Palladium steps

The 5-oxohexanal 27 is prepared by the following three-step procedure (1) 1,2-addition of allylmagnesium bromide to an a, / -unsaturated aldehyde to give the 3-hydroxy-1,5-diene 25, (2) oxy-Cope rearrangement of 25 to give 26, and (3) palladium catalyzed oxidation to afford 27. The method was applied to the synthesis of A -2-octalone (28), which is difficult to prepare by the Robinson annulation[25]. 

Allenes also react with aryl and alkenyl halides, or triflates, and the 7r-allyl-palladium intermediates are trapped with carbon nucleophiles. The formation of 283 with malonate is an example[186]. The steroid skeleton 287 has been constructed by two-step reactions of allene with the enol trillate 284, followed by trapping with 2-methyl-l,3-cyclopentanedione (285) to give 286[187]. The inter- and intramolecular reactions of dimethyl 2,3-butenylmalonate (288) with iodobenzene afford the 3-cyclopentenedicarboxylate 289 as a main product) 188]. 

CO, and methanol react in the first step in the presence of cobalt carbonyl catalyst and pyridine [110-86-1] to produce methyl pentenoates. A similar second step, but at lower pressure and higher temperature with rhodium catalyst, produces dimethyl adipate [627-93-0]. This is then hydrolyzed to give adipic acid and methanol (135), which is recovered for recycle. Many variations to this basic process exist. Examples are ARCO s palladium/copper-catalyzed oxycarbonylation process (136—138), and Monsanto s palladium and quinone [106-51-4] process, which uses oxygen to reoxidize the by-product... 

Figure 2 illustrates the three-step MIBK process employed by Hibernia Scholven (83). This process is designed to permit the intermediate recovery of refined diacetone alcohol and mesityl oxide. In the first step acetone and dilute sodium hydroxide are fed continuously to a reactor at low temperature and with a reactor residence time of approximately one hour. The product is then stabilized with phosphoric acid and stripped of unreacted acetone to yield a cmde diacetone alcohol stream. More phosphoric acid is then added, and the diacetone alcohol dehydrated to mesityl oxide in a distillation column. Mesityl oxide is recovered overhead in this column and fed to a further distillation column where residual acetone is removed and recycled to yield a tails stream containing 98—99% mesityl oxide. The mesityl oxide is then hydrogenated to MIBK in a reactive distillation conducted at atmospheric pressure and 110°C. Simultaneous hydrogenation and rectification are achieved in a column fitted with a palladium catalyst bed, and yields of mesityl oxide to MIBK exceeding 96% are obtained. 

Sumitomo Chemical Co. (98—100) and Mitsubishi Kasei Co. (101) have patented single-step catalysts containing niobium and palladium. A Sumitomo example reports 93.5% MIBK selectivity at 41.8% acetone conversion and conditions of 160°C and 2 MPa. Other significant processes have been reported (60,102—110). 

Another of the few selective syntheses of aLkylpyridines is one for a-picoline (2) (76). This is a two-step process (eq. 24) where acrylonitrile is used to monocyanoethylate acetone in the Hquid phase at 180°C and at autogenous pressure, 2 MPa (300 psig). The monoadduct, 5-cyano-2-pentanone, is then passed over a palladium-containing catalyst to reduce, cyclize, and dehydrogenate, in sequence. 

The first CO route to make adipic acid is a BASF process employing CO and methanol in a two-step process producing dimethyl adipate [627-93-0] which is then hydroly2ed to the acid (43—46). Cobalt carbonyl catalysts such as Co2(CO)g are used. Palladium catalysts can be used to effect the same reactions at lower pressures (47—49). 

Another alternative method to produce sebacic acid iavolves a four-step process. First, butadiene [106-99-0] is oxycarbonylated to methyl pentadienoate which is then dimerized, usiag a palladium catalyst, to give a triply unsaturated dimethyl sebacate iatermediate. This unsaturated iatermediate is hydrogenated to dimethyl sebacate which can be hydrolyzed to sebacic acid. Small amounts of branched chain isomers are removed through solvent crystallizations giving sebacic acid purities of greater than 98% (66). 

The nickel or cobalt catalyst causes isomerization of the double bond resulting in a mixture of C-19 isomers. The palladium complex catalyst produces only the 9-(10)-carboxystearic acid. The advantage of the hydrocarboxylation over the hydroformylation reaction is it produces the carboxyUc acids in a single step and obviates the oxidation of the aldehydes produced by hydroformylation. 

Catalysts for dielectric surfaces are more complex than the simple salts used on metals. The original catalysts were separate solutions of acidic staimous chloride [7772-99-8J, used to wet the surface and deposit an adherent reducing agent, and acidic palladium chloride [7647-10-17, which was reduced to metallic palladium by the tin. This two-step catalyst system is now essentially obsolete. One-step catalysts consist of a stabilized, pre-reacted solution of the palladium and staimous chlorides. The one-step catalyst is more stable, more active, and more economical than the two-step catalyst (21,23). A separate acceleration or activation solution removes loose palladium and excess tin before the catalyzed part is placed in the electroless bath, prolonging bath life and stability. 

Acceleration modifies the surface layer of palladium nuclei, and stannous and stannic hydrous oxides and oxychlorides. Any acid or alkaline solution in which excess tin is appreciably soluble and catalytic palladium nuclei become exposed may be used. The activation or acceleration step is needed to remove excess tin from the catalyzed surface, which would inhibit electroless plating. This step also exposes the active palladium sites and removes loose palladium that can destabilize the bath. Accelerators can be any acidic or alkaline solution that solubilizes excess tin. 

Surfaces. Essentially any electrically conductive surface can be electroplated, although special techniques may be required to make the surface electrically conductive. Many techniques ate used to metalline nonconductive surfaces. These are weU-covered ia the Hterature (3) and can range from coating with metallic-loaded paints or reduced-silver spray, to autocatalytic processes on tin—palladium activated surfaces or vapor-deposited metals. Preparation steps must be optimized and closely controlled for each substrate being electroplated. 

In terms of cost, the effectiveness of the catalytic cycle in the ring closure makes this process economical in palladium. The first three steps in the reaction sequence -- ring opening of an epoxide by a Grignard reagent, converison of an alcohol to an amine with inversion, and sulfonamide formation from the amine — are all standard synthetic processes. 

Seven procedures descnbe preparation of important synthesis intermediates A two-step procedure gives 2-(HYDROXYMETHYL)ALLYLTRIMETH-YLSILANE, a versatile bifunctional reagent As the acetate, it can be converted to a tnmethylenemethane-palladium complex (in situ) which undergoes [3 -(- 2] annulation reactions with electron-deficient alkenes A preparation of halide-free METHYLLITHIUM is included because the presence of lithium halide in the reagent sometimes complicates the analysis and use of methyllithium Commercial samples invariably contain a full molar equivalent of bromide or iodide AZLLENE IS a fundamental compound in organic chemistry, the preparation... 

The catalyst is previously prepared in an apparatus for catalytic hydrogenation, in which are placed 0.5 g. of palladous chloride, 3.0 g. of Norite, and 20 ml. of distilled water. The bottle is swept out with hydrogen and then shaken with hydrogen for 2-3 hours at 2-3 atmospheres (40 lb.) pressure. The palladium on carbon is collected on a Biichner funnel, washed with five 50-ml. portions of distilled water, then with five 50-ml. portions of 95% ethanol, and finally twice with ether. Upon drying, about 3 g. of the catalyst is obtained. It is stored in a vacuum desiccator over solid sodium hydroxide. If the reduction of the chloro-lepidine does not proceed normally, the used catalyst should be removed by suction filtration and a fresh 3-g. portion of catalyst added. Failure of the reduction step is usually due to an inactive catalyst or to impurities in the acetic acid or chlorolepidine. The palladium catalysts, prepared as described elsewhere in this volume, are presumably also satisfactory for the reduction of 2-chlorolepidine (p. 77). 

Product stereochemistry is a function of the specific catalyst used for hydro-genation. For example, palladium generally gives more of the thermodynamically stable product than other catalysts. This effect has been attributed to an increased rate of equilibration of the steps in the hydrogenation process. Consequently, palladium should not be used to hydrogenate readily isomerizable olefins such as A - and A -steroids. ... 

The Hegedus indole synthesis involves one of the earlier (formal) examples of olefin hydroamination. An ortho-vinyl or ortho-nllyl aniline derivative 1 is treated with palladium(II) to deliver an intermediate resulting from alkene aminopalladation. Subsequent reduction and/or isomerization steps then provide the indoline or indole unit 2, respectively. 

The first example of an indolo[2,3-a]carbazole derivative reported with a reasonably estabhshed structure was the mono N-methylated system 9, prepared via dehydrogenation with palladium on charcoal of the octahydro derivative 10, available via reaction of the aminocarbazole 11 with 2-hydroxycyclohexanone in the presence of a trace amount of anihnium bromide (Scheme 1). An approach toward the parent compound 1 using the same method has also been attempted, although without success (56JCS4783). The utility of this route is impaired by the complexity of the starting material, which requires multistep preparation, and the harsh conditions of the final step. 

Due to their successful synthesis of 2-(4 -chlorophenyl)-4-iodoquinoline from the corresponding precursor acetylene, Arcadi et al. (99T13233) developed a one-step synthesis of 2,4-disubstituted quinolines via palladium-catalyzed coupling reactions. An example is the Heck reaction of 4-iodoquinoline (131) with a-acetamidoacrylate (132). This one-pot synthesis yielded adduct 133 in 50% overall yield after purification via flash chromatography. 

This reaction is not a bona fide Heck reaction per se for two reasons (a) the starting material underwent a Hg Pd transmetallation first rather than the oxidative addition of an aryl halide or triflate to palladium(O) (b) instead of undergoing a elimination step to give an enone, transformation 134 136... 

As in case of other palladium-catalyzed reactions, the general mechanism of the Stille reaction is best described by a catalytic cycle—e.g. steps a) to c) ... 

When the products are partially or totally miscible in the ionic phase, separation is much more complicated (Table 5.3-2, cases c-e). One advantageous option can be to perform the reaction in one single phase, thus avoiding diffusional limitation, and to separate the products in a further step by extraction. Such technology has already been demonstrated for aqueous biphasic systems. This is the case for the palladium-catalyzed telomerization of butadiene with water, developed by Kuraray, which uses a sulfolane/water mixture as the solvent [17]. The products are soluble in water, which is also the nucleophile. The high-boiling by-products are extracted with a solvent (such as hexane) that is immiscible in the polar phase. This method... 

The first step in producing caprolactam from benzoic acid is its hydrogenation to cyclohexane carboxylic acid at approximately 170°C and 16 atmospheres over a palladium catalyst ... 

---