Development of a Tunable Chiral Pyridine Ligand Unit for Enantioselective Iridium-Catalyzed C–H Borylation

Abstract

Although pyridine derivatives are versatile supporting ligands in catalysis, the development of their chiral versions has been relatively limited. Herein, we report the design, synthesis, and proof-of-concept application of a structurally tunable chiral pyridine framework featuring an annulated compact ring system. Using an N,B-bidentate ligand skeleton containing the chiral pyridine moiety, we have developed an enantioselective iridium-catalyzed desymmetrizing C–H borylation reaction of diaryl­(2-pyridyl)­methane compounds with up to 96% ee and 93% yield. The resulting borylation products could be readily transformed into various chiral tri­(hetero)­arylmethane compounds. Density functional theory investigations revealed that the two chair conformations of the flexible ketal motif both favored the enantiomer that was consistent with experimental results. This work has thus introduced an effective and tunable chiral pyridine ligand framework that may be used in many catalytic asymmetric transformations.

Development of Chiral Ligands for the Transition‐Metal‐Catalyzed Enantioselective Silylation and Borylation of C−H Bonds

“…Very recently, another type of N,B‐ligand that contains a chiral pyridyl unit and a planar boron‐containing scaffold was developed by Li, Xu, and co‐workers (Figure 29). [43] Desymmetrization of 2‐pyridinyl‐substituted diarylmethane derivatives with iridium catalysts bearing this new N,B‐ligand led to the borylated products with high enantioselectivity and in good yields.…”

Metal-catalysed C–H bond activation and borylation

“…In 2021, the Li group reported an iridium-catalysed enantioselective borylation of benzylpyridine derivatives using a new chiral ligand system (L14) (Scheme 35). 143 Earlier the same group reported a N,B-bidentate ligand for the directed ortho C-H borylation of several substrates. 106 In this report, the authors modified their N,B-bidentate ligand by introducing a chiral group at the pyridine ring, which exhibited very good reactivity and enantioselectivity.…”

Catalyst Engineering through Heterobidentate (N–X-Type) Ligand Design for Iridium-Catalyzed Borylation

“…In 2021, the Li group developed a chiral pyridine containing N,B-bidentate ligand L9 and utilized it in the enantioselective C-H borylation of diaryl(2-pyridyl)methanes (Scheme 12). 44 They hypothesized that the compact framework of the ligand with annulated polycyclic rings would be beneficial in asymmetric catalysis and that the annulated cyclopentane and cyclopropane rings would minimize local steric hindrance and allow structural tunability of their ligand framework. A tunable chiral pyridine unit was designed and attached to their previously developed boryl ligand partner of N,B-ligand for the iridium-catalyzed asymmetric C-H borylation.…”