BF ⋅Et O-Catalyzed Selective C-4 Alkylation of Isoquinolin-1(2H)-ones Employing p-Quinone Methides.

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.