Dual-Ligand-Enabled Ir(III)-Catalyzed Enantioselective C–H Amidation for the Synthesis of Chiral Sulfoxides

Abstract

A rational designed Ir­(III)-catalyzed enantioselective C–H amidation of dibenzyl sulfoxides through desymmetrization and parallel kinetic resolution is demonstrated. An Ir­(III) complex equipped with a t-butyl cyclopentadienyl ligand and paired with a modified chiral proline enables the highly enantioselective sulfoxide-steered C–H bond activation, providing an efficient and straightforward way to construct sulfur chiral centers. A wide range of dibenzyl sulfoxides and dioxazolones are compatible with this process, giving access to a variety of highly functionalized sulfoxide compounds with synthetically attractive amide substitution groups in good yields and enantioselectivities. Moreover, the flexible derivatization of the amidated sulfoxide was elaborated, providing various types of chiral sulfoxide scaffolds that would be potentially useful in asymmetric catalysis as chiral bidentate and tridentate ligands.

Lewis acid-assisted Ir(iii) reductive elimination enables construction of seven-membered-ring sulfoxides

“…When 2 equivalents of dibenzyl sulfoxide 1a were treated with a stoichiometric amount of the Cp*Ir(III)Cl 2 dimer in the presence of a silver salt and NaOAc in TFE (tri-uoroethanol), we observed a new organoiridium complex (Ir-I) where C-H activation had taken place twice at each of the phenyl groups proximal to the sulfoxide group (Scheme 2). 44 Inspired by this sulfoxide-steered Ir(III)-mediated C-H bond activation mode, we questioned whether we could conduct the direct reductive elimination of this sulfoxide iridacycle (Ir-I), . We next carried out reactions under oxidative conditions.…”

Rhodium‐Catalyzed Enantioselective Synthesis of β‐Amino Alcohols via Desymmetrization of gem‐Dimethyl Groups

“…In 2014, the Chang group reported racemic synthesis of β‐amino alcohols via Ir III ‐catalyzed C−H amidation of alcohol derivatives containing an N ‐directing group [13a] . On the other hand, Chang, [13b] Cramer, [14] He, [15] Shi, [16] Matsunaga, [17] and our group [18] recently reported enantioselective desymmetrization of arenes in annulation, arylation, and amidation reactions, which occurred via enantiodetermining C(aryl)‐H activation catalyzed by rhodium and iridium complexes [19] . Meanwhile, desymmetrization of the coupling partner has also been reported [20] .…”

Recent Progress in the C−N Bond Formation via High‐Valent Group 9 Cp*M(III)‐Catalyzed Directed sp2 C−H Activation

“…Sterically hindered [ t Bu Cp*Ir(III)Cl 2 ] 2 catalysts and tert ‐leucine derived bulky chiral amino acid ligand 147 (synthesized from the ligand 50 by Pd(II)‐catalyzed γ ‐C(sp 3 )‐H arylation) were necessary to achieve high enantioselectivity for products 43 (Scheme 48a). He group reported the same Ir(III)‐catalyst along with proline derived chiral amino acid ligand 148 could provide a wide range of chiral sulfoxides 150 with reasonable yields and enantioselectivities via desymmetrization and parallel kinetic resolution (Scheme 48b) [52b] …”