1H-Isoindolynes: Arynes Accessible by a One-Pot, Ambient Temperature, Three-Component Cascade

We describe here a new type of aryne: 1H-isoindolynes. These can be accessed by variants of a process in which a primary propargylic diynol, a propargylic aminodiyne, and an aryne-trapping agent are treated with an oxidizing agent capable of producing, in situ, a 2,4-diynal. This mixture undergoes a room temperature cascade of events involving imine condensation, imine E-to-Z isomerization, hexadehydro-Diels-Alder cycloisomerization, and a final aryne-trapping reaction. This convergent strategy gives isoindolyne adducts in good to excellent yields. Insights into subtle aspects of the mechanism were gained by examining the reaction by ¹H NMR spectroscopy, through control reactions involving isolable iminotriynes, and using density functional theory calculations.