Synthesis and Applications of Novel Chiral Monophosphine Ligands

Chiral monodentate phosphines are rapidly developing ligand class in asymmetric catalysis. Despite the synthetic utility, full exploration of their application potential remains hampered due to elaborated preparation protocols, especially for scaffolds with axially chiral backbones. Recently, the ortho-directed atroposelective C-H arylation has emerged as efficient tool for atom- and step-economical preparation of atropisomers. Herein we report our results on the synthesis of new family of axially chiral biaryl monophosphines via Ir-catalyzed, phosphine oxide directed C-H arylation as a key step. A large ligand library with a diverse chemical space was successfully prepared, and its application potential was thoroughly evaluated in various benchmark asymmetric reactions. Excellent levels of reactivity and enantioselectivity have been achieved Au(I)-catalyzed cyclisation of enynes and Pd-catalyzed arylative dearomatization of phenols. Moreover, using our new ligand library, an unprecedented atroposelective direct C - H arylation of thiazole derivatives was developed for the first time, providing straightforward access to unique axially chiral N-oxide frameworks. These scaffolds were readily amenable to downstream derivatization and showed promising potential as organocatalysts.