P. Andrew Evans

Background:

• NATO Postdoctoral Fellow, University of Texas at Austin, 1991-93.
• Outstanding Young Scholar Award, Francis Alison Society, University of Delaware, 1997
• Excellence in Chemistry Award, Zeneca Pharmaceuticals, 1997
• NIH First Award, 1997
• Camille and Henry Dreyfus Teacher-Scholar Award, 1998
• Eli Lilly Grantee Award, 1998
• Glaxo Wellcome Chemistry Scholar Award, 1999
• Novartis Pharmaceuticals Academic Achievement Award, 2000
• Pfizer Distinguished Michigan Lecturer, 2000
• SFC-Rhodia Lecturer, Organic Division of the French Chemical Society, 2000
• Johnson & Johnson Focused Giving Award, 2001
• Pfizer Award for Creativity in Organic Chemistry, 2002

The Evans research group is engaged in the exploration and development of reactive intermediates for the expeditious synthesis of complex biologically important natural products. Specifically, we are developing diastereoselective radical cyclizations, temporary silicon-tethered ring-closing metathesis, and a variety of new asymmetric transition-metal catalyzed cross-coupling and carbocyclization reactions.

The first area of investigation is currently focused on the application of free radical cyclization reactions to the total synthesis of complex biologically important polycyclic guanidine-containing alkaloids. The batzelladines are a growing family of novel and highly complex polyguanidinium alkaloids that were isolated from a Caribbean sponge, in which batzelladine A is particularly pertinent because it competitively inhibits the binding of the HIV envelope protein gp-120 to the human CD4 receptor with micromolar affinity.

Other methodology being developed in the Evans group includes the novel temporary silicon-tethered homo- and cross-coupling ring-closing metathesis reactions of allylic and homo-allylic alcohols. The cross-coupling strategy was recently utilized in a highly convergent total synthesis of the potent antitumor agent mucocin. We have also combined this chemistry with bismuth-mediated reductive etherification reactions for the construction of fused polycyclic ethers applicable to the synthesis of potent antifungal agents—gamberic acids.

We are also interested in transition-metal-catalyzed cross-coupling and carbocyclization reactions. In the course of these studies, we were intrigued by the problem of controlling regiochemistry in allylic systems. This stimulated the development of the regio- and enantiospecific rhodium-catalyzed allylic substitution reaction, with a variety of stabilized carbon and heteroatom nucleophiles. More recently we have focused on combining these cross-coupling reactions with metal-mediated carbocyclization reactions. This has led to the development of the first transition metal-mediated [4 2 2], which provides a novel entry into eight-membered rings. Additional studies will now focus on the development of this new and exciting carbocyclization reaction.

Selected Publications:

P. A. Evans, T. Manangan and A. L. Rheingold "Stereoselective Construction of trans-Disubstituted Azabicycles using Oxauracil as a Novel Free Radical Acceptor" J. Am. Chem. Soc. 2000, 122, 11009.

P. A. Evans and L. J. Kennedy "Regioselective Rhodium-Catalyzed Allylic Linchpin Cross-Coupling Reaction: Diastereospecific Construction of anti-1,3-Carbon Stereogenic Centers and C₂-Symmetrical Fragments" J. Am. Chem. Soc. 2001, 123, 1234.

P. A. Evans and J. E. Robinson "Regio- and Diastereoselective Tandem Rhodium-Catalyzed Allylic Alkylation/Pauson-Khand Annulation Reactions" J. Am. Chem. Soc. 2001, 123, 4609.

P. A. Evans and D. K. Leahy "Regio- and Enantiospecific Rhodium-Catalyzed Allylic Etherification Reactions using Copper(I) Alkoxides: Influence of the Copper Halide Salt on Selectivity" J. Am. Chem. Soc. 2002, 124, 7882.

P. A. Evans, J. E. Robinson, E. W. Baum and A. N. Fazal "Intermolecular Transition Metal-Catalyzed [4 2 2] Cycloaddition Reactions: A New Approach to the Construction of Eight-Membered Rings" J. Am. Chem. Soc. 2002, 124, 8782.

P. A. Evans, J. Cui and G. P. Buffone "Diastereoselective Temporary Silicon-Tethered Ring-Closing Metathesis Reactions with Prochiral Alcohols: A New Approach to Long-Range Asymmetric Induction Angew. Chem. Int. Ed. 2003, 42, 762, (Cover and VIP).

P. A. Evans, and D. Uraguchi "Regio- and Enantiospecific Rhodium-Catalyzed Arylation of Unsymmetrical Fluorinated Acyclic Allylic Carbonates: Inversion of Absolute Configuration" J. Am. Chem. Soc. 2003, 125, 7158.

P. A. Evans and D. K. Leahy "Regioselective and Enantiospecific Rhodium-Catalyzed Allylic Alkylation Reactions with Copper(I) Enolates: Total Synthesis of (-)-Sugiresinol Dimethyl Ether" J. Am. Chem. Soc. 2003, 125, 8974.

P. A. Evans, J. Cui, S. J. Gharpure and R. J. Hinkle "Stereoselective Construction of Cyclic Ethers using a Tandem Two-Component Etherification: Elucidation of the Role of Bismuth Tribromide" J. Am. Chem. Soc. 2003, 125, 11456.

P. A. Evans, S. J. Gharpure, A. Polossoukhine, J. Cui and H. -R. Zhang "Enantioselective Total Synthesis of (-)-Mucocin using a Temporary Silicon-Tethered (TST) Ring-Closing Metathesis (RCM) Cross-Coupling Reaction" J. Am. Chem. Soc. 2003, 125, 14702.