Coupling reactions Palladium acetate-Triphenylphosphine

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... 

Disubstituted alkenes are generally less reactive towards coupling than are monosubstituted alkenes. However, the use of the more reactive aryl iodides can result in reasonable yields of the coupled product, usually as a mixture of (E) and (Z) isomers. The reaction has been applied to a coupling of 2-iodoaniline derivatives with dimethyl maleate (eq 18), the product of which spontaneously cyclizes to form quinolone derivatives in 30-70% yield. If, instead, the 2-iodoaniline is coupled with isoprene or cyclohexadiene in the presence of palladium acetate, triphenylphosphine, and triethylamine, indole and carbazole derivatives are obtained by a coupling followed by intramolecular nucleophilic attack by the heteroatom. ... 

The palladium-catalyzed cross-coupling reaction featured in this procedure occurs under neutral conditions in the presence of many synthetically useful functional groups (e.g. alcohol, ester, nitro, acetal, ketone, and aldehyde). The reaction works best in N,N-dimethylformamide with bis(triphenylphosphine)palladium(ll) chloride, PdCI2(PPh3)2, as the catalyst. Lithium chloride is added to prevent decomposition of the catalyst.143 13 It is presumed that conversion of the intermediate aryl palladium triflate to an aryl palladium chloride is required for the transmetallation step to proceed.9... 

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). 

The Heck coupling is also efficient in the formation of pyrane derivatives. By starting from the appropriately substituted 1,3,5-tribromobenzene derivative, three fused pyrane rings were constructed in the same reaction. The triple Heck reaction in the presence of palladium acetate and triphenylphosphine led to the formation of the tetracyclic product in good yield accompanied by a minor amount of the tricyclic intermediate(4.12.).13... 

Joint catalysis by tin(IV) chloride and zinc chloride induces coupling of the acetal 114 with the alkyne 115 to give the propargyl ether 116. Allyl halides condense with terminal alkynes in DMF in the presence of copper(I) iodide, potassium carbonate and tetrabutylammonium chloride under phase-transfer conditions to afford eneynes, e.g. equation 19. Palladium-catalysed coupling reactions of 1-bromoallenes with terminal acetylenes have been reported for the first time thus acetylene and the allenes 117 (R R = Me or Et) in triethylamine in the presence of tetrakis(triphenylphosphine)palladium and... 

An organobase including guanidine is often used as co-catalyst (or base) in palladium coupling reactions [84]. The 2-methylenepropane-l,3-diol diacetate reacts with 7,8-dihydroquinoline derivative in the presence of palladium acetate [Pd(OAc)2], TMG (1) and triphenylphosphine (PPhs) to give the methylene bridged compound in 92% yield, which can be converted to a diamino analogue of huperzine A, an inhibitor of acetylcholine esterase [84a](Scheme 4.32). 

Wilkinson s catalyst is also capable of mediating the formation of C-C bonds in reactions which apparently proceed via oxidative addition of an unsaturated organohalide across the metal (eq 48)7 or via transmetalation from an organometallic (eq 49)7 These two transformation types are very similar to couplings developed by Heck so, predictably, some palladium complexes also mediate these reactions (see Tetrakis(triphenylphosphine)palladium(0) and Palladium(II) Acetate). 

An early example of this arene coupling was reported by Ames and BuU,t who noted the formation of benzofuro[3,2-c]cinnoline in the reaction of 3-bromo -phenoxycinnohne with ethyl acrylate in the presence of a catalytic amount of paUadium(n) acetate (Scheme 2, Eq. 1). Subsequent studies showed that ethyl acrylate is not necessary, and the arylation reaction was achieved by using 0.1 equiv of palladium acetate, 0.2 equiv of triphenylphosphine, and 3 equiv of sodium acetate in DMA at 170 °C (Scheme 2, Eq. 

A coordinatively unsaturated 14-electron palladium(O) complex, usually coordinated with weak donor ligands (mostly tertiary phosphines), has meanwhile been proved to be the catalytically active species [13]. This active complex is always generated in situ, for example, from tetrakis(triphenylphosphine)palladium(0), which exists in equilibrium with tris(triphenylphosphine)palladium(0) and free triphe-nylphosphine in solution. The endergonic loss of a second phosphine ligand [14] leads to the catalytically active bis(triphenylphosphine)palladium(0). However, pal-ladium(II) complexes or salts such as bis(triphenylphosphine)palladium dichloride or palladium acetate, which are easily reduced (e.g., by triarylphosphines, see later discussion) in the reaction medium, are more commonly employed for convenience, as they are inherently stable toward air. The mechanistic situation is a bit more complicated with palladium acetate in that anionic acetoxypalladium species Pd(PPh3) (AcO ) (n = 2, 3) are formed in the presence of acetate ions [13], and these actually participate in the oxidative addition step as well as the following coupling reaction. 

Alkylidenetetrahydrofurans can be prepared via intramolecular oxypalladation and subsequent coupling by treatment of aryl or alkyl alkynic alcohols with butyllithium followed hy palladium acetate and triphenylphosphine. The reaction proceeds to yield furans in moderate yields. ... 

We will begin, as in the Suzuki coupling reaction, with the Pd(0) catalyst. In the Heck reaction, the catalyst forms in the reaction mixture from palladium(II) acetate in the presence of triphenylphosphine. 

The reaction of /V-pentenyl-2-iodoindole in the presence of a palladium-triphenylphosphine catalyst led to the formation of a mixture of isomeric products in good yield (4.8.), Addition of thallium(I) acetate favoured the formation of an exocyclic double bond, while in its absence the product containing the endocyclic olefin moiety is formed preferentially. The shortening of the A-alkenyl chain by one carbon leads to the selective formation of a five membered ring.9 Starting from indole-carboxamide derivatives both /3-. and carbolinones are available in intramolecular Heck coupling. 

Coupling of aliylstannanes and ally acetates.- This reaction is also catalyzed by tetrakis(triphenylphosphine)palladium. 

Researchers from Merck elaborated a convergent synthesis for the AT II antagonist losartan 30 with the key biaryl coupling step in the final stage of the protocol [100]. The two reaction partners 28 and 29 were coupled very efficiently (99% yield) utilizing 1 mol% of palladium(II) acetate and 4 mol% triphenylphosphine. As the solvent, a 1 4 mixture of THF and diethoxymethane containing a defined amount of water was crucial for the high reaction rates and yields. 

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