Understanding the C−F Bond Activation Mediated by Frustrated Lewis Pairs: Crucial Role of Non-covalent Interactions

The activation of a single C−F bond in di- and trifluoromethyl groups by frustrated Lewis pairs (FLPs) has been computationally explored by means of Density Functional Theory calculations. It is found that in this activation reaction the FLP partners exhibit a peculiar cooperative action, which is markedly different from related FLP-mediated processes, and where non-covalent interactions established between the Lewis base and the substrate play a decisive role. In addition, the process proceeds through the intermediacy of a hypervalent species featuring a pentacoordinate carbon atom, which is rare in the chemistry of FLPs. The physical factors controlling this process as well as the bonding situation of these hypervalent intermediates have been quantitatively analyzed in detail by using state-of-the-art computational methods to not only rationalize the mechanism of the transformation but also to guide experimentalists towards the realization of these so far elusive hypervalent systems.     

Frustrated Lewis Pairs Comprising Nitrogen Lewis Acids for Si–H Bond Activation

N-heterocyclic nitrogen Lewis acids are a recent addition to the field of organic chemistry. Based on nitrenium cations, these acids where previously shown to generate Lewis adducts when combined with the appropriate Lewis bases. Herein, a triazinium-based Lewis acid was combined with tBu₃P to generate a frustrated Lewis pair (FLP) capable of cleaving, for the first time, Si−H bonds in silanes. Whereas low yields were initially encountered owing to insufficient Lewis acidity, a new nitrenium-based Lewis acid was synthesized, and its superior Lewis acidity was experimentally and computationally confirmed. A FLP based on this acid cleaved the Si−H bond in PhSiH₃, generating the triazane product in a quantitative yield. This unprecedented N−H triazane was fully characterized by multinuclear NMR techniques and single-crystal X-ray crystallography. A new class of compounds, N-H triazanes display the potential capacity to participate in hydride transfer reactions.     

Al/P- and Ga/P-Based Frustrated Lewis Pairs and Electronically Unsaturated Substrates: Ring Cleavage and Ring Closure,C−C and C−N Bond Formation

Al/P- and Ga/P-based frustrated Lewis pairs (FLPs) reacted with an azirine under mild conditions under cleavage of the heterocycle on two different positions. Opening of the C−C bond yielded an unusual nitrile–ylide adduct in which a C−N moiety coordinated to the FLP backbone. Cleavage of a C−N bond afforded the thermodynamically favored enamine adduct with the N atom bound to P and Al or Ga atoms. Ring closure was observed upon treatment of an Al/P FLP with electronically unsaturated substrates (4-(1-cyclohexenyl)-1-aza-but-1-en-3-ynes) and yielded by C−N bond formation hexahydroquinoline derivatives, which coordinated to the FLP through P−C and Al−C bonds. Diphenylcyclopropenone showed a diverse reactivity, which depending on steric shielding and the polarizing effect of Al or Ga atoms afforded different products. An AltBu₂/P FLP yielded an adduct with the C=O group coordinated to P and Al. The dineopentyl derivative gave an equilibrium mixture consisting of a similar product and a simple adduct with O bound to Al and a three-coordinate P atom. Both compounds co-crystallize. The Ga/P FLP only formed the simple adduct with the same substrate. Rearrangement resulted in all cases in C₃-ring cleavage and migration of a mesityl group from P to a former ring C atom by C−C bond formation. Diphenylthiocyclopropenone (evidence for the presence of P=C bonds) and an imine derivative afforded similar products.     

Coordination Defect-Induced Frustrated Lewis Pairs in Polyoxo-metalate-Based Metal–Organic Frameworks for Efficient Catalytic Hydrogenation

Precise control of the structure and spatial distance of Lewis acid (LA) and Lewis base (LB) sites in a porous system to construct efficient solid frustrated Lewis pair (FLP) catalyst is vital for industrial application but remains challenging. Herein, we constructed FLP sites in a polyoxometalate (POM)-based metal–organic framework (MOF) by introducing coordination-defect metal nodes (LA) and surface-basic POM with abundant oxygen (LB). The well-defined and unique spatial conformation of the defective POM-based MOF ensure that the distance between LA and LB is at ~4.3 Å, a suitable distance to activate H₂. This FLP catalyst can heterolytically dissociate H₂ into active H^δ−, thus exhibiting high activity in hydrogenation, which is 55 and 2.7 times as high as that of defect-free POM-based MOF and defective MOF without POM, respectively. This work provides a new avenue toward precise design multi-site catalyst to achieve specific activation of target substrate for synergistic catalysis.     

Palladium-Catalyzed Skeletal Rearrangement of Substituted 2-Silylaryl Triflates via 1,5-C−Pd/C−Si Bond Exchange

A palladium-catalyzed skeletal rearrangement of 2-(2-allylarylsilyl)aryl triflates has been developed to give highly fused tetrahydrophenanthrosilole derivatives via unprecedented 1,5-C−Pd/C−Si bond exchange. The reaction pathways can be switched toward 4-membered ring-forming C(sp²)−H alkylation by tuning the reaction conditions to give completely different products, fused dihydrodibenzosilepin derivatives, from the same starting materials. The inspection of the reaction conditions revealed the importance of carboxylates in promoting the C−Pd/C−Si bond exchange.     

Silylene–Nickel Promoted Cleavage of B−O Bonds: From Catechol Borane to the Hydroborylene Ligand

The first 16 valence electron [bis(NHC)](silylene)Ni⁰ complex 1 , [(^TMSL)ClSi:→Ni(NHC)₂], bearing the acyclic amido-chlorosilylene (^TMSL)ClSi: (^TMSL=N(SiMe₃)Dipp; Dipp=2,6-Prⁱ₂C₆H₄) and two NHC ligands (N-heterocyclic carbene=:C[(Prⁱ)NC(Me)]₂) was synthesized in high yield and structurally characterized. Compound 1 is capable of facile dihydrogen activation under ambient conditions to give the corresponding HSi-NiH complex 2 . Most notably, 1 reacts with catechol borane to afford the unprecedented hydroborylene-coordinated (chloro)(silyl)nickel(II) complex 3 , {[cat(^TMSL)Si](Cl)Ni←:BH(NHC)₂}, via the cleavage of two B−O bonds and simultaneous formation of two Si−O bonds. The mechanism for the formation of 3 was rationalized by means of DFT calculations, which highlight the powerful synergistic effects of the Si:→Ni moiety in the breaking of incredibly strong B−O bonds.     

Semihydrogenation of Alkynes Catalyzed by a Pyridone Borane Complex: Frustrated Lewis Pair Reactivity and Boron–Ligand Cooperation in Concert

The metal-free cis selective hydrogenation of alkynes catalyzed by a boroxypyridine is reported. A variety of internal alkynes are hydrogenated at 80 °C under 5 bar H₂ with good yields and stereoselectivity. Furthermore, the catalyst described herein enables the first metal-free semihydrogenation of terminal alkynes. Mechanistic investigations, substantiated by DFT computations, reveal that the mode of action by which the boroxypyridine activates H₂ is reminiscent of the reactivity of an intramolecular frustrated Lewis pair. However, it is the change in the coordination mode of the boroxypyridine upon H₂ activation that allows the dissociation of the formed pyridone borane complex and subsequent hydroboration of an alkyne. This change in the coordination mode upon bond activation is described by the term boron-ligand cooperation.     

Skeletal Transformation Triggered by C−F Bond Activation after Photochemical Rearrangement of Fluorinated [7]Helicenes

Tri- and tetra-fluorinated [7]helicenes are photolabile and undergo a double fluorine atom transfer. Herein, we show that the transferred product further undergoes a skeletal transformation on silica gel. The transformation begins with activation of the allylic C−F bond on the silanol surface. Then, the resulting carbocation readily undergoes a regioselective nucleophilic aromatic substitution with water, depending on the position of the fluorine substituents. Hexafluoro-2-propanol also activated the allylic C−F bond and acted as a nucleophile. These findings support the generation of a highly reactive cationic electrophilic intermediate in the successive transformations involving fluorine atoms.     

Synthesis of Diverse Aromatic Ketones through C−F Cleavage of Trifluoromethyl Group

An efficient synthetic method of aromatic ketones through C−F cleavage of trifluoromethyl group is disclosed. The high functional group tolerance of the transformation and the remarkable stability of trifluoromethyl group in various reactions enabled multi-substituted aromatic ketone synthesis in an efficient route involving useful transformations such as ortho-lithiation, aryne chemistry, and cross-couplings.     

Redox-Induced Oxidative C−C Bond Cleavage of 2,2′-Pyridil in Diruthenium Complexes

In the recent years, there has been an emerging research interest in the domain of C−C bond-cleavage reactions. The present contribution deals with the redox-mediated dioxygen activation and C−C bond cleavage in a diruthenium complex [(acac)₂Ru^II(μ-L1)Ru^II(acac)₂], 1 (acac=acetylacetonate) incorporating 2,2′-pyridil (L1) as the bridging ligand. The above process leads to a C−C-cleaved monomeric product [(acac)₂Ru^III(pic⁻)], 2 (pic⁻=piconilate). Intriguingly, similar diastereomeric complexes [(acac)₂Ru^II(μ-L2)Ru^II(acac)₂], meso (ΔΛ): 3 a and rac (ΔΔ/ΛΛ): 3 b , involving an analogous diimine bridge (L2=N1,N2-diphenyl-1,2-di(pyridin-2-yl)ethane-1,2-diimine), were stable towards such oxidative transformations. Electrochemical and spectroelectrochemical studies, in combination, establish the potential non-innocent feature of the 2,2′-Pyridil (L1) and its derivative (L2) both in oxidation and reduction processes. Additionally, theoretical calculations have been employed to verify the redox states and their behavior. Furthermore, transition state (TS) calculations at the M06L/6-31G*/LANL2DZ level of theory together with detailed kinetic studies outline a putative mechanism for the selective transformation of 1 → 2 involving the formation of an intermediate bearing peroxide linkage to complex 1 .     

Metal-Free,Visible-Light-Induced Selective C−C Bond Cleavage of Cycloalkanones with Molecular Oxygen

A metal-free, visible-light-induced oxidative C−C bond cleavage of cycloketones with molecular oxygen is described. Cooperative Brønsted-acid catalysis and photocatalysis enabled selective C−C bond cleavage of cycloketones to generate an array of γ-, δ- and ϵ-keto esters under very mild conditions. Mechanistic studies indicate that singlet molecular oxygen (¹O₂) is responsible for this transformation.     

Intramolecular Nitrene Insertion into Saturated C−H-Bond-Mediated C−N Bond Cleavage of a Coordinated NHC Ligand

Ruthenium(II) complexes bearing a tridentate bis(N-heterocyclic carbene) ligand reacted with iminoiodanes (PhI=NR) resulting in the formation of isolable ruthenium(III)–amido intermediates, which underwent cleavage of a C−N bond of the tridentate ligand and formation of an N-substituted imine group. The Ru^III–amido intermediates have been characterized by ¹H NMR, UV/Vis, ESI-MS, and X-ray crystallography. DFT calculations were performed to provide insight into the reaction mechanism.     

Copper-Catalyzed Dynamic Kinetic Asymmetric P−C Coupling of Secondary Phosphine Oxides and Aryl Iodides

Transition-metal-catalyzed enantioselective P−C cross-coupling of secondary phosphine oxides (SPOs) is an attractive method for synthesizing P-stereogenic phosphorus compounds, but the development of such a dynamic kinetic asymmetric process remains a considerable challenge. Here we report an unprecedented highly enantioselective dynamic kinetic intermolecular P−C coupling of SPOs and aryl iodides catalyzed by copper complexes ligated by a finely modified chiral 1,2-diamine ligand. The reaction tolerates a wide range of SPOs and aryl iodides, affording P-stereogenic tertiary phosphine oxides (TPOs) in high yields and with good enantioselectivity (average 89.2 % ee). The resulting enantioenriched TPOs were transformed into structurally diverse P-chiral scaffolds, which are highly valuable as ligands and catalysts in asymmetric synthesis.     

Strategy of Controlling Ru Particles Size for Regulating Cleavage Rate of C−C and C−O Bonds of Biomass Polyols to Enhance the Yield of Methane

A series of porous silica were prepared by alkyl-trimethyl-ammonium bromide with different carbon chain lengths (PS-n, n corresponds to the carbon chain length). These templates carried out precise structure regulation of porous silica. The Ru particles supported on porous silica behaved in precisely controlled size according to the pore diameter. When used in the hydrogenolysis of biomass polyols, a higher methane yield was achieved over Ru/PS-16. This result can be explained by the higher C₂/C₃ over Ru/PS-16 than others.     

Enantioselective Cleavage of Cyclobutanols Through Ir-Catalyzed C−C Bond Activation: Mechanistic and Synthetic Aspects

The Ir-catalyzed conversion of prochiral tert-cyclobutanols to β-methyl-substituted ketones proceeds under comparably mild conditions in toluene (45–110 °C) and is particularly suited for the enantioselective desymmetrization of β-oxy-substituted substrates to give products with a quaternary chirality center with up to 95 % ee using DTBM-SegPhos as a chiral ligand. Deuteration experiments and kinetic isotope effect measurements revealed major mechanistic differences to related Rh^I-catalyzed transformations. Supported by DFT calculations we propose the initial formation of an Ir^III hydride intermediate, which then undergoes a β-C elimination (C−C bond activation) prior to reductive C−H elimination. The computational model also allows the prediction of the stereochemical outcome. The Ir-catalyzed cyclobutanol cleavage is broadly applicable but fails for substrates bearing strongly coordinating groups. The method is of particular value for the stereo-controlled synthesis of substituted chromanes related to the tocopherols and other natural products.     

Photocatalytic C−C Cleavage of Methylenecyclobutanes for γ,δ-Unsaturated Aldehydes by Strain Release

Radical additions onto olefins have surfaced as an increasingly powerful strategy for the synthesis of difunctionalized scaffolds. However, despite of major advances, known approaches continue to be largely limited to two manifolds, namely 1,2-difunctionalization of alkenes and remote difunctionalization via hydrogen atom transfer (HAT). Herein, we describe a mechanistically distinct approach by photoinduced carbon-carbon (C−C) activation/ring-opening to access γ,δ-unsaturated aldehydes from methylenecyclobutanols and sulfonyl chlorides by strain release. Remarkably, the sulfonyl motif on the products was easily removed by another photocatalytic process, which enabled the concise assembly of the natural product alatanone A. The synthetic utility of our approach was reflected by versatile functional group tolerance, ample substrate scope, and scalability. The photocatalysis represents a conceptually distinct alternative to existing approaches for remote 1,4-diversifications, with a double bond remaining in the thus obtained products.     

Highly Conjugated π-Systems Arising from Cannibalistic Hexadehydro-Diels–Alder Couplings: Cleavage of C−C Single and Triple Bonds

We have investigated the cannibalistic self-trapping reaction of an ortho-benzyne derivative generated from 1,11-bis(p-tolyl)undeca-1,3,8,10-tetrayne in an HDDA reaction. Without adding any specific trapping agent, the highly reactive benzyne is trapped by another bisdiyne molecule in at least three different modes. We have isolated and characterized the resulting products and performed high-level calculations concerning the reaction mechanism. During the cannibalistic self-trapping process, either a C≡C triple bond or an sp–sp³ C−C single bond is cleaved. Up to seven rings and nine C−C bonds are formed starting from two 1,11-bis(p-tolyl)undeca-1,3,8,10-tetrayne molecules. Our experiments and calculations provide considerable insight into the variety of reaction pathways which the ortho-benzyne derivative, generated from a bisdiyne, can take when reacting with another bisdiyne molecule.     

Re-Catalyzed Annulations of Weakly Coordinating N-Carbamoyl Indoles/Indolines with Alkynes via C−H/C−N Bond Cleavage

Described herein are rhenium-catalyzed [3+2] annulations of N-carbamoyl indoles with alkynes via C−H/C−N bond cleavage, which provide rapid access to fused-ring pyrroloindolone derivatives. For the first time, the weakly coordinating O-directing group was successfully employed in rhenium-catalyzed C−H activation reactions, enabled by the unique catalytic trio of Re₂(CO)₁₀, Me₂Zn and ZnCl₂. Mechanistic studies revealed that aminozinc species plays an important role in the reaction. Based on the mechanistic understanding, a more powerful catalytic trio of Re₂(CO)₁₀, [MeZnNPh₂]₂ and Zn(OTf)₂ was devised and applied successfully in the [4+2] annulations of indolines and alkynes affording pyrroloquinolinone derivatives.     

Direct C−C Double Bond Cleavage of Alkenes Enabled by Highly Dispersed Cobalt Catalyst and Hydroxylamine

The utilization of a single-atom catalyst to break C−C bonds merges the merits of homogeneous and heterogeneous catalysis and presents an intriguing pathway for obtaining high-value-added products. Herein, a mild, selective, and sustainable oxidative cleavage of alkene to form oxime ether or nitrile was achieved by using atomically dispersed cobalt catalyst and hydroxylamine. Diversified substrate patterns, including symmetrical and unsymmetrical alkenes, di- and tri-substituted alkenes, and late-stage functionalization of complex alkenes were demonstrated. The reaction was successfully scaled up and demonstrated good performance in recycling experiments. The hot filtration test, catalyst poisoning and radical scavenger experiment, time kinetics, and studies on the reaction intermediate collectively pointed to a radical mechanism with cobalt/acid/O₂ promoted C−C bond cleavage as the key step.     

Dienone—phenol Rearrangement of C—9 Oxygenated Decalinic Dienone and Analogs through B—Ring Cleavage

Dehydrogenation of 9-hydroxy decalinic enones and analogs with DDQ resulted in a formal dienone-phenol type rearrangement via B-ring cleavage, while the corresponding dienone acetates underwent base-catalyzed formal dienone-phenol type rearrangement analogously.