Diels–Alder Reaction of Photochemically Generated (E)‑Cyclohept-2-enones: Diene Scope, Reaction Pathway, and Synthetic Application

Upon irradiation at λ = 350 nm, cyclohept-2-enone undergoes an isomerization to the strained (E)-isomer. The process was studied by XMS-CASPT2 calculations and found to proceed by two competitive reaction channels on either the singlet or the triplet hypersurface. (E)-Cyclohept-2-enone is a reactive dienophile in thermal [4 + 2] cycloaddition reactions with various dienes. Ten different dienes were probed, most of whichexcept for 1,3-cyclohexadieneunderwent a clean Diels–Alder reaction and gave the respective trans-fused six-membered rings in good yields (68–98%). The reactions with furan were studied in detail, both experimentally and by DLPNO–CCSD­(T) calculations. Two diastereoisomers were formed in a ratio of 63/35 with the exo-product prevailing, and the configuration of both diastereoisomers was corroborated by single crystal X-ray crystallography. The outcome of the photoinduced Diels–Alder reaction matched both qualitatively and quantitatively the calculated reaction pathway. Apart from cyclohept-2-enone, five additional cyclic hept-2-enones and cyclooct-2-enone were employed in their (E)-form as dienophiles in the Diels–Alder reaction with 1,3-cyclopentadiene (80–98% yield). The method was eventually applied to a concise total synthesis of racemic trans-α-himachalene (four steps, 14% overall yield).