Palladium methyl ketone synthesis

Silyl enol ethers of alkenyl methyl ketones can be efficiently cyclized to cyclopentenones and cyclohexenones by treating them with stoichiometric amounts of palladium acetate244 an example indicating the elaboration of this approach to the synthesis of a reduced benzoxepinone derivative, and the suggested244 mechanism of the reaction, are depicted in Scheme 174. 

An organic/fluorous biphasic approach (CsFnBr/benzene) to the synthesis of methyl ketones from terminal alkenes with TBHP in the presence of catalytic amounts of the palladium catalyst 215 was presented by Betzemeier and Knochel in 1998 (Scheme 139) °. 

Terminal alkenes can be selectively oxidized to aldehydes by reaction with oxygen, using a palladium-copper catalyst in tertiary butanol (equation 35)160. This reaction is contrary to the normal oxidation process which yields a ketone as the major product. The palladium(II) oxidation of terminal alkenes to give methyl ketones is known as the Wacker process. It is a very well established reaction in both laboratory and industrial synthesis161162. The Wacker oxidation of alkenes has been used in the key step in the synthesis of the male sex pheromone of Hylotrupes bajulus (equation 36)163. 

In contrast, early in the synthesis of the hexahydrobenzofuran portion of the avermectins, Ireland reported that palladium-catalyzed acylation of tetramethyltin was the most effective method for preparing the required methyl ketone as shown in equation (96). The sensitive 3,4-0-isopropylidene-L-threonyl chloride was converted in high yield to the corresponding methyl ketone without epimerization at C-3. To avoid decarbonylation, the reaction was mn under a carbon monoxide atmosphere until completion (4h). 

Lead tetraacetate initiates a similar type of oxidation with terminal alkenes, in the presence of acid, to give an aldehyde hy selective oxidation of the terminal carhon. l Ajj example is the conversion of styrene to phenylacetaldehyde in 98% yield. Palladium chloride (PdCl2) reacts with terminal alkenes, in the presence of oxygen and copper salts, to give a methyl ketone (this reaction is called the Wacker process and is discussed in sec. 12.6.A). It is more useful than the LTA oxidation. Oxidation of terminal alkenes with LTA leads to the aldehyde, whereas oxidation with PdCl2 leads to the methyl ketone. The PdCl2 oxidation is illustrated hy conversion of 402 to 403 in 77% yield, in Ikegami s synthesis of coriolin. ... 

Conversion of a terminal alkene to a methyl ketone is a useful transformation in organic synthesis. The reaction is typically carried out in aqueous DMF as solvent, using palladium(II) chloride as a catalyst (commonly 10 mol%) with copper(II)... 

Tsuji et al. have further exemplified the palladium(ii)-catalysed functionalization of terminal olefins into methyl ketones, in the synthesis of rethrolones, ° jasmonates ° (Scheme 27), and in a bisannelation sequence. The same group... 

Palladium-catalyzed bis-silylation of methyl vinyl ketone proceeds in a 1,4-fashion, leading to the formation of a silyl enol ether (Equation (47)).121 1,4-Bis-silylation of a wide variety of enones bearing /3-substituents has become possible by the use of unsymmetrical disilanes, such as 1,1-dichloro-l-phenyltrimethyldisilane and 1,1,1-trichloro-trimethyldisilane (Scheme 28).129 The trimethylsilyl enol ethers obtained by the 1,4-bis-silylation are treated with methyllithium, generating lithium enolates, which in turn are reacted with electrophiles. The a-substituted-/3-silyl ketones, thus obtained, are subjected to Tamao oxidation conditions, leading to the formation of /3-hydroxy ketones. This 1,4-bis-silylation reaction has been extended to the asymmetric synthesis of optically active /3-hydroxy ketones (Scheme 29).130 The key to the success of the asymmetric bis-silylation is to use BINAP as the chiral ligand on palladium. Enantiomeric excesses ranging from 74% to 92% have been attained in the 1,4-bis-silylation. 

Terminal allenes.1 A synthesis of 1,2-dienes (3) from an aldehyde or a ketone involves addition of ethynylmagnesium bromide followed by reaction of the adduct with methyl chloroformate. The product, a 3-methoxycarbonyloxy-l-alkyne (2), can be reduced to an allene by transfer hydrogenolysis with ammonium formate catalyzed by a zero-valent palladium complex of 1 and a trialkylphosphine. The choice of solvent is also important. Best results are obtained with THF at 20-30° or with DMF at 70°. 

Both uncalcined and calcined LDHs have also been shown to be effective supports for noble metal catalysts [18-25]. For example, palladium supported on Cu/Mg/Al LDHs has been used in the liquid phase oxidation of limonene [24], and on calcined Mg/Al LDHs for the one-pot synthesis of 4-methyl-2-pentanone (methyl isobutyl ketone) from acetone and hydrogen at atmospheric pressure [25]. In the latter case, the performance depends on the interplay between the acid-base and hydrogenation properties. More recently. 

An example prepared by tin-lithium transmetallation is compound 637, which reacts with enolizable ketones, after transmetallation with cerium(III) chloride895. This intermediate was transformed into the corresponding vinylzinc reagent and, after palladium(O)-catalyzed cross-coupling reactions with aryl iodides, was used in the synthesis of the antitumor antibiotic rineomycinone B2 methyl ester940,941. The vinyllithium 627 has also been transformed into the corresponding vinyl iodide by stannylation followed by reaction with iodine. The arylation has been performed in this case by a palladium(0)-catalyzed... 

As shown below, allene derivatives have been adopted as starting materials in the synthesis of furans. Palladium(II)-catalyzed cyclization of a-allenic ketones afforded 2,3-disubstituted furans in good yields <07EJO2844>. The substituent at the a-position of a carbonyl group influences the reaction pathway. Cyclization products were provided when the substituent was a methyl group or a phenyl group, while dimerization products were produced when the substituent was a hydrogen atom. 

Palladium complexes provide a catalytic means for introducing a carbonyl functionality to many organic substrates [185]. The unique value of PdCl2(dppf) as a carbonylation catalyst was realized over a decade ago in the synthesis of acetylenic ketones from terminal acetylenes and organic halides (Scheme 1-25) [186]. Catalytic carbonylation of arylacetylenes in the presence of HI in methanol gives methyl... 

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