Enantioselective Intermolecular Mannich-Type Interception of Phenolic Oxonium Ylide for the Direct Assembly of Chiral 2,2-Disubstituted Dihydrobenzofurans

An enantioselective intermolecular Mannich-type interception of phenolic oxonium ylides with imines has been developed. The cooperative catalysis with achiral dirhodium complex and chiral phosphoric acid has been introduced to circumvent the competitive phenolic O-H bond insertion via dual H-bonding, enabling the synthesis of enantioenriched 2,2-disubstituted dihydrobenzofurans with good to high yield and high to excellent enantioselectivity under mild conditions. Preliminary antitumor activity study of these generated products indicated that the reduction product 7 exhibits high anticancer potency against human lung adenocarcinoma cells (A549 cells, IC50 = 9.13 mu M).

Automated summary

An enantioselective intermolecular Mannich-type interception of phenolic oxonium ylides with imines has been developed using cooperative catalysis with achiral dirhodium complex and chiral phosphoric acid. The synthesis of enantioenriched 2,2-disubstituted dihydrobenzofurans with good to high yield and high to excellent enantioselectivity under mild conditions was achieved. Preliminary antitumor activity study showed high anticancer potency of the reduction product 7 against human lung adenocarcinoma cells (A549 cells, IC50 = 9.13 mu M).