Remote Functionalization of 4‐(Alk‐1‐en‐1‐yl)‐3‐Cyanocoumarins via the Asymmetric Organocatalytic 1,6‐Addition

Abstract

An organocatalytic 1,6‐addition using 4‐(alk‐1‐en‐1‐yl)‐3‐cyanocoumarins as acceptors has been developed. Dienolates derived from 5‐substituted‐furan‐2(3H)‐ones have been employed as pronucleophiles, therefore, enabling the synthesis of hybrid molecules bearing two biologically relevant units. Appropriate design of substrates and the application of quinine‐derived catalyst resulted in very good site‐selectivity as well as chemical and stereochemical efficiency of the process.

Asymmetric Organocatalysis in the Remote (3 + 2)-Cycloaddition to 4-(Alk-1-en-1-yl)-3-cyanocoumarins

“…The pyrrolidine derivatives are widely distributed in alkaloids isolated from plant extracts or microorganisms that exhibit a broad spectrum of various biological properties, including anticancer, antimicrobial, antioxidant, antihyperglycemic, antifungal, or anti-inflammatory activities (Scheme ). In recent years, stereocontrolled organocatalytic approaches for the preparation of both coumarin and pyrrolidine derivatives have gained increased importance …”

“…In recent years, stereocontrolled organocatalytic approaches for the preparation of both coumarin and pyrrolidine derivatives have gained increased importance. 11 …”

Organocatalytic Asymmetric Approach to γ,δ-Functionalization of 3-Cyano-4-styrylcoumarins via Bifunctional Catalysis

“…Moreover, Wang and Chen established an efficient NHC-catalyzed oxidative γ,δ-functionalization leading to the chiral derivatives containing a cyclohexanone unit . Very recently, we have demonstrated that 3-cyano-4-styrylcoumarins readily participate in the doubly vinylogous 1,6-addition with dienolates derived from 5-substituted-furan-2­(3 H )-ones . Despite these achievements, the remote transformations of this class of compounds remain limited.…”

“…To the best of our knowledge, the reaction between coumarins 1 and 2-mercaptocarbonyl compounds 2 promoted by a modified cinchona alkaloid catalyst has never been achieved. As part of our continuing efforts on organocatalytic asymmetric construction of polycyclic frameworks containing δ-lactone and coumarin motifs, , a new approach for the remote γ,δ-functionalization of 1 based on a stereocontrolled cascade involving thia -Michael/aldol/annulation reactions was devised (Scheme , bottom). As a consequence, the unique polycyclic chiral products 3 containing coumarin, 2 H -pyran-2-imine and tetrahydrothiophene units were obtained.…”

“… 11 Very recently, we have demonstrated that 3-cyano-4-styrylcoumarins readily participate in the doubly vinylogous 1,6-addition with dienolates derived from 5-substituted-furan-2(3 H )-ones. 12 Despite these achievements, the remote transformations of this class of compounds remain limited.…”