Selectivity in palladium-catalyzed cross-coupling reactions involving halo-heterocycles

ORGN 105

Yeimy Garcia, ygarcia@chem.ucla.edu, Claude Y. Legault, cyl@chem.ucla.edu, K. N. Houk, houk@chem.ucla.edu, and Craig A. Merlic, merlic@chem.ucla.edu. Department of Chemistry and Biochemistry, University of California, Los Angeles, 405 Hilgard Ave., Los Angeles, CA 90095
Polysubstituted heterocycles are widely used in the pharmaceutical industry for their interesting biological activities. Palladium-catalyzed cross-coupling reactions are one of the most powerful methods to access these compounds. Selective displacement on heterocycles possessing multiple identical halogens is critical to achieve synthetic utility. Five- and six-membered heterocycles that are disubstituted with the same halogen react preferentially at the two-position when submitted to palladium-catalyzed cross-coupling conditions. Calculations of transition states for Pd(0) insertion into the CX bond show that this results from a combination of CX bond strength and Pd(0)-CX interactions. DFT, G3B3 and CBS-RAD have been used to calculate the bond dissociation energy (BDE) of various halo-heterocycles. The role of the neighboring heteroatom has been determined.

 

Process R&D, Physical Organic Chemistry, Heterocycles, Aromatics, Metal-Mediated Reactions
8:00 PM-10:00 PM, Sunday, March 25, 2007 Hyatt Regency Chicago -- Riverside Center, Poster

Division of Organic Chemistry

The 233rd ACS National Meeting, Chicago, IL, March 25-29, 2007