A Modular Approach to Atropisomeric Bisphosphines of Diversified Electronic Density on Phosphorus Atoms

Abstract

The series of C2-symmetric biaryl core-based non-racemic bisphosphines possessing substituents of different electronic properties: both EDG and EWG were obtained in a short sequence of good yielding transformations, started from commercial 1,3-dimethyl-2-nitrobenzene. Several different approaches leading to the desirable ligands were practically evaluated. Notably, the synthesis of the entire series of ligands could be performed with the utilization of a single early-stage precursor DIDAB (6,6’-diiodo-2,2’,4,4’-tetramethylbiphenyl-3,3’-diamine), which could be easily obtained in enantiomerically pure form. The obtained compounds at concentrations of 50 and 200 µM showed various biological activity against normal human dermal fibroblast, ranging from inactivity through time-dependent action and ending up with high toxicity.

A Single Biaryl Monophosphine Ligand Motif—The Multiverse of Coordination Modes

“…On the other hand, the steric hindrance caused by the voluminous substituents at the phosphorus atom in the biaryl molecular core enhances the reaction selectivity. Thus, in many types of cross-coupling reactions, such ligands promote both the oxidative addition and reductive elimination steps [8,9]. The field of biaryl monophosphine ligands has seen a significant development during recent years, including the design and synthesis of numerous derivatives with tailored catalytic properties.…”