Microwave (MW) heating is more effective than conventional (CONV) heating for promoting a high-temperature oxidative cycloisomerization reaction that was previously reported as a key step in a total synthesis of the natural product illudinine. The thermal reaction pathway as envisioned is an inverse electron-demand dehydro-Diels-Alder reaction with in situ oxidation to generate a substituted isoquinoline, which itself is unstable to the reaction conditions. Observed reaction yields were higher at a measured bulk temperature of 200 °C than at 180 °C or 220 °C; at 24 hours than at earlier or later time points; and when the reaction solution was heated using MW energy as opposed to CONV heating with a metal heat block. Selective MW heating of polar solute aggregates is postulated to explain these observations.