John G. Verkade
Novel Green Catalysts for Organic Reactions, Organometallic Self-Assembled Systems.
Not Accepting Students
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Research Interests
Research students in our group consist of undergraduates, graduates, and postdoctorals who enjoy working on organic or inorganic projects, or on projects that span both fields. Although the research approaches they use are fundamental ones, they keep their eyes open for applications of their chemistry as you will see in some examples below. This strategy has resulted in 12 patents, and an industrial license to Aldrich chemical Company to manufacture and market three of our group's "superbase"/catalysts of type 1. One of our group's organic Ph.D.'s, Dr. John Tang, won a 1994 national BF Goodrich Collegiate Team Inventor Award for discovering these technologies that are still being developed.
We are currently working with two industrial partners to commercialize improved catalytic processes we have discovered for the production of value-added products from soybean oil.
Introduction
It all began several years ago with the accidental discovery by a Ph.D. inorganic student in our group, Mary Laramay, who is now a Senior Chemist at Haliburton Services. She discovered that football-shaped molecules of type 1 are terrific bases. Not long afterwards, an organic Ph.D. student Dr. John Tang (now a Senior Principal Scientist at Mylan Technologies) accidentally discovered that they are superior catalysts for a wide variety of important organic reactions. Several of these applications have produced patents bearing the names of students in our group as co-inventors.
One of the novel features of our catalysts is the extraordinary stability of structure 2. This stability is so great that 1is about 8 orders of magnitude stronger as a Lewis base than any amine known, including commercially used DBU, DBN and Proton Sponge! We have successfully utilized molecules of type 1 in a variety of syntheses catalyzed by bases, such as alkylations, dehydrohalogenations, acylations, a variety of condensations and a series of organometallic reactions useful for making carbon-carbon and carbon-nitrogen bonds. Our nonionic superbase catalysts have the advantage that, unlike strong ionic bases, unwanted side reactions are minimized or eliminated completely.
A second novel characteristic of our cages of type 1 is that substituents (Z in 3) other than a proton can cause only partial transannulation as shown in 3. These substituents can be organometallic or nonmetallic groups. This flexibility in transannular P-N bonding is a crucial factor in the ability of 1 to act as a superior catalyst for a continuously widening range of important reactions such as protecting alcohol groups (e.g., of pharmaceutical intermediates) with various silyl groups during multistep syntheses, converting isocyanates to isocyanourates (which are commercially important in the stabilization of Nylon-6 during its manufacture) and the synthesis of alpha, beta-unsaturated nitriles (which are important in the synthesis of pharmaceuticals, pigments and perfumes).
Project in development: Heterogeneously catalytic super bases
Experiments are currently underway to bind our superbase/catalysts 1 to solid supports (such as mesoporous silicas and to resins) so that product separation will be much easier. The organic supports include long-chain polymers, and also spherical dendrimers (known as "starburst" polymers) that have been synthesized in recent years. Dendrimers have increasingly branched chains that radiate out from the core to the surface of the molecule. These dendrimers and long-chain polymers are often soluble in organic solvents, which increases the activity of catalyst molecules bound to their surface. Soluble dendrimeric catalysts, although technically homogeneous in nature, act like heterogeneous catalysts in that can be easily separated from the reaction mixture by size exclusion filtration.
Dr. Brandon Fetterly, a very recent organic Ph. D. student in our group, is a co-inventor on a patent application for a simple but elegant synthesis of a polymer chemically linked to molecules of our super base/catalyst 1. Here the phosphorus is free to act as a very strong base and also as an electron-rich atom for complexing metals that facilitate metal-assisted C-C and C-N couplings, for example. This achievement opens new applications of our super base/catalyst chemistry, because now the catalyst can be easily recovered for recycling via filtration. This will be particularly important in economizing certain steps in drug syntheses in the pharmaceutical industry, for example. This also allows fine tuning of the basicity of the phosphorus for wider applications of these heterogeneous catalysts, by placing groups such as =O, =S, RN= and RN=N-N= on the phosphorus atom (as we have shown for the polymer unattached analogous molecules in homogeneous reactions).
Project in development: Chiral super base catalysts for asymmetric induction
We have begun a program to synthesize enantiomeric versions of 1. This can be done by making one (or more) of the R groups a chiral one, or by having each R group be a different nonchiral one thus making the phosphporus the chiral center. This opens up the possibility of carrying out asymmetric reactions (e.g., chiral deprotonation of racemic compounds to generate carbanionic nucleophiles of a specific chirality).
Project in development: Even stronger super bases
To further expand the scope of important transformations promoted by 1, we are interested in developing even stronger superbase/catalyst systems by placing substituents on the equatorial nitrogens of 1 that can better stabilize structures of types 2 and 3 by further delocalizing a whole or partial positive charge.
Project in development: A new type of separable super base catalysts
We are placing perfluorinated organic chains on the equatorial nitrogens of 1 to make our suberbase/catalysts soluble in commercially available perfluorinated solvents, such as perfluoroheptane. Such solutions are insoluble in many other non-fluorinated solvents so that reactants in a solvent of the latter type which need a very strong nonionic base to catalyze their reactions have the base at the interface between the two solutions, thereby allowing recycling of the catalyst solution after mechanical separation of the two phases.
Ionic liquid superbase catalysts
We are interested in synthesizing modified forms of our superbases in which the equatorial nitrogens are decorated with substituents containing alkyl or aryl ammonium ions that would allow these molecules to dissolve in room temperature ionic liquids which are now becoming increasingly commercially available as advantageous reaction solvents. Not only could the basicities and catalytic activities of our superbase/catalysts become enhanced in such solvents, but the ammonium functionalities on these compounds would allow them to be retained in the ionic liquid for recycling after separation of the the organic phase containing the product.
Project in development: Super base salts with catalytically active anions
We have recently discovered that cation 2 has very little attraction for anions because of the delocalization of its positive charge over the other three nitrogens and the phosphorus. This result has important consequences for the nitrate counter anion, for example, which because of its lack of interaction with the cation in the 2(NO3) salt, can now display its full capability as a catalytic Lewis base "shuttle" for protons in transformations such as the aza and thia-Michael reactions. Other anions such as chloride, sulfate and perchlorate, are also known to catalyze certain organic reactions and we are now investigating the acceleration of such reactions when the cation in these salts is 2. We have also chemically linked 2 in 2(NO3) to a polymer backbone, thus enabling re-use of the solid catalyst via simple filtration. We are currently collaborating with Energetics of California in developing these types of ionically conducting polymers for a new type of fuel cell.
Project in development: New types of Lewis acid catalysts
It seems counterintuitive, but a positively charged species such as 2 can behave as a Lewis acid. We have shown this to be the case when certain other substituents such as a fluorine atom or CN are placed at the apical position instead of a hydrogen. Preliminary evidence suggests that the phosphorus atom is the Lewis acidic site that becomes coordinated by a nucleophile. We have also synthesized 4 in which the Lewis acidity of the aluminum is reduced but not eradicated by nitrogen donation of its lone pair. As with our electronically flexible super base catalysts, the Lewis acidity of the aluminum will be "adjusted" by the requirements of a Lewis basic site on the reactant by temporarily weakening the N?Al bond. Then, after this activation has resulted in a chemical reaction with a second reactant, the new molecule is released and the N?Al bond is restored. As an example, aldehyde and ketone oxygens could be activated by 4 for nucleophilic attack at the carbonyl carbon.
