Allylation Wacker oxidation

Scheme 91 Sequential halo allylation-Wacker oxidation [160]...

The phenolic oxygen on 2-allyl-4-bromophenol (7) readily underwent oxypalladation using a catalytic amount of PdCl2 and three equivalents of Cu(OAc)2, to give the corresponding benzofuran 8. This process, akin to the Wacker oxidation, was catalytic in terms of palladium, and Cu(OAc)2 served as oxidant [17]. Benzofuran 10, a key intermediate in Kishi s total synthesis of aklavinone [18], was synthesized via the oxidative cyclization of phenol 9 using stoichiometric amounts of a Pd(II) salt. 

We found that under the conditions of the Wacker oxidation,27 the terminal double bonds of the metathesis products were cleanly transformed to the corresponding aldehydes. While the regioselective oxidation of protected allylic alcohols has been reported,28 the selective Wacker oxidation of an allylic amine derivative to the aldehyde is unprecedented. The Ns protected precursor 19 produced only the starting amine (NsN(H)CH2CH2CH2CH(OEt)2). Consequently, the Ns protecting groups were exchanged with Cbz (27) which successfully led to the desired aldehyde 28. 

Acetals result from oxidative coupling of alcohols with electron-poor terminal olefins followed by a second, redox-neutral addition of alcohol [11-13]. Acrylonitrile (41) is converted to 3,3-dimethoxypropionitrile (42), an intermediate in the industrial synthesis of thiamin (vitamin Bl), by use of an alkyl nitrite oxidant [57]. A stereoselective acetalization was performed with methacrylates 43 to yield 44 with variable de [58]. Rare examples of intermolecular acetalization with nonactivated olefins are observed with chelating allyl and homoallyl amines and thioethers (45, give acetals 46) [46]. As opposed to intermolecular acetalizations, the intramolecular variety do not require activated olefins, but a suitable spatial relationship of hydroxy groups and the alkene[13]. Thus, Wacker oxidation of enediol 47 gave bicyclic acetal 48 as a precursor of a fluorinated analogue of the pheromone fron-talin[59]. 

The conditions for allylic acyloxylation of internal olefins are, for reasons which are not clear, unsuitable for terminal olefins. They undergo Wacker oxidation (Markovnikov oxypalladation//) - h yd ride elimination) to yield mixtures of vinyl acetates and methyl ketones [37a]. A combination of Pd(OAc)2/BQ with air as cooxidant in a mixture of DMSO/AcOH (1 1) enables conversion of a broad range of functionalized terminal olefins to the corresponding linear allylic acetates in acceptable yields (Scheme 5) [41]. 

Quite a surprising reaction has recently been reported [74]. With a catalyst of palladium metal on carbon in aqueous phase, propene is oxidized with oxygen to give acrylic acid, probably via allyl alcohol in a allylic-type oxidation (for allylic oxidation see Section 3.3.14). In the presence of chloride or oxidants the normal Wacker-type reaction product acetone arises. 

An intramolecular Wacker oxidation of allyl hydroxypyridinone gave rise to furopyridinone derivatives in excellent yields <05JOC8055>. 

This reaction is part of a useful cyclopentannelation sequence. Allylation of ketones is among the easiest alkylations subsequent Wacker oxidation and cyclisation creates anew five-membered ring 76. This is the a-acyl cation strategy discussed in chapter 6, though this version of it was not mentioned. 

An illustration that demonstrates stereoselectivity as well comes in Ikegama s synthesis of coriolin.12 Allylation of the sodium enolate of cyclopentanone 77 gives one diastereoisomer of the precursor 78 for a Wacker oxidation and cyclisation to give the tricyclic intermediate 79. 

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. ... 

Cycloheptanophenols have been formed from 1-formyl-2-(2-oxopropyl)-cyclohept-1-enes by the route shown. The 2-enol of 2-formylcycloheptanone as the trimethylsilyl ether reacted with an allylic Grignard reagent to afford, upon acidification, an intermediate which underwent Wacker" oxidation to a ketoaldehyde. Cyclisation of this with methanolic potassium hydroxide gave the product (ref. 59). 

Nevertheless, it must be pointed out that the formation of such transient species has never been spectroscopically observed. Native CDs are effective inverse phase-transfer catalysts for the deoxygenation of allylic alcohols, epoxydation,or oxidation " of olefins, reduction of a,/ -unsaturated acids,a-keto ester,conjugated dienes,or aryl alkyl ketones.Interestingly, chemically modified CDs like the partially 0-methylated CDs show a better catalytic activity than native CDs in numerous reactions such as the Wacker oxidation,hydrogenation of aldehydes,Suzuki cross-coupling reaction, hydroformylation, " or hydrocarboxylation of olefins. Methylated /3-CDs were also used successfully to perform substrate-selective reactions in a two-phase system. 

Cuprous chloride tends to form water-soluble complexes with lower olefins and acts as an IPTC catalyst, e.g., in the two-phase hydrolysis of alkyl chlorides to alcohols with sodium carboxylate solution [10,151] and in the Prins reactions between 1-alkenes and aqueous formaldehyde in the presence of HCl to form 1,3-glycols [10]. Similarly, water-soluble rhodium-based catalysts (4-diphenylphosphinobenzoic acid and tri-Cs-io-alkylmethylam-monium chlorides) were used as IPTC catalysts for the hydroformylation of hexene, dodecene, and hexadecene to produce aldehydes for the fine chemicals market [152]. Palladium diphenyl(potassium sulfonatobenzyl)phosphine and its oxide complexes catalyzed the IPTC dehalogenation reactions of allyl and benzyl halides [153]. Allylic substrates such as cinnamyl ethyl carbonate and nucleophiles such as ethyl acetoactate and acetyl acetone catalyzed by a water-soluble bis(dibenzylideneacetone)palladium or palladium complex of sulfonated triphenylphosphine gave regio- and stereo-specific alkylation products in quantitative yields [154]. Ito et al. used a self-assembled nanocage as an IPTC catalyst for the Wacker oxidation of styrene catalyzed by (en)Pd(N03) [155]. 

The Wacker reaction provides a method for the preparation of 1,4-dicarbonyl compounds, by formation of an enolate, allylation with an allyl halide, followed by palladium-catalysed oxidation of the terminal alkene. The product 1,4-dicarbonyl compounds can be treated with base to promote intramolecular aldol reaction (Robinson annulation - see Section 1.1.2) to give cyclopentenones. Thus, in a synthesis of pentalenene, Wacker oxidation of the 2-aUyl ketone 115 gave the 1,4-diketone 116, which was converted to the cyclopentenone 117 (5.115). ... 

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