Copper-catalyzed asymmetric 1,4-conjugate addition of Grignard reagents to linear α,β,γ,δ-unsaturated ketones

Abstract

A highly regioselective and enantioselective copper-catalyzed 1,4-conjugate addition of Grignard reagents to linear α,β,γ,δ-unsaturated ketones was developed. The 1,4-addition products were obtained regioselectively in high yields with up to 98% ee.

Enantioselective 1,6‐Conjugate Addition of Dialkylzinc Reagents to Acyclic Dienones Catalyzed by Cu‐DiPPAM Complex—Extension to Asymmetric Sequential 1,6/1,4‐Conjugate Addition

“…The ee obtained with 1 m appears attractive, since it surpasses that obtained by Zhang in the Cu/L1catalyzed addition of EtMgBr. [10] These results show the particular efficiency of DiPPAM to orient the ACA of diethylzinc to linear aryldienones in favor of the 1,6-adduct.…”

“…[8] Furthermore, Zhang reported recently a highly 1,4-selective and enantioselective addition of Grignard reagents to linear dienones bearing two aromatic substituents, catalyzed by a Cu/ferrocene-based phosphinooxazoline L1 (Figure 1). [10] Finally, it must be noted that only one example of Cu-catalyzed enantioselective 1,6-addition of dialkylzinc reagents to linear dienones has been reported, but gave a poor enantiocontrol. [5a] We report herein an unprecedented Cu-catalyzed highly regio-and enantio-selective sequential 1,6/1,4-conjugate addition of dialkylzinc to linear dienones.…”

Regio‐ and Enantioselective Copper‐Catalyzed 1,4‐Conjugate Addition of Trimethylaluminium to Linear α,β,γ,δ‐Unsaturated Alkyl Ketones

“…However, only three examples of copper‐catalyzed 1,4‐ACA reactions have been reported by Alexakis, and our group . These methodologies utilized linear nitrodienes and nitroenynes, α,β,γ,δ‐unsaturated cyclic enones and linear α,β,γ,δ‐unsaturated aryl ketones, all of which rely on specific structural features of the substrates.…”

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

“…In 2013, Xie, Zhang and co-workers investigated the reactivity of extended unsaturated linear ketones in the presence of Grignard reagents, with the aim of selectively forming the 1,4-ACA adducts [ 38 ]. Various ligands were tested and the best catalytic performance was achieved using bidentate ferrocene-based ligand L14 in combination with tetrakis(acetonitrile)copper(I) perchlorate as the copper source.…”