Construction of All-Carbon Quaternary Stereocenters via Michael Initiated Ring Closure Reaction

Abstract

All-carbon quaternary centers are widely present in many natural products, bioactive molecules and drugs. Despite their potential to be incorporated in natural product syntheses and preparation of therapeutics, developing catalytic methods to construct this interesting scaffold, have been a difficult goal to attain. Furthermore, not only is it challenging to synthesize all-carbon quaternary centers, but doing so in an enantioselective fashion is even more elusive. This is due to the strong steric repulsion between the carbon substituents; and for this reason, not many enantioselective synthetic methods have been developed to this day. This structural motif is especially difficult to install in acyclic systems where there is great conformational flexibility. In this study, the construction of enantioselective all-carbon quaternary stereocenters is reported through a Michael Initiated Ring Closure reaction. This reaction enables the formation of substituted cyclopropyl ring, with the possibility to establish quaternary and tertiary chiral centers, with both cyclic and acyclic α,β-unsaturated carbonyls. The current study involves the addition of sulfur ylides to α,β-unsaturated carbonyls using chiral Lewis acid catalysis leading to substituted cyclopropanes. Nickel(II) salts including Ni(BF4)2·6H2O and Ni(ClO4)2·6H2O were utilized as Lewis acids with chiral indane-derived bisoxazoline ligand, resulting in excellent enantiomeric excess as high as 93%. It is hoped that through the results of this study, a contribution can be made to the existing methodologies on the formation of enantioselective C-C bonds and specifically, to the formation of enantioselective quaternary centers.