A Five-Step Synthesis of (<i>S</i>)-Macrostomine from (<i>S</i>)-Nicotine

A concise synthesis of (<i>S</i>)-macrostomine has been accomplished in five steps from natural nicotine in 19% overall yield via a pyridyne Diels−Alder cycloaddition reaction as the key step. A Kumada cross-coupling reaction on a 1-chloroisoquinoline intermediate provided the natural product.