Domino Addition/Cycloisomerization Reactions of 2-Alkynyl-Arylaldehydes: Silver Catalyzed Synthesis of 1,3-Dicarbo-Substituted Isochromenes

One of the most efficient methods for the construction of 1-substituted isochromenes (and related heteroaryl compounds) is the metal catalyzed regioselective domino cycloisomerization/nucleophilic addition reaction of a 2-alkynyl(hetero)arylaldehyde in the presence of a suitable nucleophile.(1) The reaction with oxygen nucleophiles is the probably the most studied one. Several metal catalyst have been used, and our group recently gave a contribution in the field of silver catalyzed(2) synthesis of 1-alkoxyisochromenes.(3) Conversely, the reaction with carbon nucleophiles, and in particular with enolizable carbonyl compounds, is relatively less investigated.(4) We report here our recent results regarding the silver catalyzed synthesis of 1,3-dicarbo-substituted isochromene derivatives starting from 2-alkynyl(hetero)arylaldehydes and enolizable carbonyl compounds.(5) The reaction proceeded in a cascade fashion under mild reaction conditions with absolute regioselectivity and moderate-to-good yields. In some cases, the reaction produced unexpected diastereoisomeric couple of homodimeric products. The divergent formation of the 1-carbosubstituted isochromenes and the alternative homodimeric products has been tentatively explained by some experiments and two conceivable competitive paths have been proposed.