Enantioselective Synthesis of Chromanones through Organocatalytic Tandem Reactions

Abstract

An enantioselective approach to lactonefused chromanone derivatives from 1-(2-hydroxyaryl)-1,3-diketones and α,β-unsaturated aldehydes under mild conditions has been developed, which included organocatalytic stepwise Michael addition/ cycloketalization/hemiacetalization and followed by oxidation reaction. In the presence of chiral amine organocatalyst and an additional salicylic acid, a wide range of 1-(2-hydroxyaryl)-1,3-diketones and α,β-unsaturated aldehydes were tolerated, furnishing a spectrum of lactone-fused tricyclic chromanones bearing three contiguous stereocenters in high yields with good to excellent selectivities (90-> 99% ee, > 19:1 d.r.).

Strategies and Methods for the Catalytic Asymmetric Synthesis of Benzofuran/Benzopyran Fused Acetals: A Review

“…Notably, our group independently reported very similar results around the same time [50] . In general, the substituents on the 1,3‐diketones 55 and α,β‐unsaturated aldehydes 48 had a limited effect on the enantioselectivity, and high ee values were obtained in most of cases (Scheme 30, up to 99% ee and>19:1 dr.).…”

“…[49] Furthermore, the desired ketals were oxidized with PCC to the corresponding chromanone derivatives 60 in excellent yields and enantioselectiv- Notably, our group independently reported very similar results around the same time. [50] In general, the substituents on the 1,3-diketones 55 and α,β-unsaturated aldehydes 48 had a limited effect on the enantioselectivity, and high ee values were obtained in most of cases (Scheme 30, up to 99% ee and > 19:1 dr.). Several transformations proceeded smoothly to afford more versatile chiral chromenone derivatives.…”

Access to Chiral Chromenones through Organocatalyzed Mannich/Annulation Sequence

“…Recently, we and Chen’s group introduced 1-(2-hydroxyaryl)-1,3-diketones as a class of efficient reaction partners for asymmetric tandem reactions with α,β-unsaturated aldehydes to synthesize tricyclic chromanone derivatives . With our great interest in developing facile methodologies to access biologically active compounds, we wish to report an asymmetric organocatalyzed approach by using 1-(2-hydroxyaryl)-1,3-diketones for the formation of chiral chromenones under mild reaction conditions.…”