Keywords

Enter a program, idea, office, or department into the field above and click go

Li Deng


Orrie Friedman Distinguished Professor of Chemistry
Ph.D., Harvard University
781-736-2529
deng@brandeis.edu

To fulfill the promises and challenges for chemistry in the 21st century, chemists must develop new methods to manipulate and create substances of increasing complexity and diversity with dramatically enhanced efficiency and practicality. Our research program focuses on the invention and development of new catalytic and selective reactions because of their fundamental importance to the future of chemistry and other branches of science studying molecular properties. Our approach involves the discovery and design of accessible catalysts for highly enantioselective asymmetric organic reactions of broad synthetic importance, the elucidation of the reaction mechanism and molecular recognition events underlying the catalytic activity and selectivity, and the illustration of their applications in the synthesis of chiral compounds of varying complexity.

Our studies following the approach outlined above have led us to the discovery of a new class of chiral amine organic catalysts, modified cinchona alkaloids. These modified cinchona alkaloids were first developed by Professor Sharpless at Scripps Research Institute as chiral ligands for the transition metal-catalyzed asymmetric dihydroxylation of olefins. We recently found that these now commercially available compounds are remarkably efficient and versatile chiral organic catalysts. Our investigations of Lewis base and nucleophilic catalysis of these modified cinchona alkaloids have already led to the development of several highly enantioselective, general, and clean catalytic reactions, transforming simple achiral compounds into a wide range of important chiral building blocks while generating no or environmentally benign by-products (Scheme 1). Some of these new reactions also represent conceptually new approaches towards highly challenging and desirable goals in asymmetric synthesis, such as the development of catalytic enantioselective construction of quaternary stereocenters and the dynamic kinetic resolution of racemic mixtures. We have also demonstrated that the amine catalysts can be easily and quantitatively recovered. These highly selective and clean reactions catalyzed by readily accessible and recyclable catalysts are expected to find wide applications in organic synthesis. Furthermore, mechanistic and structural studies of these reactions could provide us with new insights into the rationally design of new and highly efficient reactions for asymmetric synthesis.




References

  1. “Catalytic Enantioselective Peroxidation of a,b-Unsaturated Ketones,” Lu, X.; Liu, Y.; Sun, B.; Cindric, B.; Deng, L. J. Am. Chem. Soc. 2008, 130, 8134-8135.
  2. “Enantioselective Diels-Alder Reactions of Simple a,b-Unsaturated Ketones with a Cinchona Alkaloid Catalyst,” Singh, R. P.; Bartelson, K., Wang, Y.; Su, H.; Lu, X.; Deng, L. J. Am. Chem. Soc. 2008, 130, 2422-2423.
  3. “Asymmetric Diels-Alder Reactions of 2-Pyrones with Bifunctional Organic Catalysts,” Wang, Y.; Li, H.; Wang, Y.-Q.; Liu, Y.; Foxman, B. M.; Deng, L. J. Am. Chem. Soc. 2007, 129, 129, 6364-6365.
  4. “An Approach to Skeletal Diversity Using Functional Group Pairing of Multifunctional Scaffolds” Comer E.; Deng, L.; Proco, Jorco, J. A. Jr. Organic Lett. 2007, 9, 2123-2126.
  5. “Asymmetric Mannich Reactions with in situ Generation of Carbamate-Protected Imines by an Organic Catalyst,” Song, J.; Shih, H.; Deng, L.Organic Lett.2007, 9, 603-606.
  6. “Control of Diastereoselectivity in Tandem Asymmetric Reactions Generating Nonadjacent Stereocenters with Bifunctional Catalysis by Cinchona Alkaloids,” Wang, B.; Wu, F.; Wang, Y.; Liu, X.; Deng, L. J. Am. Chem. Soc. 2007, 129, 768-769.
  7. "Enantioselective Friedel-Crafts Reaction of Indoles with Carbonyls Catalyzed by Bifunctional Cinchona Alkaloids," Li, H.; Wang, Y.: Deng, L. Organic Lett. 2006, 8, 4063-4065." Enantioselective Cyanocarbonation of Ketones with Chiral Base,"  Tian, S.-K.; Deng, L. Tetrahedron, 2006, 62, 11320-11330 (invited contribution to MacMillan TSIP).
  8. “Control of Diastereoselectivity in Tandem Asymmetric Reactions Generating Nonadjacent Stereocenters with Cooperative Asymmetric Catalysis by Cinchona Alkaloids,” Wang, B.; Wu, F.; Wang, Y.; Liu, X.; Deng, L. J. Am. Chem. Soc. 2007, 129, 768-769.
  9. “Asymmetric Friedel-Crafts Reaction of Indoles with Imines by an Organic Catalyst,” Wang, Y.; Song, J.; Hong R.; Li, H.; Deng, L. J. Am. Chem. Soc. 2006, 128, 8156-8157.
  10. "Asymmetric Synthesis of Chiral Aldehydes via Conjugate Additions with Bifunctional Organocatalysis by Cinchona Alkaloids,” Wu, F.-H.; Ran, H.; Khan, J.; Deng, L. Angew. Chem. Int. Ed.  2006, 45, 4301-4305. (Designated as a “Hot Paper”).
  11. “The Mannich Reaction of Malonates with Simple Imines Catalyzed by Bifunctional Cinchona Alkaloids:  Enantioselective Synthesis of b‑Amino Acids,” Song, J.; Wang, Y.; Deng, L. J. Am. Chem. Soc. 2006, 128, 6048-6049.
  12. “Dual-Function Cinchona Alkaloid Catalysis: Catalytic Asymmetric Tandem Conjugate Addition-Protonation for the Direct Creation of Nonadjacent Stereocenters,” Wang, Y.; Liu, X.; Deng, L. J. Am. Chem. Soc. 2006, 128, 3928-3930.
  13. “Enantioselective Nitroaldol Reaction of a-Ketoesters Catalyzed by Cinchona Alkaloids,” Li, H.; Wang, B.; Deng, L.  J. Am. Chem. Soc. 2006, 128, 732-733.  
  14. “Construction of Quaternary Stereocenters via Efficient and Practical Conjugate Additions to, Unsaturated Ketones with a Chiral Organic Catalyst,” Wu, F.-H.; Li, H.; Hong, R.; Deng, L. Angew. Chem. Int. Ed.  2006, 45, 947-950.
  15. “Catalytic Enantioselective Conjugate Additions with Vinyl Sulfones,” Li, H.; Song, J.; Liu, X.; Deng, L.  J. Am. Chem. Soc. 2005, 127, 8948-8949.
  16. "Catalytic Enantioselective Total Syntheses of Bisorbicillinolide, Bisorbicillinol and Bisorbibutenolide," Hong, R.; Chen, Y.; Deng, L. Angew. Chem. Int. Ed. 2005, 44, 3478-3481.
  17. “Catalytic Construction of Nitrogen-Substituted Quaternary Stereocenter by Highly Enantioselective Amination with Chiral Catalyst Derived from Both Quinine and Quinidine,” Liu, X.; Li, H.; Deng, L. Organic Lett. 2005, 8, 167-169.
  18. “Stereocontrolled Creation of Adjacent Quaternary and Tertiary Stereocenters via a Catalytic, Diastereoselective and Enantioselective Conjugate Addition,” Li, H.; Wang, Y.; Tang, L.; Wu, F.;  Liu, X.; Guo, C.; Foxman, B.; Deng, L. Angew. Chem. Int. Ed. 2005, 44, 105-108 (designated as a “Very Important Paper (VIP)” paper).
  19. “Highly Enantioselective Conjugate Addition of Malonate and b-Ketoester to Nitroalkenes: Asymmetric C-C Bond Formation via New Bifunctional Organic Catalysts Based on Cinchona Alkaloids,” Li, H.; Wang, Y.; Tang, L.; Deng, L.  J. Am. Chem. Soc. 2004, 126, 9906-9907.
  20. “Asymmetric Organic Catalysis with Modified Cinchona Alkaloids,” Tian, S.-K.; Chen, Y.; Hang, Jianfeng.; Tang, Liang.; McDaid, P.; Deng, L. Accounts of Chemical Research 2004, 37, 621-631 (invited contribution for a special issue of asymmetric organic catalysis).
  21. “Dynamic Kinetic Resolution for Asymmetric Synthesis of a-Alkyl Amino Acids via Dual-Function Catalysis of Modified Cinchona Alkaloids,” Hang, J.; Deng, L. Synlett, 2003, 1927-1930 (invited paper for cluster papers of organic catalysis).
  22. “Asymmetric Alcoholysis of Cyclic Anhydrides,” Chen, Y.; McDaid, P.; Deng, L. Chem. Review 2003, 103, 2965-2984 (invited review article for a thematic issue of Enantioselective Catalysis).
  23. “Catalytic Asymmetric Cyanosilylation of Ketones with Chiral Lewis Base,” Tian, S.-K.; Hong, R.; Deng, L.  J. Am. Chem. Soc. 2003, 125, 9900-9901.
  24. “Development of a Rapid, Room Temperature Dynamic Kinetic Resolution for Efficient Asymmetric Synthesis of a-Aryl Amino Acids,” Hang, J.; Li, H.; Deng, L. Organic Lett. 2002, 4, 3321-3324.
  25. “Dynamic Kinetic Resolution via Dual-Function Catalysis of Modified Cinchona Alkaloids: Asymmetric Synthesis of a-Hydroxy Carboxylic Acids,” Tang, L.; Deng, L. J. Am. Chem. Soc. 2002, 124, 2870-2871.
  26. “A Highly Enantioselective and General Conjugate Addition of Thiols to Cyclic Enones with an Organic Catalyst,” McDaid, P.; Chen, Y.; Deng, L.  Angew. Chem. Int. Ed. 2002, 41, 338-340. Angew. Chem. 2002, 114, 348-350. (Designated as a “Hot Paper”). 
  27. “Asymmetric Synthesis of a-Amino Acids via Cinchona Alkaloid-Catalyzed Kinetic Resolution of Urethane-Protected a-Amino Acid N-Carboxyanhydrides (UNCA),” Hang, J.; Tian, S.-K.; Tang, L.; Deng, L. J. Am. Chem. Soc. 2001, 123, 12696-12697.
  28. “Parallel Kinetic Resolutions of Monosubstituted Succinic Anhydrides Catalyzed by a Modified Cinchona Alkaloid,” Chen, Y.; Deng, L. J. Am Chem. Soc. 2001, 123, 11302-11303.
  29. “A Formal Catalytic Asymmetric Synthesis of (+)-Biotin with Modified Cinchona Alkaloids,” Choi, C.; Tian, S.-K.; Deng, L. Synthesis, 2001, 1737-1741 (invited contribution for a special issue of organic catalysis).
  30. "A Highly Enantioselective Chiral Lewis Base-Catalyzed Asymmetric Cyanation of Ketones," Tian, S.-K.; Deng, L.  J. Am. Chem. Soc. 2001, 123, 6195-6196.
  31. "A Highly Enantioselective Catalytic Desymmetrization of Cyclic Anhydrides with Modified Cinchona Alkaloids," Chen, Y.; Tian, S.-K.; Deng, L. J. Am. Chem. Soc. 2000, 122, 9542-9543.