Coumarins and related structures are commonly found in pharmaceuticals, materials, and natural products. However, catalytic enantioselective synthesis methods for chiral cyclopenta[c]-fused chromenones, which are coumarin derivatives, with high asymmetric induction had not been realized to date.
Xiang-Yu Chen, Dieter Enders, RWTH Aachen University, Germany, and colleagues have developed the first N-heterocyclic carbene (NHC)-catalyzed quadruple-domino reaction for the asymmetric synthesis of cyclopenta[c]chromenones (pictured). The team used a tetracyclic NHC derived from aminoindanol as the catalyst, tetramethylethylenediamine (TMEDA) as the base, diphenoquinone as the oxidant, lithium chloride as a cooperative Lewis acid, and 1,2-dimethoxyethane (DME) as the solvent.
The method tolerates various enals and malonates bearing an ortho-hydroxy phenyl group. The protocol enables the direct organocatalytic assembly of cyclopenta[c]-fused chromenones in good yields and with high enantioselectivities. A subsequent reductive lactone–ester conversion under ring opening allows the preparation of highly functionalized cyclopentanes.
- N-Heterocyclic Carbene Catalyzed Quadruple Domino Reactions: Asymmetric Synthesis of Cyclopenta[c]chromenones,
Qiang Liu, Xiang-Yu Chen, Rakesh Puttreddy, Kari Rissanen, Dieter Enders,
Angew. Chem. Int. Ed. 2018.