Access to Chiral Chromenones through Organocatalyzed Mannich/Annulation Sequence

Abstract

Herein we report an efficient and practical method to access chiral chromenones bearing one α-amino stereogenic center in the β position of the carbonyl group. The quinine-derived squaramide could efficiently promote Mannich/ cycloketalization/dehydration tandem reactions between 1-(2-hydroxyaryl)-1,3-diketones and functionalized imines generated in situ, providing a wide range of chiral chromenones with propargylamine or α-amino ester moieties with good results (54 examples, up to 98% ee).

Visible-light-enabled cascade cross-dehydrogenative-coupling/cyclization to construct α-chromone substituted α-amino acid derivatives

“…3 Consequently, tremendous efforts have been devoted to constructing various C3-functionalized chromones. 4 Conventional methods for 3-substituted chromones are mainly focused on the transition-metal-catalyzed cross-coupling reactions of halochromones as well as direct C–H functionalization of chromones. 4 b ,5 In recent years, cascade vinyl C–H functionalization and chromone annulation of o -hydroxyphenylenaminones has emerged as a powerful and reliable strategy to synthesize various C3-substituted chromones.…”

Rapid Construction of Tricyclic Furanobenzodihydropyrans by Asymmetric Tandem Reaction

“…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).…”