Stereoselective Synthesis of Functionalized Cyclopentane Frameworks Using Anthracene Templates

Enantiopure allylic alcohols are very powerful synthons for the synthesis of a variety of natural products, agrochemicals and pharmaceuticals; therefore, the synthesis of these compounds has received considerable attention. For this purpose, several strategies involving asymmetric Diels-Alder reaction with 9-methylanthracene 202 have been used to generate the Diels-Alder adduct 203 in high enantioselectivity and acceptable yield, which would be used as a key starting material towards enantiopure allylic alcohols. Among these approaches are: catalytic enantioselective reactions via chiral Lewis acids and organocatalysts, as well as chiral dienes. Unsuccessful attempts to perform asymmetric Diels-Alder reactions highlighted the use of a chiral dienophile strategy. Thus, a modified dienophile protocol by the addition of electron-withdrawing groups was considered. Despite the failure of a sulfone dienophile 272 to perform an asymmetric Diels-Alder reaction in an enantioselective manner, the utilisation of a chiral sulfoxide dienophile 302 was successful in providing (after desulfinylation) an optically pure cycloadduct 203 in 68% yield. An enantiomeric adduct 203 underwent different asymmetric transformations, including dehydrogenation–conjugate addition reaction and reduction, furnishing alkylated alcohols 322-325 with complete conversion and high levels of diastereoselectivity (> 99:1 dr) which was controlled by anthracene system ring. Subsequent retro Diels-Alder reactions via flash vacuum pyrolysis (FVP) demonstrated a valuable method for the synthesis of functionalised allylic alcohols 330-3332 in high enantiomeric excess (67-100% ee).