Coupling reactions Tetrakis palladium

Alkenyl-alkenyl cross-coupling. Baba and Negishi have prepared a catalyst from this Pd(II) complex and 2 equiv. of diisobutylaluminum hydride that promotes this coupling reaction. Tetrakis(triphenylphosphine)palladium(0) is inactive, as is material prepared in situ from palladium chloride, triphenylphos-phine and HAKr-CtHg) . A nickel catalyst prepared from Ni(acac)2, PfCnHsja, and diisobutylaluminum hydride is somewhat less efficient. The coupling Involves (E)-alkenylalanes (4, 158, 159) and alkenyl halides. The products are (E,E)- and (E,Z)-dienes. 

In 1988, Linstrumelle and Huynh used an all-palladium route to construct PAM 4 [21]. Reaction of 1,2-dibromobenzene with 2-methyl-3-butyn-2-ol in triethylamine at 60 °C afforded the monosubstituted product in 63 % yield along with 3% of the disubstituted material (Scheme 6). Alcohol 15 was then treated with aqueous sodium hydroxide and tetrakis(triphenylphosphine)palladium-copper(I) iodide catalysts under phase-transfer conditions, generating the terminal phenylacetylene in situ, which cyclotrimerized in 36% yield. Although there was no mention of the formation of higher cyclooligomers, it is likely that this reaction did produce these larger species, as is typically seen in Stephens-Castro coupling reactions [22]. 

Various intermolecular coupling reactions involving acetylene hydrocarbons have been reported to lead to vinylallenes. For example, 1-phenylpropyne (93), after activation with Hg(II) chloride, is first metalated by butyllithium treatment, then trans-metalated with zinc bromide and finally coupled with 1-iodo-l-phenylethene (94) in the presence of tetrakis(triphenylphosphine)palladium to provide the diphenylvinyl-allene 95 in moderate yield (Scheme 5.12) [31]. 

Trialkylstannyl groups can also be replaced by reactive electrophiles in certain cases, but most commonly stannylated azaheterocycles are employed in palladium catalyzed cross-coupling reactions [85PAC1771 86AG(E)508 92S413]. For example, trimethylstannylpyridines can be reacted with bromopyridines in the presence of catalytic amounts of tetrakis-(triphenylphosphine)palladium to give a variety of different bipyridines (Scheme 158)(86S564). 

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). 

Enynes can also be synthesized in excellent yields with high regio- and stereoselectivity by transition metal catalyzed cross-coupling reaction. Thus, ( >l-alkenyl-disiamylboranes react with 1-halo-1-alkynes in the presence of catalytic amount of tetrakis(tripheny]phosphine)palladium to afford conjugated trans enynes (Eq. 100)145). 

Tetraki s(tri phenyl phosphine) palladium was prepared by treating palladium chloride, available from Matthey Bishop, Inc., with hydrazine hydrate 1n the presence of triphenyl phosphine according to an Inorganic Syntheses procedure. The submitters used a freshly prepared, shiny yellow, crystalline sample of the palladium complex. On standing for an extended period of time (> a few weeks), its color gradually darkens. Even such samples are effective in many palladium-catalyzed cross-coupling reactions, but have not been tested in this reaction. Tetraki s( tri phenyl phosphine) palladium is also available from Aldrich Chemical Company. 

Beginning with a discussion of the utility of tin-substituted glycals, Dubois and Beau [198] utilized 2,3,6-tri-O-benzyl-l-tri-fx-butylstannyl-glucal in coupling reactions with various aromatic substrates. As shown in Scheme 7.74, tetrakis(triphenylphosphine)palladium catalyzed reaction with bromobenzene provided an 88% yield of the desired product. Additionally, when... 

A coordinatively unsaturated 14-electron palladium(O) complex, usually coordinated with weak donor ligands (usually tertiaiy phosphanes), has meanwhile been proven to be the catalytically active species [5]. This complex is mostly generated in situ. Tetrakis(triphenylphosphane)palladium(0) [6J, which exists in an equilibrium with tris(triphenylphosphane)palladium(0) and free triphenylphosphane in solution, is frequently employed. The endergonic loss of a second phosphane ligand [7] leads to the catalytically active bis(triphenylphosphane)palladium(0). However, palladium(D) complexes such as bis(triphenylphosphane)palladium dichloride or palladium acetate, which are easily reduced (e.g. by triarylphosphanes see below) in the reaction medium, are more commonly employed for convenience, as they are inherently stable towards air. The mechanistic situation is a little more complicated with palladium acetate, in that anionic acetoxypalladium species Pd(PPh3) (AcO ) (n = 2, 3) are formed in the presence of acetate ions [5], and these actually participate in the oxidative addition step and the following coupling reaction. 

Other oxidants like thallium(III) oxide, vanadium(V) oxyfluoride, palladium ) acetate, and ruthenium(IV) tetrakis(trifluoracetate) have been developed as powerful tools for the intramolecular biaryl coupling reaction [7,93,113]. Nevertheless, DDQ is still one of the most versatile reagents in oxidative coupling reactions (see Scheme 14 and 29 [82,114]). The highly strained dioxa[8](2,7)pyrenophane (65), portraying an overall curvature of nearly 90° for the pyrene subunit, was finally obtained from the mefa-cyclophanediene (66) by dehydrogenation with DDQ in refluxing benzene in 67% yield [114]. 

To the vinyl iodide (1.442 g, 4.938 mmol) in benzene (100 mL) was added vinyl magnesium bromide (1.0 M in THF, 19.75 mL, 19.75 mmol) and tetrakis(triphenylphosphine) palladium (286 mg, 0.247 mmol). Note degassing of the solvent is usually recommended for palladium cross-coupling reactions. This reaction mixture was heated to 60-70 °C for 30 min, diluted with hexanes, and filtered through a pad of silica. After evaporation of the solvents, bulb to bulb Kugelrohr distillation provided 834 mg (88%) of the triene as a colorless oil. 

The oxidative palladium 1 1-insertion complex intermediates (300) and (301) in the coupling reaction between 2,4-dichloropyrimidine, or 5-bromo-2-methanesulfonylpyrimidine, and tetra-kis(triphenylphosphine)- or tetrakis(triisopropyl phosphite)-palladium can be isolated and purified by conventional methods (Scheme 49). The regioselectivity of the insertion reaction in 2,4-dichloropyrimidine is in accord with the 4-regiochemistry in coupling reactions (Section 6.02.5.5.4). The palladized pyrimidines react readily with organnostannnanes, and may serve as catalysts in coupling reactions between the respective pyrimidine precursor and stannanes <90ACS927>. 

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