Allyl-aryl coupling

Since this method allows us easily to construct structures branched at benzylic positions, it was applied to the synthesis of -arylpropionic acids, including anti-inflammatory agents. An example is the facile synthesis of ibuprofen by such an allyl-aryl coupling and subsequent oxidation (Scheme 10-8) [29]. The cross-coupling was more effective when the substrate had an electron-withdrawing group. 

The reaction of (4-benzenesulfonylphenyl) benzylsulfoxide (91) with allylmagnesium halide afforded only the benzyl derived ligand coupling product (69), without any allyl-aryl coupling product. 

Table 10.4 Chirality transfer in allyl-aryl coupling reaction...

The reaction was extended to allyl-aryl coupling with excellent results. Treatment of the triarylsulfonium salt with allyllithium (generated from tetraallylstannane) produced allylarenes in quantitative yields. Nevertheless the reaction could not be extended to benzylHthium nor saturated alkyl-lithiums. In the former case, a complex reaction mixture which was not analyzed was obtained. The addition of -butyUithium exemplifies the latter case. Only biaryl and aryl- butylsulfide was obtained. This result clearly indicates the requirement of a tt system for coupling. 

TABLE 3. Pd-Catalyzed Allyl-Aryl Coupling with Allyltributylstannane... 

Scheme 12.62 Regio- and stereospecific allyl-aryl coupling via retro-allylation [6].

According to these considerations, the authors have developed Pd-catalyzed 7-selective and stereoselective allyl-aryl coupling between allylic ester and arylboronic acids according to the general Scheme 7.10. 

The key step in this approach, allyl-aryl coupling between allylic ester 24 and phenylboronic acid to 25, provides a catalytic cycle in which the catalytic components indicated in Scheme 7.10 participate as outlined in Scheme 7.13. 

Scheme 7.13 Catalytic cycle of allyl-aryl coupling between allylic esters and arylboronic acids...

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