Laura H. Carnell Professor of Chemistry

B.S. ('62), University of Wisconsin
Ph.D. (66) Syracuse University
Welch Postdoctoral Fellow ('66-68) University of Texas

OFFICE
Beury Hall 450

MAILING ADDRESS
Department of Chemistry
Beury Hall 130
1901 N. 13th Street
Philadelphia, PA 19122

PHONE
office: 215-204-0477
fax: 215-204-0478
lab: 215-204-8799, -4348

E-MAIL
fdavis@temple.edu

Medicinal / Organic

Research Interests

Asymmetric Synthesis using Sulfur–Nitrogen Reagents

With the realization that biological activity often critically depends on molecular shape and absolute stereochemistry, the synthesis of enantiomerically pure compounds and the elucidation of the underlying principles of molecular recognition have emerged as increasingly important objectives.  The focus of our research programs at Temple is the development of new reagents and methodologies for the asymmetric synthesis of biologically and pharmacologically active amine derivatives (amino acids, amino phosphonates, and alkaloids).

Asymmetric Synthesis of Bioactive Amines.  Our studies at Temple have demonstrated that sulfinimines (N-sulfinyl imines) offer a general solution to the problem of addition of organometallic reagents to imines because the N -sulfinyl group activates the C=N bond for addition, is highly stereodirecting and easily removed in the sulfinamide without epimerization of the amine product.  The most direct and reliable method for the asymmetric synthesis of diverse amines is the addition of an organometallic reagent to an enantiopure sulfinimine. In this regard sulfinimines have been utilized in the asymmetric syntheses of amines; a- and b-amino acids; a- and b-amino phosphonates; nitrogen heterocycles including aziridine 2-carboxylated and 2-phosphonates; isoquinolines; 2 H-azirine carboxylates and phosphonates; pyrrolidines and piperidines.

Currently efforts are aimed at the design and synthesis of a series of sulfinimine-derived polyfunctionalized chiral building blocks for the asymmetric synthesis of bioactive nitrogen heterocycles.  We require these building blocks to be easily prepared in both enantiomerically pure forms and provide efficient access to classes of amine heterocycles with a minimum of chemical manipulation.

Selected Publications

1. Davis, F. A. Theddu, N.; Gaspari, P. A. “Asymmetric Synthesis of Substituted Tropinones using the Intramolecular Mannich Cyclization Reactions and Acyclic N-Sulfinyl -Amino Ketone Ketals,” Org. Lett. 2009, 11, 164236.
2. Davis F. A.; Zhang, Y. “Asymmetric Synthesis of (2S,3R)-(-)-epi-CP-99,994 using Sulfinimine-Derived anti-2,3-Diamino Esters.” Tetrahedron Lett. 2009, 50, 5205.
3. Davis, F. A. ; Zhang, J.; Zhang, Y.; Qiu, H., “Improved Synthesis of (-)-Agelastatin A,” Synthetic Communications, 2009, 39. 1914.
4. Davis, F. A.; Qiu, H.; Song, M.; Gaddiraju, N. V., “Vinylaliminium Addition to Sulfinimines (N-Sulfinyl Imines). Asymmetric Synthesis of anti-a-Alkyl b-Amino Esters,” J. Org. Chem. 2009, 74, 2798.
5. Davis, F. A.; Gaspari, P. M.; Nolt, M. B.; Xu, P., “Asymmetric Synthesis of Acyclic 1,3-Amino Alcohols by Reduction of N- Sulfinyl b-Amino Ketones. Formal Synthesis of (-)-Pinidinol and (+)-Epipinidinol,” J. Org. Chem. 2008, 73, 9619.
6. Davis, F. A.; Bowen, K. A.; Xu, H., "Synthesis of polysubstituted pyrroles from sulfinimines (N-sulfinyl imines)," Tetrahedron 2008, 64 , 4174.
7. Davis, F.A.; Zhang, J.; Qiu, H., "Asymmetric Synthesis of cis- and trans-2,5-disubstituted pyrrolidines from 3-oxo pyrrolidine 2-phosphonates: Synthesis of (+)-Preussin and Analogs," Org. Lett. 2008, 10 , 1433.
8. Davis F. A.; Deng, J. “Asymmetric Synthesis of 2H-Azirine 3-Carboxylates,” Org. Lett, 2007, 9, 1707.
9. Davis F. A.; Song, M. “Asymmetric Synthesis of syn--Substituted -Amino Ketones using Sulfinimines and Prochiral Weinreb Amide Enolates,” Org. Lett. 2007, 9, 2413.
10. Davis, F. A.; Zhang, Y.; Qiu, H., “Asymmetric Synthesis of anti- and syn-2,3-Diamino Esters using Sulfinimines. Water and Concentration Effects,” Org. Lett. 2007, 9, 833.


For reviews on the chemistry of sulfinimines see:
1. Davis, F. A., “Adventures in Sulfur-Nitrogen Chemistry,” J. Org. Chem. 2006, 71, 8993.
2. Zhou, P.; Chen, B.-C.; Davis, F. A., "Recent advances in asymmetric reaction using sulfinimines ( N -sulfinyl imines)," Tetrahedron 2004 , 60 , 8003.