KOtBu‐Mediated Regioselective Hydroxymethylation of Thiazoles and Benzothiazoles: Synthesis of Biologically Active Heteroaromatic Compounds

Abstract

AbstractWe present a transition metal‐free direct C‐2 hydroxymethylation of thiazoles using ketones in the presence of KOtBu, leading to the synthesis of thiazole‐2‐diarylcarbinols. The regioselective deprotonation promotes the Csp2−Csp3 bond formation, resulting in the creation of a quaternary centre. The method offers a complementary strategy to traditional cross‐coupling technologies utilizing azole halides and organometallic reagents, thereby expanding the substrate scope. Furthermore, benzothiazoles exhibit compatibility under the mild reaction conditions. Moreover, this method enables the synthesis of thiazolyl diarylcarbinols and bioactive compounds on a multigram scale.