The following is a description of some of the successful chemical research projects I've been involved in, including literature references where appropriate. Today, I consider myself an organic chemist who explores his art with computer programming and molecular simulation... but as another great computational chemist once put it:
" I was once a respectable experimental chemist."
Undergraduate Research: Cal Berkeley, Rapoport GroupAs an undergraduate, I studied the design, preparation, and application of radiolabeling reagents which culminated in the publication of a technique for preparation of the novel labeling agent tritiated methylene diiodide. This research required me to develop proficiencies with glove box and gas line chemistry and to determine isotope incorporation by liquid scintillation counting and deuterium and tritium NMR techniques. The greatest difficulty in this project was developing a method for preparing the agent in high enough levels of radioincorporation that it would be useful in the preparation of in vivo radiotracers, without producing harmful radioactive waste products. Satisfactory levels of incorporation were arrived at by preparing 4.4 Ci ml^-1 HTO via hydrogen exchange with tritium gas (a process used to trap waste tritium gas from other experiments), then quantitatively consuming the HTO by reduction of idodoform with Na3AsO3.
Tritiated Methylene Diiodide: A New Synthetic Labeling Reagent
Manouchehr Saljoughian, Hiromi Morimoto, Philip G. Williams, Nicholas C. DeMello
J. Chem. Soc., Chem. Comm. (1990) 22 : 1652-1653.
Graduate Research: Univ. of Pittsburgh, Curran GroupMy graduate work involved the development of two novel--time dependent--strategies for stereoselection. First, we achieved stereoselection relative to transient chiral conformations of otherwise achiral molecules. 1-(2,5-Di-tert-butyl-phenyl)-3-methyl-pyrrole-2,5-dione and similiar atropisomeric molecules are synthesized. High temperature NMR and other techniques are used to determine the barrier to interconversion of the chiral conformation of some of these compounds, and thus the half life of enantiomerically pure samples of these compounds. Alkylation, bromination, Diels-Alder addition, nitrile oxide addition, radical addition and other functionalizations were shown to occur stereoselectively relative to the chiral forms of these compounds, and the degree of selectivity was measured with low temperature NMR before racemization occurs. These experiments demonstrated that it is possible to capture the momentary asymmetries of aryl amides and imides and stereoselectively functionalize molecules relative to those instantaneous shapes.
Origins of Regioselectivity in Radical Reactions of Axially Twisted Anilides
Dennis P. Curran, Nicholas C. DeMello
J. Chem. Soc., Chem. Comm. (1993) 17 : 1314-1317.
Atroposelective Thermal Reactions of Axially Twisted Amides and Imides
Dennis P. Curran, Hongyan Qi, Steven J. Geib, Nicholas C. DeMello
J. Am. Chem. Soc. (1994) 116: 3131-3132.
Our second strategy involves achieving stereoselection by engineering reactions to occur through a unique kinetic scheme of our own design--a scheme which involves stereoselection as a result of intermediates partitioning successively between competing chemical transformations. All stereoselective reactions we are aware of involve at least one event where either a single intermediate partitions between diastereomeric transition states or where enantiomeric intermediates undergo kinetic resolution. By presenting an organization of stereoselective reactions into classes based on the kind of stereoselective event, the number of stereoselective events and-in the case of reactions with multiple stereoselective events-whether multiple stereoselective events occur simultaneously or in series, we demonstrate that our strategy is unique. A mathematical description of the ratio of products produced in our kinetic strategy is derived, and computer simulation of that model demonstrates two principle advantages of this method: higher selectivity and more efficient conversion of substrates. Furthermore, that mathematical description is used to develop computer programs for determining key rate constants in the intramolecular cyclization of 3-(3-iodo-iodomethyl-propyl)-cyclohexene and three other reactions which subscribe to our stereoselective kinetic strategy which were subsequently used to determine conditions for maximum stereoselection in these reactions.
Substrate-Controlled Group Selective Radical Cyclizations. A New Strategy for Stereocontrolled Transformations of Diasteomeric Reactive Intermediates
Dennis P. Curran, Hongyan Qi, Nicholas C. DeMello, and Chien Hsing-Lin
J. Am. Chem. Soc. (1994) 116: 8430-8432.
(expect to see some more publications on this subject in '96)
Post-Doctoral Research: UCLA, Houk GroupOh, why not just look for yourself. Visit the Houk Group! ;-)