Enantioselective Desymmetrization: Group-Selective Diels-Alder Reaction

Significance

This paper describes the synthesis of the trans-hydrindene ring, which is a common motif in steroids and subsequently many biologically important molecules. The synthesis of the Diels-Alder precursor requires the synthesis of a skipped diene containing a tertiary carbon in the skipped position. This synthesis was nicely accomplished through protonation of a lithium enolate with acetic acid, generating an unconjugated dienyl ester, which was converted into the aldehyde and subjected to Wittig-Horner olefination. The use of the Evans Cu-bis(oxazoline) catalyst generated the product in 56% yield and 82:18 dr, giving the major isomer in 90% ee.