Synthesis of Isocoumarins

Direct Synthesis of 3‐Aryl Substituted Isocoumarins and Phthalides through Palladium Acetate Catalyzed C(sp2)−H Activation in Ionic Liquids

“…Isocoumarins and 3,4‐dihydroxycoumarins are an important class of molecules that play a crucial role in pharmacology and medicine, with biological properties ranging from anti‐HIV, [1] diuretic and antihypertensive activity [2] to the treatment of lymphatic system disease [3,4] . Furthermore, phyllodulcin, [5] a 3,4‐dihydroxicoumarin derived from flowers of hydrangea serrata and hydrangea macrophylla , is a powerful sweetener used for nearly a thousand years in amatcha tea in Japan. Moreover, they can also exhibit a strong toxicity as the skeleton of isocoumarin is present in ochratoxin compounds, natural molecules possessing neurotoxic, teratogenic, genotoxic, or immunotoxic properties [6] …”

Total Synthesis of (−)-Citreoisocoumarin, (−)-Citreoisocoumarinol, (−)-12-epi-Citreoisocoumarinol, and (−)-Mucorisocoumarins A and B Using a Gold(I)-Catalyzed Cyclization Strategy

“…Isocoumarins (1 H -2-benzopyran-1-ones) are a well-known class of naturally occurring lactones and have attracted the attention of many chemists because of their significant biological properties including antidiabetic, anti-HIV, antibacterial, antiangiogenic, antioxidative, antifungal, anti-inflammatory, and other antimicrobial activities . The isocoumarin (+)-LL-Z1640-6 ( 1 ) was originally isolated from an unidentified fungus, Lederle culture Z1640, along with two other isocoumarins in 1978 .…”

Enantioselective Synthesis of Fused Isocoumarins via Palladium-Catalyzed Annulation of Alkyne-Tethered Malononitriles

“…Ring-fused isocoumarins are commonly encountered as a core in natural products and pharmaceuticals and are widely used as key intermediates for the synthesis of bioimportant molecules . Consequently, numerous synthetic approaches have been established . In 1977, the Mckillop group reported a copper-catalyzed α-arylation of 1,3-cyclohexanedione with 2-bromobenzoic acids followed by intramolecular esterification for the synthesis of fused isocoumarins .…”

“…Intramolecular oxypalladation of alkynoic acid derivatives and sequential addition to electrophiles (e.g., carbonyls, α, β-unsaturated compounds) have been established as a powerful tool to construct condensed oxygen-containing heterocycles . Palladium-catalyzed annulations of ortho -alkynylbenzoates to afford isocoumarin scaffolds were reported by Lu, Li, Jiang, Sridharan, and others . It is worth noting that a cyclization reaction of alkynylbenzoate-tethered carbonyl compounds was elegantly realized by the Lu group for the synthesis of cyclohexane-fused isocoumarins (Scheme a(ii)) .…”