Enantioselective alkylative cross-coupling of unactivated aromatic C-O electrophiles.

ABSTRACT: Nonpolar alkyl moieties, especially methyl group, are frequently used to modify bioactive molecules during lead optimization in medicinal chemistry. Thus transition-metal catalyzed alkylative cross-coupling reactions by using readily available and environmentally benign C-O electrophiles have been established as powerful tools to install alkyl groups, however, the C(sp³)-C(sp²) cross-coupling via asymmetric activation of aromatic C-O bond for the synthesis of alkylated chiral compounds remains elusive. Here, we unlock a C(sp³)-C(sp²) cross-coupling via enantioselective activation of aromatic C-O bond for the efficient synthesis of versatile axially chiral 2-alkyl-2'-hydroxyl-biaryl compounds. By employing a unique chiral N-heterocyclic carbene ligand, this transformation is accomplished via nickel catalysis with good enantiocontrol. Mechanistic studies indicate that bis-ligated nickel complexes might be formed as catalytically active species in the enantioselective alkylative cross-coupling. Moreover, further derivation experiments suggest this developed methodology holds great promise for complex molecule synthesis and asymmetric catalysis.

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC9135759 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature