Abstract
Several 4‐azaphthalides (=furo[3,4‐b]pyridin‐5(7__H__)‐ones) and 5‐azaisocoumarins (=5__H__‐pyrano[4,3‐b]pyridin‐5‐ones) were prepared through a tandem heterogeneous Pd/C‐mediated Sonogashira coupling and a 5‐exo‐dig or 6‐endo‐dig intramolecular cyclization of 2‐bromonicotinic acid (=2‐bromopyridine‐3‐carboxyclic acid) with various ethynylarenes or 3‐ethynylthiophene. In the presence of Pd/CPh~3~PCuI and Et~3~N in dry dioxane under Ar at 90°, a mixture of 4‐azaphthalides (usually the major product) and 5‐azaisocoumarins was obtained after 3.5 h under normal heating (Schemes 3 and 4; Tables 1 and 2). This mixture of compounds was also obtained with the same catalytic system under microwave (MW) irradiation in only 25 min (Tables 3 and 4). The 1‐ethynyl‐3‐methoxybenzene gave on heating only the corresponding 4‐azaphthalide (Table 2), while under MW irradiation, both the 5‐exo‐dig and the 6‐endo‐dig products were obtained (Table 4). For the 3‐ethynylthiophene, the regioselectivity for the corresponding 4‐azaphthalide was achieved with both methods (Tables 2 and 4). Although the yields and the regioselectivity of the reaction generally remained the same with both methods, the use of MW allowed us to obtain the corresponding products in a shorter reaction time. From 4‐ethynyl‐N,N‐dimethylaniline (=4‐ethynyl‐N,N‐dimethylbenzenamine), the corresponding 4‐azaphthalide and 5‐isocoumarin were only obtained under MW irradiation (Tables 2 and 4). To the best of our knowledge, it is the first time that this kind of tandem reaction was applied to a pyridine derivative giving the corresponding 4‐azaphthalides and 5‐azaisocoumarins which are easily separated and may both show biological activity.