Catalytic Synthesis of 8‐Membered Ring Compounds via Cobalt(III)‐Carbene Radicals

The metalloradical activation of o‐aryl aldehydes with tosylhydrazide and a cobalt(II) porphyrin catalyst produces cobalt(III)‐carbene radical intermediates, providing a new and powerful strategy for the synthesis of medium‐sized ring structures. Herein we make use of the intrinsic radical‐type reactivity of cobalt(III)‐carbene radical intermediates in the [Co^II(TPP)]‐catalyzed (TPP=tetraphenylporphyrin) synthesis of two types of 8‐membered ring compounds; novel dibenzocyclooctenes and unprecedented monobenzocyclooctadienes. The method was successfully applied to afford a variety of 8‐membered ring compounds in good yields and with excellent substituent tolerance. Density functional theory (DFT) calculations and experimental results suggest that the reactions proceed via hydrogen atom transfer from the bis‐allylic/benzallylic C?H bond to the carbene radical, followed by two divergent processes for ring‐closure to the two different types of 8‐membered ring products. While the dibenzocyclooctenes are most likely formed by dissociation of o‐quinodimethanes (o‐QDMs) which undergo a non‐catalyzed 8π‐cyclization, DFT calculations suggest that ring‐closure to the monobenzocyclooctadienes involves a radical‐rebound step in the coordination sphere of cobalt. The latter mechanism implies that unprecedented enantioselective ring‐closure reactions to chiral monobenzocyclooctadienes should be possible, as was confirmed for reactions mediated by a chiral cobalt‐porphyrin catalyst.     

Catalytic Synthesis of 8-Membered Ring Compounds via Cobalt(III)-Carbene Radicals

The metalloradical activation of o-aryl aldehydes with tosylhydrazide and a cobalt(II) porphyrin catalyst produces cobalt(III)-carbene radical intermediates, providing a new and powerful strategy for the synthesis of medium-sized ring structures. Herein we make use of the intrinsic radical-type reactivity of cobalt(III)-carbene radical intermediates in the [Co^II(TPP)]-catalyzed (TPP=tetraphenylporphyrin) synthesis of two types of 8-membered ring compounds; novel dibenzocyclooctenes and unprecedented monobenzocyclooctadienes. The method was successfully applied to afford a variety of 8-membered ring compounds in good yields and with excellent substituent tolerance. Density functional theory (DFT) calculations and experimental results suggest that the reactions proceed via hydrogen atom transfer from the bis-allylic/benzallylic C−H bond to the carbene radical, followed by two divergent processes for ring-closure to the two different types of 8-membered ring products. While the dibenzocyclooctenes are most likely formed by dissociation of o-quinodimethanes (o-QDMs) which undergo a non-catalyzed 8π-cyclization, DFT calculations suggest that ring-closure to the monobenzocyclooctadienes involves a radical-rebound step in the coordination sphere of cobalt. The latter mechanism implies that unprecedented enantioselective ring-closure reactions to chiral monobenzocyclooctadienes should be possible, as was confirmed for reactions mediated by a chiral cobalt-porphyrin catalyst.     

Recent Advances in Catalytic Alkyne Transformation via Copper Carbene Intermediates

As one of the abundant and inexpensive metals on the earth, copper has demonstrated broad applications in synthetic chemistry and catalysis. Among these copper-catalyzed advances, copper carbenes are versatile and reactive intermediates that can mediate a variety of transformations, which have attracted much attention in the past decades. The present review summarizes two different reaction models that take place between a copper carbene intermediate and alkyne species, including the cross-coupling reaction of copper carbene intermediate with terminal alkyne, and the addition of copper carbene intermediate onto the C–C triple bond. This article will cover the profile from 2010 to 2021 by placing emphasis on the detailed catalytic models and highlighting the synthetic applications offered by these practical and mild methods.     

Main‐Chain Organometallic Microporous Polymers Bearing Triphenylene–Tris(N‐Heterocyclic Carbene)–Gold Species: Catalytic Properties

Two triphenylene‐based tris(N‐heterocyclic carbene)–gold–acetylide main‐chain organometallic microporous polymers (MOMPs) were obtained and fully characterized. Both materials show spherical shapes, and their size is highly dependent on the type of acetylene used in the synthetic protocol. The new solids were tested in the catalytic reduction of nitroarenes with NaBH₄ and in the three‐component Strecker reaction for the synthesis of α‐aminonitriles, and showed high activity in both processes. Whereas the activity of the solids in the reduction of nitroarenes may be attributed to the formation of Au nanoparticles due to the use of NaBH₄ as reducing agent, the activity in the Strecker reaction may originate from the Lewis acidic activation of the ketone or imine on coordination to Au.     

Interception of Cobalt‐Based Carbene Radicals with α‐Aminoalkyl Radicals: A Tandem Reaction for the Construction of β‐Ester‐γ‐amino Ketones

The interception of cobalt‐based carbene radicals with α‐aminoalkyl radicals was combined with the Kornblum–DeLaMare reaction and provides β‐ester‐γ‐amino ketones, which are otherwise difficult to obtain in high chemoselectivity. Mechanistically, this transformation is an interplay of cobalt‐based carbene radicals, organoradicals, and ionic intermediates and involves the construction of two C? C bonds and one C?O bond in a one‐pot process. The reaction also features a wide substrate scope and is highly efficient and insensitive to moisture and air.     

Elevated Catalytic Activity of Ruthenium(II)–Porphyrin‐Catalyzed Carbene/Nitrene Transfer and Insertion Reactions with N‐Heterocyclic Carbene Ligands

Bis(NHC)ruthenium(II)–porphyrin complexes were designed, synthesized, and characterized. Owing to the strong donor strength of axial NHC ligands in stabilizing the trans M?CRR′/M?NR moiety, these complexes showed unprecedently high catalytic activity towards alkene cyclopropanation, carbene C? H, N? H, S? H, and O? H insertion, alkene aziridination, and nitrene C? H insertion with turnover frequencies up to 1950 min^?1. The use of chiral [Ru(D₄‐Por)(BIMe)₂] ( 1 g ) as a catalyst led to highly enantioselective carbene/nitrene transfer and insertion reactions with up to 98 % ee. Carbene modification of the N terminus of peptides at 37 °C was possible. DFT calculations revealed that the trans axial NHC ligand facilitates the decomposition of diazo compounds by stabilizing the metal–carbene reaction intermediate.     

Acyclic Palladium(II)‐N‐heterocyclic Carbene Metallacrown Ether Complexes: Synthesis,Structure and Catalytic Activity

Novel acyclic Pd(II)‐N‐heterocyclic carbene (NHC) metallacrown ethers 5a , 5b have been synthesized. Reaction of the imidazolium salts bearing a long polyether chain with Ag₂O afforded Ag‐NHC complexes, which then reacted as carbene transfer agent with PdCl₂(MeCN)₂ to give the desired acyclic Pd(II)‐NHC metallacrown ether complexes 5a and 5b . The ¹H NMR and ¹³C NMR spectra show 5a and 5b exist as mixtures of cis and trans isomers in solution. The trans isomer of 5a was characterized by X‐ray diffraction, which clearly demonstrated two pseudo‐crown ether cavities in trans‐ 5a . Pd(II)‐NHC complexes 5a and 5b have been shown to be highly effective in the Suzuki‐Miyaura reactions of a variety of aryl bromides in neat water without the need of inert gas protection.     

Electronic and Steric Ligand Effects in the Radical Polymerization of Vinyl Acetate Mediated by β‐Ketoiminate Complexes of Cobalt(II)

Complexes Co[OC(Ph)CHC(Me)NAr]₂ [Ar=Ph, 1 ; o,o′‐C₆H₃Me₂ (Xyl), 2 ; p‐C₆H₄CF₃, 3 ] are tested in the polymerization of vinyl acetate (VAc) initiated by V‐70 (0.8 equiv) at 30 °C. Polymerization occurs without any notable induction time yielding PVAc with relatively low polydispersity, but with higher than expected M_n values, which indicates inefficient trapping processes. The apparent polymerization rate constant varies in the order 2 > 1 > 3 . Controlled polymer growth is also observed when the polymerization is conducted in the presence of a much higher V‐70/ 1 ratio, demonstrating that this system can also function as a transfer agent in a degenerative transfer process. Competition between chain growth and catalyzed chain transfer (CCT) is also observed, the latter prevailing at higher temperatures. Comparison of these results with previous reports on bis(β‐diketonato) complexes allows a separate assessment of ligand electronic and steric effects in the ability to control polymerization.     

Mesoionic Carbene Cobalt Complexes as Multipurpose Catalyst Precursors for Hydrosilylation and Dihydropyrimidinone Synthesis

Metalation of CH₂OH-substituted triazolium salts with CoCl₂ under basic conditions affords C,O-bidentate chelating carbene Co(III) complexes ( 3a , 3b ), while analogous phenyl-substituted triazolium salts produce monodentate carbene Co(II) complexes ( 3c , 3d ). The distinct substituent-induced properties of the metal centers were demonstrated by electrochemical measurements and catalytic activities in two specific processes. The complexes showed appreciable activity in the reduction of C=O bonds through hydrosilylation, with methoxybenzene-functionalized triazolylidene Co(III) complex 3a achieving a high selectivity towards aldehydes vs. ketones with turnover frequencies (TOFs) up to 200 h⁻¹. The C,O-chelate systems were also active catalysts in the Biginelli process, a one-step three-component reaction for efficient dihydropyrimidinone synthesis. Optimization of reaction conditions provides high activity with complex 3a , reaching TOFs of 800 h⁻¹, the highest activity known for cobalt NHC complexes to date.     

Strong Exchange Coupling in a Trimetallic Radical‐Bridged Cobalt(II)‐Hexaazatrinaphthylene Complex

Reducing hexaazatrinaphthylene (HAN) with potassium in the presence of 18‐c‐6 produces [{K(18‐c‐6)}HAN], which contains the S=1/2 radical [HAN]^.?. The [HAN]^.? radical can be transferred to the cobalt(II) amide [Co{N(SiMe₃)₂}₂], forming [K(18‐c‐6)][(HAN){Co(N′′)₂}₃]; magnetic measurements on this compound reveal an S=4 spin system with strong cobalt–ligand antiferromagnetic exchange and J≈?290 cm^?1 (?2 J formalism). In contrast, the Co^II centres in the unreduced analogue [(HAN){Co(N′′)₂}₃] are weakly coupled (J≈?4.4 cm^?1). The finding that [HAN]^.? can be synthesized as a stable salt and transferred to cobalt introduces potential new routes to magnetic materials based on strongly coupled, triangular HAN building blocks.     

Intramolecular Radical Aziridination of Allylic Sulfamoyl Azides by Cobalt(II)‐Based Metalloradical Catalysis: Effective Construction of Strained Heterobicyclic Structures

Cobalt(II)‐based metalloradical catalysis (MRC) has been successfully applied for effective construction of the highly strained 2‐sulfonyl‐1,3‐diazabicyclo[3.1.0]hexane structures in high yields through intramolecular radical aziridination of allylic sulfamoyl azides. The resulting [3.1.0] bicyclic aziridines prove to be versatile synthons for the preparation of a diverse range of 1,2‐ and 1,3‐diamine derivatives by selective ring‐opening reactions. As a demonstration of its application for target synthesis, the metalloradical intramolecular aziridination reaction has been incorporated as a key step for efficient synthesis of a potent neurokinin 1 (NK₁) antagonist in 60 % overall yield.     

Synthesis,Characterization, and Reactivity of Cobalt(III)–Oxygen Complexes Bearing a Macrocyclic N‐Tetramethylated Cyclam Ligand

Mononuclear metal–dioxygen species are key intermediates that are frequently observed in the catalytic cycles of dioxygen activation by metalloenzymes and their biomimetic compounds. In this work, a side‐on cobalt(III)–peroxo complex bearing a macrocyclic N‐tetramethylated cyclam (TMC) ligand, [Co^III(15‐TMC)(O₂)]⁺, was synthesized and characterized with various spectroscopic methods. Upon protonation, this cobalt(III)–peroxo complex was cleanly converted into an end‐on cobalt(III)–hydroperoxo complex, [Co^III(15‐TMC)(OOH)]²⁺. The cobalt(III)–hydroperoxo complex was further converted to [Co^III(15‐TMC‐CH₂‐O)]²⁺ by hydroxylation of a methyl group of the 15‐TMC ligand. Kinetic studies and ¹⁸O‐labeling experiments proposed that the aliphatic hydroxylation occurred via a Co^IV–oxo (or Co^III–oxyl) species, which was formed by O? O bond homolysis of the cobalt(III)–hydroperoxo complex. In conclusion, we have shown the synthesis, structural and spectroscopic characterization, and reactivities of mononuclear cobalt complexes with peroxo, hydroperoxo, and oxo ligands.     

A Ruthenium(III)–Oxyl Complex Bearing Strong Radical Character

Proton‐coupled electron‐transfer oxidation of a Ru^II?OH₂ complex, having an N‐heterocyclic carbene ligand, gives a Ru^III?O^. species, which has an electronically equivalent structure of the Ru^IV=O species, in an acidic aqueous solution. The Ru^III?O^. complex was characterized by spectroscopic methods and DFT calculations. The oxidation state of the Ru center was shown to be close to +3; the Ru?O bond showed a lower‐energy Raman scattering at 732 cm^?1 and the Ru?O bond length was estimated to be 1.77(1) Å. The Ru^III?O^. complex exhibits high reactivity in substrate oxidation under catalytic conditions; particularly, benzaldehyde and the derivatives are oxidized to the corresponding benzoic acid through C?H abstraction from the formyl group by the Ru^III?O^. complex bearing a strong radical character as the active species.     

A Two‐Coordinate Cobalt(II) Imido Complex with NHC Ligation: Synthesis,Structure, and Reactivity

The synthesis, structural characterization, and reactivity of the first two‐coordinate cobalt complex featuring a metal–element multiple bond [(IPr)Co(NDmp)] ( 4 ; IPr=1,3‐bis(2′,6′‐diisopropylphenyl)imidazole‐2‐ylidene; Dmp=2,6‐dimesitylphenyl) is reported. Complex 4 was prepared from the reaction of [(IPr)Co(η²‐vtms)₂] (vtms=vinyltrimethylsilane) with DmpN₃. An X‐ray diffraction study revealed its linear C? Co? N core and a short Co? N distance (1.691(6) Å). Spectroscopic characterization and calculation studies indicated the high‐spin nature of 4 and the multiple‐bond character of the Co? N bond. Complex 4 effected group‐transfer reactions to CO and ethylene to form isocyanide and imine, respectively. It also facilitated E? H (E=C, Si) σ‐bond activation of terminal alkyne and hydrosilanes to produce the corresponding cobalt(II) alkynyl and cobalt(II) hydride complexes as 1,2‐addition products.