Atroposelective Suzuki-Miyaura Coupling to form 2-Amino-2’-Hydroxybiphenyls Enabled by sRuPhos

Abstract

Atropisomeric biaryls are increasingly important in molecules of pharmaceutical interest. Asymmetric versions of the Suzuki-Miyaura coupling arguably constitute the most direct and attractive route to these without resorting to wasteful preparative separations or resolution steps. Herein we report a new chiral phosphine ligand sRuPhos, a sulfonated form of RuPhos, which permits the coupling of unprotected ortho-bromoanilines and ortho-phenolic boronate esters with extremely high ee (up to 99%) to form 2-amino-2’-hydroxybiphenyls. N-alkylation can be accommodated on the aniline nitrogen and sRuPhos is also able to form highly hindered 2,2’-biphenols, which could not be achieved in our previous studies using the related chiral ligand sSPhos. Given the great importance of biaryl atropisomers in medicinal chemistry, as well as the potential utility of the 2-amino-2’-hydroxybiphenyl motif in chiral catalyst design, we anticipate that this reaction will soon find utility and that sRuPhos may be a useful ligand in the development of other asymmetric palladium-catalysed processes.