Pd -pyridine

Table 4 Substrate scope for direct dioxygen-coupled heterocyclization using the Pd/pyridine catalyst system...

Gouverneur and coworkers showed that a,b-unsaturated esters can be cy-clized in good to excellent yields (Eq. 31) [156]. Optimization of the reaction conditions revealed that four equivalents of BQ were necessary to achieve good yields (73%). Aerobic conditions, without a copper cocatalyst, proved to be superior, resulting in 89% yield over extended reaction times. No cycli-zation product was observed with the Pd/pyridine catalyst system described above. 

Reagents i, heat ii, H2-Pd-pyridine iii, BF3,Et20 iv, LiAlH4. Scheme 13... 

As shown in the mechanism depicted in (Scheme 18), the Pd-catalyzed silyl-carbocyclization of 1,6-dienes involves a reversible insertion of an olefin moiety into the [Pd]-Si bond (E-II to E-III). However, the coordination of the second olefin moiety to the Pd metal (forming E-IV) would fill the coordination site required for the j8-silyl-elimination and would therefore render the C—Si bond formation irreversible, which leads to the irreversible carbometalation to jdeld E-V. Accordingly, when the chiral Pd(pyridine-oxazoline) complex is used as the catalyst, the enantioselectivity should be determined at the first olefin insertion step forming -silylalkyl-[Pd] complex E-III. 

If high chloride concentrations are present in these reactions, the selectivity of the second step is strongly increased for the formation of C-Cl bonds, and P-hydride elimination is inhibited. This effect seems to originate from the saturation of the Pd coordination sites by the Cl and consequent inhibition of hydrogen coordination and thus prevention of the ehmination reactions [108]. The observation that the use of Pd pyridine complexes favored chlorination even at lower chloride concentrations gave rise to an asymmetric chlorohydrin synthesis from allyl ether 154 with the use of chiral bimetallic Pd complex 156 (Scheme 16.42). 

Stahl and coworkers conducted mechanistic studies on both the Pd/DMSO and the Pd/pyridine system [77,78]. Kinetic studies revealed that in the Pd/pyridine system the rate exhibits no dependence on the oxygen pressure, and kinetic isotope effect studies support turnover-limiting substrate oxidation. In contrast the Pd/DMSO system features turnover-hmiting oxidation of paUadiumfO) (see Figure 5.13). Moreover in the Pd/pyridine system, pyridine is very effective in oxidizing palladium(O) by molecular oxygen, but at the same time inhibits the rate of alcohol oxidation by palladium(II). 

Figure 5.13 Mechanistic insights on Pd/pyridine and Pd/DMSO systems.

Three different N-heterocyclic carbene (NHC)-Pd-pyridine complexes (A, B, and C), where NHC is 1,2,4-trimethyltriazolyldiylidene, 1,3-dimethylimidazoly-lidene, and 1,4-dimethyltriazolylidene, have been reported to efficiently catalyze a domino sequence of alkyne coupling of an ortho-iodo phenol or an ortho-iodo benzylalcohol and the subsequent cycloisomerization of the intermediate tolane derivative to afford benzofuran 25 or benzoisofuran 26 (Scheme 12.17) [49]. 

High catalytic activity (TOF = 282h ) and selectivity to the branched product ( 91%) were found in the biphasic hydrocarboxylation of vinyl aromatic compounds to the isomeric atylpropanoic adds using a novel water-soluble palladium complex, ]Pd(pyridine-2-carboxylato)(TPPTS)] hrsO , as the catalyst [138]. 

Dihydroisobenzofurans are obtained also in a one-pot procedure, without the isolation of 2-alkynyl benzyl alcohols, in a domino process that comprises a Sonogashira coupling followed by an intramolecular hydroalkoxylation, starting from 2-halobenzyl alcohols and phenylacetylene, using only NHC-Pd-pyridine complexes prepared to this aim [106]. The choice of the catalyst was fundamental, very low reactivity in the hydroalkoxylation step was observed performing the... 

The oxidative coupling of toluene using Pd(OAc)2 via />-tolylmercury(II) acetate (428) forms bitolyl[384]. The aryl-aryl coupling proceeds with copper and a catalytic amount of PdCl2 in pyridine[385]. Conjugated dienes are obtained by the coupling of alkenylmercury(II) chlorides[386]. 

Methyl-5-(4-pyridyl)-7-aza- 2-Araino-3-iodo-6-methyl-,S- (4-pyridyl)pyridine Trimethylsilylethyne. Pd(PPh,)jCl4, Cut 96,40 ... 

Production is by the acetylation of 4-aminophenol. This can be achieved with acetic acid and acetic anhydride at 80°C (191), with acetic acid anhydride in pyridine at 100°C (192), with acetyl chloride and pyridine in toluene at 60°C (193), or by the action of ketene in alcohoHc suspension. 4-Hydroxyacetanihde also may be synthesized directiy from 4-nitrophenol The available reduction—acetylation systems include tin with acetic acid, hydrogenation over Pd—C in acetic anhydride, and hydrogenation over platinum in acetic acid (194,195). Other routes include rearrangement of 4-hydroxyacetophenone hydrazone with sodium nitrite in sulfuric acid and the electrolytic hydroxylation of acetanilide [103-84-4] (196). 

The immediate outcome of the Hantzsch synthesis is the dihydropyridine which requires a subsequent oxidation step to generate the pyridine core. Classically, this has been accomplished with nitric acid. Alternative reagents include oxygen, sodium nitrite, ferric nitrate/cupric nitrate, bromine/sodium acetate, chromium trioxide, sulfur, potassium permanganate, chloranil, DDQ, Pd/C and DBU. More recently, ceric ammonium nitrate (CAN) has been found to be an efficient reagent to carry out this transformation. When 100 was treated with 2 equivalents of CAN in aqueous acetone, the reaction to 101 was complete in 10 minutes at room temperature and in excellent yield. 

A different set of tautomeric tetrahydropyridines was obtained on partial hydrogenation of 2-alkoxy-3-acylpyridines 25 on PtOa or Pd/C catalyst (Scheme 9) (79JHC939). The tetrahydropyridines 26 formed exist exclusively as single tautomers, the type of tautomer, however, being determined by the substitution in the pyridine ring. 

Amines (7a,12a), especially pyridine (75), have also been used as solvents in the hydrogenation of acetylenes. Hydrogenation of 3 over 5% Pd-on-BaS04 in pyridine gave df-cis-jasmanate (4) quantitatively (40). The authors comment that this combination for reduction of acetylenes was superior to the Lindlar catalyst in all cases examined. (See also Refs. 12 and 24 for similar conclusions.)... 

Excellent yields of the oximes of phenylacetaldehydes are obtained by reduction of 6-nitrostyrenes over Pd-on-C in a pyridine solvent (74,75). The technique gives yields of only about 60% when applied to aliphatic unsaturated nitrocompounds better yields are obtained in acidic media(6 5). Over 5% Rh-on-Al203 in ethanol-acetic acid-ethyl acetate, 2- 6-dinitro-styrenes are converted to 2-nitrophenylacetaldehyde oximes (13). 

Reduction of 3,5-dimethylisoxazolo[5,4-h]pyridine over 5% Pd-on-C proceeded with loss of the aromatic system to give 3-(l-aminoethyliden)-5-methyl-2-oxopiperidine (94). The product is a vinylogous amide, a type of structure resistant to further hydrogenation (118). 

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