Distinctive Features of 3-Acetyl- and 3-Benzoyl-Isocoumarins' Interaction with Active Primary Amines

Isoquinolones and isoquinolines are crucial natural and synthetic heterocyclic compounds exhibiting a range of biological activities. A less explored strategy for the recyclization of isocoumarins to isoquinolones involves the transformation of 1H-isochromen-1-ones with a carbonyl group at position 3 using primary amines. This study presents a straightforward one-pot protocol for the recyclization of 3-acetyl- and 3-benzoylisocoumarins into their corresponding isoquinolone derivatives using structurally diverse primary amines. This provides versatile and scalable routes for accessing a variety of 2-R-isoquinolin-1(2H)-ones. Interestingly, the acyl group also reacted with the hydroxyl group of 2-aminoethanol, leading to the simultaneous formation of 3,4-dihydro[1,4]oxazino[4,3-b]isoquinolin-6(1H)-ones alongside lactone recyclization. Moreover, the recyclization process was accompanied by more complex alternative cyclizations, including an oxidative-reductive stage. For instance, the recyclization of isocoumarins with benzylamine resulted in the formation of isochromeno[3,4-c]pyrroles, whereas with glycine derivatives, 1,2-dihydro-6H-pyrazino[1,2-b]isoquinolin-3,6(4H)-diones were obtained.