Asymmetric Catalytic Friedel-Crafts Reactions of Unactivated Arenes

Since its discovery more than a century ago, the Friedel-Craftsreaction has manifested itself as a powerful method for the introductionof carbon substituents to arenes. Despite its potential generality,the scope of the reaction is intrinsically limited by the arene'snucleophilicity, which has previously restrained the applicabilityof asymmetric variants to activated substrates. To overcome this fundamentallimitation, we report herein an asymmetric Friedel-Crafts reactionof unactivated, purely hydrocarbon arenes, alkoxybenzenes, and heteroareneswith N,O-acetals to give enantioenrichedarylglycine esters. Highly regio- and stereoselective C-C bondformation was achieved using strong and confined Bronsted acidorganocatalysts, enabling the first asymmetric catalytic Friedel-Craftsreaction of simple alkylbenzenes.