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 μM).