Asymmetric desymmetrization of 2,5-cyclohexadienones initiated by organocatalytic conjugate addition to 4-nitro-5-styrylisoxazoles

Abstract

A highly regio-, enantio- and diastereo-selective strategy involving initial enantioselective conjugate addition to 4-nitro-5-styrylisoxazoles serves as a key step for the desymmetrization of 2,5-cyclohexadienones has been disclosed. We have designed a new class of 2,5-cyclohexadienones appended with 4-nitro-5-styrylisoxazoles to undergo organocatalytic asymmetric double or triple conjugate addition in a domino sequence depending on the substrate type leading to desymmetrization of the 2,5-cyclohexadienone core. The developed protocol allows the construction of a valuable hydrophenanthrene core or a unique bridged scaffold bearing multiple chiral centers with excellent enantio- (up to >99.5 : 0.5 er) and diastereo-control for diverse substrates.