A convenient domino Ferrier rearrangement-intramolecular cyclization for the synthesis of novel benzopyran-fused pyranoquinolines

Abstract

The Ferrier rearrangement and the Povarov reaction have proven indispensable tools in carbohydrate chemistry and the synthesis of N-heterocycles, respectively. We hereby report a one-pot cyclization sequence involving the Ferrier and Povarov-like reactions in the synthesis of novel pentacyclic N-heterocycles: benzopyran-fused pyranoquinolines. The reaction entails three component condensation of a glycal with a variety of anilines and 2-hydroxybenzaldehydes under Lewis acid catalysis to yield the title compounds in 4-24 hours of reaction time, in moderate to high yields and excellent diastereoselectivity. Of the Lewis acid catalysts deployed [Sc(OTf)3, Al(OTf)3, Cu(OTf)2, CuOTf, I2, InCl3, and La(OTf)3] in various solvents (acetonitrile, THF, dichloromethane, 1,2-dichloroethane and diethyl ether) at room and elevated temperatures, Sc(OTf)3 (10 mol%) in acetonitrile at 70 °C gave the best results, with excellent diastereoselectivity. CAN-mediated oxidative ring opening of the pentacyclic N-heterocycle gave the corresponding enantiometrically pure chromenoquinoline bearing a pendant sugar moiety.

Progress in the Chemistry of Tetrahydroquinolines

“…Kinfe and co-workers developed an approach for the synthesis of highly substituted pentacyclic N-heterocycles including benzopyran-fused pyranoquinolines 637 consisting of a Ferrier rearrangement and the Povarov reaction domino sequence (Scheme 164). 300 In this transformation, a wide range of arylamines 634 and salicylaldehyde derivatives 635 reacted with glycols 636 in the presence of Sc(OTf) 3 in acetonitrile to deliver the pentacyclic compounds 637.…”

The 15th Frank Warren Organic Chemistry Conference

“…Prof. Dr. Hans‐Günther Schmalz gave an account of his group's work in the development of modular chiral P , P ‐ligands, for the enantioselective synthesis of structurally complex marine natural products . Prof. Henok Kinfe used his keynote lecture to exhibit the utility of glycals in synthetic organic chemistry for the construction of complex bioactive heterocycles, while Prof. Gareth Arnott detailed the potential of inherently chiral calixarenes and his journey toward selective derivatization of these molecules . Several further contributions from Dr. Temitope Olomola, Prof. Jack Mphahele (University of South Africa), Prof. Isaiah Ramaite (University of Venda), Dr. Parvesh Singh (University of KwaZulu‐Natal), and Dr. Mamalosi Selepe (University of Pretoria) described their recent progress in the construction of biologically relevant heterocycles.…”

Scandium(III)‐Triflate‐Catalyzed Multicomponent Reactions for the Synthesis of Nitrogen Heterocycles

“…Lewis‐acid catalyzed Ferrier rearrangement followed by an intramolecular Povarov‐like cyclization was used to synthesize complex pentacyclic nitrogen heterocycles [41] . In this approach, different protected glycals 16 (dienophiles), along with several substituted anilines and salicylaldehydes, were exploited for Povarov‐like MCR catalyzed by 10 mol% of Sc(OTf) 3 in MeCN (Scheme 6).…”