Oxidative functionalizations alkenes, palladium acetate

The importance of palladium acetate lies in its ability to catalyse a wide range of organic syntheses functionalizing C-H bonds in alkanes and in aromatics, and in oxidizing alkenes. It has been used industrially in the... 

Allylic acetoxylation with palladium(II) salts is well known however, no selective and catalytic conditions have been described for the transformation of an unsubstituted olefin. In the present system use 1s made of the ability of palladium acetate to give allylic functionalization (most probably via a palladium-ir-allyl complex) and to be easily regenerated by a co-oxidant (the combination of benzoquinone-manganese dioxide). In contrast to copper(II) chloride (CuClj) as a reoxidant,8 our catalyst combination is completely regioselective for allcyclic alkenes with aliphatic substrates, evidently, both allylic positions become substituted. As yet, no allylic oxidation reagent is able to distinguish between the two allylic positions in linear olefins this disadvantage is overcome when the allylic acetates are to... 

This cyclization has been used in an efficient synthesis of chokol A 11.219, an anti-fungal compound (Scheme 11.74). The acetal 11.216, in which the tartrate moiety functions as an economical chiral auxiliary, cyclized using palladium acetate to give an 8.5 1 mixture of stereoisomers. Aeidic hydrolysis removed the acetal to give a ketone 11.217, which could be taken through to the natural product 11.219 by selective reduction of the electron-poor alkene, stereoselective addition of a methyl group, allylic oxidation and desilylation. 

Palladium-catalyzed Direct Arylation of Indoles and Thiophenes. Five-membered ring heterocycles possessing only one heteroatom and no Af-oxide function can also be arylated using palladium(II) complexes, a phosphine ligand, and an inorganic base. In one example, a tandem palladium-catalyzed Heck coupling reaction and direct intramolecular C2 arylation reaction on a )V-(2-chlorobenzyl)-5-bromoindole was reported (eq 30). The procedure, which is catalyzed by palladium acetate, uses tn-tert-butylphosphonium tetrafluoroborate as a ligand and ferf-butyl acrylate as the alkene for the Heck reaction (eq 30). ... 

In 2006, Gaunt and co-workers described a regioselective alkenylation of pyrroles under mild aerobic oxidative conditions. A catalytic amount of palladium acetate was able to selectively functionalize tert-butojycarbamate (BOC)-protected pyrrole at the C2-position while a C3-selectivity was achieved with triisopropylsilyl (TIPS)-protected pyrroles (Scheme 9.4). The aerobic conditions worked well for reactive alkenes such as acrylate derivatives, nevertheless the use of peroxide ( BuOOBz) appeared necessary in order to achieve good yields with more challenging substrates [i.e., methyl vinyl sul-fone). Interestingly, intermolecular alkenylation of pyrrole can also be effected with complete selectivity and good yields. 

Direct functionalization of the C2 position of thiophene can be accomplished through an oxidative-Heck reaction employing palladium(II) acetate in the presence of silver carbonate. The resulting products are obtained in good to high yields with the trans-alkene isomer being favored. Typically less than 10% branched coupling products were observed (not shown). ... 

The most ambitious application of this chemistry is in the ring closure to form 6-deoxyerythronolide B 3.104 (Scheme 3.45). Macrolides are most commonly prepared by lactonization of a hydroxy acid, so there is a need to carry the hydroxy functional group through the synthesis. The allylic CH activation method avoids this need, requiring just an alkene. Controlled by the conformation of the substrate, allylic oxidation of the precursor 3.101 provided a single diastereoisomer of the macrolide 3.103. A bis-sulfoxide 3.102 was found to be the optimum ligand for palladium. The macrolide 3.103 could be converted to 6-deoxyerythronolide B 3.104 by simultaneous reduction of the alkene and the PMP acetal, selective oxidation of one hydroxyl group, and acetonide removal. 

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