Brønsted Acid-Catalyzed Formal (3+3)-Annulation of Propargylic (Aza)-para-Quinone Methides with 4-Hydroxycoumarins and 1,3-Dicarbonyl Compounds

Abstract

Herein, we describe a highly effective 1,8-conjugateaddition-mediated formal (3+3)-annulation of (aza)-para-quinone methides in situ generated from propargylic alcohols with 4hydroxycoumarins and 1,3-dicarbonyl compounds under the catalysis of a Brønsted acid. This methodology affords efficient and practical access to synthetically important and highly functionalized pyranocoumarins and pyrans in excellent yields under mild conditions. Importantly, these products exhibit impressive inhibitory activity toward α-glucosidase.

Lewis-Acid-Catalyzed (3+2) Annulation of 2-Indolylmethanols with Propargylic Alcohols to Access Cyclopenta[b]indoles

“…However, to the best of our knowledge, no method has been reported for the synthesis of 1,2,3-trisubstituted cyclopenta [b]indoles by formal (3+2) annulation between 2-indolylmethanols and propargylic alcohols. With our continuing research interest in propargylic alcohols [38][39][40][41] and the importance of cyclopenta [b]indoles, herein, we describe a Sc(OTf) 3 -catalyzed (3+2) annulation of 2-indolylmethanols with propargylic alcohols to synthesize cyclopenta[b]indoles (Scheme 1c). Propargylic alcohols have shown promise as feedstocks for the synthesis of carboand heterocyclic compounds.…”

Construction of 4-hydroxycoumarin derivatives with adjacent quaternary and tertiary stereocenters via ternary catalysis

“…In the past few decades, a variety of important advances have made for the construction of dihydropyran-fused coumarin derivatives with commercially available 4-hydroxycoumarin [7][8][9][10][11][12][13] (Scheme 1b). For example, the Shivashankar group developed a Mitsunobu etherication to provide fused pyranobiscoumarin analogues from 1,2-diols at 80 °C.…”

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

“…9 Independently, Zhang et al realized the preparation of pyrano[3,2- c ]chromen-5-ones from an organocatalytic reaction between propargyl alcohols and 4-hydroxycoumarins (Scheme 1D). 10 In the presence of diphenyl phosphoric acid, aza- p -quinone methides were formed in situ from propargylic alcohols, followed by 1,8-conjugate addition of 4-hydroxycoumarins and intramolecular formal (3 + 3)-annulation. Very recently, we achieved a chiral phosphoric acid catalyzed 1,10-addition of alkynyl indole imine methides generated in situ from α-(6-indolyl) propargylic alcohols.…”