Chiral Tertiary Amine Catalyzed Asymmetric [4 + 2] Cyclization of 3-Aroylcoumarines with 2,3-Butadienoate

Abstract

Coumarins and 2H-pyran derivatives are among the most commonly found structural units in natural products. Therefore, the introduction of 2H-pyran moiety into the coumarin structural unit, i.e., dihydrocoumarin-fused dihydropyranones, is a potentially successful route for the identification of novel bioactive structures, and the synthesis of these structures has attracted continuing research interest. Herein, a chiral tertiary amine catalyzed [4 + 2] cyclization of 3-aroylcoumarines with benzyl 2,3-butadienoate was reported. In the presence of Kumar’s 6’-(4-biphenyl)-β-iso-cinchonine, the desired dihydrocoumarin-fused dihydropyranone products could be obtained in up to 97% yield and 90% ee values.

Syntheses, reactivity, and biological applications of coumarins

“…Zeng et al reported the synthesis of dihydrocoumarin-fused dihydropyranones ( 106 ) via a tertiary amine ( 105 ) catalyzed [4 + 2] cyclization of 3-aroylcoumarines ( 103 ) with benzyl 2,3-butadienoate ( 104 ) ( Scheme 5 — path c ) ( Li et al, 2021 ). Pyran moieties have been incorporated into numerous bioactive compounds, so that the synthesis of such structures attracted considerable interest during the last years.…”

Coumarin and Its Derivatives—Editorial

“…The development of new chemical tools and strategies to obtain different coumarins, and the update of the traditional ones, are a continuous field of research. Chiral tertiary amine catalyzed asymmetric [4 + 2] cyclization of 3-aroylcoumarins with 2,3-butadienoate has been described [20]. Two reviews on the synthetic strategies to obtain coumarin(benzopyrone)fused five-membered aromatic heterocycles built on the α-pyrone moiety, one centered on five-membered aromatic rings with a single heteroatom and the other one with multiple heteroatoms, have also been published [21,22].…”