Strategies for Regio- and Enantiocontrol in Nickel-Catalyzed ReductiveCouplings of Aldehydes and Alkynes.

[摘要] A highly regioselective nickel-catalyzed reductive couplings of propargyl alcohol derivatives and aldehydes have been developed. Consideration of the interplay of sterics and electronics between reactive starting materials and the Ni(COD)2/NHC/R3SiH catalyst system allows for a strategy to predictably control regiochemistry in the coupling of propargyl alcohol derivates, aldehydes, and silanes. The derivatization of these products can lead to several otherwise largely inaccessible regioisomers in an indirect but efficient manner. The ability to reverse alkyne regioselectivity via divergent chemical pathways is known, but to do so with high selectivity across a broad range of substrates is unprecedented. With internal alkynes that lack a strong steric or electronic bias, regioselective couplings to provide either regioisomer selectively are now possible, whereas previously reported protocols were uniformly unselective. With alkynes that possess a strong steric and/or electronic bias, such as aryl alkynes, 1,3-enynes, or terminal alkynes, only a single regioisomer was previously accessible, but our strategy now allows either regioisomer to be selectively obtained. Therefore, the ligand-based control reported herein can override even substantial substrate biases. This study thus provides the first general strategy for controlling regioselectivity in the reductive coupling of aldehydes and alkynes. Regioselectivity reversal for the range of alkynes studied herein rivals that documented for any class of alkyne 1,2-difunctionalization processes. Studies are ongoing for a general regio- and enantioselective nickel-catalyzed aldehyde-alkyne reductive coupling using chiral N-heterocyclic carbenes.

[发布机构] University of Michigan

[效力级别] Chemistry

[关键词] Nickel-Catalyzed Reductive Couplings;Chemistry;Science;Chemistry