ChemInform Abstract: Diethylaminosulfurtrifluoride‐Catalyzed Efficient One‐Pot Three‐Component Aza‐Diels—Alder Reactions: A Facile Synthesis of Substituted Hexahydrofurano[3,2‐c]quinolines.

Abstract

Pyranoand furanoquinoline derivatives are an important class of natural products and exhibit a wide spectrum of biological activities, such as anti-allergic, anti-inflammatory, anti-pyretic, analgesic, antiplatelet, psychotropic and estrogenic activity 1 . Many biologically active alkaloids, such as simulenoline 1, huajiaosimuline 2, zanthodioline 3, flindersine 4, teclealbine 5 and flindersiamine 6, contain pyranoquinoline and furanoquinoline moieties (Figure 1) 1d,1e,2 . The hetero-Diels-Alder reaction is becoming a mainstay for heterocycle and natural product synthesis 3 . The imino Diels-Alder reaction provides easy access to the preparation of pyrano, and furanoquinolines. The imines derived from aromatic amines act as heterodienes and undergo imino DielsAlder reaction with various dienophiles in the presence of acid catalysts 4-6 . Lewis acids (BF3·Et2O, TiCl4, AlCl3, InCl3) are known to catalyze these reactions and replace advantageously Bronsted acids 7–9 . More recently lanthanide triflates (Yb(OTf)3, Sc(OTf)3, GdCl3, etc.) have also been used as catalysts for this reaction 10,11 . The reaction can be carried out in one-pot starting from an aniline, an aldehyde, and an electron-rich alkene, which is known as one pot three-component reactions 12 . However, many of these reactions cannot be carried out in a one-pot operation with a carbonyl compound, amine and enol-ether because the amines and water that exist during imine formation can decompose or deactivate the Lewis acids. Even when the desired reactions proceed, more than stoichiometric amounts of the Lewis acids are required because the acids are trapped by nitrogen 3 . Furthermore, most of the imines are hygroscopic, unstable at high temperatures, and difficult to purify by distillation or column chromatography. Subsequently, one-pot procedures have been developed for this transformation using lanthanide triflates as catalysts 13 . These procedures do not require the isolation of unstable imines prior to the reactions, but metal triflates are strongly acidic and highly expensive, and so the development of other alternatives like ionic liquids would extend the scope of this useful transformation to synthesize functionalized quinoline derivatives. We explore the possibility of using diethylaminosulfur-trifluoride for a targetoriented synthesis of the active diastereomer by enhancement of diastereoselectivity for IED DielsAlder reaction. On the basis of reactivity of the diethylaminosulfurtrifluoride in acetonitrile, several further derivatives of diethylaminosulfur-trifluoride were examined to probe the effect of substituents on the salen backbone, in enhancing the diastereoselectivity of the reaction.