Empowering Asymmetric Phosphine Catalysis via Novel Modes of Activation

This proposal describes new approaches to empower asymmetric phosphine catalysis, our short-term goal is to uncover novel asymmetric organic transformations via the discovery of new modes of activation/asymmetric induction, and our long-term objective is to develop innovative processes for production of important pharmaceutical agents. Significance: This proposal addresses a crucial and fundamental challenge in organic chemistry catalytic asymmetric preparation of chiral molecules, which is of particular importance to biological sciences and pharmaceutical industry. Despite the discovery of countless asymmetric reactions and vast number of catalysts to date, novel and powerful catalytic modes of activation are rather limited. In this proposal, we propose a number of novel approaches to empower asymmetric phosphine catalysis to create unprecedented catalytic systems. The new systems to be developed are highly practical and economical, which in combination of anticipated high efficiency, may prove to be very practical for industrial applications. This project is targeting both academic and industrial significance. All the novel concepts described in this proposal are scientifically novel, and have never been investigated. Successful implementation of the proposed work will significantly advance the state-of-the-art of the field of asymmetric phosphine catalysis. In addition, the targeted synthetic methods will likely provide practical solutions for sustainable and innovative production of important pharmaceutical products. Hypotheses: Phosphine catalysis has been proven to be very powerful in organic synthesis. It is hypothesized that combining phosphines and other powerful catalysis methods can result in novel reactivity/new modes of activation, leading to the discovery of unprecedented reactions useful for chemical production. Approach: We intend to take the following approaches to empower phosphine catalysis so that new asymmetric reactions/novel catalytic systems/new modes of activations can be discovered for practical synthesis of useful pharmaceutical agents. Specifically, we would like: (1) to design binary catalytic systems containing achiral phosphines and chiral co-catalysts, e.g. small peptides/chiral diols. (2) to explore phosphine catalysis in conjunction with iminium catalysis. (3) to apply bifunctional chiral phosphine organic catalysts to various asymmetric organic transformations.