Catalytic enantioselective dearomatization: Dihydrobenzofuran synthesis via α-arylation of aldehydes

ORGN 670

David Kenneth Cox, dkc23@cam.ac.uk and Matthew J. Gaunt, mjg32@cam.ac.uk. Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, United Kingdom
An oxidative dearomatization strategy has been developed to provide the rapid construction of optically active dihydrobenzofurans using organocatalysis. Under oxidizing conditions, para-aminophenols are converted to quinonimines, which may undergo a regioselective 1,4-addition reaction with catalytically generated chiral enamines. Following re-aromatization, the newly formed α-chiral aldehyde undergoes annulation with the phenol, revealing the dihydrobenzofuran core. This work stems from previous work carried out in the Gaunt group, where an intramolecular oxidative dearomatization strategy was used for the enantioselective synthesis of polycyclic structures from substituted phenols. Methods such as this provide mild, enantioselective, ways to form new carbon-carbon bonds between aromatic and aliphatic centres, which are prevalent in many natural products and biologically important molecules. The dihydrobenzofuran core is present in biologically active natural products including (+)-lithospermic acid and calycopterone, and so the rapid construction of this core motif would be a highly useful tool to the synthetic chemical community.