Copper-catalyzed asymmetric addition of olefin-derived nucleophiles to ketones

Abstract

Enantioenriched alcohols found in an array of bioactive natural products and pharmaceutical agents are often synthesized by asymmetric nucleophilic addition to carbonyls. However, this approach generally shows limited functional group compatibility, requiring the use of preformed organometallic reagents in conjunction with a stoichiometric or sub-stoichiometric amount of chiral controller to deliver optically active alcohols. Herein we report a copper-catalyzed strategy for the stereoselective nucleophilic addition of propargylic and other alkyl groups to ketones using easily accessible (poly)unsaturated hydrocarbons as latent carbanion equivalents. Our method features the catalytic generation of highly enantioenriched organocopper intermediates and their subsequent diastereoselective addition to ketones, allowing for the effective construction of highly substituted stereochemical dyads with excellent stereocontrol. Moreover, this process is general, scalable, and occurs at ambient temperature.

Copper‐Catalyzed Alkynylboration of Alkenes with Diboron Reagents and Bromoalkynes

“…When cyclohexyl allene was used, the product was obtained in 51 % yield ( 4 d ). Interestingly, when 1,3‐enyne was used as alkene for the alkynylboration, 1,4‐alkynylboration product was obtained (Scheme , 4 e ). As a comparison, 3,4‐carboboration and 3,4‐hydroboration, to 1,3‐enynes is the most common reaction pattern.…”

“…Akynylation with the bromoalkyne then occurs, which forms the desired alkynylboration product along with the regeneration of the Cu I catalyst. As for 1,3‐enyne, 1,3‐isomerization of the propargylcopper III affording an allenylcopper intermediate IV , then oxidative addition with the bromoalkyne to form intermediate V , which undergoes a reductive elimination to furnish the target product.…”

Enantio‐ and Diastereoselective Synthesis of Homopropargyl Amines by Copper‐Catalyzed Coupling of Imines, 1,3‐Enynes, and Diborons

“…Regioselective borocupration provides intermediate A (1), which is proposed to undergo propargyl‐to‐allenyl isomerization to B (2) (Scheme A) . We propose that intermediate B is the major allenyl–copper isomer in the reaction .…”

Ausbalancieren von C=C‐Funktionalisierung und C=O‐Reduktion in der Cu‐H‐Katalyse

“…[9] DFT-Rechnungen hatten darauf hingedeutet, dass eine Ketonhydrocuprierung,d.h.eine 1,2-Reduktion, bei richtiger Wahl des Bisphosphanliganden gegen die Eninhydrocuprierung verliert. [9] DFT-Rechnungen hatten darauf hingedeutet, dass eine Ketonhydrocuprierung,d.h.eine 1,2-Reduktion, bei richtiger Wahl des Bisphosphanliganden gegen die Eninhydrocuprierung verliert.…”