Zn(OTf)₂-Catalyzed Formal [3 + 3] Cascade Annulation of Propargylic Alcohols with 2-Aminochromones: Accessing the Chromeno[2,3-b]pyridines

Abstract

A Zn­(OTf)2-catalyzed formal [3 + 3] cascade annulation strategy for the synthesis of functionalized chromeno­[2,3-b]­pyridines has been developed using propargylic alcohols and 2-aminochromones as the substrates. The protocol provides a convenient and atom-economical method of accessing a broad range of chromeno­[2,3-b]­pyridine derivatives in excellent yields with good functional-group tolerance. The method is also effective on the gram scale, which highlights the inherent practicality of this synthetic transformation.

Acid‐Promoted Cascade Reaction of 4H‐Chromenes: Access to Hexahydronapthalenes via Decarboxylative Intramolecular Cyclization

“…Initially, 2‐amino‐7,7‐dimethyl‐5‐oxo‐4‐phenyl‐5,6,7,8‐tetrahydro‐4 H ‐chromene‐3‐carbonitrile, [,14a] ( 1 , 1.0 equiv) was reacted with 1,1,3‐triphenylprop‐2‐yn‐1‐ol [17] ( 2 , 1.0 equiv) in presence of Zn(OTf) 2 (0.05 equiv) in 1,2‐dichloroethane at ambient temperature for 8 h as per the reported method [18] anticipating the formation of 3 . However, products 4 , 5 , 6 in the ratio of 46 %, 20 % and 30 % yields were observed (Scheme 2).…”

Recent approaches for the synthesis of pyridines and (iso)quinolines using propargylic Alcohols

“…The research group of Li reported a Zn(OTf) 2 -catalyzed [3 + 3] annulation strategy for the synthesis of functionalized chromeno[2,3- b ]pyridine scaffolds, which are part of many pharmacologically active molecules. 31 They employed 2-aminochromones 55 and propargyl alcohols 56 as reaction partners (Scheme 11A). The product 57 structure was confirmed by X-ray diffraction analysis of one of the products.…”

Acid-catalyzed chemoselective C- and O- prenylation of cyclic 1,3-diketones

“…Owing to its atom-and step-economy, the [3+3] annulation of 1,3-cyclohexanedione with unsaturated precursors represents a more convenient and straightforward strategy. In the presence of acids or water, α,β-unsaturated aldehydes [11][12][13][14][15] and propargylic alcohols [16][17][18][19][20][21] are suitable coupling partners in this process. Despite these advances, exploiting new [3+3] annulation reactions to access 5-chromenone frameworks from other easily accessible and low-cost chemicals is still in high demand.…”