New rhodium-sp3 diphosphine catalytic systems for the asymmetric addition of aryl boronic acids to azaarenes

Catalytic asymmetric conjugate reaction stands out as one of the most useful synthetic tools for the preparation of chiral compounds although its application to the synthesis of chiral azaarenes has been scarcely investigated till now (Ad. Synth. Catal. 2020, 362, 3142). Starting from the established expertise gained in my research group in the synthesis of chiral phosphine ligands and their application in homogeneous catalysis (Inorg. Chem. 2021, 60(5), 976; Catalysts 2020, 10(8), 914) we prepared a novel chiral phosphorus ligand, called (R,R)-EPHOS, designed and synthesized starting from the optically active 1,4-(E)-2-butene. Its cis analogue, called (R,R)-ZEDPHOS had been already successfully employed in the enantioselective reduction of carbonyl groups affording satisfactory enantioselectivity. This new diphosphine features a stereogenic sp3 carbon atom combined to the presence of a C2 axial chirality, the one featuring the atropoisomeric diphosphines. A combined 31P-NMR and computational approach shed light on the different coordination mode to the rhodium centre respect to (R,R)-ZEDPHOS, suggesting the ability of (R,R)-EPHOS to form complexes with phosphorus atoms in cis configuration and revealing the asymmetric disposition of the aryl groups responsible for the chiral recognition of the substrate enantiofaces. Thus, (R,R)-EPHOS was applied to the asymmetric rhodium catalyzed 1,4-addition of different substituted arylboronic acids to azaarenes in comparison with other. When applied to (E)-1-phenyl-3-(pyridin-2-yl)prop-2-en-1-one (1), (R,R)-EPHOS-Rh( catalytic system afforded the product 1a in a remarkable 94% e.e.