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
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
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
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,
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.