Site‐Selective Cu‐Catalyzed Alkylation of α‐Amino Acids and Peptides toward the Assembly of Quaternary Centers

Abstract

The Cu I -catalyzed selective a-alkylation of a-aminoa cid and peptided erivatives with 2-alkyl-1,3-dioxolanes is reported.T his oxidative coupling is distinguished by its site-specificity, high diastereoselectivity,a nd chirality preservation and exhibits absolute chemoselectivity for N-aryl glycine motifs over other amino acid units.C ollectively,t he methoda llows for the assembly of challenging quaternary centers, as well as compounds derived from natural products of high structuralc omplexity,w hich may provide ample opportunities for late-stage functionalization of peptides.Scheme1.CDCs with ethers and a-amino acid derivatives.[a] M.

Radical‐Mediated C−H Alkylation of Glycine Derivatives: A Straightforward Strategy for Diverse α‐Unnatural Amino Acids

“…Afterward TBHP as an oxidizing agent (Scheme 4). [20][21][22] The mechanism of the Cu-catalyzed reaction commenced with the dissociation of TBHP to generate the t BuO radical species and a Cu(II) intermediate. The t BuO radical then abstracted the hydrogen atom from glycine derivative 7 to furnish α-alkyl radical 10.…”

“…described a novel approach for the α ‐alkylation of glycine derivatives with 1,3‐dioxolanes under Cu‐ and Co‐catalysis respectively, by using TBHP as an oxidizing agent (Scheme 4). [20–22] The mechanism of the Cu‐catalyzed reaction commenced with the dissociation of…”

Advances in C(sp3)–H Bond Functionalization via Radical Processes

“…The reaction is promoted by the photochemical activity of an electron donor-acceptor (EDA) Similarly, Correa and San Segundo reported the selective -alkylation of -amino acids with 2-alkyl-1,3-dioxolanes catalyzed by Cu(I) (Scheme 66). 63 This oxidative coupling features regioselectivity, high diastereoselectivity, and chirality preservation, and exhibits absolute chemoselectivity.…”

Molecular Oxygen-Mediated Radical Alkylation of C(sp3)–H Bonds with Boronic Acids

“…For instance, Xu and co-workers developed a visible-light-driven decarboxylative alkylation of glycine and peptide in 2018 . Peroxide-mediated double C­(sp 3 )–H bond functionalization was also accomplished by Yu and Correa . Very recently, Wang et al achieved C­(sp 3 )–H bond alkylation utilizing peroxide as the alkyl radical source .…”