Enantioselective Synthesis of Axially Chiral Biaryl Monophosphine Oxides via Direct Asymmetric Suzuki Coupling and DFT Investigations of the Enantioselectivity

Direct asymmetric Suzuki coupling
between arylboronic acids and
2-diarylphosphinyl-1-naphthyl bromides was successfully developed
for the first time with the use of Pd–L1 or Pd–(Cy-MOP)
as the catalyst. A variety of axially chiral 2-functionalized-2′-diarylphosphinyl-1,1′-biaryls
were afforded in 34–99% yields with up to 94% ee. This methodology
provides a highly efficient and practical strategy for the synthesis
of novel axially chiral biaryl monophosphine oxides and the corresponding
phosphines. The existence of an ortho formyl group in arylboronic
acids greatly improves the coupling efficiency and permits further
versatile transformations in organic synthesis. Density functional
calculations were used to determine the origin of stereoselectivity
during the reductive elimination step of the closely related coupling
of 2-formylphenylboronic acid with naphthylphosphonate bromide. These
studies indicate that both the significant transition metal hydrogen
bond between the H atom of the formyl group and palladium­(II) and
the weak interaction between the Pd center and the phosphoryl oxygen
atom in the transition state are crucial for high enantioselectivity
of the coupling products.