Cobalt(III)-Catalyzed Enantioselective C–H Functionalization: Ligand Innovation and Reaction Development

Accounts of Chemical Research, Год журнала: 2025, Номер unknown

Опубликована: Фев. 26, 2025

ConspectusIn contrast to precious transition metals, such as palladium and rhodium, the development of novel chiral ligands for enantioselective C-H functionalizations catalyzed by earth-abundant, cost-effective, environmentally friendly 3d metals poses substantial challenges, primarily due variable oxidation states, intricate coordination patterns, limited mechanistic insights. In this Account, we summarize our research endeavors in three types Co(III) catalysis: pseudotetrahedral achiral Cp*Co(III)/chiral carbonyl acid (CCA) catalysis, situ-generated octahedral cobalt(III) via cobalt/salicyloxazoline (Salox) Co(II)/chiral phosphoric (CPA) cooperative achieved through strategic ligand design. Our initial objective was achieve functionalization Cp*Co(III) catalysts with external ligands, aiming circumvent laborious preparation CpxCo(III) complexes. To end, developed several CCA incorporating non-covalent interactions (NCIs) a crucial design element. Next, address limitations associated lengthy synthesis Cp-ligated complexes difficulties modification, explored concept situ generation catalysis using commercially available cobalt(II) salts tailor-made ligands. This exploration led two innovative catalytic systems, namely, Co(II)/Salox Co(II)/CCA sequential catalysis. The emerged versatile strategy, demonstrating excellent enantioselectivities across range asymmetric reactions construct various molecules central, axial, planar, inherent chirality. facile single step, along ease further enhances versatility applicability approach. Moreover, successfully applied cobalt/Salox electro- photochemical-catalyzed functionalization, electrons or oxygen traceless oxidant, thereby eliminating need stoichiometric chemical oxidants. Through studies reaction developments, elucidated detailed structure-enantioselectivity relationships which are expected inform future endeavors. Finally, Co(II)/CPA enabled spiro-γ-lactams olefination/asymmetric [4 + 1] spirocyclization. Mechanistically, establishment stereochemistry occurs during cyclization where CPA serves both neutral Brønsted acid, stereoinduction independent cleavage step. We anticipate that insights advancements Account will inspire innovations drive progress metal-catalyzed reactions.

Язык: Английский

---

Copper/BINOL-Catalyzed Enantioselective C–H Functionalization toward Planar Chiral Ferrocenes Under Mild Conditions

ACS Catalysis, Год журнала: 2024, Номер 14(6), С. 4030 - 4039

Опубликована: Фев. 28, 2024

Copper-catalyzed enantioselective C–H activation proceeding through an inner-sphere mechanism remains a huge challenge. Herein, copper-catalyzed alkynylation with terminal alkynes assisted by 8-aminoquinoline using readily available (S)-BINOL as the chiral ligand was disclosed. The reaction proceeded under mild conditions catalytic amount of copper salt, providing range ferrocenes in good yields and enantioselectivities (0 °C, up to 77% yield 94% ee). alteration stoichiometric chemical oxidant renewable electricity is also feasible at ambient temperature, demonstrating robustness this copper/BINOL catalysis. Notably, first cupraelectrocatalyzed reaction. Gram-scale synthesis, versatile transformations, application resulting oxazoline–olefin asymmetric synthesis highlight utility protocols.

Язык: Английский

---

Atroposelective Synthesis of Pyridoindolones Bearing Two Remote Distinct C–N Axes through Cobalt-Catalyzed Enantioselective C–H Activation

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Март 13, 2025

C–N axially chiral compounds represent an important class of atropisomers that are prevalent in bioactive and material molecules. Despite recent advances synthetic methodologies, the asymmetric construction featuring multiple axes has been rarely explored, significantly limiting their further applications. Herein, we report a novel atroposelective synthesis diaxially pyridoindolones both six–five six–six through cobalt-catalyzed C–H annulation. This approach demonstrates exceptional efficiency, yielding diverse array with excellent yields atroposelectivities (60 examples, up to >99% yield, ee, >20:1 dr). Mechanistic studies revealed stereochemistry were generated fixed simultaneously during cyclometalation step, along unexpected amplification effect. The practicality this protocol is underscored by successful gram-scale syntheses various transformations, including formation phosphine ligand. Notably, photoluminescence quantum (ΦF 0.99) positive solvatochromism observed, coupled significant chiroptical properties, underscoring potential applications these organic fluorescent materials.

Язык: Английский

---

Enantioselective Cobaltaphotoredox-Catalyzed C–H Activation

Journal of the American Chemical Society, Год журнала: 2024, Номер 146(34), С. 24105 - 24113

Опубликована: Авг. 15, 2024

The quest for sustainable strategies in molecular synthesis has spurred the emergence of photocatalysis as a particularly powerful technique. In recent years, application this context greatly promoted development asymmetric catalysis. Despite impressive advances, enantioselective photoinduced strong arene C-H activations by cobalt catalysis remain unexplored. Herein, we report strategy that merges organic photoredox and cobalt-catalyzed activation, enabling regio- stereoselective dual functionalization indoles an fashion. Thereby, assembly various chiral indolo[2,3-

Язык: Английский

---

Nickel(II)/Salox-Catalyzed Enantioselective C–H Functionalization

ACS Central Science, Год журнала: 2025, Номер 11(1), С. 127 - 135

Опубликована: Янв. 2, 2025

Recently, nickel catalysts have garnered considerable attention for their efficacy and versatility in asymmetric catalysis, attributed to distinctive properties. However, the use of cost-effective sustainable divalent C–H activation/asymmetric alkene insertion poses significant challenges due intricate control stereochemistry transformation tetracoordinate C–Ni(II) intermediate. Herein, we report a Ni(II)-catalyzed enantioselective C–H/N–H annulation with oxabicyclic alkenes. This protocol offers straightforward access chiral [2,2,1]-bridged bicyclic compounds bearing four consecutive stereocenters high enantioselectivity (up 96% ee). The development sterically hindered salicyloxazoline (Salox) ligand, TMS-Salox, is key success this protocol. Mechanistic investigations unveiled that Ni(III)-metalacyclic intermediate was formed through situ oxidation achiral organometallic Ni(II) species coordination Salox ligand. process led creation tailored pocket guides approach alkenes, thereby influencing determining stereochemistry.

Язык: Английский

---

Cobalt(II)-Catalyzed Selective C2–H Heck Reaction of Native (N–H) Indoles Enabled by Salicylaldehyde Ligand

The Journal of Organic Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 8, 2025

Direct functionalization of native (N–H) indoles via C–H activation remains a challenge. Herein, we report salicylaldehyde-promoted cobalt-catalyzed selective C2–H Heck reaction with both active and unactivated olefins in the presence free N–H bonds. A series structurally diverse C2-alkenylated including natural product drug derivatives were prepared directly effectively without additional preprotection deprotection procedures.

Язык: Английский

---

Mechanistic Investigations of Cobalt-Catalyzed, Aminoquinoline-Directed C(sp²)–H Bond Functionalization

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 10, 2025

Monoanionic, bidentate-auxiliary-directed, cobalt-catalyzed C–H bond functionalization has become a very useful tool in organic synthesis. A comprehensive investigation into isolated organometallic intermediates and their reactivity within the catalytic cycle is lacking. We report here mechanistic studies of cobalt-catalyzed, aminoquinoline-directed C(sp2)–H functionalization. number Co(III) have been structurally characterized, including, for first time aminoquinoline system, complexes arising from migratory insertion cobalt–carbon bonds. The stoichiometric reactions cobalt(III) aryls with alkenes, alkynes, carbon monoxide, cyclic secondary amines, benzamides explored. oxidation state cobalt product-forming step depends on nature coupling component. Specifically, annulation alkynes carbonylation CO likely proceed via Co(I)/Co(III) cycle. Carbon–hydrogen alkenes as well benzamide homocoupling, (formally) Co(IV) species involve oxidatively induced reductive elimination.

Язык: Английский

---

Copper-Mediated Enantioselective C–H Thiolation of Ferrocenes Enabled by the BINOL Ligand

Journal of the American Chemical Society, Год журнала: 2025, Номер unknown

Опубликована: Янв. 30, 2025

Transition-metal-catalyzed enantioselective C-H activation has transformed the landscape of asymmetric synthesis, enabling efficient conversion bonds into C-C and carbon-heteroatom (C-X) bonds. However, formation C-S through thiolation remains underdeveloped due to challenges such as catalyst deactivation competitive coordination sulfur-containing compounds with chiral ligands. Herein, we report an unprecedented approach constructing sulfur-substituted planar ferrocenes (PCFs) copper-mediated enabled by only a 2.5 mol % 1,1'-bi-2,2'-naphthol (BINOL) ligand. A variety PCFs were obtained in good yields (up 83%) excellent enantioselectivity >99% ee). Mechanistic studies reveal that irreversible serves both stereo- rate-determining step can be achieved catalytic amounts Cu species. Furthermore, utility this protocol is illustrated gram-scale removal directing group, synthesis N,S-chiral ligands well rotaxanes. This significant advancement not expands tool kit for organosulfur but also highlights potential synthesis.

Язык: Английский

---

Progress on Cobalt-Catalyzed C(sp²)—H Activation for the Construction of Nitrogen-Containing Benzo Heterocycles

Chinese Journal of Organic Chemistry, Год журнала: 2025, Номер 45(2), С. 655 - 655

Опубликована: Янв. 1, 2025

Язык: Английский

---

Cobalt-Catalyzed Domino Transformations via Enantioselective C–H Activation/Nucleophilic [3+2] Annulation Towards Chiral Bridged Bicycles

Опубликована: Фев. 27, 2024

Selective synthesis of chiral bridged (hetero)bicyclic scaffolds via asymmetric C–H activation constitutes substantial chal-lenges, due to the multiple reactivities strained bicyclic structures. Herein, we develop domino transformations through an unprecedent cobalt-catalyzed enantioselective activation/nucleophilic [3+2] annulation with symmetrical alkenes. The methods offer straightforward accesses a wide range molecules bearing [2.2.1]-bridged bicy-clic cores four and five consecutive stereocenters in single step. Two elaborated salicyloxazoline (Salox) ligands were synthesized based on rational design mechanistic understanding. well-defined pockets generated from coordination around trivalent cobalt catalyst direct orientation alkenes, leading excellent enantioselectivity.

Язык: Английский

---