Asymmetric Formal Abnormal Claisen Rearrangement Enabled by Rh-Catalyzed Regio- and Enantioselective Allylic Alkylation

Abnormal Claisen rearrangement of phenyl allyl ether with the gamma-alkyl group is longstanding. However, the asymmetric version of this named reaction has never been reported. Herein, a highly regio-and enantioselective allylic alkylation of 4-hydroxycoumarin and stereospecific Conia-ene/ene sequence has been developed as a formal abnormal Claisen rearrangement. Chiral 4-hydroxycoumarins with 3-allyl groups could be synthesized in up to 95% yield and 96% ee under the catalysis of Rh and chiral bioxazolinephosphine ligand. Experimental and density functional theory calculation investigations support that the stereospecific rearrangement is based on the reversible formation of the kinetically favored cis-disubstituted spirocyclopropane intermediate.

Automated summary

The abnormal Claisen rearrangement of phenyl allyl ether with the gamma-alkyl group is well-known, but its asymmetric version has not been reported before. In this study, a highly regio- and enantioselective allylic alkylation of 4-hydroxycoumarin was developed as a formal abnormal Claisen rearrangement. Chiral 4-hydroxycoumarins with 3-allyl groups were synthesized with high yield and enantiomeric excess using rhodium catalyst and chiral bioxazolinephosphine ligand. Experimental and theoretical investigations revealed that the stereospecific rearrangement occurs through the reversible formation of a kinetically favored cis-disubstituted spirocyclopropane intermediate.