Enantioselective alkoxypalladations

Although diastereoselective intramolecular al-koxypalladations have been investigated intensively and have found application in synthesis (see above), there are few examples of enantioselective alkoxypalladations [2bJ. For instance, Hosokawa et al. were able to cyclize unsaturated phenol derivatives of type 62 in the presence of chiral (// -allyl-PdOAc complexes, i.e. 63), but only with modest enantioselectivities. Under the same conditions the conversion of the phenol 65 to chroman 66 (a compound related to vitamin E) proceeded in acceptable yields, but with only low asymmetric induction. Newer results by Uozumi et al., for instance the Pd-catalyzed cyclization of 67 to 68 in the presence of a chiral bis-oxazolin ligand [15], show that much higher enantioselectivities can be achieved, at least for certain substrates. 

The intramolecular alkoxypalladation has been developed into a remarkable (catalytic) methodology which exhibits a great synthetic potential, especially in combination with carbonyla-tion. This is reflected by convincing applications in natural product syntheses. This chemistry opens reliable and highly diastereoselective approaches to several hydropyran and hydrofuran systems. The development of efficient enantioselective protocols for the various chirogenic transformations is still a challenging goal for the future. 

An enantiosdective version of this reaction was presented shortly thereafter, which uses the oxazohne ligand (Eq. (4.14)) [27]. The reaction results in good to excellent enantioinduction for a series of 2 -monosubstituted alkenes, while a dimethyl substitution at the terminal alkene carbon leads to 0% ee. This was interpreted by an overall mechanism for which the enantioselection is derived from the first step of alkoxypalladation followed by faster palladium loss from the corresponding quinone methide intermediate than nucleophilic attack by the second alkoxide. 

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See also in sourсe #XX -- [ ]

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