Development of Nickel-Catalyzed Cycloaddition and Coupling Reactions.

[摘要] Nickel-catalyzed carbon-carbon bond-forming reactions provide a potentially useful strategy to generate a variety of organic compounds efficiently,regioselectively, chemoselectively, and stereoselectively. The versatility of thesetypes of reactions makes them a powerful tool in organic synthesis. This dissertation mainly focuses on methodology development involving nickelcatalysis. In this work, a number of highly selective reactions of readily availableprecursors, such as alkynes, enals and enones were developed.In one application, a novel, nickel-catalyzed [3+2] cycloaddition of enalsand alkynes was explored. This reaction provides a diastereoselective andchemoselective entry to five-membered rings, which are a common structuralmotif in many architecturally complex and biologically active naturalproducts. In another application, a novel, nickel-catalyzed intermolecular reductivecoupling of enones and alkynes was developed. The key feature of this reactionis the chemoselective coupling of two potential Michael acceptors such asenones and alkynoates. The direct participation of alkynes as an alternative topreparing and handling sensitive vinyl cuprate reagents provides potentiallysignificant improvements in accessing γ,δ-unsaturated ketones.An intriguing, nickel-catalyzed, intermolecular reductive coupling of enalsand alkynes has also been developed. The unique features of this reaction arethe construction of geometrically pure Z-enol silanes and high functional grouptolerance. The direct participation of enals, alkynes and silanes as an alternativeto existing methods provides potentially significant improvements in accessingenol silanes. Additionally, this reaction provides direct evidence for the catalyticinvolvement of a seven-membered oxametallacycle intermediate.A novel, nickel-catalyzed intermolecular three-component coupling ofaldehydes, alkynes, and enones has been developed. This new process involvesan internal redox mechanism and proceeds in the absence of reducing agentsthat have previously been required in related nickel-catalyzed couplings. Thehigh extent of chemoselectivity is unusual, particularly for aldehyde, enone,alkyne couplings that involve three different π-components.Together, these new methods provide access to interesting chemicalscaffolds and greatly expand the versatility of nickel-catalyzed reactions.

[发布机构] University of Michigan

[效力级别] Chemistry

[关键词] DEVELOPMENT OF NICKEL-CATALYZED CYCLOADDITION AND;Chemistry;Science;Chemistry