Optimization and Development of Nickel-Catalyzed [3+2]-Reductive and Alkylative Cycloadditions.

Cycloaddition;Chemistry;Science;Chemistry

Jenkins, Aireal D.Wolfe, John P. ;

University of Michigan

关键词: Cycloaddition;    Chemistry;    Science;    Chemistry;   

Others  :  https://deepblue.lib.umich.edu/bitstream/handle/2027.42/98078/ahaley_1.pdf?sequence=1&isAllowed=y

瑞士|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

Five-membered carbocycles are important structural motifs in natural products and biologically active compounds. One way to construct these rings is to combine a two-atom component and a three-atom component together in a [3+2] cycloaddition. Many traditional cycloaddition methodologies make use of polar reagents, vinyl carbenoids, or strained rings, but use of these methods can create synthetic difficulties. It is therefore desirable to use simple, readily available pi-components for these purposes similar to more conventional cycloaddition reactions such as Diels Alder processes. Other methodologies, which use simple pi-components, have been developed that circumvent the problems of traditional methodologies by changing the substrate oxidation state or rearranging the atomic connectivity of the molecule. The Montgomery group has long worked on methodologies that take advantages of changes in substrate oxidation state. This dissertation presents the development and optimization of nickel-catalyzed [3+2]-reductive cycloadditions for the synthesis of cyclopentenone products. This methodology utilizes enoate and alkyne simple pi-components and combines them with a nickel catalyst under mild conditions. This methodology is also tolerant of a variety of functional groups and substitution patterns. Reductive coupling products isolated from some reactions lend support to our proposed mechanism. Sometimes further functionalization of carbocyclic products is necessary, but functionalization requires further reaction and purification steps. Multicomponent reactions offer a solution to this difficulty by combining many reactants in a single pot to form a highly functionalized product. There are many examples of [3+2] cycloadditions involving polar reagents, but these methods suffer from the same difficulties as the two-component cycloadditions. Methods that make use of simple pi-components for multicomponent cycloadditions are rare. This dissertation describes the optimization and development of nickel-catalyzed multicomponent [3+2]-alkylative cycloadditions for the synthesis of highly functionalized cyclopentenones. This methodology is an extension of the enoate-alkyne [3+2]-reductive cycloaddition methodology and adds an aldehyde as the third component. The mechanism of the reaction is presently unclear. Internal redox products isolated from some reactions suggest a mechanism similar to that of the [3+2]-reductive cycloadditions. On the other hand, experiments conducted in aprotic solvents by the Ogoshi group are suggestive of a mechanism involving a ketene intermediate.