2H-Chromenes are present in numerous natural products and medicinally important agents. While racemic approaches to construct this structural motif are well documented, a paucity exists in the literature for the synthesis of 2H-chromenes in their enantiopure form. We present an enantioselective Pd-catalyzed 6-endo-trig reaction to generate 2-aryl chromenes. A novel monodentate phosphoramidite ligand – identified through a systematic optimization of a TADDOL-derived ligand set – enabled the synthesis of a wide range of 2-aryl-2H-chromenes with high yield and enantioselectivity under mild conditions. To illustrate the utility of this new methodology, the products obtained from this reaction were transformed into two bioactive flavonoids (namely, catechin and hydroxyflavanone) through functionalization of the benzopyran olefin. A proposed mechanism involving the generation of an achiral o-quinone methide intermediate will also be presented.

Catalytic enantioselective synthesis of 2-aryl chromenes

249th National Meeting (2015)

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