Palladium/Acid Relay Catalyzed Tandem Heck Coupling/6‐Endo Cyclization between ortho‐Halogenated Benzoates and Unactivated Terminal Alkenes for the Synthesis of 1‐Isochromanones

Abstract

We report a unique and expeditious route to synthesize 1-isochromanone derivatives through palladium catalyzed tandem Heck coupling/6-endo hydroacyloxylation cyclization between readily available ortho-halogenated benzoates and unactivated alkenes. Various 2-bromo or 2-iodo benzoates can be coupled efficiently with a broad range of alkenes to afford functionalized 1isochromanones in high yields. Significantly, this cost-efficient and easy-to-handle synthetic methodology will have great prospect application in the synthetic and medicinal chemistry.

HFIP in Organic Synthesis

“… A range of electron-deficient alkenes were suitable partners for this reaction. Complementary access to six-membered 1-isochromanone derivatives via a palladium/acid relay-catalyzed tandem Heck coupling/6- endo hydroacyloxylation cyclization between ortho -halogenated benzoates and unactivated alkenes was reported in a 1:1 mixture of o- xylene/HFIP . Reaction in o- xylene or HFIP alone and in a 1:1 mixture of dioxane/HFIP was less efficient.…”

Tailor-Made POLITAG-Pd0 Catalyst for the Low-Loading Mizoroki–Heck Reaction in γ-Valerolactone as a Safe Reaction Medium

“…Among the many methods, a palladium-catalyzed cross-coupling Mizoroki–Heck reaction has played a key role since it is widely used in different synthetic areas, i.e., pharmaceuticals, , fine chemicals, and organic semiconductors . Furthermore, slight modification of reaction conditions may also allow a consecutive series of Mizoroki–Heck reactions, − obtaining synthetic advantages in terms of step-economy …”

Palladium-Catalyzed 1,1-Alkynyloxygenation of 2-Vinylbenzoates with Alkynyl Bromides

“…The intermediate IV can be converted to the π-allenylpalladium intermediate V . Cyclization via the intramolecular attack of a carbonyl group on the π-allenyl ligand provides the oxonium intermediate VI . The subsequent nucleophilic dealkylation of VI gives 3 and an alkyl bromide, with the release of Pd(0).…”