Synthesis of 3,4-Dihydroisoquinolin-1-ones from N-Boc-(β-Arylethyl)-carbamates via Isocyanate Intermediates

Mild reaction conditions for the regioselective synthesis of isoquinolin-1-ones and related fused-ring heterocycles from N-Boc-protected (beta-arylethyl) carbamates are described. The reactions involved the use of Tf2O and 2-chloropyridine and isocyanates are likely to be key intermediates. The method was extended to substrates bearing less nucleophilic aryl moieties by using Lewis acid additives, such as BF3 center dot Et2O, to enhance the Friedel-Crafts-type cyclization of the isocyanate intermediates. This method allowed the synthesis of various substituted isoquinolin-1-ones, beta-carbolines, thiophene-fused ring systems and tetrahydrobenzoazepin-1-ones in good yields and with high regioselectivities.