Enantioselective Organocatalytic Synthesis of δ‐Lactone‐Fused 4‐Chromanones

Abstract

An organocatalytic enantioselective synthesis of δ‐lactone‐fused 4‐chromanones was demonstrated using 1‐(2‐hydroxyaryl)‐1,3‐butanedione and α,β‐unsaturated aldehydes in the presence of the Jørgensen‐Hayashi catalyst. The reaction proceeded through a Michael addition/cycloketalization/hemiacetalization sequence, and the resulting hemiacetals were oxidized into the corresponding lactone derivatives in a one‐pot manner. The desired fused O,O‐ketal tricyclic lactone motifs containing three contiguous chiral centers were obtained in excellent chemical yields (up to 97%) and with high stereoselectivities (up to >20:1 dr and up to 95% ee).

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

“…Soon later, Chen et al applied a similar approach in the synthesis of pyrano-annulated benzopyran scaffolds via a Michael addition/cycloketalization/acetalization sequence. [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.).…”

“…Soon later, Chen et al. applied a similar approach in the synthesis of pyrano‐annulated benzopyran scaffolds via a Michael addition/cycloketalization/acetalization sequence [49] . Furthermore, the desired ketals were oxidized with PCC to the corresponding chromanone derivatives 60 in excellent yields and enantioselectivities.…”

Rapid Construction of Tricyclic Furanobenzodihydropyrans by Asymmetric Tandem Reaction

“…With the power of organocatalyzed asymmetric tandem reactions, numerous protocols have been developed for the construction of polycyclic skeletons . In 2021, Chen and our group found the tandem reactions of 1-(2-hydroxyaryl)-1,3-diketones and α,β-unsaturated aldehydes by iminium catalysis could efficiently provide tricyclic chromanone derivatives . As part of our continuous research in the enantioselective synthesis of benzopyran core through organocatalytic tandem reactions, , we envisioned that the asymmetric catalytic Mannich/ketalization/transesterification tandem reaction of β,γ-alkynyl α-imino esters and 1,3-diketones would allow ready access to the tricyclic chromanone-propargylamine derivatives with multiple stereogenic centers (Scheme e).…”