1,2,3,4-Tetrasubstituted Chiral η ⁶ -Benzene Ligand: Design and Application in Ruthenium-Catalyzed Asymmetric Synthesis of Tertiary Indenols via C–H Activation

Chiral η⁶-benzene-ligand-controlled asymmetric catalysis represents an emerging paradigm in stereoselective synthesis, particularly for ruthenium-catalyzed asymmetric C-H activation. The catalytic efficiency of these systems is profoundly influenced by the substitution pattern of the η⁶-benzene ligand. While existing designs are restricted to 1,2,4-trisubstituted and 1,2,4,5-tetrasubstituted frameworks, the 1,2,3,4-tetrasubstitution pattern remains uncharted territory. In this work, we disclose a novel class of chiral η⁶-benzene ligands featuring this unexplored 1,2,3,4-tetrasubstitution pattern, which combines three key advantages: (1) high tunability, (2) facile accessibility, and (3) outstanding catalytic performance. The derived chiral η⁶-benzene-ruthenium catalysts enable highly enantioselective C-H activation of aryl ketones with alkynes, delivering tertiary indenols (77 examples) with exceptional efficiency (up to 99% yield) and stereocontrol (up to 98% ee). Furthermore, our reinvestigation of the nonasymmetric [RuCl₂(<i>p</i>-cymene)]₂-catalyzed variant revealed the dual role of silver additives: while essential for catalysis, excess Ag⁺ promotes deleterious side reactions, including product dehydration and dimerization.