Highly efficient Pd-catalyzed intramolecular asymmetric double allylic substitution reaction toward the synthesis of Huperzine-A

ORGN 713

Stephen J. Chaterpaul, stephenchaterpaul@gmail.com, Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400 and Iwao Ojima, Department of Chemistry and ICB&DD, State University of New York at Stony Brook, The Chemistry Bldg, Stony Brook, NY 11794-3400.
Chiral transition-metal catalysis can provide products with high enantiomeric purity. A new class of monodentate phosphoramidite as well as phosphite ligands based on axially chiral biphenol have been successfully developed in our laboratory. These ligands possess fine-tuning capabilities, which provide systematic modification sites on the amine, alcohol and alkyl moieties, and also at the 3,3'-positions of the biphenol moiety. These novel phosphoramidite ligands have been successfully applied to a Pd-catalyzed double allylic alkylation reaction as the key step in the total synthesis of Huperzine-A, a promising drug for the treatment of Alzheimer's disease. In optimized conditions, this process afforded the tricyclic key intermediate with >99% ee in 68% isolated yield. Herein we present a full account of our work, including mechanistic study on the origin of enantioselectivity.

 

Heterocycles and Aromatics, Asymmetric Reactions and Syntheses and Total Synthesis of Complex Molecules
7:00 PM-9:00 PM, Wednesday, August 19, 2009 Walter E. Washington Convention Center -- Ballroom C, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, August 17, 2009 Walter E. Washington Convention Center -- Hall D, Sci-Mix

Division of Organic Chemistry

The 238th ACS National Meeting, Washington, DC, August 16-20, 2009