Palladium-catalyzed 1,4-additions to conjugated dienes

Additions to nonactivated olefins and dienes are important reactions in organic synthesis [1]. Although cycloadditions may be used for additions to double bonds, the most common way to achieve such reactions is to activate the olefin with an electrophilic reagent. Electrophilic activation of the olefin or diene followed by a nucleophilic attack at one of the sp carbons leads to a 1,2- or 1,4-addition. More recently, transition metals have been employed for the electrophilic activation of the double bond [2]. In particular, palladium(II) salts are known to activate carbon-carbon double bonds toward nucleophihc attack [3], and this is the basis for the Wacker process for industrial oxidation of ethylene to acetaldehyde [4]. In this process, the key step is the nucleophilic attack by water on a 7t-ethylenepalladium complex. 

Palladium-catalyzed 1,4-additions to conjugated dienes can be divided into two classes (i) nonoxidation reactions and (ii) oxidation reactions. In the former type of reaction, a palladium(O) catalyst is employed, and the first step in the catalytic cycle is often an activation of one of the reactants by its oxidative addition to Pd(0). 

1) The contents of this chapter have been previously published in de Meijere, A. and Diederich, F. (eds). Metal-Catalyzed Cross-Coupling Reactions, 2nd edn. Wiley-VCH Verlag GmbH Co. KGaA Weinheim, 2004. ISBN 978-3-527-30518-6. 

Metal-Catalyzed Cross-Coupling Reactions and More, First Edition. 

Edited by Armin de Meijere, Stefan Erase, and Martin Oestreich. 

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J.-E. Backvall, Palladium-Catalyzed 1,4-Additions to Conjugated Dienes, review in Metal-catalyzed Cross Coupling Reactions, Eds P. Stang and F. Diederich, WILEY-VCH, Weinham, 1998, pp. 339-385. 

Palladium(ll)-catalyzed 1,4-additions to conjugated dienes also involve the foimation of a (jr-allyl)palladium intermediate. These, in all known cases, are oxidation reactions. 

Palladium(II)-catalyzed 1,4-additions to conjugated dienes, in which at least one alkoxide function is added, require the presence of an alcohol function. In all cases known so far, this involves an alkoxypalladation of tlie conjugated diene to give an intermediate 4-alkoxy-l,2,3-(jr-allyl)palladium complex. Subsequent nucleophilic attack on the jr-allyl... 

A palladium-catalyzed 1,4-dialkoxylation of conjugated dienes was obtained when the 1,4-oxidation was performed in an alcohol as the solvent [105]. In this case it is necessary to run the reaction in the presence of a catalytic amount of a strong acid such as methanesulfonic acid or perchloric acid. Cyclic dienes gave a highly stereoselective 1,4-ds addition of the two alkoxy groups [Eq.(48)j. Also, the reaction with acyclic conjugated dienes proceeded in a, 4-syn addition. Thus, ( , )-hexa-2,4-diene gave E)- 2R, 5R ) dimethoxyhex-3-ene. The mechanism is depicted in Scheme 8-27. 

Palladium-Catalyzed Intramolecular 1,4-Additions to Conjugated Dienes. 

A number of intramolecular Pd-catalyzed 1,4-oxidations of conjugated dienes were developed.f In these reactions, two nucleophiles are added across the diene, one of which adds intramolecularly. So far, only heteroatom nucleophiles have been employed. In order to extend these intramolecular 1,4-oxidations to carbon nucleophiles, it was found that a vinylpalladium species can be obtained in situ from an alkyne via a chloropalladation. The approach is particularly attractive since it involves a Pd(II) chloride salt and could be compatible with the rest of the catalytic cycle. Reaction of dienyne with LiCl, and benzoquinone in the presence of palladium acetate as the catalyst, afforded the carbocyclization products. The reaction resulted in an overall stereoselective fltiri-addition of carbon and chlorine across the diene t B (Scheme 23). 

Palladium-catalyzed reaction of conjugated dienes in the presence of a halide anion can be controlled to give a l-acyloxy-4-halo-2-alkene selectively under appropriate reaction conditions. The catalyst for this system is a palladium(II) salt, usually Pd(OAc)2 or Li2PdCl4. The reaction may be intermolecular or intramolecular. In most cases, it is stereoselective and results in a 1,4-cis addition to the diene. The products obtained from such reactions are useful synthetic intermediates since they have two allylic leaving groups with a large difference in reactivity (see below, under Synthetic applications ). 

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