Synthesis of Enantioenriched Building Blocks

Many biologically important compounds contain a chiral center who’s absolute configuration is critical for activity.  Compounds found in nature that are identified with prospective utility in human health frequently exist as a complex mixture and are produced in such small quantities that they cannot be fully vetted for their potential.  The exploration and future use of these precious materials often is contingent on the ability of a synthetic chemist to prepare them in an efficient and selective manner.  Key to success of a laboratory synthesis of an enantioenriched complex molecule is the availability of simple enantioenriched building blocks.  The ideal building block would have handles that are readily transformed into a variety of functionalities that can be incorporated into the biologically important molecule.   A major focus of our research laboratory is the development of asymmetric methodologies for the synthesis of versatile enantioenriched building blocks.

Current efforts have been directed toward an efficient synthesis of enantioenriched a-substituted hydroxy esters via a kinetic resolution event is described.  Bulky racemic esters in the presence of a chiral Brønsted acid selectively lactonize to yield a recoverable en-antioenriched hydroxy ester and lactone.  These esters are highly versatile building blocks that can readily be converted to synthetically useful materials.



Qabaja, G.; Benavides, A. R.; Shubin, L.; Petersen, K. S. Facile Synthesis of Versatile Enantiosenriched α-Substituted Hydroxy Esters through a Brønsted Acid Catalyzed Kinetic Resolution Asymmetric Synthesis of Hydroxy Esters with Multiple Stereocenters via a Chiral Phosphoric Acid Catalyzed Kinetic Resolution. J. Org. Chem.

Qabaja, G.; Wilent, J. E.; Benavides, A. R.; Bullard, G. E.; Petersen, K. S. Facile Synthesis of Versatile Enantiosenriched α-Substituted Hydroxy Esters through a Brønsted Acid Catalyzed Kinetic Resolution.Org. Lett. 2013, 15, 1266–1269.

Wilent, J. E.; Petersen, K. S. Enantioselective Desymmetrization of Diesters. J. Org. Chem. 201479, 2303–2307.