Direct Alkylation of Quinolines with Organolithium-Activated 1,1-Diborylalkanes

Abstract

We report a regioselective alkylation of quinolines enabled by activation of 1,1-diborylalkanes with organolithiums. Direct C2-alkylation occurs in THF with tert-butyllithium, whereas C4-alkylation of C2-substituted quinolines proceeds in toluene with phenyllithium. The regioselectivity arises from solvent-dependent lithium aggregation and substrate blocking of the C2-position. This protocol features a broad substrate scope and offers an alternative to multi-step alkylation sequences.