Enantioselective Synthesis of N‐N Atropisomers by Palladium‐Catalyzed C−H Functionalization of Pyrroles

The catalytic asymmetric construction of N−N atropisomeric biaryls remains a formidable challenge. Studies of them lag far behind studies of the more classical carbon‐carbon biaryl atropisomers, hampering meaningful development. Herein, the first palladium‐catalyzed enantioselective C−H activation of pyrroles for the synthesis of N−N atropisomers is presented. Structurally diverse indole‐pyrrole atropisomers possessing a chiral N−N axis were produced with good yields and high enantioselectivities by alkenylation, alkynylation, allylation, or arylation reactions. Furthermore, the kinetic resolution of trisubstituted N−N heterobiaryls with more sterically demanding substituents was also achieved. Importantly, this versatile C−H functionalization strategy enables iterative functionalization of pyrroles with exquisite selectivity, expediting the formation of valuable, complex, N−N atropisomers. Enantioselective synthesis of N−N indole‐pyrrole and bisindole atropisomers was achieved by a palladium‐catalyzed TDG‐enabled C−H functionalization. A wide variety of the N−N atropisomers were produced in good yields with excellent enantioselectivities by C−H alkenylation, alkynylation, allylation or arylation reactions.