FACULTY & STAFF

Anthony J. Pearson

Rudolph and Susan Rense Professor of Chemistry
ajp4@case.edu

Organic Chemistry

B.Sc., University of Leeds (U.K.) 1971
Ph.D., University of Aston (U.K.) 1974
Postdoctoral Fellow, Australian National University, 1974-77
Sir Gilbert Morgan Medal, Society for Chemical Industry, U.K., 1973
SERC Advanced Fellow, Cambridge University (U.K.), 1977-82
CWRU Sigma XI Research Award, 1984
John S. Diekhoff Award for disginguished graduate teaching, 1994

Research Synopsis

The overall thrust of the research carried out in the Pearson laboratories is the application of organometallic chemistry in organic synthesis. This involves a fairly broad array of projects outlined here.

Total Synthesis of the Aglycone of Ristocetin A:

We are currently defining a new approach to the synthesis of complex glycopeptide antibiotics, which uses ruthenium-promoted intramolecular nucleophilic aromatic substitution reactions to set in place a diaryl ether bond, a key linkage in the structures of all of these molecules. An important example of these glycopeptide antibiotics is vancomycin, which has been the focus of much attention in recent years, owing to the emergence of vancomycin resistant infectious bacteria. Ristocetin A is a molecule that is structurally related to vancomycin, and the total synthesis of the aglycone of this compound is currently under way in our laboratories. The overall (modular) approach is shown in the following retrosynthetic scheme.

The discovery and development of new reactions is a very exciting outcome in organic synthesis research. Our group has been fortunate to discover a number of new reactions (all by accident!), some of which are illustrated here.

Iron Carbonyl Promoted [6+2] Ene Reactions:

This [6+2] ene-type reaction was discovered by graduate student Mark Zettler, the example given here showing how a densely substituted multicyclic structure can be constructed, that relates to the sesquiterpenoid verrucarol.

Subsequent work by graduate student Xiaolong Wang has resulted in a two-step procedure for stereospecific conversion of a readily prepared cylohexadiene into a molecule that has much of the structure in place for synthetic approaches to the complex alkaloid gelsemine.

Iron Carbonyl Catalyzed Oxidative Cyclization of N-Hydroxyethylpyrrolidines:

This reaction was discovered by graduate student Yoonhyun Kwak during some unrelated studies. This interesting chemistry promises to furnish methodology for stereocontrolled functionalization of pyrrolidines, which will allow the synthesis of numerous important alkaloids.

Iron Carbonyl Promoted Intramolecular [2+2+1] Cyclocouplings and Further Chemistry of the Resulting Cyclopentadienones.

Our modifications of a previously known, but low-yielding cyclocarbonylation has resulted in a practical method for the synthesis of cyclopentadienones that are anticipated to be very valuable intermediates for the synthesis of numerous interesting compounds. Our recent work has led to an efficient silicon-tethered method for intramolecular alkyne cross coupling to afford cyclopentadienones, that can be subjected to conjugate addition reactions to afford useful cyclopentanone building blocks, as well as cycloaddition chemistry to afford biaryl structures.

Stereocontrolled Nucleophile Additions to Arene Chromium Tricarbonyl Complexes:

We have developed methodology for the enantioselective conversion of anisole derivatives, via their chromium tricarbonyl complexes, into 5-substituted cyclohexenones. The generalized reaction is shown here, and we have achieved enantiomeric excesses of up to 94% (using the enolate of tert-butyl acetate as nucleophile). A further development of this reaction is the diastereoselective addition of tert-butyl propionate enolate to anisole-chromium tricarbonyl complexes, which will ultimately allow efficient synthesis of natural producst such as juvabione, an insect pheromone.

Cascade Cationic Cyclizations of Diene Iron Tricarbonyl Complexes:

Iron tricarbonyl can act as a neighboring group during formation of reactive carbocations and allows stereocontrol during their reactions with attached alkenes to form carbocyclic ring systems. One recent result from an ongoing project in our group is shown here.

PET Fluorescent Chemosensors:

Electron transfer from a strong electron donor to a photoexcited acceptor molecule can lead to fluorescence quenching of the latter (photoinduced electron transfer = PET). If the electron donor is fitted with a receptor that binds to an analyte, and if this binding leads to an increased oxidation potential of the donor, the PET can be suppressed and fluorescence is restored. This principle is used to produce PET fluorescent sensors. A proof-of-principle study in our laboratory has established that p-phenylenediamines can be made using iron- or ruthenium-mediated nucleophilic aromatic substitution chemistry. A number of aza-crown ether substituted phenylenediamines that show PET fluorescence quenching have been screened as potential sensors, using the well-known crown ether metal cation binding properties. One example of this behavior is shown here.

Selected Publications

Textbook and Monograph Publications