Acid‐Catalyzed Regiodivergent Annulation of 4‐Hydroxycoumarins with Isoprene: Entry to Pyranocoumarins and Pyranochromones

Abstract

An acid‐catalyzed regiodivergent formal [3+3] annulation of 4‐hydroxycoumarins with isoprene is developed. A variety of pyranocoumarins were obtained exclusively in the presence of strong Brønsted acid, while varying to Lewis acid delivered pyranochromones as main products. The protocol also features high atom‐economy, wide substrate scope, easy scale‐up, and good applications in natural product synthesis.

Isoprene: A Promising Coupling Partner in C–H Functionalizations

“…25 In this context, an acidcatalyzed regiodivergent annulation of 4-hydroxycoumarin with isoprene was developed by our group, which provides an atom-economical protocol for the assembly of dimethylpyran skeletons (Scheme 6). 26 The utilization of strong Brønsted acid 2,4-(NO 2 ) 2 C 6 H 3 SO 3 H as catalyst exclusively delivered pyranocoumarins 12, whereas pyranochromones 13 turned out to be predominant in the presence of Lewis acid Sm(OTf) 3 . Both electron-deficient (12b, 13b) and elec-tron-rich (12c, 13c) 4-hydroxycoumarins were applicable to both catalytic systems.…”

Six-membered ring systems: with O and/or S atoms

“…Regiodivergent annulation reactions of 4-hydroxycoumarins with isoprene were promoted by different acids: Brønsted acid [2,4-(NO 2 ) 2 C 6 H 3 SO 3 H] in 1,4-dioxane leads to coumarino[4,3-b]dihydropyrans, while in the presence of Lewis acid Sm(OTf) 3 in 1,2-dichloroethane (DCE), several chromen-4-ono[2,3-b]dihydropyrans are obtained (19EJO6510). High yields of 4-alkyl/4-aryl-2-alkylidene pyrazolo[5,4b]dihydropyrans are produced from annulation reactions of alkylidene/arylidene pyrazolones with allenoates mediated by 4-dimethylaminopyridine (DMAP) in dichloromethane (Scheme 6) (19T3609) and by a quinidine catalyst in toluene (19TL703).…”

Organocatalytic formal [3 + 3] cyclization of α-(6-indolyl) propargylic alcohols

“…As a privileged class of core frameworks, pyranocoumarins are widely distributed in bioactive natural products and drugs such as ferprenin, bothrioclinin and nor-bothrioclinin (Scheme 1A). 1 Accordingly, many synthetic strategies have been developed based on the reaction of 4-hydroxycoumarins with diverse electrophiles such as α,β-unsaturated carbonyl compounds, 2 alkenes, 3 nitroalkenes, 4 MBH acetates, 5 and so on. 6 Moreover, C3-alkylation of 4-hydroxycoumarins with propargyl alcohols followed by intramolecular annulation has been developed towards pyranocoumarin-related products.…”