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

Abstract

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.