Catalytic Enantioselective Friedel-Crafts Allenylation

The first enantioselective Friedel-Crafts (FC) allenylation reaction for the creation of central chirality is developed under cooperative Ir(I)/(phosphoramidite,olefin) and Lewis acid catalysis. This enantioconvergent reaction utilizes racemic allenylic alcohol as the electrophile and shows compatibility with a variety of electron-rich arenes and heteroarenes. The resulting highly enantioenriched (up to >99.5 : 0.5 e.r.) 1,1-disubstituted allenylic methanes, bearing a benzylic carbon stereocenter, are obtained with complete regiocontrol - both on (hetero)arenes as well as on the allenylic fragment. This protocol allows for the enantioselective formal introduction of a 4-carbon alkyl chain into (hetero)arenes, along with the creation of a benzylic stereocenter. Judicious synthetic elaborations not only lead to formal enantioselective FC alkylation products of less electron-rich arenes but also of substituted arenes in ortho- and even meta-selective fashion. An intramolecular version of this FC allenylation is shown to proceed with promising enantioselectivity under the same catalytic conditions. Mechanistic studies revealed the involvement of dynamic kinetic asymmetric transformation (DyKAT) of racemic allenylic alcohols in this reaction.