Catalytic Enantioselective Friedel-Crafts Allenylic Alkylation

The first catalytic enantioselective Friedel-Crafts (FC) allenylic alkylation for the creation of central chirality has been developed under cooperative Ir(I)/(phosphoramidite,olefin) and Lewis acid catalysis. Using racemic allenylic alcohol as the electrophile, this enantioconvergent reaction proceeds through an Ir(I)-stabilized allenylic carbocation intermediate, which is intercepted with a variety of electron-rich arenes and heteroarenes. The resulting highly enantioenriched (up to >99.5:0.5 er) 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 4 carbon alkane chains into (hetero)arenes with the creation of a benzylic stereocenter. An intramolecular version of this FC allenylic alkylation has also been shown to proceed with promising enantioselectivity under the same catalytic conditions.