faculty

Associate Professor of Chemistry
Ph.D., Massachusetts Institute of Technology
NIH Postdoctoral, University of California, Irvine

Organic Chemistry, Organometallic Chemistry, New Synthetic Methods, Catalysis and Asymmetric Catalysis, Synthesis of Natural Products

Phone: (734)-763-3432
Email: jpwolfe@umich.edu

Wolfe Research Lab
Organometallic Chemistry

The invention of new methods, strategies, and reactions is of great importance to the progress of organic synthesis. Chemical technology and knowledge have advanced to a point where, given a sufficient amount of time, money, and manpower, it is possible to synthesize almost any organic molecule known to man.   However, the synthesis of important, biologically active molecules in an efficient, practical, economical, and environmentally benign fashion still remains a great challenge to organic chemists. One way to address this challenge is to devise new means of assembling molecules by taking advantage of the unique reactivity of transition metals. To this end, our research is focused on the creation of new metal-catalyzed reactions that are applicable to the synthesis of important molecules. Research in my group involves the development of new synthetic methodology and new transition metal catalysts, asymmetric catalysis and synthesis, the study of new reaction mechanisms, and the total synthesis of natural products. Three representative areas of interest are described below.

The Palladium-catalyzed stereoselective synthesis of tetrahydrofurans and Pyrrolidines.
We have recently developed new palladium-catalyzed reactions of gamma-hydroxy or gamma-amino olefins with aryl and vinyl bromides that affords substituted tetrahydrofuran products. These reactions form both a carbon-carbon and a carbon-heteroatom bond in a single step, and proceed with diastereoselectivities of up to >20:1. Preliminary mechanistic studies suggest these reactions proceed through an unusual intramolecular insertion of an alkene into a Pd(Ar)(OR) or a Pd(Ar)(NRR') intermediate. These new reactions have potential applications to the stereocontrolled synthesis of a number of interesting, biologically active compounds including members of the acetogenin and the amphidinolide families of natural products .

The metal-catalyzed insertion of olefins into small heterocycles. 
A large number of tetrahydrofuran and pyrrolidine derivatives have been shown to possess useful and interesting biological activity.   One of our approaches to these compounds involves the development of a transition metal-catalyzed insertion reaction of olefins into small, strained heterocycles.   This strategy would produce complex molecules in a single step from simple starting materials in a stereocontrolled manner.   In addition to providing a new, useful method for organic synthesis, studies in this area will also address significant issues in organometallic chemistry. The utility of this methodology may be demonstrated in the total synthesis of several natural products including plakortone E, hyacinthacine B2, and cylindricines C and D.

Tandem Wittig-Rearrangment/Aldol Reactions. 
We have recently discovered a new transformation that effects the coupling of O -alkyl glycolate esters with aldehydes to afford syn -1,2-diols bearing a quaternary stereocenter. These transformations proceed via an unprecedented one-pot sequential 1,2-Wittig-rearrangement/aldol reaction, and provide the products with excellent diastereoselectivity (>20:1 dr). We are currently exploring asymmetric versions of these reactions, along with applications to the synthesis of natural products such as alternaric acid and leuhistin

.

AWARDS

• 2008-2009 GlaxoSmithKline Chemistry Scholar Award
• 2006 William R. Roush Junior Faculty Development Award
• 2006 Camille Dreyfus Teacher-Scholar Awards
• 2005 Lilly Grantee Award
• 2004 Amgen Young Investigator Award
• 2003-05 3M Untenured Faculty Award
• 2002 Dreyfus New Faculty Award
• 2002 Research Corporation Innovation Award
• 2002 Lilly Unrestricted Research Award

REPRESENTATIVE PUBLICATIONS

1. Nakhla, J. S.; Wolfe, J. P. "A Concise Asymmetric Synthesis of cis -2,6-Disubstituted N -Aryl Piperazines via Pd-Catalyzed Carboamination Reactions" Org. Lett. 2007 , 9 , 3279.
   
2. Bertand, M. B.; Wolfe, J. P. "A Concise Stereoselective Synthesis of Preussin, 3-epi-Preussin and Analogs" Org. Lett. 2006 , 8 , 2353.
   
3. Bertrand, M. B.; Wolfe, J. P. "Tandem Wittig Rearrangement/Aldol Reactions for the Synthesis of Glycolate Aldols." Org. Lett. 2006 , 8 , 4661.
   
4. Ney, J. E.; Wolfe, J. P. "Selective Synthesis of 5- or 6-Aryl Octahydrocyclopenta[ b ]pyrroles from a Common Precursor Through Control of Competing Pathways in a Pd-Catalyzed Reaction" J. Am .Chem. Soc. 2005 , 127 , 8644.
   
5. Lira, R.; Wolfe, J. P. "Palladium-Catalyzed Synthesis of N-Aryl-2-Benzylindolines via Tandem Arylation of 2-Allylaniline: Control of Selectivity Through in situ Catalyst Modification." J. Am Chem Soc. 2004 , 126 , 13906.
   
6. Wolfe, J. P.; Rossi, M. A., "Stereoselective Synthesis of Tetrahydrofurans via the Palladium-Catalyzed Reaction of Aryl Bromides with gamma-Hydroxy Alkenes. Evidence for an Unusual Intramolecular Olefin Insertion into a Pd(Ar)(OR) Intermediate," J. Am. Chem. Soc. 2004 , 126 , 1620.