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.