Suzuki coupling 347 tetrakis palladium

The Suzuki-Miyaura synthesis is one of the most commonly used methods for the formation of carbon-to-carbon bonds [7]. As a palladium catalyst typically tetrakis(triphenylphosphine)palladium(0) has been used, giving yields of44—78%. Recently, Suzuki coupling between aryl halides and phenylboronic acid with efficient catalysis by palladacycles was reported to give yields of 83%. 

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). 

Since the Suzuki coupling of purine derivatives was covered by recent reviews,1 we only present a selection lfom these reactions. Xanthine (3,6-dihydropurine-2,6-dione) derivatives were coupled with different boronic acids, including styrylboronic acid, in the presence of the conventional tetrakis(triphenylphosphino)palladium catalyst and tripotassium phosphate as a mild base (8.1.), to obtain the appropriate 8-substituted xanthines in acceptable yield.4 The advantage of the use of anhydrous tripotassium phosphate as base over the classical aqueous carbonate or hydroxide reagents might be attributed to the sensitivity of the 8-halopurine core towards nucleophilic attack. 

Early examples of the total synthesis of naturally occurring indole alkaloids employing the Suzuki reaction include ellipticine (10) as repotted by Miller et al. [34], The aryl bromide, 6-amino-7-bromo-5,8-dimethylisoquinoline (45) was derived from 2,5-dimethylanilinc in nine steps. The Suzuki coupling of 45 with phenylboronic acid was carried out using catalytic tetrakis(triphenylphosphine)palladium in benzene and with Na,CO, serving as the base to furnish... 

The starting point for the development of the Suzuki coupling was a procedure described by Carrera and Sheppard [9]. The protocol was chosen due to the technical feasibility and the structural similarity of the products. Carrera and Sheppard reacted 7-brom-indoles with boronic acids in a biphasic mixture of toluene, ethanol, and water. Sodium carbonate was used as the base, and palladium (O)tetrakis (triphenylphospine) as the catalyst. 

The step following was a Suzuki coupling of triflate 765 and boronic acid 769 in the presence of tetrakis(triphenylphosphine)palladium, potassium phosphate, and potassium bromide to obtain the coupling product 770 504). Alkaline hydrolysis of... 

The Suzuki-Miyaura reaction is perhaps one of the most well-known coupling protocols developed to date. A seareh of the literature reveals over 15000 citations to work employing this eoupling protocol that was first developed in 1979 and for whieh Akira Suzuki shared the Nobel Prize in Chemistry in 2010. The two seminal papers in 1979 co-authored by Suzuki and Miyaura deseribe the eross-eoupling of vinyl boronic acids with vinyl bromides (Scheme 13.1) or aryl halides (Scheme 13.2), employing 1 mol.% tetrakis(triphenylphosphene)palladium and a base such as sodium ethoxide. The stereoselectivity of the reactions was excellent with >99% retention of double bond geometry. The evolution of the various Suzuki coupling partners is shown in Scheme 13.3. 

A new tetraphosphine, as-cis-cis-l,2,3,4-tetrakis(diphenylphosphinomethyl)cyclo-pentane (36, Tedicyp) has been synthesized and used in palladium-catalyzed reactions. This tetraphosphine in combination with [Pd(C3H5)Cl 2 affords a very efficient catalyst for the Suzuki coupling reaction, with a turnover of97 000 0(X) (Equation 63) [85]. 

Polymers were prepared using Suzuki cross coupling with tetrakis triphenylphosphine palladium (0). 

Thus, for our present purposes a similar approach was followed using Suzuki cross-coupling reactions as the key steps in the synthesis of our target compounds. Symmetrically substituted compounds were synthesized in a twofold Suzuki crosscoupling reaction from commercially available p-substituted phenylboronic acids or esters and 4,4 -dibromobiphenyl or 4,4 -biphenyl-bis-boronic acid ester and a p-substituted arylhalide, respectively, using tetrakis (triphenylphosphino) palladium as catalyst together with cesium fluoride as base in dry tetrahydrofurane as shown in Scheme 8.1. The desired products were obtained in respectable yields after heating at reflux for 50 h. 

A similar Suzuki cross-coupling reaction has also been employed by Gill and Lubell in a synthesis of an unsaturated kainoid analogue.50 Vinyl triflates 97 and 98 were cross-coupled with phenylboronic acid using tetrakis(triphenylphosphine)palladium(0) to give the corresponding coupled products 99 and 100 with high efficiencies (Scheme 42). 

In respect to the Suzuki and the Negishi couplings, quinoline stannanes provide an easy entry to highly substituted derivatives. As a highlighted example, 2-trimethylstannyl-5,8-dimethoxyquinoline reacts with appropriately substituted pyridyltriflate in the presence of palladium tetrakis-(triphenylphospine), lithium chloride, and copper bromide to produce 2-pyridylquinoline, an advance intermediate for the total syntheses of antitumor compounds streptonigrin and lavendamycin. ... 

Using of 3-bromo-4-triflyloxy-thiophenes 142, a ligand-dependent chemoselective Suzuki-Miyaura cross-coupling with diverse arylboronic acids mediated by different palladium catalysts can be achieved (Scheme 57, Table 35) [355]. When tetrakis (triphenylphosphine)palladium(O) (Pd(PPh3)4) is utilized, the triflate group (143) reacts preferentially. In contrast, couplings promoted by bis(tri-tert-... 

TMS-alkynes are oxidized at the terminal carbon to carboxylic acids by hydroboration/oxidation (dicyclohexylborane/NaOH, H2O2). This does not work with TIPS-alkynes. Instead, TIPS-alkynes are cleanly monohydroborated at the internal carbon by 9-borabicyclo[3.3.1]nonane dimer to give (Z)- -borylvinyl-silanes. These can be oxidized in high yields to a-silyl ketones, or cross coupled with a bromide R Br (R = aryl, benzyl, dimethyl-vinyl) in the presence of NaOH and tetrakis(triphenylphos-phine)palladium(0) to give /3,/3-disubstituted vinylsilanes (Suzuki reaction eq 14). The same nucleophilic substituted vinylsilane can be added to an aromatic aldehyde to provide access to ( )-3-silyl allyl alcohols. ... 

Cyclotrimerizations of phenylethynes using palladium-dppf complexes have been studied, and the coordination chemistry of l,T-bis(diphenylselenophosphoryl)ferrocene with gold and silver has been investigated. The novel l,l, 2,2 -tetrakis(diphenylphosphino)-4,4 -di-/ tt-butylferrocene-type phosphines may be used as ligands in palladium-catalyzed Suzuki cross-coupling and Heck alkylation of aryl halides. 

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