Ni(0)-promoted activation of Csp2–H and Csp2–O bonds

A dinickel(0)–N₂ complex, stabilized with a rigid acridane-based PNP pincer ligand, was studied for its ability to activate C(sp²)–H and C(sp²)–O bonds. Stabilized by a Ni–μ–N₂–Na⁺ interaction, it activates C–H bonds of unfunctionalized arenes, affording nickel–aryl and nickel–hydride products. Concomitantly, two sodium cations get reduced to Na(0), which was identified and quantified by several methods. Our experimental results, including product analysis and kinetic measurements, strongly suggest that this C(sp²)–H activation does not follow the typical oxidative addition mechanism occurring at a low-valent single metal centre. Instead, via a bimolecular pathway, two powerfully reducing nickel ions cooperatively activate an arene C–H bond and concomitantly reduce two Lewis acidic alkali metals under ambient conditions. As a novel synthetic protocol, nickel(ii)–aryl species were directly synthesized from nickel(ii) precursors in benzene or toluene with excess Na under ambient conditions. Furthermore, when the dinickel(0)–N₂ complex is accessed via reduction of the nickel(ii)–phenyl species, the resulting phenyl anion deprotonates a C–H bond of glyme or 15-crown-5 leading to C–O bond cleavage, which produces vinyl ether. The dinickel(0)–N₂ species then cleaves the C(sp²)–O bond of vinyl ether to produce a nickel(ii)–vinyl complex. These results may provide a new strategy for the activation of C–H and C–O bonds mediated by a low valent nickel ion supported by a structurally rigidified ligand scaffold.

A structurally rigidified nickel(0) complex was found to be capable of cleaving both C(sp²)–H and C(sp²)–O bonds.     

Rh-catalyzed reagent-free ring expansion of cyclobutenones and benzocyclobutenones

Here we report a reagent-free rhodium-catalyzed ring-expansion reaction via C–C cleavage of cyclobutenones. A variety of poly-substituted cyclopentenones and 1-indanones can be synthesized from simple cyclobutenones and benzocyclobutenones. The reaction condition is near pH neutral without additional oxidants or reductants. The potential for developing a dynamic kinetic asymmetric transformation of this reaction has also been demonstrated. Further study supports the proposed pathway involving Rh-insertion into the cyclobutenone C–C bond, followed by β-hydrogen elimination, olefin insertion and reductive elimination.     

Cobalt-catalyzed intramolecular decarbonylative coupling of acylindoles and diarylketones through the cleavage of C–C bonds

We report here cobalt–N-heterocyclic carbene catalytic systems for the intramolecular decarbonylative coupling through the chelation-assisted C–C bond cleavage of acylindoles and diarylketones. The reaction tolerates a wide range of functional groups such as alkyl, aryl, and heteroaryl groups, giving the decarbonylative products in moderate to excellent yields. This transformation involves the cleavage of two C–C bonds and formation of a new C–C bond without the use of noble metals, thus reinforcing the potential application of decarbonylation as an effective tool for C–C bond formation.

A method for cobalt–N-heterocyclic carbene catalytic systems for the intramolecular decarbonylative coupling of ketones was achieved.     

Reversible assembly of enantiomeric helical polymers: from fibers to gels

A novel class of stereocomplexes is described by the interaction of helically complementary poly(phenylacetylene)s (PPAs) carrying an α-methoxy-α-trifluoromethylphenylacetamide pendant group. The formation of the stereocomplex requires the presence of cis amide bonds on the external crest of the polymer to provide efficient cooperative supramolecular hydrogen bonding between matching enantiomeric helical structures. The interlocking of the chains gives rise to supramolecular fiber-like aggregates that, at higher concentrations, result in gels. The modification of the cis–trans amide conformation at the pendant groups allows the controlled formation and cleavage of the stereocomplex due to a dramatic change between the intermolecular and intramolecular hydrogen bond interactions.     

Ruthenium-catalyzed cascade C–H activation/annulation of N-alkoxybenzamides: reaction development and mechanistic insight

A highly selective ruthenium-catalyzed C–H activation/annulation of alkyne-tethered N-alkoxybenzamides has been developed. In this reaction, diverse products from inverse annulation can be obtained in moderate to good yields with high functional group compatibility. Insightful experimental and theoretical studies indicate that the reaction to the inverse annulation follows the Ru(ii)–Ru(iv)–Ru(ii) pathway involving N–O bond cleavage prior to alkyne insertion. This is highly different compared to the conventional mechanism of transition metal-catalyzed C–H activation/annulation with alkynes, involving alkyne insertion prior to N–O bond cleavage. Via this pathway, the in situ generated acetic acid from the N–H/C–H activation step facilitates the N–O bond cleavage to give the Ru-nitrene species. Besides the conventional mechanism forming the products via standard annulation, an alternative and novel Ru(ii)–Ru(iv)–Ru(ii) mechanism featuring N–O cleavage preceding alkyne insertion has been proposed, affording a new understanding of transition metal-catalyzed C–H activation/annulation.

A highly selective ruthenium-catalyzed C–H activation/annulation through a pathway involving N–O bond cleavage prior to alkyne insertion is developed.     

Ceramic boron carbonitrides for unlocking organic halides with visible light

Photochemistry provides a sustainable pathway for organic transformations by inducing radical intermediates from substrates through electron transfer process. However, progress is limited by heterogeneous photocatalysts that are required to be efficient, stable, and inexpensive for long-term operation with easy recyclability and product separation. Here, we report that boron carbonitride (BCN) ceramics are such a system and can reduce organic halides, including (het)aryl and alkyl halides, with visible light irradiation. Cross-coupling of halides to afford new C–H, C–C, and C–S bonds can proceed at ambient reaction conditions. Hydrogen, (het)aryl, and sulfonyl groups were introduced into the arenes and heteroarenes at the designed positions by means of mesolytic C–X (carbon–halogen) bond cleavage in the absence of any metal-based catalysts or ligands. BCN can be used not only for half reactions, like reduction reactions with a sacrificial agent, but also redox reactions through oxidative and reductive interfacial electron transfer. The BCN photocatalyst shows tolerance to different substituents and conserved activity after five recycles. The apparent metal-free system opens new opportunities for a wide range of organic catalysts using light energy and sustainable materials, which are metal-free, inexpensive and stable.

A metal-free photoredox system was introduced for the transformation of organic halides to afford C–H, C–C, and C–S bonds without the addition of any metals, ligands, extra reductants or additives.     

Formation of a C–C double bond from two aliphatic carbons. Multiple C–H activations in an iridium pincer complex

The search for novel, atom-economic methods for the formation of C–C bonds is of crucial importance in synthetic chemistry. Especially attractive are reactions where C–C bonds are formed through C–H activation, but the coupling of unactivated, alkane-type C_sp³–H bonds remains an unsolved challenge. Here, we report iridium-mediated intramolecular coupling reactions involving up to four unactivated C_sp³–H bonds to give carbon–carbon double bonds under the extrusion of dihydrogen. The reaction described herein is completely reversible and the direction can be controlled by altering the reaction conditions. With a hydrogen acceptor present a C–C double bond is formed, while reacting under dihydrogen pressure leads to the reverse process, with some of the steps representing net C_sp³–C_sp³ bond cleavage. Mechanistic investigations revealed a conceptually-novel overall reactivity pattern where insertion or deinsertion of an Ir carbene moiety, formed via double C–H activation, into an Ir–C bond is responsible for the key C–C bond formation and cleavage steps.     

Visible light driven deuteration of formyl C–H and hydridic C(sp3)–H bonds in feedstock chemicals and pharmaceutical molecules

Deuterium labelled compounds are of significant importance in chemical mechanism investigations, mass spectrometric studies, diagnoses of drug metabolisms, and pharmaceutical discovery. Herein, we report an efficient hydrogen deuterium exchange reaction using deuterium oxide (D₂O) as the deuterium source, enabled by merging a tetra-n-butylammonium decatungstate (TBADT) hydrogen atom transfer photocatalyst and a thiol catalyst under light irradiation at 390 nm. This deuteration protocol is effective with formyl C–H bonds and a wide range of hydridic C(sp³)–H bonds (e.g. α-oxy, α-thioxy, α-amino, benzylic, and unactivated tertiary C(sp³)–H bonds). It has been successfully applied to the high incorporation of deuterium in 38 feedstock chemicals, 15 pharmaceutical compounds, and 6 drug precursors. Sequential deuteration between formyl C–H bonds of aldehydes and other activated hydridic C(sp³)–H bonds can be achieved in a selective manner.

A selective hydrogen deuterium exchange reaction with formyl C–H bonds and a wide range of hydridic C(sp³)–H bonds has been achieved by merging tetra-n-butylammonium decatungstate photocatalyst and a thiol catalyst under 390 nm light irradiation.     

Decarbonylative ether dissection by iridium pincer complexes

A unique chain-rupturing transformation that converts an ether functionality into two hydrocarbyl units and carbon monoxide is reported, mediated by iridium(i) complexes supported by aminophenylphosphinite (NCOP) pincer ligands. The decarbonylation, which involves the cleavage of one C–C bond, one C–O bond, and two C–H bonds, along with formation of two new C–H bonds, was serendipitously discovered upon dehydrochlorination of an iridium(iii) complex containing an aza-18-crown-6 ether macrocycle. Intramolecular cleavage of macrocyclic and acyclic ethers was also found in analogous complexes featuring aza-15-crown-5 ether or bis(2-methoxyethyl)amino groups. Intermolecular decarbonylation of cyclic and linear ethers was observed when diethylaminophenylphosphinite iridium(i) dinitrogen or norbornene complexes were employed. Mechanistic studies reveal the nature of key intermediates along a pathway involving initial iridium(i)-mediated double C–H bond activation.

A unique chain-rupturing transformation that converts an ether functionality into two hydrocarbyl units and carbon monoxide is reported.     

Site-selective functionalization of remote aliphatic C–H bonds via C–H metallation

Directing group assistance provided a paradigm for controlling site-selectivity in transition metal-catalyzed C–H functionalization reactions. However, the kinetically and thermodynamically favored formation of 5-membered metallacycles has greatly hampered the selective activation of remote C(sp³)–H bonds via larger-membered metallacycles. Recent development to achieve remote C(sp³)–H functionalization via the C–H metallation process largely relies on employing specific substrates without accessible proximal C–H bonds. Encouragingly, recent advances in this field have enabled the selective functionalization of remote aliphatic C–H bonds in the presence of equally accessible proximal ones by taking advantage of the switch of the regiodetermining step, ring strain of metallacycles, multiple non-covalent interactions, and favourable reductive elimination from larger-membered metallacycles. In this review, we summarize these advancements according to the strategies used, hoping to facilitate further efforts to achieve site- and even enantioselective functionalization of remote C(sp³)–H bonds.

Recent advances in site-selective functionalization of remote aliphatic C–H bonds in organometallic pathways are summarized.     

Selective cleavage of unactivated arene ring C–C bonds by iridium: key roles of benzylic C–H activation and metal–metal cooperativity

The cleavage of aromatic C–C bonds is central for conversion of fossil fuels into industrial chemicals and designing novel arene functionalisations through ring opening, expansion and contraction. However, the current progress is hampered by both the lack of experimental examples of selective oxidative addition of aromatic C–C bonds and limited understanding of the factors that favour insertion into the C–C rather than the C–H bonds. Here, we describe the comprehensive mechanism of the only reported chemo- and regioselective insertion of a transition metal into a range of substituted arene rings in simple iridium(i) complexes. The experimental and computational data reveal that this ring cleavage requires both reversible scission of a benzylic C–H bond and cooperativity of two Ir centres sandwiching the arene in the product-determining intermediate. The mechanism explains the chemoselectivity and scope of this unique C–C activation in industrially important methylarenes and provides a general insight into the role of metal–metal cooperativity in the cleavage of unsaturated C–C bonds.

The detailed mechanism of iridium-mediated C–C cleavage in unactivated arenes reveals the key factors enabling the process and helps predict the scope of the cleavage reaction.     

Estimation of Enthalpies of Alkoxy Radical Formation and Bond Strengths in Alcohols and Ether

Kinetic data on the thermal decomposition of peroxides were analyzed, and energies of the O–O bond dissociation were calculated. Enthalpies of formation of various alkoxy radicals and peroxides were determined. The dissociation energies for the O–H bonds in alcohols and C–O bonds in ethers were estimated. Comparative analysis of literature and obtained data was performed.     

Mechanisms and energetics of free radical initiated disulfide bond cleavage in model peptides and insulin by mass spectrometry

We investigate the mechanism of disulfide bond cleavage in gaseous peptide and protein ions initiated by a covalently-attached regiospecific acetyl radical using mass spectrometry (MS). Highly selective S–S bond cleavages with some minor C–S bond cleavages are observed by a single step of collisional activation. We show that even multiple disulfide bonds in intact bovine insulin are fragmented in the MS2 stage, releasing the A- and B-chains with a high yield, which has been challenging to achieve by other ion activation methods. Yet, regardless of the previous reaction mechanism studies, it has remained unclear why (1) disulfide bond cleavage is preferred to peptide backbone fragmentation, and why (2) the S–S bond that requires the higher activation energy conjectured in previously suggested mechanisms is more prone to be cleaved than the C–S bond by hydrogen-deficient radicals. To probe the mechanism of these processes, model peptides possessing deuterated β-carbon(s) at the disulfide bond are employed. It is suggested that the favored pathway of S–S bond cleavage is triggered by direct acetyl radical attack at sulfur with concomitant cleavage of the S–S bond (S_H2). The activation energy for this process is substantially lower by ∼9–10 kcal mol^–1 than those of peptide backbone cleavage processes determined by density functional quantum chemical calculations. Minor reaction pathways are initiated by hydrogen abstraction from the α-carbon or the β-carbon of a disulfide, followed by β-cleavages yielding C–S or S–S bond scissions. The current mechanistic findings should be generally applicable to other radical-driven disulfide bond cleavages with different radical species such as the benzyl and methyl pyridyl radicals.     

Nickel-catalyzed C–O/N–H,C–S/N–H,and C–CN/N–H annulation of aromatic amides with alkynes: C–O,C–S,and C–CN activation

The Ni-catalyzed reaction of ortho-phenoxy-substituted aromatic amides with alkynes in the presence of LiO^tBu as a base results in C–O/N–H annulation with the formation of 1(2H)-isoquinolinones. The use of a base is essential for the reaction to proceed. The reaction proceeds, even in the absence of a ligand, and under mild reaction conditions (40 °C). An electron-donating group on the aromatic ring facilitates the reaction. The reaction was also applicable to carbamate (C–O bond activation), methylthio (C–S bond activation), and cyano (C–CN bond activation) groups as leaving groups.

The Ni-catalyzed reaction of ortho-phenoxy-substituted aromatic amides with alkynes in the presence of LiO^tBu as a base results in C–O/N–H annulation with the formation of 1(2H)-isoquinolinones.     

Addition of aluminium,zinc and magnesium hydrides to rhodium(iii)

We report the addition of M–H bonds (M = Al, Zn, Mg) to a Rh(iii) intermediate generated from the reductive elimination of triethylsilane from [Cp*Rh(H)₂(SiEt₃)₂]. A series of new heterobimetallic complexes possessing Rh–M bonds have been isolated and characterised by a number of spectroscopic (¹H, ²⁹Si, ¹³C, ¹⁰³Rh NMR, infrared, and X-ray diffraction) and computational techniques (NBO and QTAIM analysis). Experimental and computational data are consistent with cleavage of the M–H bond upon addition to rhodium with formation of new Rh–M and Rh–H bonds. Upon photolysis the Al analogue of this series undergoes a further elimination reaction producing triethylsilane and a highly unusual Rh₂Al₂H₄ containing cluster proposed to contain an Al(i) bridging ligand.     

Electron‐Transfer and Hydride‐Transfer Pathways in the Stoltz–Grubbs Reducing System (KOtBu/Et3SiH)

Recent studies by Stoltz, Grubbs et al. have shown that triethylsilane and potassium tert ‐butoxide react to form a highly attractive and versatile system that shows (reversible) silylation of arenes and heteroarenes as well as reductive cleavage of C−O bonds in aryl ethers and C−S bonds in aryl thioethers. Their extensive mechanistic studies indicate a complex network of reactions with a number of possible intermediates and mechanisms, but their reactions likely feature silyl radicals undergoing addition reactions and S_H2 reactions. This paper focuses on the same system, but through computational and experimental studies, reports complementary facets of its chemistry based on a) single‐electron transfer (SET), and b) hydride delivery reactions to arenes.     

Sequential C–O decarboxylative vinylation/C–H arylation of cyclic oxalates via a nickel-catalyzed multicomponent radical cascade

A selective, sequential C–O decarboxylative vinylation/C–H arylation of cyclic alcohol derivatives enabled by visible-light photoredox/nickel dual catalysis is described. This protocol utilizes a multicomponent radical cascade process, i.e. decarboxylative vinylation/1,5-HAT/aryl cross-coupling, to achieve efficient, site-selective dual-functionalization of saturated cyclic hydrocarbons in one single operation. This synergistic protocol provides straightforward access to sp³-enriched scaffolds and an alternative retrosynthetic disconnection to diversely functionalized saturated ring systems from the simple starting materials.

A selective, sequential C–O decarboxylative vinylation/C–H arylation of cyclic alcohol derivatives enabled by visible-light photoredox/nickel dual catalysis has been described.     

Catalytic Cleavage of Ether CO Bonds by Pincer Iridium Complexes

The development of efficient catalytic methods to cleave the relatively unreactive C? O bonds of ethers remains an important challenge in catalysis. Building on our group’s recent work, we report the dehydroaryloxylation of aryl alkyl ethers using pincer iridium catalysts. This method represents a rare fully atom‐economical method for ether C? O bond cleavage.     

Ion-molecule reactions catalyzed by a single gold atom

We report that Au atoms within van der Waals complexes serve as catalysts for the first time. This was observed in ionization-induced chemistry of 1,6-hexanediol–Au and 1,8-octanediol–Au complexes formed in superfluid helium nanodroplets, where the addition of Au atom(s) made C₂H₄⁺ the sole prominent product in dissociative reactions. Density functional theory (DFT) calculations showed that the Au atom significantly strengthens all of the C–C bonds and weakens the C–O bonds in the meantime, making the C–C bonds stronger than the two C–O bonds in the ionized complexes. This leads to a preferential cleavage of the C–O bonds and thus a strong catalytic effect of the Au atoms in the reactions.

Single Au atoms within van der Waals complexes are found to serve as catalysts in ionisation-induced chemistry for the first time.     

Metal-free tandem carbene N–H insertions and C–C bond cleavages

A metal-free C–H [5 + 1] annulation reaction of 2-arylanilines with diazo compounds has been achieved, giving rise to two types of prevalent phenanthridines via highly selective C–C cleavage. Compared to the simple N–H insertion manipulation of diazo, this method elegantly accomplishes a tandem N–H insertion/S_EAr/C–C cleavage/aromatization reaction, and the synthetic utility of this new transformation is exemplified by the succinct syntheses of trisphaeridine and bicolorine alkaloids.

A metal-free C–H [5 + 1] annulation reaction of 2-arylanilines with diazo compounds has been achieved, giving rise to two types of prevalent phenanthridines via highly selective C–C cleavage.