A Practical Asymmetric Synthesis of trans-4,5-Benzhydrindan-1-ones as a Precursor of A-Nor B-Aromatic Steroidal Compounds

The enantio-controlled synthesis of trans-4,5-benzhydrindan-1-ones was achieved by means of a stereoselective [4+2] cycloaddition of o-quinodimethanes generated by a thermal cleavage of benzocyclobutene derivatives as a key step. The chiral substrates of the thermal reaction were synthesized by a diastereoselective Grignard addition to the chiral O-isopropylideneglyceroketones connected to a benzocyclobutene ring, which were simply prepared from d-mannitol as a chiral source. This approach can provide a new efficient access to A-nor B-aromatic steroidal compounds.