Remote Enantioselective [4 + 1] Annulation with Copper-Vinylvinylidene Intermediates

Abstract

The first copper-catalyzed enantioselective [4 + 1] annulation of yne-allylic esters with 1,3-dicarbonyl compounds was realized through an elegant remote stereocontrol strategy. The very remote ε regioselective nucleophilic substitution was developed by employing a novel chiral copper-vinylvinylidene species from the new C4 synthon yne-allylic esters. Thus, greatly diverse spirocycles were obtained with ample scope and excellent levels of chemo-, regio-, and enantioselectivities. Moreover, detailed mechanistic studies suggest an yne-allylic substitution and Conia-ene cascade pathway on the remote stereochemical induction progress.

Asymmetric Substitution by Alkynyl Copper Driven Dearomatization and Rearomatization

“…As the para-substituents in the PyBox ligands affect the catalytic reactivity and stereocontrol in alkynyl Cu chemistry, [49,57,58] modifications at the para-position of pyridyl skeleton of L2 were performed. When L10 bearing an electron-withdrawing Cl group was used for the substitution, the reactivity for 3 a decreased obviously, presumably due to the lowered Lewis basicity of Cu catalyst that was unfavorable for the donation of d-orbital electron of the metal center for critical dearomatization process (entry 5).…”

Asymmetric copper-catalyzed alkynylallylic dimethylamination

“…Recently, Fang, 32 Xu 33 and our group 34,35 independently demonstrated the concept of Cu-catalyzed remote propargylic substitution reactions. In these studies, an olefin 32–34 or aryl unit 35 was used to link the alkyne unit and the γ-leaving group, and the reactive alkene-tethered or dearomatization-induced Cu-allenylidene intermediate was smoothly formed to induce the expected substitution. In particular, our group 34 and Xu 33 sequentially described the first asymmetric alkynylallylic substitution processes, in which both S N 2′ and in situ substitution models were shown to be feasible to form chiral 1,4-enyne products and spirocycles, respectively.…”

Cu/Ag-Mediated One-Pot Enantioselective Synthesis of Fully Decorated 1,2,3-Triazolo[1,5-a]pyrazines

“…Asymmetric propargylic substitution (APS) has been proved as a powerful approach for the efficient construction of diverse chiral propargylic compounds, and a great deal of effort has been dedicated in recent decades. − Lately, we have developed a practical and efficient catalyst system to realize copper-catalyzed APS efficiently . In continuation of our interest in this field, we envisioned that asymmetric propargylic amination of propargylic esters with propargylamines could form the 1,6-diynes species, which might be possible to be followed by a cascade hydroazidation of the terminal alkynes and intramolecular alkyne–azide cycloaddition in situ to realize one-pot synthesis of 1,2,3-triazolo­[1,5- a ]­pyrazines (Figure c) .…”