Pd-Catalyzed Enantioselective C(sp3)–H Arylation for Synergized Construction of C(sp2)–C(sp3) Axial and Central Chirality

In contrast to the conventional biaryl atropisomers, C(sp2)–C(sp3)-based axially chiral scaffolds generally exhibit limited configurational stability due to facile rotation around the tetrahedral sp3 carbon, rendering the enantioselective construction of such atropisomers a formidable challenge. Here, we report proof-of-concept studies on asymmetric C–H bond functionalization of a sterically hindered sp3 cycle toward the construction of C(sp2)–C(sp3) axis, which is realized in Pd-catalyzed C(sp3)–H arylation of 9H-fluorenes with 1-bromoarenes, delivering synergized C(sp2)–C(sp3) axial chirality and central chirality. The reaction proceeded under mild conditions, accommodating a broad range of substrates (excellent dr and up to 97:3 er). Mechanistic studies revealed that the central chirality and the axial chirality are synergistically induced during the reductive elimination, with the central chirality being controlled by a Curtin–Hammett scenario. The resulting scaffolds can be readily converted into a class of chiral phosphine ligands that demonstrate promising utility in asymmetric catalysis.