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 (β‐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·Et2O, to enhance the Friedel–Crafts‐type cyclization of the isocyanate intermediates. This method allowed the synthesis of various substituted isoquinolin‐1‐ones, β‐carbolines, thiophene‐fused ring systems and tetrahydrobenzoazepin‐1‐ones in good yields and with high regioselectivities. Isoquinolin‐1‐ones and related fused‐ring heterocycles have been prepared from N‐Boc‐protected (β‐arylethyl)carbamates. The N‐Boc‐carbamates were first converted into isocyanates by using the reagents Tf2O and 2‐chloropyridine. These isocyanates were then subjected to in situ intramolecular Friedel–Crafts‐type reaction to give the products in good yields and with high regioselectivities.