Catalytic Atroposelective Catellani Reaction Enables Construction of Axially Chiral Biaryl Monophosphine Oxides

An unprecedented atroposelective Catellani reaction between phosphine oxide-containing aryl bromides, aryliodides, and nucleophiles for the construction of phosphine-containing biaryl atropisomers was established using an enantiopure norbornene derivative as the chiral mediator. A broad range of atropisomeric biaryl-based monophosphine oxides were obtained in good efficiency with excellent enantioselectivity. This set of three component catalytic systems successfully inhibited two-component cross-couplings and promoted the formation of an aryl-aryl chiral axis via a key atropisomeric Pd intermediate. Meanwhile, an optically active atropisomeric biaryl with two stereogenic axes was also obtained with this strategy. The synthetic utility of this methodology was illustrated through further transformations into monophosphine ligands which have been used for further applications in asymmetric catalysis. In addition, a detailed mechanism study by DFT calculation was conducted. [GRAPHICS] .

Automated summary

This study successfully established an unprecedented atroposelective Catellani reaction between phosphine oxide-containing aryl bromides, aryliodides, and nucleophiles for the construction of phosphine-containing biaryl atropisomers, showing promising synthetic utility and potential for further applications.