Asymmetric Synthesis of Hydrophenanthrenones Bearing Multiple Stereogenic Centers via Squaramide-Catalyzed Domino 1,4-/1,4-Addition Desymmetrization Sequence

An unprecedented stereoselective route for procuring tetrahydrophenanthren-2(1H)-ones bearing up to five contiguous stereogenic centers has been accomplished. A bifunctional squaramide enables a domino 1,4-/1,4-addition desymmetrization reaction sequence between the newly developed β-nitrostyrene-tethered 2,5-cyclohexadienones and trisubstituted enolizable nucleophiles to provide direct access to the polyfunctionalized hydrophenanthren-2(1H)-ones in excellent enantio- (up to >99%) and diastereoselectivity (up to >20:1). By using a psedoenantiomeric squaramide, the enantiomers of hydrophenanthrene derivatives were also accessed with excellent stereocontrol.