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David Myers

My research interests are divided into four major areas: A) Carbene Chemistry; B) Synthesis of Highly Strained Organic Molecules, C) Modeling of Strained Organic Molecules and Reaction Pathways, and D) Natural Products Chemistry (Bactericidal Compounds from Fungi.) In addition, I have a long-standing, abiding interest in Chemical Education and the methodologies we use to instruct chemistry.

A) Carbene Chemistry: As a result of my sabbatical several years ago, I have become quite interested in reinvestigating the chemistry, explored by Myers and Jones in 1988, of diadamantylcarbene, 1 in cis and trans-2-butene. These investigators employed a nitrogenous precursor to this carbene, diadamantyldiazomethane, 2. Later research in the field showed that excited states of such nitrogenous precursors could lead to chemistry heretofore attributed to carbenes. Recently, Jones et al. have employed gem diiodocompounds reacted with alkyl lithiums to produce "true" carbenes. The current project is to synthesize diadamantyldiiodomethane, 3 and then react it with e.g. butyl lithium in the presence of cis-2-butene to observe the products. The big question is: will this carbene react as carbenes are purported to react to form the cyclopropane? And with what stereochemistry?

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A pressing question, and one that has been partially answered, is: to what degree does the presence of an aromatic ring system stabilize and/or alter a bridgehead double bond? Both 2-phenyladamantene, 4, and 4-phenylhomoadamant-3-ene, 5, have been “synthesized”, and some of the their future reactions characterized; however, it is not clear that the bridgehead double bonds have truly been produced, nor has the effect of electron-withdrawing or electron-donating groups on the stabilization of the double bond been fully investigated. The pathways to the needed precursors are fairly straight-forward, and simply need to be done. Also, gem-diiodo compounds, similar to those given above, need to be employed to verify all previous claims.

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            A further project, again an offshoot of some previous work, is the investigation of the products formed from the photochemical (and thermal) decomposition of the pyrazoline, 6, arising from the reaction of trans-cyclooctene and dimethyldiazomalonate.

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            One additional offshoot of this work has recently begun. In a senior thesis (Allyson Sgro ’01), the methanolysis of diadamantyldiazomethane (2 above) was examined. Rough kinetics calculations (for which I am grateful to Prof. Okazaki of Kyoto University, Japan) show that this methanolysis should take on the order of 2 years to complete! This work needs to be completed, and more acidic alcohols (e.g. 2,2,2-trifluoroethanol, TFE) also need to be examined, and will be.

B) Highly Strained Organic Molecules: An offshoot of the previous area, as well as of the sabbatical, is the synthesis of some highly strained organic molecules. Both 1,1,2,2- tetra(1-adamantyl)ethene, 7 and cis-1,2-di(1-norbornyl)ethene, 8 are to be undertaken. The synthetic technology exists, so all that really remains is to do it.

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Calculations on both these molecules show, no surprise, that they should be highly strained.

An offshoot of the 1,2-di(1-norbornyl)ethene project is that, once the cis-1,2- di(1-norbornyl)ethene is in hand, to do the photolysis of this strained olefin and see to what degree and extent it isomerizes to the trans-1,2-di(1-norbornyl)ethene, 9.

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C) Modeling of Strained Organic Molecules and Reaction Pathways:

 

            As part of a follow-up to the question of the degree to which aryl substituents stabilize a bridgehead double bond, calculational work (at levels from AM1 to 6-31G*) has been undertaken. In particular, examination of the effect on the energies and bond lengths of the conjugated bridgehead double bond compounds versus the isolated systems has been, and continues to be a focus. Furthermore, the isodesmic reactions of shifting an aryl ring from a strain-free cycloalkene to the Bredt compound have been investigated to measure any potential stabilization. Preliminary results indicate a trend towards stabilization of the Bredt compound by the shift of the aryl group to it from the cycloalkene. The substituent in the para position of the aryl ring has been varied from electron-donating to electron-withdrawing, and the effect of those changes modeled also. This work has been extended (to the B3LYP/6-311++G(d,p) level via a grant of computer time at the National Center for Supercomputing Applications (NCSA). The last part of this material is based upon work supported by the National Science Foundation under the following NSF Programs: Partnerships for Advanced Computational Infrastructure, Distributed Terascale Facility (DTF) and Terascale Extensions: Enhancements to the Extensible Terascale Facility.

 

D) Natural Products Chemistry

 

            Briefly put, there is a large need for new bactericidal compounds in the medical armory; several recent (after 1996, for example) studies have shown that certain species of mushrooms, known in the East as parts of Traditional Chinese Medicine, have strong anti-bacterial and anti-cancer properties. Multiple solvent extracts of indigenous mushrooms will be similarly screened. Very preliminary results indicate antibacterial activity in these indigenous fungi, which are members of the Polypore family, and suggest that the variety in Berkshire County, Massachusetts, USA is different from the variety found in Korea (Kim et al. 2001). These results need to be repeated and verified, and then the active compounds extracted and fully characterized. Collaborators have been lined up to perform the structural work. Other members of Polyporaceae will be examined for similar properties and components.

            In addition to antibacterial work, these fungi will be screen for anti-oxidant properties, and promising fractions more fully characterized. Such screening formed the basis of Maung Kyaw “Freddy” Tun’s Senior thesis during academic year 2008-2009, and anti-oxidant activity was found. Chemical elucidation now needs to be performed and further screenings done.

            It is anticipated that I will continue this area of work, expanding into marine organisms during my sabbatical during 2008-2009 at the Institute for Molecular Biosciences, University of Queensland, Brisbane, Queensland, Australia.

            Additional work in this area will involve the synthesis of 4-substituted-butenolides (5-substituted-2(5H)furanones), analogues of which have been isolated from natural sources and have been found to exhibit anti-inflammatory properties.