The synthesis of carbon-carbon bonds in complex molecules is essential for the construction of new pharmaceutical agents. Over the past several years, olefin metathesis has become a new general method for the construction of such compounds. Key to this transformation is the availability of catalysts that are active, efficient and selective. Over the past several years, a family of catalysts has been developed that shows high activity in the presence of a wide array of unprotected functional groups. Further applications will require catalysts that are enantio and stereoselective and will carry out metathesis on highly functionalized olefins. During the last granting period, progress was made in the development of a model to direct ligand design. During the next granting period, this model will be used to construct new ligand systems for enantioselective cross metathesis, for the stereoselective (control the E:Z ratio of the double bonds formed) in cross metathesis and increase the reactivity of sterically hindered olefins. A variety of new N-heterocyclic carbene ligands will be prepared that will not only have applications in the preparation of selective olefin metathesis catalysts but will be of general use in catalyst design. Successful construction of such catalysts will open efficient new routes to the construction of bioactive molecules.
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