This project will address the development of catalysts for the stereoselective formation of C-C bonds using nitroalkanes. The ease of deprotonation adjacent to nitroalkanes along with their facile conversion to other functionality such as amines and ketones makes them attractive targets for reaction control. Organocatalysts have been developed that achieve asymmetric conjugate addition of nitroalkanes with a variety of substrates, presumably through non-covalent stabilization of the anionic intermediates. Catalyst design continues through investigation of additional scaffolds that are complementary to nitroalkane structure as well as expanding the scope of applicable nitroalkanes.
With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Linton of the Department of Chemistry at Bowdoin College. Professor Linton's research efforts revolve around the development of molecular catalysts that control the reactions of nitroalkanes. Since stereoselective syntheses are required for numerous pharmaceutical and biological substrates, these catalysts have broad applicability to a wide variety of relevant target molecules. Additionally this approach uses environmentally friendly organocatalysts that can perform these reactions with minimal use of reagents and minimal production of waste.
This award to the College of the Holy Cross was in support of the investigation of receptors that control the chemical reactivity of nitrolkanes. There are a multitude of chemical reactions that are utilized by synthetic chemists to create novel products, materials, pharmaceuticals and many ofter substances that play so many roles in daily life. If one wanted to change the inherent nature of a chemical reaction, one way to do so is to grab onto a molecule and control how it reacts. This type of molecular recognition is possible using hydrogen bonds, which are also utilized in biological substrates such as proteins and DNA. In our case we are using hydrogen bonds to bind to a target and change its reactivity in a number of ways. We have designed a scaffold that positions an accumulating number of hydrogen bonds that increases the association strength with nitroalkanes and also accellerates their chemical reactions. We have used similar receptors to change what region of the molecule reacts in the opening of cyclic esters. Most interestingly, we have used these hydrogen bonding interactions to control the three-dimensional orientation, or handedness, of nitroalkane reactions. Many pharmaceuticals have a specific three-dimensional structure, much the way a left hand differs from a right hand. Just like you can not shake a right hand with another persons left hand, a drug that is "left-handed" can not fit in a target that fits a "right-handed" drug. In the course of these investigations we have also discovered a novel example o he Curtin-Hammett principle in the use of the peptide coupling additive HOBt. We have also developed a new technique to synthesize protected primary amides. Ten undergraduate researchers have benefitted from the support of this award. Four of these are currently pursuing graduate studies in chemistry, two are engaged in teaching and two are enrolled medical school. undergraduate research provides the ultimate capstone experience for education in the sciences, helping to build knowledge, technical skills, scientific sophistication as well as gaining experience in presenting scientific results.
