Enantioselective Copper‐Catalyzed Propargylic Etherification of Propargylic Esters with Phenols Promoted by Inorganic Base Additives

Abstract

An enantioselective copper-catalyzed propargylic etherification of botha romatic anda liphatic propargylic esters with phenols hasb een developed, in which the employment of inorganic base additives,i np articularc esium carbonate (Cs 2 CO 3 ), was found to significantly promote not only the reactivity but also the enantioselectivity of the reaction. By using as tructurally hindered chiral ketimine P, N,N-ligand, aw ide range of optically active propargylic ethers were prepared in high yields and with excellent enantioselectivities (up to 98% ee).

Using Ligand-Accelerated Catalysis to Repurpose Fluorogenic Reactions for Platinum or Copper

“…Figure b indicates that electron-rich phosphines are superior to electron-deficient phosphines possibly because electron-rich phosphine can facilitate the cleavage of the propargylic C–O bond when Cu-2 is converted to Cu-3 . Unlike other copper-catalyzed propargylation methods performed in aprotic solvents, − polydentate ligands did not accelerate the reaction in water in this study. Therefore, the copper-catalyzed propargylic C–O bond cleavage in water requires different ligand design principles.…”

“…This phosphine did not render other metals, including palladium, reactive toward PPE. Copper-catalyzed propargylic C–O bond cleavage has been known in synthetic chemistry, but the ligands were mostly amines or amine–phosphine hybrids and were designed for stereoselectivity. − Additionally, fluorescent probes for copper ions are primarily based on sulfides and amines as the binding motifs. − The reaction of copper with PPE in the presence of phosphines 2 , 15 , 18 , and 34 resulted in a fluorescence increase of 2-fold or more (Table S2). It appears that electron-rich phosphines were more effective.…”

Scope and advances in the catalytic propargylic substitution reaction

“…In search of an alternate catalytic system with broad substrate scope, Hu and co-workers in the year 2016 developed an efficient and highly enantioselective copper-catalyzed propargylic etherication of both aliphatic and aromatic propargylic esters with phenols 174 as oxygen nucleophiles, Scheme 77. 106 Addition of Cs 2 CO 3 was found to signicantly promote the reaction rate as well as enhance the enantioselectivity of the reaction. With the use of structurally rigid tridentate ketimine P,N,N-ligand 138 variety of aryl propargylic ethers 175 could be prepared in good to high yields and excellent enantioselectivities.…”

“…In search of an alternate catalytic system with broad substrate scope, Hu and co-workers in the year 2016 developed an efficient and highly enantioselective copper-catalyzed propargylic etherification of both aliphatic and aromatic propargylic esters with phenols 174 as oxygen nucleophiles, Scheme 77 . 106 …”

Cu-Catalyzed Chemodivergent, Stereoselective Propargylic Dearomatization and Etherification of 2-Naphthols

“…In this context, naphthol derivatives are anticipated to be valuable substrates because the resulting naphthalenone frameworks are present as the basic skeleton in various biologically active natural products and therapeutic reagents . Dearomatization reactions of phenols/naphthols are relatively less explored compared with those of other electron-rich arenes like indoles because of the competitive O -alkylation (ether formation) and the Friedel–Crafts (alkylation) reaction pathways. Therefore, it is very challenging to develop efficient methods for the dearomatization reaction of naphthols with high levels of chemoselectivity and stereoselectivity.…”