Synthesis of Triazolo Isoquinolines and Isochromenes from 2-Alkynylbenzaldehyde via Domino Reactions under Transition-Metal-Free Conditions

Abstract

We describe two simple straightforward syntheses of triazolo isoquinolines (3) and isochromenes (7) from 2-alkynylbenzaldehydes (1) as a common synthon. The synthetic strategy for 3 involves formation of the (E)-1-(2-nitrovinyl)-2-(alkynyl)benzene species 2 via condensation of synthon 1 with nitromethane followed by a [3 + 2] cycloaddition/extrusion of the nitro group/regioselective 6-endo cyclization domino sequence. In yet another strategy, the synthon 1 was condensed with nitromethane followed by electrophilic iodo cyclization of the resulting 2-nitro-1-(2-(alkynyl)phenyl)ethanol (6) to furnish iodo isochromene derivatives. The salient feature of the above two strategies involves formation of the corresponding heterocycles under metal-free conditions in good yields.