Nickel-Catalyzed Reductive Couplings of Aldehydes and Alkynes: ControllingStereochemistry and Regioselectivity using N-Heterocyclic Carbene Ligands.
[摘要] Allylic alcohols are a common substructure in natural products and useful intermediates for a variety of organic transformations.One of the most direct synthetic approaches for the synthesis of allylic alcohols is the reductive coupling of an aldehyde and an alkyne.While many different methods have been developed, the use of N-heterocyclic carbenes as ligands in nickel-catalyzed aldehyde-alkyne reductive couplings has allowed the reaction to be synthetically useful for a broad range of substrates.In this body of work, strategies for both enantioselectivity and regioselectivity using N-heterocyclic carbenes as ligands will be discussed.A new N-heterocyclic carbene ligand, analogous to ligands used in asymmetric ring-closing metathesis, was developed that exhibited high enantioselectivities in the asymmetric reductive coupling of aldehydes and alkynes.Its scope was examined for a wide variety of intermolecular couplings as well as a macrocyclization.Advances in the control of alkyne regioselectivity have been made, with the ability to produce either regioisomer, with the complementary use of smallcyclopropenylidene carbene ligands or highly hindered N-heterocyclic carbene ligands.Regioselectivities were typically quite high in cases where the standard conditions were unselective.In some cases with strong substrate biases for a single regioisomer, the opposite regioisomer was achievable using our highly hindered N-heterocyclic carbene ligands.Finally, studies to combine these two concepts, regiocontrol and enantiocontrol, were executed, exploring N-heterocyclic carbene ligands which allowed for the both high regiocontrol and enantiocontrol within aldehyde-alkyne reductive coupling.Advances were made in the understanding of the impacts of different N-aryl substitutions and backbone structures on both regiocontrol and enantiocontrol.
[发布日期] [发布机构] University of Michigan
[效力级别] Chemistry [学科分类]
[关键词] Nickel-Catalyzed Reductive Couplings of Aldehydes and Alkynes: Controlling Stereochemistry and Regioselectivity Using N-Heterocyclic Carbene Ligands;Chemistry;Science;Chemistry [时效性]
