Oxidation palladium-catalysed

Oxidative palladium-catalysed rearrangement of diaryl alkenyl carbinols to /1,/1-diaryl Q ,j8-unsaturated ketones occurs with the geometry of the alkene product determined by the substitution pattern on the aryl rings (Scheme 139). ... 

Addition of tributylstannyl-lithium to crotonaldehyde and protection of the resulting alcohol with chloromethyl methyl ether gives the stannane (192), which reacts with both alkyl and aryl aldehydes RCHO to form specifically the t/rr o-hydroxy-enol ethers (193). These latter compounds have been used to prepare tra/i5-4,5-disubstituted butyrolactones by hydrolysis and subsequent oxidation. Palladium-catalysed carbonylation of RX in the presence of organotin species constitutes a useful synthesis of unsymmetrical ketones, and in the example reported this year RX is an arenediazonium salt. The reaction, which is basically an aromatic acylation, proceeds in good to excellent yield. Another Pd-catalysed reaction of aromatics, this time aryl bromides, is their reaction with acetonyltributyltin (194), prepared from methoxytributyltin and isopropenyl acetate, to give the arylacetones (195). ... 

A copper-catalysed CDC of benzothiazoles with thiazoles and polyfluoroarene leads to the synthesis of the 2,2 -linkage of thiazoles and 2-polyfluoroarylthiazoles. Silver carbonate has been used as a terminal oxidant. Palladium-catalysed dual C-H functionalization of benzophenones to form fluorenones by oxidative dehydrogenative cyclization has been developed using silver oxide as the oxidant. The reaction is postulated to involve a five-membered palladacycle intermediate. Os(VIII)-catalysed oxidation of 6-aminopenicillanic acid and chlorpheniramine by diperiodatoar-gentate(III) involves an initial formation of an Os(VIII)-reductant complex followed... 

There are also palladium-catalysed procedures for allylation. Ethyl 3-bromo-l-(4-methylphenylsulfonyl)indole-2-carboxylate is allylated at C3 upon reaction with allyl acetate and hexabutylditin[27], Ihe reaction presumably Involves a ir-allyl-Pd intermediate formed from the allyl acetate, oxidative addition, transmetallation and cross coupling. 

Carbon-carbon bond formation reactions and the CH activation of methane are another example where NHC complexes have been used successfully in catalytic applications. Palladium-catalysed reactions include Heck-type reactions, especially the Mizoroki-Heck reaction itself [171-175], and various cross-coupling reactions [176-182]. They have also been found useful for related reactions like the Sonogashira coupling [183-185] or the Buchwald-Hartwig amination [186-189]. The reactions are similar concerning the first step of the catalytic cycle, the oxidative addition of aryl halides to palladium(O) species. This is facilitated by electron-donating substituents and therefore the development of highly active catalysts has focussed on NHC complexes. 

The cycloaddition of alkynes and alkenes to nitrile oxides has been used in the synthesis of functionalised azepine systems <96JHC259>, <96T5739>. The concomitantly formed isoxazole (dihydroisoxazole) ring is cleaved by reduction in the usual way. Other routes to 1-benzazepines include intramolecular amidoalkylation <96SC2241> and intramolecular palladium-catalysed aryl amination and aryl amidation <96T7525>. Spiro-substituted 2-benzazepines have been prepared by phenolic oxidation (Scheme 5) <96JOC5857> and the same method has been applied to the synthesis of dibenzazepines <96CC1481>. 

Some companies are successfully integrating chemo- and biocatalytic transformations in multi-step syntheses. An elegant example is the Lonza nicotinamide process mentioned earlier (.see Fig. 2.34). The raw material, 2-methylpentane-1,5-diamine, is produced by hydrogenation of 2-methylglutaronitrile, a byproduct of the manufacture of nylon-6,6 intermediates by hydrocyanation of butadiene. The process involves a zeolite-catalysed cyciization in the vapour phase, followed by palladium-catalysed dehydrogenation, vapour-pha.se ammoxidation with NH3/O2 over an oxide catalyst, and, finally, enzymatic hydrolysis of a nitrile to an amide. 

Cluster or bimetallic reactions have also been proposed in addition to monometallic oxidative addition reactions. The reactions do not basically change. Reactions involving breaking of C-H bonds have been proposed. For palladium catalysed decomposition of triarylphosphines this is not the case [32], Likewise, Rh, Co, and Ru hydroformylation catalysts give aryl derivatives not involving C-H activation [33], Several rhodium complexes catalyse the exchange of aryl substituents at triarylphosphines [34] ... 

The palladium catalysed substitution reaction of allylic systems has also been utilised in the formation of five membered rings. Intramolecular nucleophilic attack of the amide nitrogen atom on the allylpalladium complex formed in the oxidative addition of the allyl acetate moiety on the catalyst led to the formation of the five membered ring (3.63.). In the presence of a copper(II) salt the intermediate pyrroline derivative oxidized to pyrrole.80... 

V-aryl-o-haloanilines can be converted into indole derivatives in a palladium catalysed oxidative addition, C-H activation sequence. The transformation has been utilized extensively in the preparation of polycyclic compounds. In a recent example, leading to the formation of the carbazole ring system, Larock and co-workers demonstrated that the formation of the... 

Most of the studies to date have employed either palladium [222—229] or platinum [220,224,226,228—235], commonly as Adams reduced platinum oxide, although nickel [228,236,237], rhodium [238,239], ruthenium [239], iridium [239], iron [237] and tungsten [237] have also been used. Many of these studies have been concerned with the stereochemistry of the hydrogenation of disubstituted cycloalkenes. Table 32 shows some typical results for the platinum- and palladium-catalysed hydrogenation of disubstituted cyclohexenes. Table 33 shows comparative results for the hydrogenation of 1,4-dialkylcyclohexenes over palladium, platinum and rhodium catalysts. 

Palladium-catalysed chemo- and enantio-selective oxidation of allylic esters and carbonates has been achieved using nitronates as nucleophilic oxidants. The products, o /3-unsaturalcd carbonyl compounds, were obtained in excellent yields and ees. The mechanism in Scheme 5 has been suggested for the reaction.108... 

The palladium-catalysed intramolecular 3 + 2-cycloaddition of alk-5-enylidene-cyclopropanes produced a variety of bicyclo[3.3.0]octane systems with up to three stereocentres.62 The oxidative addition of cyclopropyl phenyl ketone to Ni(Pcy3) gave nickeladihydropyran, which is a key intermediate in the Ni(0)-catalysed homo-... 

Palladium-catalysed reactions of dimetallic compounds 358 such as X2B—BX2, R3Sn—SnR3, R3S11—SiR3 or R3Si—SiR3 with halides via oxidative addition and transmetallation are useful for the preparation of carbon main group metal bonds 359. 

Palladium-catalysed directed C-H oxidation with (diacetoxy)iodobenzene of a series of meta -substituted aryl pyridine and aryl amide derivatives resulted in the formation of the corresponding acetoxy compounds. The reactions generally proceed with high levels of regioselectivity for functionalization of the less sterically hindered ortho-C-H bond.144 The mechanism shown in Scheme 4 has been proposed for the oxidation of 2,6-dimethylphenol with (diacetoxyiodo)benzene for the formation of 3,5,3, 5 -tetramethyl-biphenyl-4,4 -diol, via C-C coupling.145... 

Jacques M (2003) Palladium-catalysed oxidation of primary and secondary alcohols. Tetrahedron 59(31) 5789-5816... 

J. Tsuji, Synthetic Applications of the Palladium-Catalysed Oxidation of Olefins to Ketones, Synthesis 1984, 369. 

The palladium-catalysed addition of aryl, vinyl, or substituted vinyl groups to organic halides or triflates, the Heck reaction, is one of the most synthetically useful palladium-catalysed reactions. The method is very efficient, and carries out a transformation that is difficult by more traditional techniques. The mechanism involves the oxidative addition of the halide, insertion of the olefin, and elimination of the product by a p-hydride elimination process. A base then regenerates the palladi-um(0) catalyst. The whole process is a catalytic cycle. 

Mori started with the early introduction of the chiral centre [298] in using (3-oxidation of pentanoic acid A by the yeast, Candida rugosa, IFO 0750 [299]. The obtained (R)-3-hydroxypentanoic acid B was transformed into C in a few conventional steps. The second building block was prepared from methyl 2-pentynoate D conjugate addition of lithium dimethyl cuprate yielded E, which was further converted into the frans-configured vinyl bromide F. Hydro-boration of C yielded G which upon Suzuki s palladium catalysed cross-coupling with F furnished 157 after treatment of the reaction product with hydrochloric acid followed by chromatographic purification. The synthesis of ent-157 used (S)-3-hydroxypentanoic acid. 

The palladium-catalysed cross-coupling of aryl halides or vinyl halides with dialkyl phosphonates (31) to yield dialkyl arylphosphonates and dialkyl vinylphosphonates, respectively, was first reported by Hirao and co-workers 69 the halides used most frequently are bromides and the reaction is stereospecific with haloalkenes. Subsequently, analogous reactions of alkyl alkylphosphinates (32), alkyl arylphosphinates (32), alkyl phosphinates (33), and secondary phosphine oxides (34), replacing [P—H] bonds with [P—C] bonds to yield various phosphinates and tertiary phosphine oxides, have been developed (Figure 7.1). Alkyl phosphinates (33) may be mono- or diarylated as desired by the selection of appropriate conditions. Aiyl and vinyl triflates have also found limited... 

Very few examples of the oxidation of olefins to ketones in ionic liquids have been reported. In one case, [C4Ciim][BF4] or [C4Ciim][PF6] were used in the palladium-catalysed oxidation of styrene to acetophenone with H2O2 as oxidant, however the concept of biphasic catalysis was not exploited and no attempts were made to recycle the catalyst.[131 The ionic liquid serves the purpose of a co-catalyst rather than that of a reaction medium. 

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