Construction of C-B axial chirality via dynamic kinetic asymmetric cross-coupling mediated by tetracoordinate boron

Catalytic dynamic kinetic asymmetric transformation (DyKAT) provides a powerful tool to access chiral stereoisomers from racemic substrates. Such transformation has been widely employed on the construction of central chirality, however, the application in axial chirality remains underexplored because its equilibrium of substrate enantiomers is limited to five-membered metalacyclic intermediate. Here we report a tetracoordinate boron-directed dynamic kinetic asymmetric cross-coupling of racemic, configurationally stable 3-bromo-2,1-azaborines with boronic acid derivatives. A series of challenging C-B axially chiral compounds were prepared with generally good to excellent enantioselectivities. Moreover, this transformation can also be extended to prepare atropisomers bearing adjacent C-B and C-C diaxes with excellent diastereo- and enantio-control. The key to the success relies on the rational design of a reversible tetracoordinate boron intermediate, which is supported by theoretical calculations that dramatically reduces the rotational barrier of the original C-B axis and achieves the goal of DyKAT. The application of catalytic dynamic kinetic asymmetric transformation (DyKAT) in axial chirality is limited to fivemembered metalacyclic intermediate-directed equilibrium of substrate enantiomers. Here, the authors report a tetracoordinate boron-directed DyKAT of racemic, configurationally stable 3-bromo- 2,1-azaborines for the construction of C-B axial chirality.

Automated summary

The authors report a tetracoordinate boron-directed dynamic kinetic asymmetric transformation (DyKAT) method for the construction of C-B axial chirality using racemic, configurationally stable 3-bromo-2,1-azaborines. By rational design of a reversible tetracoordinate boron intermediate, a series of challenging C-B axially chiral compounds were prepared with generally good to excellent enantioselectivities. This method can also be extended to prepare atropisomers bearing adjacent C-B and C-C diaxes with excellent diastereo- and enantio-control.