Methyl ketones alkene oxidation

Table 1 Palladium(II)-catalyzed Oxidation of Functionalized Terminal Alkenes to Methyl Ketones Alkene Product...

Acetalization of l-alkenes. The Wacker uinversion of l-alkenes to methyl ketones by oxidation catalyzed by PdCE-CuCl takes a different course when applied to vinyl ketones (1). Thus oxygenation of mixtures of I and 1,3- or 1,2-diols catalyzed by PdCE-CuCl results in cyclic acetals formed by exclusive attaek at the terminal carbon atom. A similar reaction occurs with l-alkenes substituted with COOCH,. 

The asymmetric total synthesis of the putative structure of the cytotoxic diterpenoid (-)-sclerophytin A was accomplished by L.A. Paquette and co-workers/ At the beginning of the synthesis, a bicyclic intermediate was subjected to the Wacker oxidation to oxidize its terminal alkene into the corresponding methyl ketone. The oxidation took place in high yield, although the reaction time was long. The spectra obtained for the final product (proposed structure) did not match that of the natural product, consequently a structural revision was necessary. 

Oxidation. The system is best known for oxidation of 1-alkenes to methyl ketones (Wacker oxidation). It has been employed to remove the allyl group of allyl glycosides directly or after photolysis of the products. In the presence of CO dihy-droisobenzofuran is oxidized to phthalide in 86% yield. ... 

Oxidation of Terminal Alkenes to Methyl Ketones. The oxidation of ethylene to acetaldehyde with water acting as the nucleophile using a Pd Cl2-Cu Cl2 catalyst under an oxygen atmosphere is known as the Wacker process. On a laboratory scale the... 

Higher terminal alkenes are oxidized to methyl ketones and this unique oxidation of alkenes has extensive synthetic applications[23]. The terminal alkenes can be regarded as masked methyl ketones, which are stable to acids, bases, and nucleopliiles[24]. The oxidation of terminal alkenes to methyl ketones has been extensively applied to syntheses of many natural products[77]. 

In contrast to oxidation in water, it has been found that 1-alkenes are directly oxidized with molecular oxygen in anhydrous, aprotic solvents, when a catalyst system of PdCl2(MeCN)2 and CuCl is used together with HMPA. In the absence of HMPA, no reaction takes place(100]. In the oxidation of 1-decene, the Oj uptake correlates with the amount of 2-decanone formed, and up to 0.5 mol of O2 is consumed for the production of 1 mol of the ketone. This result shows that both O atoms of molecular oxygen are incorporated into the product, and a bimetallic Pd(II) hydroperoxide coupled with a Cu salt is involved in oxidation of this type, and that the well known redox catalysis of PdXi and CuX is not always operalive[10 ]. The oxidation under anhydrous conditions is unique in terms of the regioselective formation of aldehyde 59 from X-allyl-A -methylbenzamide (58), whereas the use of aqueous DME results in the predominant formation of the methyl ketone 60. Similar results are obtained with allylic acetates and allylic carbonates[102]. The complete reversal of the regioselectivity in PdCli-catalyzed oxidation of alkenes is remarkable. 

Acetoxy-l,7-octadiene (40) is converted into l,7-octadien-3-one (124) by hydrolysis and oxidation. The most useful application of this enone 124 is bisannulation to form two fused six-membered ketonesfl 13], The Michael addition of 2-methyl-1,3-cyclopentanedione (125) to 124 and asymmetric aldol condensation using (5)-phenylalanine afford the optically active diketone 126. The terminal alkene is oxidi2ed with PdCl2-CuCl2-02 to give the methyl ketone 127 in 77% yield. Finally, reduction of the double bond and aldol condensation produce the important intermediate 128 of steroid synthesis in optically pure form[114]. 

Oxidation. The use of l,4-ben2oquinone in combination with paHadium(Il) chloride converts terminal alkenes such as 1-hexene to alkyl methyl ketones in high yield (81%) (32). The quinone appears to reoxidi2e the palladium. 

The chemistry of alkynes is dominated by electrophilic addition reactions, similar to those of alkenes. Alkynes react with HBr and HC1 to yield vinylic halides and with Br2 and Cl2 to yield 1,2-dihalides (vicinal dihalides). Alkynes can be hydrated by reaction with aqueous sulfuric acid in the presence of mercury(ll) catalyst. The reaction leads to an intermediate enol that immediately isomerizes to yield a ketone tautomer. Since the addition reaction occurs with Markovnikov regiochemistry, a methyl ketone is produced from a terminal alkyne. Alternatively, hydroboration/oxidation of a terminal alkyne yields an aldehyde. 

Wacker oxidation of l-alkenes. The Wacker oxygenation of 1-alkenes to methyl ketones involves air oxidation catalyzed by PdCl2 and CuCU, which is necessary for reoxidation of Pd(0) to Pd(II).1 This oxygenation is fairly sluggish and can result in chlorinated by-products. A new system is comprised of catalytic amounts of Pd(OAc)2, hydroquinone, and 1, used as the oxygen activator.2 The solvent is aqueous DMF, and a trace of HClOj is added to prevent precipitation of Pd(0). Oxygenation using this system of three catalysts effects Wacker oxidation of 1-alkenes in 2-8 hours and in 67-85% yield. 

Anodic oxidation is used to promote the recycling of palladium(il) in the Wacker process for the conversion terminal alkenes to methyl ketones. Completion of the catalytic cycle requires the oxidation of palladium(O) back to the palla-dium(li) state and this step can be achieved using an organic mediator such as tri(4-bromophenyljamine. The mediator is oxidised at the anode to a radical-cation and... 

Similar 0—4 generations silica-supported Pd-PAMAM dendrimers with various spacer lengths were used by Alper et al. as recyclable catalysts for the hydroesterification reaction of alkenes (55) and the oxidation of terminal alkenes to methyl ketones (56). The hydroesterification experiments (Scheme 16) showed that (PPh3)2Pd-PPh2-PAMAM-Si02 complexes were highly active catalysts for styrene derivatives and linear long-chain alkenes (numbers of turnovers up to 1200). 

SCHEME 137. Proposed mechanism for the palladium-catalyzed oxidation of terminal alkenes to methyl ketones using TBHP oxidant... 

With this method styrene derivatives are oxidized in very good yields (complete conversion at 56 °C after 2-5 hours), whereas aliphatic alkenes require longer reaction time (8-20 h) and increased amounts of oxidant (3.5 eq.), and afford methyl ketones in moderate to good yields. Besides terminal olefins also stilbene and ethyl cinnamate have been converted to benzyl phenyl ketone and /3-ketoester. The catalyst solution can be reused 8 times without decrease in yield. 

Bis(trimethylsilyl)monoperoxysulfate 6 is also an excellent agent for oxygen transfer to nucleophilic substrates such as alkenes and heteroatoms. Compound 6 could oxidize alkenes such as 1-methylcyclohexene and fraw5-/3-methylstyrene, producing 2-methyl-cyclohexanone and benzyl methyl ketone, respectively, in high yield, most likely via the... 

In 1960, Moiseev and coworkers reported that benzoquinone (BQ) serves as an effective stoichiometric oxidant in the Pd-catalyzed acetoxylation of ethylene (Eq. 2) [19,20]. This result coincided with the independent development of the Wacker process (Eq. 1, Scheme 1) [Ij. Subsequently, BQ was found to be effective in a wide range of Pd-catalyzed oxidation reactions. Eor example, BQ was used to achieve Wacker-type oxidation of terminal alkenes to methyl ketones in aqueous DMF (Eq. 3 [21]), dehydrogenation of cyclohexanone (Eq. 4 [22]), and alcohol oxidation (Eq. 5 [23]). In the final example, 1,4-naphthoquinone (NQ) was used as the stoichiometric oxidant. 

These multicomponent catalyst systems have been employed in a variety of aerobic oxidation reactions [27]. For example, use of the Co(salophen) cocatalyst, 1, enables selective allylic acetoxylation of cyclic alkenes (Eq. 6). Cyclo-hexadiene undergoes diacetoxylation under mild conditions with Co(TPP), 2 (Eq. 7), and terminal alkenes are oxidized to the corresponding methyl ketones with Fe(Pc), 3, as the cocatalyst (Eq. 8). 

Rhodium complexes were generally found to be more effective than iridium, but on the whole they show moderate activity in alkene oxygenation reactions. Significantly, epoxides, a typical product of the oxidation of olefins catalyzed by the middle transition metals, have rarely been evoked as products [18-22]. Although allylic alcohols [23] or ethers [24] have sometimes been described as products, the above cited rhodium and iridiiun complexes are characterized by an excellent selectivity in the oxygenation of terminal alkenes to methyl ketones. 

The Cope rearrangement of 24 gives 2,6,10-undecatrienyldimethylamine[28], Sativene (25j[29] and diquinane (26) have been synthesized by applying three different palladium-catalyzed reactions [oxidative cyclization of the 1,5-diene with Pd(OAc)2, intramolecular allylation of a /i-keto ester with allylic carbonate, and oxidation of terminal alkene to methyl ketone] using allyloctadienyl-dimethylamine (24) as a building block[30]. 

The selective oxidation of terminal alkenes to the corresponding methyl ketones was reported by Roussel and Mimoun in 1980 and can be carried out using t-butylperoxypalladium(II) trifluoroacetate (PPT) or alternatively catalytic amounts of... 

Oxidation of 1-alkenes to methyl ketones. This Pd catalyst allows air oxidation of 1-alkenes to alkyl methyl ketones in yields of about 350% (based on Pd). The oxidation is also possible under nitrogen (about 90% isolated yield), but then I is not functioning as a catalyst (equation 1). 2-Alkenes can be oxidized slowly in this way but a number of products are formed. 

Methyl ketones. Hydrogen peroxide in the presence of Pd(OAc)-. as catalyst converts terminal alkenes to methyl ketones in high yield and with high selectivity (equation I).1 Internal and cycloalkenes are inactive. The actual oxidant is... 

Oxidation of —CH=CH2 to —COCH3. Mimoun et al. have prepared a number of reagents in which the CF3 group of I is replaced by other groups. However 1 is the most effective for conversion of terminal alkenes to methyl ketones. Yields are high and the reaction is usually complete within an hour. The reaction can be catalytic with respect to 1 if r-BuOOH is present (equation I). 

Wacker oxidation. Tsuji et al.s have developed two procedures for oxidation of 1-alkenes to methyl ketones with oxygen that are catalyzed by PdCl2 (7, 278 9, 327). The solvent in both cases is aqueous DMF. One method uses PdCl2-CuCl (molar ratio 1 10) the other uses PdCl2 and p-benzoquinone (molar ratio 1 100). Both procedures are about equivalent for oxidation of simple l-alkenes to methyl ketones, but the former method is usually more effective for oxidation of more complex 1-alkenes. 

Oxidation with Palladium in the Homogeneous Phase. The most thoroughly studied reaction concerning the transformation of alkenes to carbonyl compounds is their oxidation catalyzed by palladium in homogeneous aqueous media.243 244 494-503 As a rule, ethylene is oxidized to acetaldehyde, and terminal alkenes are converted to methyl ketones.504 505... 

A Co(II) Schiff-base complex converts 1- and 2-alkenes into methyl ketones and the corresponding secondary alcohols in the presence of oxygen or H2O2 in primary alcohol solvent.543 A radical oxidation with cobalt hydroperoxide through the formation and subsequent decomposition of alkyl hydroperoxide was suggested.543 An efficient conversion of alkenylarenes to ketones was achieved by the use of molecular oxygen and EtjSiH in the presence of a catalytic amount of Co(II) porphyrin in 2-propanol.544... 

Aqueous biphasic catalysis is also used in homogeneous hydrogenations.117-119 In new examples Ru clusters with the widely used TPPTN [tris(3-sulfonatophenyl) phosphine] ligand120 and Rh complexes with novel carboxylated phosphines121 were applied in alkene hydrogenation, whereas Ru catalysts were used in the hydro-genation of aromatics. Aerobic oxidation of terminal alkenes to methyl ketones was carried out in a biphasic liquid-liquid system by stable, recyclable, water-soluble Pd(II) complexes with sulfonated bidentate diamine ligands.124... 

An enantioselective synthesis of (+)-estradiol has been accomplished from 1,3-dihy-drobenzo[c]thiophene 2,2-dioxide (306) by successive thermal S02-extrusion and cycloaddition (80HCA1703). Treatment of the optically active iodide (307) with two mole equivalents of the masked quinodimethane (306) in the presence of two mole equivalents of sodium hydride gave (308) as a 1 1 mixture of diastereoisomers. Thermolysis of this alkenic sulfone in 1,2,4-trichlorobenzene furnished the trans-anti-trans steroid (309) in 80% yield. Treatment of (309) with methyllithium gave the methyl ketone, which was subjected to a Baeyer-Villiger oxidation and then silyl ether-acetate cleavage to afford (-l-)-estradiol (310 Scheme 66). 

There are also several situations where the metal can act as both a homolytic and heterolytic catalyst. For example, vanadium complexes catalyze the epoxidation of allylic alcohols by alkyl hydroperoxides stereoselectively,57 and they involve vanadium(V) alkyl peroxides as reactive intermediates. However, vanadium(V)-alkyl peroxide complexes such as (dipic)VO(OOR)L, having no available coordination site for the complexation of alkenes to occur, react homolyti-cally.46 On the other hand, Group VIII dioxygen complexes generally oxidize alkenes homolytically under forced conditions, while some rhodium-dioxygen complexes oxidize terminal alkenes to methyl ketones at room temperature. 

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