Suzuki coupling palladium acetate

The procedure described here incorporates a number of modifications to the Suzuki coupling that result in a sound, efficient and scaleable means of synthesizing biaryls. First, the catalytic use of palladium acetate and triphenylphosphine to generate palladium(O) eliminates the need for the expensive air and light sensitive tetrakis(triphenylphosphine)palladium(0). No purification of reagents is necessary, no special apparatus is required, and rigorous exclusion of air from the reaction mixture is not necessary. Furthermore, homo-coupled products are not present in significant levels (as determined by 500 MHz 1H NMR). 

An attempt to functionalize position 6 of the oxazolo[4,5- ]pyridine 112 was unsuccessful when using -butyllithium and an electrophile at —78°C however, successful Heck coupling was achieved using palladium(ll) acetate and tri-o-tolylphosphine in dimethylformamide (DMF) with triethylamine as base (Equation 20 Table 19) <1996TL2409, 1997T5159, 1998BMC1963>. The Stille (Equation 21 Table 20) and Suzuki couplings were also found to be successful (Equation 22). 

The bromo derivative of A -mcthylsuccinimide did also undergo Suzuki coupling when treated with naphthylboronic acid in the presence of palladium acetate, triphenylphosphine and potassium carbonate (6.3.). The coupled product was deprotected under the reaction conditions and an indole derivative was isolated in good yield, which was successfully converted into the hexacyclic naphthopyrrolo[3,4-c]carbazole structure. Using the analogous trimethylstannyl-naphthalene derivative and optimised Stille coupling conditions the desired product was isolated only in 56% yield.5... 

The Suzuki coupling of aryl halides was also extended to tosylates recently. Benzothiazole 5-tosylate reacted with m-xylene-2-boronic acid (6.13.) to give the coupled product in 94% yield using palladium acetate and a stericly congested biphenyl based phosphine ligand as catalyst.17 Another class of less commonly utilised cross-coupling partners are methyltio derivatives. In the presence of a copper salt, which activates the carbon-sulphur bond, 2-methyltio-benzotiazol coupled readily with a series of arylboronic acids.18... 

An improved procedure of Suzuki-couplings was recently described by Buchwald [5] et al. By using 0-(di-tert.butyl-phosphino)-biphenyl as ligand, palladium acetate and potassium carbonate couplings are facilitated at room temperature [eq. (c)]. 

A modification of the Suzuki coupling reaction proved to be a clean and useful method for the preparation of monosubstituted arylferrocenes. Iodoferrocene was reacted with a series of substituted arylboronic acids in the presence of sodium carbonate and palladium acetate in aqueous ethanol at room temperature to produce a range of substituted monoarylfer-rocenes (Eq. (19)). A systematic investigation undertaken to determine the optimal reaction conditions indicated that scrupulous deoxygenation of the solvent is critical. The use of... 

Thereafter, Buchwald et al. [129] reported that mixtures of palladium acetate and o-(di-tert-butylphosphino)biphenyl (43) (see Table 8) catalyze the room temperature Suzuki coupling... 

The last and key step in the total synthesis of mvxalamide A by C.H. Heathcock et al. was a Suzuki cross-coupling between an ( )-vinylborane and a (Z)-iodotriene. The (E)-vinylborane was prepared prior to the coupling by reacting the precursor enyne with 2 equivalents of cathecholborane. Upon completion of the hydroboration, it was combined with the (Z)-iodotriene and catalytic amounts of palladium acetate. 

Palladium acetate is better than PdCl2(dppf) in terms of cost and catalyst removal and effectively catalyzes the cross-coupling of a wide variety of aryl halides with bis(pinaco-lato)diboron to form the corresponding boronates. These boronates can be conveniently isolated or used in situ for Suzuki cross-coupling reactions with aryl halides to provide biaryls [189b]. 

The Heck coupling is an example of another key metal-catalyzed transformation. Again, this has been incorporated into the undergraduate laboratory curriculum in conjunction with the use of microwave heating (Scheme 6.20). Similar conditions to those developed for the Suzuki reaction were used with either palladium acetate (0.4 mol%) or palladium chloride (ICP standard, 0.004 mol%) as catalyst. 

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