Atropo-Enantioselective Oxidation-Enabled Iridium(III)-Catalyzed C-H Arylations with Aryl Boronic Esters

Abstract

Atropo-enantioselective biaryl coupling through C-H bond functionalization is an emerging technology allowing direct construction of axially chiral molecules. This approach is largely limited to electrophilic coupling partners. We report a highly atropo-enantioselective C-H arylation of tetralone derivatives paired with aryl boronic esters as nucleophilic components. The transformation is catalyzed by chiral cyclopentadienyl (Cp^x ) iridium(III) complexes and enabled by oxidatively enhanced reductive elimination from high-valent cyclometalated Ir-species.

Keywords: C-H functionalization; asymmetric catalysis; atropselectivity; chiral cyclopentadienyl; iridium.

Scheme 1

a) Coupling partners strategies in atropo‐enantioselective C−H arylations; b) Oxidative Cp^xIr^III‐catalyzed atropo‐enantioselective C−H arylation with aryl boronic esters.

Scheme 2

Scope for the Ir‐catalyzed atropo‐enantioselective C−H arylation with boronic esters 2 x. Conditions: 0.10 mmol 1 a, 0.20 mmol 2 x, 5 μmol Ir5, 30 μmol AgNTf₂, 0.10 mmol Cu(CO₂CF₃)₂⋅H₂O, 0.22 mmol AgF in PhCF₃ (0.2 M) at 45 °C for 14 h.

Scheme 3

Scope for the Ir‐catalyzed atropo‐enantioselective C−H arylation of different oximes and tetralones 1 y. Conditions: 0.10 mmol 1 y, 0.20 mmol 2 a, 5 μmol Ir5, 30 μmol AgNTf₂, 0.10 mmol Cu(CO₂CF₃)₂⋅H₂O, 0.22 mmol AgF in PhCF₃ (0.2 M) at 45 °C for 14 h; a) with 5 μmol Ir1; b) with 5 μmol Ir1 at 23 °C in PhCF₃ (0.125 M). Crystal structure of 3 da as ORTEP drawing with 50 % probability thermal ellipsoids; Hydrogen atoms omitted for clarity.

Scheme 4

Selective transformations of biaryl oxime 3 aa. Crystal structure of 6‐H⁺ as ORTEP drawing with 50 % probability thermal ellipsoids; Anion omitted for clarity.