Nickel-catalyzed alkenylation and alkylation of fluoroarenes via activation of C-H bond over C-F bond

Nickel/P(c-C(5)H(9))(3) (PCyp(3)) catalyst effects the addition reactions of fluoroarenes across alkynes, 1,3-dienes, and vinylarenes via the activation of C-H bonds over C-F bonds. The acidic C-H bonds located ortho to fluorine are exclusively activated to afford a range of alkenylated and alkylated fluoroarenes.     

Intermolecular and intramolecular, platinum-catalyzed, acceptorless dehydrogenative coupling of hydrosilanes with aryl and aliphatic methyl C-H bonds

Intermolecular acceptorless dehydrogenative coupling of silanes with arene C-H bonds and intramolecular coupling of silanes with aryl and alkyl C-H bonds occur in good yield in the presence of 5 mol % of TpMe2PtMe2H (TpMe2 = hydridotris(3,5-dimethylpyrazolyl)borate) and related platinum(IV) complexes. The intermolecular reactions of arenes occurred with both trialkyl and dialkylaryl silanes. Intramolecular reactions of dialkylsilylalkylarenes occurred at aryl C-H bonds, and reactions of tributylsilane or dibutylphenylsilane occurred intramolecularly at the aliphatic, primary C-H bond. The reactions of arenes occurred preferentially at the least sterically hindered C-H bonds and preferentially with more electron-poor arenes. Crossover experiments and the lack of reactivity of the arylsilanes with H2 imply that the dehydrogenative silylation of arenes can be irreversible, even in a closed reaction vessel.     

Carbon dioxide as a carbon source in organic transformation: carbon-carbon bond forming reactions by transition-metal catalysts

Recent carbon-carbon bond forming reactions of carbon dioxide with alkenes, alkynes, dienes, aryl zinc compounds, aryl boronic esters, aryl halides, and arenes having acidic C-H bonds are reviewed in which transition-metal catalysts play an important role.     

Recent Advances in C-F Bond Cleavage Enabled by Visible Light Photoredox Catalysis

The creation of new bonds via C-F bond cleavage of readily available per- or oligofluorinated compounds has received growing interest. Using such a strategy, a myriad of valuable partially fluorinated products can be prepared, which otherwise are difficult to make by the conventional C-F bond formation methods. Visible light photoredox catalysis has been proven as an important and powerful tool for defluorinative reactions due to its mild, easy to handle, and environmentally benign characteristics. Compared to the classical C-F activation that proceeds via two-electron processes, radicals are the key intermediates using visible light photoredox catalysis, providing new modes for the cleavage of C-F bonds. In this review, a summary of the visible light-promoted C-F bond cleavage since 2018 was presented. The contents were classified by the fluorosubstrates, including polyfluorinated arenes, gem-difluoroalkenes, trifluoromethyl arenes, and trifluoromethyl alkenes. An emphasis is placed on the discussion of the mechanisms and limitations of these reactions. Finally, my personal perspective on the future development of this rapidly emerging field was provided.     

Theoretical investigation of in-plane hydrogen-bonded complexes of ammonia with partially substituted fluorobenzenes

Systematic investigation of in-plane hydrogen-bonded complexes of ammonia with partially substituted fluorobenzenes has revealed that fluorobenzene, difluorobenzene, and trifluorobenzene favor formation of cyclic complexes with a C-H...N-H...F-C binding motif. On the other hand, tetrafluorobenzene and pentafluorobenzene favor formation of linear C-H...N hydrogen-bonded complexes. The complete absence of exclusively linear N-H...F hydrogen-bonded complexes for the entire series indicates that C-F bond in fluorobenzenes is a reluctant hydrogen-bond acceptor. However, fluorine does hydrogen bond when cooperatively stabilized with C-H...N hydrogen bonds for the lower fluoro analogues. The propensity of fluorobenzenes to adapt to the C-H...N-H...F-C binding motif decreases with the progressive fluorination of the benzene ring and disappears completely when benzene ring is substituted with five or more fluorine atoms.     

Theoretical study of C-H and C-F activation in CH4-nFn (n =1-4) molecules by platinum

CASSCF followed by MRMP2 calculations have been carried out to analyze the reactions of a naked platinum atom with the fluorocarbon compounds CH(4-n)Fn (n = 1-4). For each of these interactions the potential-energy surfaces which correlate with the triplet ground state and the first excited singlet state of the free fragments were investigated for representative states evolving from different approaching modes of the reactants. For all the fluorinated fragments activation of the C-H and C-F bonds by the metal is strongly determined by the low-multiplicity channels arising from the first excited asymptote. Although stable products are predicted for insertion of the metallic atom into both the C-H and the C-F bonds of the different fluorocarbon compounds, comparison between the calculated energy barriers for reactions taking place in the same fluorinated molecule suggests in all cases a kinetic preference for the C-H bond oxidative addition to the platinum atom.     

Importance of palladium-carbon bond energies in direct arylation of polyfluorinated benzenes

Fagnou et al. reported direct arylation reactions that use palladium catalysts to couple Ar(1)-X to Ar(2)-H with the aid of a coordinated base. These reactions are particularly favourable for polyfluorinated arenes Ar(2)-H (see S. I. Gorelsky, D. Lapointe and K. Fagnou, J. Am. Chem. Soc. 2008, 130, 10848). In this paper, we show by means of a DFT analysis how the energetics and activation energies vary with fluorine substitution and examine the structures of intermediates and transition states. The reactant is modelled by Pd(OAc)(Ph)(PMe(3))(DMA) (DMA = dimethylacetamide). The sequence consists of (a) replacement of DMA by arene, (b) Concerted Deprotonation Metallation (CMD), (c) decoordination of AcOH, (d) reductive elimination of biaryl. Many of the variations are dominated by the number of fluorine substituents ortho to the C-H bond and fall into three groups labelled accordingly: Set0Fo, Set1Fo, and Set2Fo. In the first step a coordinated solvent is replaced by the arene. The arenes of Set0Fo and Set1Fo coordinate in a conventional η(2)-CH=CH mode, whereas the arenes of Set2Fo coordinate in an η(1)-CH mode assisted by an OH-C hydrogen bond from the coordinated acetate. Both the energy barriers to CMD and the product energies fall into the three typical sets with the highest barrier and highest product energy being for Set0Fo. They correlate more satisfactorily with the variations in Pd-C bond energies than with the C-H acidities. The barriers to reductive elimination from Pd(Ph)(Ar(F))(PMe(3))(AcOH) increase systematically from Set0Fo to Set2Fo as the Pd-C bond becomes stronger in a regular fashion from Set0Fo to Set2Fo. Again there is a strong correlation between the energy barriers to reductive elimination and the Pd-C bond energies. It is found overall that the key aspects of the reactions are: (a) the lowering of the energy of the CMD step by the ortho fluorine substituents, (b) the regioselective activation of C-H bonds ortho to fluorine which is also determined at the CMD step, (c) the decoordination of AcOH, which maintains the transition state for reductive elimination at low Gibbs free energy. The presence of fluorine increases the effectiveness of the reaction in the sense of points a and b via the increasing strength of the palladium-carbon bond.     

Regioselectivity of the borylation of alkanes and arenes

The borylation of alkanes and arenes has become some of the most practical C-H bond functionalization chemistry. Most striking is the high regioselectivity of these reactions. Rhodium and ruthenium complexes catalyze with exquisite selectivity the borylation of methyl C-H bonds over methylene or methine C-H bonds. Iridium complexes catalyze, with high steric control, the borylation of one aromatic C-H bond over another. In contrast, iridium-catalyzed borylation of heteroaromatic C-H bonds is more controlled by electronic effects. Detailed information on these selectivities and mechanistic information on the origins of this regioselectivity will be described in this critical review (95 references).     

A comparison of C-F and C-H bond activation by zerovalent ni and pt: a density functional study

Density functional theory indicates that oxidative addition of the C-F and C-H bonds in C6F6 and C6H6 at zerovalent nickel and platinum fragments, M(H2PCH2CH2PH2), proceeds via initial exothermic formation of an eta2-coordinated arene complex. Two distinct transition states have been located on the potential energy surface between the eta2-coordinated arene and the oxidative addition product. The first, at relatively low energy, features an eta3-coordinated arene and connects two identical eta2-arene minima, while the second leads to cleavage of the C-X bond. The absence of intermediate C-F or C-H sigma complexes observed in other systems is traced to the ability of the 14-electron metal fragment to accommodate the eta3-coordination mode in the first transition state. Oxidative addition of the C-F bond is exothermic at both nickel and platinum, but the barrier is significantly higher for the heavier element as a result of strong 5dpi-ppi repulsions in the transition state. Similar repulsive interactions lead to a relatively long Pt-F bond with a lower stretching frequency in the oxidative addition product. Activation of the C-H bond is, in contrast, exothermic only for the platinum complex. We conclude that the nickel system is better suited to selective C-F bond activation than its platinum analogue for two reasons: the strong thermodynamic preference for C-F over C-H bond activation and the relatively low kinetic barrier.     

Intramolecular oxidative addition of C-F and C-H bonds to [Pt(dba)2]. Crystal structure of [PtCl{Me2NCH2CH2NCH(2,4,5-C6HF3)}]

The reactions of compound [Pt(dba)₂] with ligands RCHNCH₂CH₂NMe₂ (1a-1f) in which R is a fluorinated aryl ring produced activation of C-F bonds when two fluorine atoms are present in the ortho positions of the aryl ring or activation of C-H bonds for ligands containing only one fluoro substituent in ortho. Both C-F and C-H bond activation are favoured by an increase of the degree of fluorination of the ring. Further reaction with lithium halides produced cyclometallated platinum (II) compounds [PtX(Me₂NCH₂CH₂NCHR)] (X = Br, Cl) (2) containing a terdentate [C,N,N′] ligand. The obtained compounds were fully characterized including a structure determination for [PtCl{Me₂NCH₂CH₂NCH(2,4,5-C₆HF₃)}] (2d′).     

Rh-catalyzed ortho-selective C-H borylation of N-functionalized arenes with silica-supported bridgehead monophosphine ligands

Supported phosphine-Rh systems, prepared in situ from silica-supported bridgehead monophosphines and [Rh(OH)(cod)](2), have enabled ortho-selective C-H borylation for a range of arenes containing nitrogen-based directing groups. The regioselectivity was excellent with various N-directing groups, including saturated and unsaturated N-heterocycles, tert-aminoalkyl groups, and imine-type C-N double bonds. The reaction showed significant tolerance toward steric repulsion around the reacting C-H bond. This Rh catalysis complements the Ir-catalyzed ortho-borylation, which is effective for arenes with oxygen-based directing groups.     

Understanding organofluorine chemistry. An introduction to the C-F bond

Fluorine is the most electronegative element in the periodic table. When bound to carbon it forms the strongest bonds in organic chemistry and this makes fluorine substitution attractive for the development of pharmaceuticals and a wide range of speciality materials. Although highly polarised, the C-F bond gains stability from the resultant electrostatic attraction between the polarised C delta+ and F delta- atoms. This polarity suppresses lone pair donation from fluorine and in general fluorine is a weak coordinator. However, the C-F bond has interesting properties which can be understood either in terms of electrostatic/dipole interactions or by considering stereoelectronic interactions with neighbouring bonds or lone pairs. In this tutorial review these fundamental aspects of the C-F bond are explored to rationalise the geometry, conformation and reactivity of individual organofluorine compounds.     

N-氟代苯磺酰亚胺参与的过渡金属催化C—H氟化和胺化的研究进展

众多胺类及含氟化合物具有重要的生理活性,在医药领域均具有不可替代的作用.过渡金属催化的C—H胺化及氟化反应因其高反应效率及原子经济性,受到了合成化学家的关注,为生物碱类天然产物及含氟分子的合成提供了便利.N-氟代双苯磺酰胺(NFSI)兼有氟原子及含氮官能团,可以在过渡金属催化下参与多种类型的有机反应,实现C—H键的氟化...     

The geometry of intermolecular interactions in some crystalline fluorine-containing organic compounds

The propensity of C-F groups to form C-F H-C interactions with C-H groups on other molecules has been analyzed. Crystal structures of molecules containing only carbon, hydrogen, and fluorine, but no oxygen, nitrogen, or other hydrogen-bond-forming elements, were chosen for an initial study in which the intermolecular interactions in crystal-structure determinations of polycyclic aromatic hydrocarbons and their analogous fluoro derivatives were analyzed. It is found that C-F H-C interactions occur, but they are weak, as judged by the intermolecular distances and the angles involved. In a study of crystal structures of molecules containing other elements in addition to carbon, hydrogen, and fluorine, it was found that when an oxygen atom is in a neighboring position on an interacting molecule, a C-O group is more likely than a C-F group to form a linear interaction to the hydrogen atom of a C-H group. Thus, in spite of the high electronegativity of the fluorine atom, a C-F group competes unfavorably with a C-O^–, C-OH, or C=O group to form a hydrogen bond to an O-H, N-H, or C-H group. It is found, however, particularly for polycyclic aromatic hydrocarbons with substituted CF₃ groups that, in the absence of other functional groups that can form stronger interactions, C-F H-C interactions may serve to align molecules and give a different crystal packing from that in the pure hydrocarbon (where fluorine is replaced by hydrogen). Thus, C-F H-X (X = C, N, O) interactions are very weak, much weaker than C=O H-X interactions, but they cannot be ignored in predictions of modes of molecular packing in complexes and in crystals.     

Pd(OAc)(2)-catalyzed oxidative C-H/C-H cross-coupling of electron-deficient polyfluoroarenes with simple arenes

Pd(OAc)(2)-catalyzed intermolecular C-H/C-H cross-coupling reactions between electron-deficient polyfluoroarenes and simple arenes for the synthesis of fluorinated biaryls have been developed. Deuterium-labeling experiments suggested that C-H bond cleavage of the simple arenes rather than the polyfluoroarenes is involved in the rate-limiting step.     

C-H activation of terminal alkynes by tris-(3,5-dimethylpyrazolyl)boraterhodiumneopentylisocyanide: new metal-carbon bond strengths

C-H bond activation of terminal alkynes by [Tp'Rh(CNneopentyl)] (Tp' = hydridotris-(3,5-dimethylpyrazolyl)borate) resulted in the formation of terminal C-H bond activation products Tp'Rh(CNneopentyl)(C≡CR)H (R = t-Bu, SiMe(3), hexyl, CF(3), p-MeOC(6)H(4), Ph, and p-CF(3)C(6)H(4)). A combination of kinetic selectivity determined in competition reactions and activation energy for reductive elimination has allowed for the calculation of relative Rh-C(alkynyl) bond strengths. The bond strengths of Rh-C(alkynyl) products are noticeably higher than those of Rh-C(aryl) and Rh-C(alkyl) analogues. The relationship between M-C and C-H bond strengths showed a linear correlation (slope R(M-C/H-C) = 1.32), and follows energy correlations previously established for unsubstituted sp(2) and sp(3) C-H bonds in aliphatic and aromatic hydrocarbons.     

Intermolecular amidation of unactivated sp2 and sp2 C-H bonds via palladium-catalyzed cascade C-H activation/nitrene insertion

This communication describes the Pd(OAc)2-catalyzed intermolecular amidation reactions of unactivated sp2 and sp3 C-H bonds using primary amides and potassium persulfate. The substrates containing a pendent oxime or pyridine group were amidated with excellent chemo- and regioselectivities. It is noteworthy that reactive C-X bonds were well-tolerated and a variety of primary amides can be effective nucleophiles for the Pd-catalyzed C-H amidation reactions. For the reaction of unactivated sp3 C-H bonds, beta-amidation of 1 degrees sp3 C-H bonds versus 2 degrees C-H bonds is preferred. The catalytic reaction is initiated by chelation-assisted cyclopalladation involving C-H bond activation. Preliminary mechanistic study suggested that the persulfate oxidation of primary amides should generate reactive nitrene species, which then reacted with the cyclopalladated complex.     

Metal-catalyzed reactions of diborons for synthesis of organoboron compounds

Metal-catalyzed borylation of alkenes, alkynes, arenes, and organic halides with B-B or H-B compounds has been developed for the synthesis of organoboron compounds from simple organic substrates. The platinum(0)-catalyzed addition of bis(pinacolato)diboron to alkenes and alkynes provided a method for the stereoselective synthesis of cis-bis(boryl)alkanes or cis-bis(boryl)alkenes. The addition of diboron to 1,3-dienes with platinum(0) complexes provided a new access to cis-1,4-bis(boryl)-2-butene derivatives, which are versatile reagents for diastereoselective allylboration of carbonyl compounds. The first one-step procedure for the syntheses of aryl-, vinyl-, and allylboronates was achieved via crosscoupling reactions of diborons with aryl and 1-alkenyl halides or triflates and allyl acetates. Direct C-H borylation of arenes catalyzed by a transition metal complex was studied as an economical protocol for the synthesis of a variety of arylboron derivatives. Ir-catalyzed C-H borylation of arenes, heteroarenes, and benzylic positions of alkylarenes by bis(pinacolato)diboron or pinacolborane furnished aryl-, heteroaryl-, and benzylboron compounds. This article discusses the mechanisms of these reactions and their synthetic applications.     

Interaction of a C-F bond with the π-system of a C═C bond or "head on" with a proximate C-H bond

We describe the synthesis and preliminary study of two molecules, in which a fluorine atom is positioned proximately above the π-orbitals of a C═C bond or else wherein a C-F bond interacts in a "head on" fashion with a proximate C-H bond. The spectroscopic characteristics of these unusual interactions are documented, X-ray crystallographic analyses are reported, and theoretical calculations are employed to support the observed spectroscopy.     

Ruthenium-catalyzed arylation of fluorinated aromatic ketones via ortho-selective carbon-fluorine bond cleavage

We report here ruthenium-catalyzed arylation of fluorinated aromatic ketones via ortho-selective carbon-fluorine bond cleavage. In the presence of trimethylvinylsilane and cesium fluoride, ortho carbon-fluoride bonds of aromatic ketones were phenylated by 5,5-dimethyl-2-phenyl-1,3,2-dioxaborinane using RuH₂(CO)(PPh₃)₃ as a catalyst. Tandem C-F phenylation/C-H alkylation was observed for substrates bearing both one ortho hydrogen and one ortho fluorine atoms.