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

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