Development of Stereoselective Olefin Functionalization Methods

ended

The ability toThe ability to readily access small-molecule building blocks at will has important consequences for the discovery and development of novel medicines and materials. It is particularly beneficial when the chemical methods are convenient while at the same time economically and environmentally tenable and sustainable. We are especially interested in catalytic processes that are easily executed and utilize readily available starting materials to produce optically active products with high regio, chemo, diastereo, and enantioselectivity. The proposal aims to discover, develop, and study a collection of enantioselective olefin functionalization reactions that provide access to useful building blocks, such as amines, azides, hydrazines, nitriles, alcohols, involving acyclic, cyclic and bicyclic structures. The catalyst will be derived from earth abundant metals, such as Fe, Mn, and Co and incorporate novel chiral ligands. The study includes the design and preparation of two structural classes of novel, chiral boric acids that are expected to serve as catalyst for the enantioselective functionalization of unsaturated carboxylic acids and boronic acids. The methods are expected to substantially impact the development of novel strategies for complex molecule synthesis. In this regard, we propose to use the catalysts form this study to convert dienes and trienes into polyols with characteristic stereochemical and oxidation patterns found in bioactive agents, including pharma- and nutraceuticals (carnitine). Such advances enable new approaches that go beyond the well-established methods such as aldol/allylation for the preparation of stereochemically complex fragments. Catalysts will also be developed that convert acyclic olefinic alcohols and amines into optically active, saturated furans, pyrans, pyrrolidines, and piperidines. The implementation of the various catalytic methods in complex settings enables efficient, convergent routes to bioactive agents.