Etherification cross-coupling

Etherification Cross-Coupling Reactions 2.11.3.1 With Palladium... 

Transition metal-catalyzed allylic substitution with phenols and alcohols represents a fundamentally important cross-coupling reaction for the construction of allylic ethers, which are ubiquitous in a variety of biologically important molecules [44, 45]. While phenols have proven efficient nucleophiles for a variety of intermolecular allylic etherification reactions, alcohols have proven much more challenging nucleophiles, primarily due to their hard, more basic character. This is exemphfied with secondary and tertiary alcohols, and has undoubtedly limited the synthetic utihty of this transformation. 

Tab. 10.7 summarizes the results of the application of rhodium-catalyzed allylic etherification to a series of ortho-substituted phenols. The etherification tolerates alkyls, including branched alkanes (entries 1 and 2), aryl substituents (entry 3), heteroatoms (entries 4 and 5), and halogens (entry 6). These results prompted the examination of ortho-disubstituted phenols, which were expected to be more challenging substrates for this type of reaction. Remarkably, the ortho-disubstituted phenols furnished the secondary aryl allyl ethers with similar selectivity (entries 7-12). The ability to employ halogen-bearing ortho-disubstituted phenols should facilitate substitutions that would have proven extremely challenging with conventional cross-coupling protocols. 

As shown in the following scheme, a SEM-ether derived phenyl acetylene was treated with PtClj in the presence of CO to give a benzo[4>]furan, which was first subjected to desilylation, followed by Pd-catalyzed intramolecular etherification, affording the tetracyclic skeleton of pterocarpane family of phytoalexins <05JA15024>. A similar type of synthetic transformation was so applied to make a key intermediate in the total synthesis of vibsanol <05JA15022>. 2,3-Disubstituted benzo[h]furans were prepared under very mild reaction conditions by the Pd/Cu-catalyzed cross-coupling of various o-iodoanisoles and terminal... 

Homoallyl bromide 314, prepared from readily available non-racemic ester 313, was converted to the Grignard reagent, which reacted with non-racemic epoxide, derived from D-maUc acid, to afford the alcohol 305. Ozonolysis of the alkene gave a ketone, which was converted into enol tri-flate 316. Ni-catalyzed cross coupling with trimethylsilylmethyl magnesium chloride afforded the allyl silane, which was converted into the allyl stan-nane 317. The asymmetric allylation of 313 with 317 provided 304 with a ration of 8.5 1. Methyl etherification and oxidative cleavage of exo-methylene... 

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