Dr. Gary A. Molander - Professor of Organic Chemistry
SYNTHETIC ORGANIC AND ORGANOMETALLIC CHEMISTRY 
 OFFICE: 4001 IAST 
LAB: 
PHONE: (215) 573-8604 
E-MAIL: gmolandr@sas.upenn.edu

EDUCATION AND ACADEMIC HISTORY:

  • Ph. D., Purdue University (1979) 
  • B.S., Iowa State University (1975) 
  • National Institutes of Health Postdoctoral Fellowship, University of Wisconsin, Madison (1980-81) 
  • Alfred P. Sloan Research Fellowship (1987-1991) 
  • American Cyanamid Academic Awardee (1989) 
  • Chemical Society Arthur C. Cope Scholar Award (1998) 
  • Japanese Society for the Promotion of Science Fellowship (2002-3)
  • American Chemical Society, Philadelphia Section Award (2003)

SYNTHETIC ORGANIC AND ORGANOMETALLIC CHEMISTRY

        The central theme of Professor Molander’s research is the development of new synthetic methods and their application to the synthesis of organic molecules. Within this context, exciting and useful new ways to form carbon-carbon bonds selectively are being explored utilizing inorganic reagents as well as organometallic catalysts. Approaches to the total synthesis of a variety of important natural products are being developed based on these methods.


        The development of lanthanide-based reagents has been a major focus of research in the Molander laboratories for some time. Many stereocontrolled reductive cyclization reactions promoted by samarium diiodide (SmI2) have been developed. These reactions permit construction of highly functionalized carbocyclic and heterocyclic rings that are difficult to access by any other means, and work continues to explore further applications of this special reductant to problems in organic synthesis. Processes that permit “sequencing” of organic reactions are of particular interest. This strategy permits the formation of multiple carbon-carbon or carbon-heteroatom bonds in a one pot process, thereby facilitating the rapid and efficient construction of complex products from relatively simple substrates.

        Total syntheses of natural products based on previously developed methods are underway. The asymmetric synthesis of isoschizandrin has recently been completed, and an asymmetric total synthesis of the potent immunosupressant variecolin is nearing completion.

        We have recently discovered a novel SN2’ reaction of propargyl ethers with organoaluminums and organozincs catalyzed by chromium complexes, leading to an enantioselective synthesis of allenes. The reaction is unusual in that the SN2’ reaction occurs with syn rather than anti displacement of the leaving group. This has important implications for the synthesis of a variety of organic molecules, and we are currently active in pursuing the broader implications of these results.

        We have recently begun a program to expand and improve the Suzuki coupling reaction for organoboron compounds. The methods utilized employ air- and water-insensitive organotrifluoroborates, and the couplings occur under relatively mild conditions using non-toxic components. Further development of this chemistry promises to allow incorporation of this chemistry into combinatorial processes as well as the enantioselective synthesis of molecules by unique carbon-carbon bond-forming reactions.

        We have recently completed a formal total synthesis of the anticancer compounds oximidine I and II based on these methods, and a synthesis of the salicylihalamides is being developed.

        A fourth area of interest is the invention of a novel annulation method for the synthesis of seven- and eight-membered rings. The unprecedented stereochemical control achievable at multiple stereocenters, combined with predictable regiochemical control, has made this process one of extraordinary utility in organic synthesis. The method has been utilized for the synthesis of a number of natural products including furanether B, davanone, dactylol, and the eunicellin deacetoxyalcyonin acetate. Efforts are currently underway to expand this technology and to apply it to the synthesis of other eunicellins such as the antimalarial polyanthellin A and the antitumor compound palmonine B.