The pentadehydro-Diels–Alder reaction

In the classic Diels–Alder (DA) [4+2] cycloaddition reaction(1), the overall degree of unsaturation of the 4π (diene) and 2π (dienophile) pairs of reactants dictates the oxidation state of the newly formed six-membered carbocycle. For example, in the classic DA reaction, butadiene and ethylene combine to produce cyclohexene. More recent developments include variants in which the hydrogen atom count in the reactant pair and in the resulting product is reduced by(2), for example, four in the tetradehydro-DA (TDDA) and by six in the hexadehydro-DA (HDDA(3,4,5,6,7)) reactions. Any oxidation state higher than tetradehydro leads to the production of a reactive intermediate that is more highly oxidized than benzene. This significantly increases the power of the overall process because trapping of the benzyne intermediate(8,9) can be used to increase the structural complexity of the final product in a controllable and versatile manner. In this manuscript, we report an unprecedented net 4π+2π cycloaddition reaction that generates a different, highly reactive intermediate known as an α,3-dehydrotoluene. This species is at the same oxidation state as a benzyne. Like benzynes, α,3-dehydrotoluenes can be captured by various trapping agents to produce structurally diverse products that are complementary to those arising from the HDDA process. We call this new cycloisomerization reaction a pentadehydro-Diels–Alder (PDDA) reaction—a nomenclature chosen for chemical taxonomic rather than mechanistic reasons. In addition to alkynes, nitriles (RC≡N), although non-participants in aza-HDDA reactions, readily function as the 2π-component in PDDA cyclizations to produce, via trapping of the α,3-(5-aza)dehydrotoluene intermediates, pyridine-containing products.