The development of new synthetic methodology for transition metal mediated [4+2] cycloaddition reaction chemistry.

摘要

Cycloaddition chemistry is one of the primary tools used to form cyclic molecules in modern organic synthesis. Many synthetically desirable natural products contain a basic ring structure at the core of the molecule. For this reason, the reaction chemistry utilized to form five- and six-membered rings is important in modern synthesis. One of the most widely known cycloaddition reactions is the Diels-Alder reaction. This reaction is a [4+2] cycloaddition reaction to form a six-membered ring with multiple stereocenters. Often high temperatures or harsh additives are required to induce ring formation. These conditions can limit the scope of the reaction to exclude sensitive substituents.;Our interests in this field of cycloaddition arose in the development of new synthetic methods designed to enhance the reactivity and stereoselectivity of traditional Diels-Alder chemistry. Cobaloxime mediated [4+2] cycloaddition reactions have been found to offer a mild, exo-selective method for the synthesis of six-membered rings. Our current research interests lie in the combination of two fields: the continued pursuit of mild means for the synthesis of transition metal complexes capable of undergoing cycloaddition reactions and the search for a one-pot reaction system in which the metal can be recycled or used in a catalytic amount.;The development of 2-substituted dienyl cobaloxime complexes in cobalt mediated cycloaddition chemistry initiated our pursuit of a new synthetic methodology for the formation of sp2 carbon-cobalt bonds. In turn, this new synthetic method led to the development of a new method for dienyl complex synthesis that we were able to incorporate into a one-pot reaction cycle for cobaloxime mediated cycloaddition reactions. We have shown this one-pot method to be successful with a range of dienophiles. For the one-pot reaction sequence to be synthetically useful the cycloadduct must be cleaved from the metal and a viable species of the transition metal must be regenerated. Our investigation of cleavage reactions to complete the one-pot cycle led to the cleavage of cobaloxime complexes with silanes. The silane cleavage reactions produced the desired cycloadduct and a mixture of cobalt salts which could be easily connected into the original 2-substitued dienyl complex. Though the cycloaddition and cleavage reactions were individually successful, attempts to generate a complete reaction cycle were met with only mediocre success. In conclusion, our results have provided a valuable insight into the pursuit of catalytic of pseudo catalytic transition metal mediated cycloaddition chemistry.