| The work presented here is divided into three projects each with a specific aim, but all sharing the common theme of extending the practical use of carbenes and carbenoids in organic synthesis.; In the first project the Grubbs' catalyst was encapsulated in paraffin wax, protecting the catalyst from laboratory air and moisture. This protected catalyst mixture was successfully used in a variety of typical alkene metathesis reactions. Unlike the unprotected catalyst, the protected catalyst was stable on the shelf for many months.; The next project is an ongoing effort to expand the selectivity of free carbene C-H insertions. The purpose of our effort is to demonstrate that steric and electronic deactivating effects can be combined in the same molecule to effectively activate a single methylene for C-H insertion. Two bicyclic ketones were proposed to test the selectivity. Conditions were developed for a model substrate to construct the properly functionalized quaternary center of one of those ketones, using a sequence of dichlorocarbene insertion followed by sigmatropic rearrangement. If successful, the projected regioselective free carbene C-H insertion will enable the total synthesis of (-)-sordaricin, the parent of a promising series of clinically-effective antifungal agents.; In the third project, rhodium-catalyzed C-H insertion was combined with intramolecular alkylation to afford a powerful new reaction sequence for the construction of polycyclic molecules. The rhodium-catalyzed intramolecular C-H insertion of a carefully-chosen diazo beta-keto ester gave as a product, a compound that was itself a substrate for intramolecular alkylation. The bicyclic products of this sequence are valuable intermediates for organic synthesis. To illustrate the usefulness of this approach, the natural product (+)-sulcatine G was synthesized starting from (-)-citronellyl bromide. |
