A three-component approach to isoquinoline derivatives by cycloaddition/Heck reaction sequence

Here, we report a three-component coupling reaction approach between an aldehyde, an allyloxyamine, and a maleimide toward isoquinoline derivatives. At first, an oxime O-allylic ether, prepared by dehydrative condensation of the aldehyde and the allyloxyamine, was reacted with the maleimide in the presence of a Pd²⁺ species. The cycloadduct obtained was then subjected to the Heck cyclization employing a Pd⁰ species to give thermodynamically stable diastereomer of isoquinoline derivatives selectively in 25-78% yields.