Orthogonal Catalysis for an Enantioselective Domino Inverse‐Electron Demand Diels−Alder/Substitution Reaction

An enantioselective domino process for the synthesis of substituted 1,2‐dihydronaphthalenes has been developed by the combination of chiral amines and a bidentate Lewis acid in an orthogonal catalysis. This new method is based on an inverse electron‐demand Diels−Alder and a subsequent group exchange reaction. An enamine is generated in situ from an aldehyde and a chiral secondary amine catalyst that reacts with phthalazine, activated by the coordination to a bidentate Lewis acid catalyst. The absolute configuration of the product is controlled by chiral information provided by the amine. The formed ortho‐quinodimethane intermediate is then transformed via a group exchange reaction with thiols. The new method shows a broad scope and tolerates a wide range of functional groups with enantiomeric ratios up to 91 : 9. All‐in‐all, this enantioselective synthesis tool provides an easy access to complex 1,2‐dihydronaphthalenes starting from readily available phthalazine, aldehydes and thiols in a combinatorial way.