Alcohols are easily accessible organic compounds and the OH group constitutes the most abundant functional group in biomass. These substrates are used in organic synthesis as nucleophiles. When alcohols are used as electrophiles, the OH group needs to be transformed to a better leaving group. This transformation requires additional reagents, purifications and reactor time in industry. If the OH group could be substituted by a non-charged nucleophile, the only by-product would be water. In addition, efficient methodologies to substitute the OH group are essential if we want to transform into a bio-based economy in the future. A further challenge is to conserve the chirality of the easily accessible stereogenic alcohols in the substitution reaction. Our group has developed several methodologies to substitute the OH-group in non-derivatized alcohols. We have developed a novel Pd[BiPhePhos] complex that can substitute the OH group of non-derivatized enantioenriched allylic alcohols by, O-, N-, S-, and C-centered nucleophiles where the products can be isolated in excellent yields and enantiospecificities. Using a sugar-based phosphite ligand on the palladium, we have also been able to perform enantioselective substitution of racemic alcohols. We have also developed a phosphinic acid-catalyzed intramolecular substitution of enantioenriched alcohols where the chirality is transferred from the starting secondary alcohols to the product. Not only allylic alcohols are reactive but also benzylic, propargylic, and alkyl alcohols are transformed to generate 5- and 6-membered heterocycles by O-, N-, and S-centered nucleophiles in excellent yields and enantiospecificities. Chirality transfers in tertiary alcohols have never been reported by a direct substitution of the OH-group. We have developed a Fe-catalyzed cyclization reaction to directly substitute the OH group in both secondary and tertiary alcohols in which the heterocyclic compounds are generated in high yields and enantiospecificities. During the talk both synthetic applications towards natural product synthesis as well as detailed mechanistic studies that reveal the activation mode of the OH-group by different catalysts will be presented.

Catalytic C-O bond cleavage in non-derivatized alcohols

255th National Meeting (2018)

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