BF₃⋅Et₂O‐Catalyzed Selective C‐4 Alkylation of Isoquinolin‐1(2H)‐ones Employing p‐Quinone Methides

Abstract

The direct C‐4 alkylation of isoquinolin‐1(2H)‐one moiety is a challenging transformation in organic synthesis. Here we present a practical and efficient synthesis of C‐4 alkylated isoquinolin‐1(2H)‐ones through conjugate addition of isoquinolin‐1(2H)‐ones to p‐quinone methides for the first time. The process is facilitated by Lewis acid catalysis and this operationally straightforward, mild, metal‐free and one‐pot transformation provides a wide range of C‐4 alkylated isoquinolin‐1(2H)‐ones at ambient temperature in good to excellent yields.