New Heterocyclic Architectures from Cascade Processes

点击翻译按钮获取中文摘要

All aspects of applied organic chemistry rely on the ability to generate a vast variety of novel molecular architectures with interesting properties. This places a persistent demand on the synthetic organic chemists to develop and fine-tune various procedures that enable the synthesis of the desired structural frameworks. With the support from NSERC, my research laboratory and research program has actively been involved in the development of new synthetic methodologies towards the synthesis of novel and complex molecular frameworks from naphthalene/tetralin core. Expanding on this expertise, I plan to invent and apply strategic use of unique bond-forming reactivity of certain reactive intermediates and their subsequent use in a cascade fashion to construct an array of important novel molecular frameworks sporting a variety of molecular topology and functional groups. The proposed work employs generating bipolar o-quinone methides, o-azaquinone methides, N-acyliminium ions and related species and their concerted/non-concerted reactions with external/internal trapping groups in a one-pot cascade process. Although known for a relatively long time, these intermediates still offer a multitude of ways to creatively exploit them in pursuit of novel and complex heterocyclic entities. The possibility of further innovative chemical transformations on the assembled framework will also be explored to prepare analogs of natural products and bioactive molecules. While developing these chemistries, asymmetric synthesis will be undertaken employing chiral induction through catalysis or chiral substrates. The specific target skeletons selected for this investigation are expected to possess a wide variety of topologies and properties. Wherever possible, studies will be undertaken to unravel any interesting spectroscopic and electronic properties of the molecules synthesized. Attempts will also be made to make the library of compounds synthesized available to fellow scientists with complementary expertise to study their potential as catalysts, fluorophores, molecular electronics, pharmaceuticals, etc. This work entails multistep synthesis, extensive reaction optimization, and structure determination. As a result, my lab offers an excellent training environment for highly qualified personnel. During the tenure of this grant, ~8 graduate students and ~15 advanced undergraduate students will receive high quality training in the art of organic synthesis and scientific writing among other research related skills. The research outcome of this endeavor will benefit a) synthetic chemistry community with the development of new methodologies, b) material science community with the development of new fluorophores and molecular electronics, and c) drug development community with the synthesis of several libraries of biologically relevant molecules.