John Wolfe

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

LSA John Dewey Award, 2012
GlaxoSmithKline Chemistry Scholar Award, 2008
Camille Dreyfus Teacher-Scholar Awards, 2006
William R. Roush Junior Faculty Development Award, 2006
Lilly Grantee Award, 2005
Amgen Young Investigator Award, 2004
3M Untenured Faculty Award, 2003-2005
Dreyfus New Faculty Award, 2002
Lilly Unrestricted Research Award, 2002
Research Corporation Innovation Award, 2002

Representative Publications

Babij, N. R.; Wolfe, J. P. "Asymmetric Total Synthesis of (+)-Merobatzelladine B." Angew. Chem. Int. Ed. 2012, 51, 4128.

Schultz, D. M.; Wolfe, J. P. "Intramolecular Alkene Carboamination Reactions for the Synthesis of Enantiomerically Enriched Tropane Derivatives" Org. Lett. 2011, 13, 2962.

Mai, D. N.; Rosen, B. R.; Wolfe, J. P. "Enantioconvergent Synthesis of (+)-Aphanorphine via Asymmetric Pd-Catalyzed Alkene Carboamination." Org. Lett. 2011, 13, 2932.

Mai, D. N.; Wolfe, J. P. "Asymmetric Palladium-Catalyzed Carboamination Reactions for the Synthesis of Enantiomerically Enriched 2-(Arylmethyl) and 2-(Alkenylmethyl)Pyrrolidines." J. Am. Chem. Soc. 2010, 132, 12157.

Neukom, J. D.; Perch, N. S.; Wolfe, J. P. "Intramolecular Alkene Aminopalladation Reactions of (dppf)Pd(Ar)[N(Ar1)(CH2)3CH=CH2] Complexes. Insertion of Unactivated Alkenes into Pd-N bonds." J. Am. Chem. Soc. 2010, 132, 6276.

Giampietro N. C.; Kampf, J. W.; Wolfe, J. P. "Asymmetric Tandem Wittig Rearrangement/Aldol Reactions." J. Am. Chem. Soc. 2009, 131, 12556.

Research Areas(s)

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

Fellowships

• American Association for the Advancement of Science Fellow, 2012