Enantioselective cyclization of symmetric diesters

Two important facets that are found in many biologically active compounds and complex natural products are chirality and heterocyclic motifs, in particular lactones and lactams. Biologically active compounds found in nature often need to be synthesized due to the fact that only a minute amount of the active molecule is produced.;In the research described herein, an asymmetric methodology known as desymmetrization is utilized to produce enantioenriched compounds that can be used as building blocks in the synthesis of biologically active natural products. We have developed an efficient synthesis of enantioenriched gamma-and delta-lactones via an enantioselective desymmetrization. In this process, racemic diesters in the presence of a chiral Bronsted acid selectively undergo cyclization to yield enantioenriched gamma- and delta-lactones. The methodology is also expanded to include the synthesis of spirocyclic molecules. The desymmetrization is highly selective and the products formed contain an all-carbon quaternary stereocenter that would be difficult to install using other methodologies.