Key points are not available for this paper at this time.
Enantioselective C(sp 2 )–H activation typically relies on forming rigid 5- or 6-membered metallacyclic intermediates. Examples involving direct metalation at remote C(sp 2 )–H bonds, which require larger metallacycles, remain scarce. Herein, we report a series of 1,1′-bi-2-naphthol (BINOL)-derived chiral bipyridine ligands that enable iridium-catalyzed regio- and enantioselective meta -borylation of α,α-diarylcarboxamides, generating an all-carbon quaternary stereocenter in high yields and excellent regio- and enantioselectivities. The chiral side arm, BINOL, holds a Lewis acid aluminum center and interacts with the Lewis basic fragment of the substrate to bring it into proximity with the bipyridine part of the iridium-catalyst for the remote-selective borylation reaction. The chiral pocket enables the effective transfer of the chiral information, overcoming the challenges of long-range asymmetric induction, presumably due to the closer proximity of the chiral scaffold of the ligand and the (pro)stereogenic center of the substrate. The prochiral substrates were desymmetrized with up to an excellent 99% ee. An unprecedented kinetic resolution for such a transformation has also been disclosed with moderate to good selectivity ( s -factor up to 19.5). The synthetic utility was demonstrated through a successful scale-up experiment and subsequent transformation of the boronate ester to various functional groups. Further, mechanistic studies indicate that the catalyst primarily governs the enantioselectivity of the desymmetrization reaction, while the kinetic resolution of the monoborylated product plays a secondary role in further enhancing the product’s enantioselectivity. Finally, density functional theory (DFT) calculations have been performed to understand the reaction mechanism and the crucial noncovalent interactions involved in the transition states that dictate observed enantioselectivity.
Aditya et al. (Mon,) studied this question.