by transmetallation of triethylsilane to yield the corresponding bis(organo)palladium(II) complex 39, which then undergoes reductive elimination to form the alkene 40 and to regenerate the palladium(O) catalyst. 

The palladium-catalyzed cross-coupling reaction of a vinyl or aryl stannane with an arylhalogenide or -triflate is known as a Stille reaction. The mechanism of this Stille reaction is outlined below The palladium precatalyst loses two ligands and forms the catalytic species 36. The catalytic cycle starts with the oxidative addition of the catalytic species 36 into the carbon-triflate bond of 23 forming complex 41, which, however, does not undergo the required transmetallation step with stannane 22. Therefore, the triflate ion is... 

Gillmann et al. (94SC2133) (Scheme 148) found a convenient method to prepare methyl 2-bromo-2,3-butadienoate 540 via oxidative ring cleavage of 4-bromopyr-azol-3-one 539 using lead tetraacetate and boron trifluoride etherate in 59% yield. Compounds such as 540 are valuable building blocks for the synthesis of 2-aryl and 2-alkenyl substituted alka-2,3-dienoates via palladium-catalyzed cross-coupling reactions. 

The development of C-H activation for cross-coupling reactions has been advanced rapidly. Extensive efforts have been devoted to the mechanistic studies in this field to shed light on the mechanism. The use of oxygen or air as sole oxidant has been successfully realized in a palladium-catalyzed cross-coupling reaction involving C-H activation. We have the right to believe that palladium-catalyzed double C-H activation would be a good alternative for the synthesis of biaryls. With further improvements in catalyst turnover, selectivity, and oxidant, the method should ultimately be able to find industrial applications. 

Fagnou K, Leclerc J-P (2006) Palladium-catalyzed cross-coupling reactions of diazine V-oxides with aryl chlorides, bromides and iodides. Angew Chem Int Ed 45 7781-7786... 

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 mechanism of the direct intramolecular Buchwald-Hartwig indole synthesis is that of a traditional palladium-catalyzed cross-coupling reaction and begins with loss of a ligand on palladium. Oxidative addition of an appropriately substituted Z-vinylhaloarene (1) generates intermediate 2. Deprotonation of 2 and displacement of a halide ligand sets up a reductive elimination on 3 to yield indole 4. 

Chloroarenes are an economical and easily available substrate, but they are rarely used for the palladium-catalyzed cross-coupling reaction of arylboronic acids because of their slow oxidative addition to palla-dium(O). Thus, palladium catalysts have been limitedly used for activated chloroarenes, such as chloropyridines (Eq. 44) and electron-deficient chloroarenes ... 

Oxidative Cross-Coupiing Reactions C(sp )-organozincs can also take part in palladium-catalyzed oxidative cross-coupling reactions. C(sp )-C(sp) couplings, not easy to achieve by more classical approaches involving haloalkynes, are readily performed. 

The palladium-catalyzed cross-coupling reactions of boronates as well as boranes (the Suzuki coupling) and stannanes (the Stille coupling), which are mechanistically related to the Heck reaction in the initial oxidative addition step, are discussed in Chapters 2 and 6. 

An enzyme-labile so-called safety catch linker 452 was used successfully in various palladium-catalyzed cross-coupling reactions [592]. The linker 452, which releases a hydroxy or an amino functionality on enzymatic cleavage of its phenylacetamide moiety and subsequent rapid lactam formation, was attached to a soluble POE 6000 (polyethylene oxide) polymer and its free phenylacetic acid moiety was transformed to an m-iodobenzyl ester. The thus immobilized m-iodobenzyl alcohol was Heck-coupled with tert-butyl acrylate, and the coupling product 453 was cleaved off the solid support with penicillin G acylase under very mild conditions (pH 7, 37°C) (Scheme 8.84). 

The formation of 2-alkenyl-substituted furans was observed in the palladium-catalyzed cross-coupling reactions between benzyl, aryl, or allyl bromides and conjugated ene-yne-ketones. This reaction involved oxidative addition, alkyne activation-cyclization, palladium carbene migratory insertion, P-hydride elimination, and catalyst regeneration (13JA13502). 

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