Isochroman-3,4-dione and Tandem Aerobic Oxidation of 4‑Bromoisochroman-3-one in the Highly Regio- and Diastereoselective Diels–Alder Reaction for the Construction of Bridged Polycyclic Lactones

Herein we report two processes facilitated by diisopropylethylamine (DIPEA) for the synthesis of novel bridged polycyclic molecule analogues to natural products. The use of 4-bromoisochroman-3-one initiated an autoxidation reaction, followed by a Diels–Alder cycloaddition in the presence of electron-deficient dienophiles. Mechanistic studies revealed isochromane-3,4-dione as a key intermediate, which undergoes in situ dienolization/dearomatization followed by a [4 + 2] cycloaddition. Subsequently, the synthesis and direct application of isochromane-3,4-diones in the Diels–Alder reaction enabled the development of an alternative method with an enhanced efficiency and improved atom economy. In addition to chalcones, other enones and common electron-poor alkenes, bearing ester, nitro and cyano electron-withdrawing groups (including both terminal, cis acyclic and cyclic alkenes), were successfully reacted. The mechanism was also investigated, and a subsequent reductive ring opening was successfully carried out.