Catalytic Regioselective Alkylation of Oxindoles Using diaryl Secondary Alcohols under Homogeneous Conditions

Abstract

A homogeneous DABCO(TfOH)₂-catalyzed protocol has been developed for the regioselective alkylation of 2-oxindoles using secondary alcohols under mild conditions. The transformation proceeds efficiently in HFIP through effective activation of the alcohol substrate, enabling direct C–C and C–N bond formation without the requirement of metal catalysts. A broad range of substituted secondary alcohols and oxindole derivatives were well tolerated, affording the corresponding alkylated products in good to excellent yields. Notably, the methodology enables selective functionalization at the nitrogen and C5 positions of the oxindole framework. In addition, control experiments were carried out to gain insight into the reaction pathway and regioselectivity of the transformation. This operationally simple and efficient protocol provides a practical approach for the synthesis of structurally diverse functionalized oxindole derivatives.