Chelation-assisted activation

Hydroamidations have been reported involving the ruthenium-catalyzed chelation assisted activation of formamide (Equation (133)).116... 

Successful examples of chelate assisted activation of aromatic C-F bonds provided the foundation for further exploration of the organometallic chemistry of fluorocarbons. While early examples were limited to perfluorinated aromatic systems, the scope of this process is now fully defined using W(CO)3 and PtMe2 metal fragments [44, 29]. In addition to these amine, imine based ligand systems, several new examples of C-F activation have been achieved using a variety of later transition metals. 

A rhodium-catalyzed one-pot synthesis of substituted pyridine derivatives from a,(3-unsaturated ketoximes and alkynes was developed in 2008 by Cheng and coworkers [99], Good yields of the desired pyri-dines can be obtained (Scheme 3.48). The reaction was proposed to proceed via rhodium-catalyzed chelation-assisted activation of the (3—C—H bond of a,(3-unsaturated ketoximes and subsequent reaction with alkynes followed by reductive elimination, intramolecular electro-cyclization, and aromatization to give highly substituted pyridine derivatives finally [100]. Later on, in their further studies, substituted isoquinolines and tetrahydroquinoline derivatives can be prepared by this catalyst system as well [101]. Their reaction mechanism was supported by isolation of the ort/jo-alkenylation products. Here, only asymmetric internal alkynes can be applied. 

Chelation-assisted activation of aliphatic C-S bonds in dihtioacetals has been described [103-105], Representative examples are shown below ... 

Structural studies on the nature of the organometallic intermediates following chelation-assisted CH additions of pincer iridium complexes have been carried out. The product was found to have an unexpected /ram-disposition of the hydride with respect to the metallated aromatic group. This is not the expected direct outcome of a chelation-assisted reaction since coordination of oxygen to iridium prior to C-H activation would be expected to afford the m-isorner (Equation (97)). 

The carbonylation of the sp3 C-H bond adjacent to a nitrogen atom is also possible by means of chelation-assisted C-H bond activation.121 The carbonylation reaction of A-(2-pyridyl)pyrrolidine occurs at the a-position of the pyrrolidine ring by using [RhCl(cod)]2 as a catalyst and 2-propanol as a solvent. Cyclic amines exhibit a high reactivity (up to 84%) (Equation (93)), while acyclic amines show relatively low reactivity (18%). The use of Ru3(CO)i2 as a catalyst does not result in a carbonylation reaction, but instead the addition of the sp3 C-H bond across the olefin bond to give an alkylation product, as mentioned before (Section 10.05.4). 

Several reaction pathways for reaction 1 are possible. A clear reaction mechanism has not been elucidated. Although it is premature to discuss the details of the reaction pathway for this silylation reaction, one possible pathway for the chelation-assisted silylation of C-H bonds is shown in Scheme 2. The catalytic reaction is initiated by oxidative addition of hydrosilane to A. Intermediate B reacts with an olefin to give C. Then, addition of a C-H bond to C leads to intermediate D. Dissociation of alkane from D provides Ru(silyl)(aryl) intermediate E. Reductive elimination making a C-Si bond gives the silylation product and the active catalyst species A is regenerated. Another pathway, addition of a C-H bond to A before addition of hydrosilane to A is also possible. At present, these two pathways cannot be distinguished. 

For the late metals where M-C bonds are less strong, CC bond activation seems always to need some special driving force, such as relief of strain, chelate assistance, or attainment of an aromatic product. For early metals, M-C bonds can be much stronger and simple CC bonds can be more easily cleaved. A classic early example from Watson (equation 1) requires chelate assistance but C-C cleavage can be competitive with the alternate CH bond cleavage (beta-elimination) that normally dominates ... 

Reaction of pentafluoroacetophenone with hexamethyldisilane for 20 h in toluene in a 130°C oil bath in the presence of 10 mol% Rh(cod)2BF4gave a 79-88% yield of 2,3,4,5-tetrafluoro-6-trimethylsilylacetophenone. Not surprisingly, 2,6-difluoroacetophenone affords the mono-Me3Si-F exchange product in somewhat lower yields (33-48%). In the case of a related oxazoline derivative some disilylation accompanied the mono-substituted product. The authors propose a chelate assisted mechanism for the initial C-F activation step [62]. It is interesting to note that these catalytic reactions all involve the later transition metal rhodium with a relatively labile Rh-F bond removed as R3Si-F or HF. However, related catalytic reactions of aromatic C-F bonds have also been discovered for early transition metals and even in the very electropositive lanthanide series. 

A chelation-assisted strategy is another useful method for C—C bond cleavage. In this method, the substrates containing a coordinating functional group will first coordinate to a metal and form a stable metallacycle. A representative example of this strategy is the activation of the a-C—C bond to the carbonyl group in 8-quinolinyl alkyl... 

Other examples of microwave-assisted catalysis include allylic alkylation, both palladium catalyzed and molybdenum catalyzed. In the latter case, air stable precursor complexes could be used under non-inert conditions. Microwave-enhanced Pauson-Khand reactions have also been reported, as have hydroamination of alkynes, and metathesis of functionalized alkynes. " Recently, microwave enhancement has been applied to C-H activation reactions, for example, for the formation of functionalized heterocycles, allowing the reaction to be performed with no solvent purification and minimal precautions to exclude air. A solvent-free chelation-assisted hydroacylation... 

Hydroacylations. Wilkinson s catalyst is an extremely powerful catalyst for intermolecular hydroacylation when combined with several organococatalysts such as 2-amino-3-picoline, aniline, and benzoic acid (for details, see 2-amino-3-picoline) Equation 63 illustrates how benzaldehyde undergoes intermolecular hydroacylation very efficiently with terminal olefins by the chelation-assistance of 2-amino-3-picoline by a process involving C-H bond activation. 

This chelation-assisted cyclometallation using Wilkinson s catalyst can be extended to /3-alkylation through aliphatic sp C-H bond activation (eq 69). When an enone is allowed to react with excess olefin in the presence of RhCl(PPh3)3, benzoic acid, and secondary amine at 130 °C for 12 h, /3-alkylated products can be obtained in good yields. 

When the iridium hydride is reacted with a hydrogen acceptor, simple oxidative addition adducts can be seen for aromatic and vinylic C-H containing substrates. With nitrobenzene, although a thermodynamic preference is seen for an orthometallated chelate product, the kinetic preference is for meta- and para-Gr-W activation, which is then followed by rearrangement to the o/n4n-activated product, which in turn coordinates the nitro group. Hence, chelate assistance is found to have no kinetic benefit for C-H activation in this complex (Equation (22)). 

Rhodium-catalyzed chelation-assisted C—H bond functionalization reactions (enantioselective annulation of aryl imines, dihydropyridine synthesis from imines and ahcynes, one-pot synthesis of pyridines from imines and alkynes, 2-arylpyridine alkylation with imines) 12ACR814. Synthesis of pyridine and dihydropyridine derivatives by regjo- and stereoselective addition to N-activated pyridines 12CRV2642. 

A chelation-assisted mthenium-catalyzed arylation of aldehyde 99 was accomplished in combination with a palladium complex [47]. This cooperative catalysis [48] proved applicable to organostannanes and aryl iodides as arylating reagents (Scheme 9.35). The direct arylation proceeded most likely through ruthenium-catalyzed C—H bond activation, subsequent transmetallation to palladium, and reductive elimination from a palladium intermediate. 

Various methodologies for catalytic direct arylations via C—H bond activation employing transition metals other than palladium have been developed in recent years. In particular, rhodium- and ruthenium-based complexes have enabled the development of promising protocols for catalytic direct arylations. Whilst rhodium catalysts were found broadly applicable to the direct aryiation of both arenes, as well as heteroarenes, ruthenium-catalyzed chelation-assisted C—H bond function-ahzations could be used for the conversion of a variety of attractive organic electrophiles. In addition, inexpensive copper and iron salts have recently been shown as economically attractive alternatives to previously developed more expensive catalysts. Given the economically and environmentally benign features of selective C—H bond functionalizations, the development of further valuable protocols is expected in this rapidly evolving research area. 

The fifth item concerns agostic interactions, C-H activation, C-X activation, C-H functionalization, chelation-assisted reactions, cross-coupling reactions, etc., which are indicated as titles. The reactions indicated by these titles are mostly related to cyclometalation reactions. The reaction mechanisms of these reactions include metal activation by the coordination of a hetero atom to the central metal atom and the chelate effect of the formation of a five-membered ring. 

Keywords C-H activation C-H functionalization Chelate effect Chelation-assisted C-X activation Cyclometalation Five-membered ring Intramolecular coordination Metal activation... 

Chen et al. [20], for example, reported on chelation-assisted reactions in an article entitled Chelation-Assisted Carbon-Halogen Bond Activation by a Rhodium(I) Complex in 2009. These reactions proceed by C-Br bond activation via an oxidative addition mechanism. They take place in reactions of [Rh(PPh3)2(acetone)2] PFg" with 2-(2-bromophenyl)pyridine at room temperature to give the cyclometa-lated rhodium bromide shown in Eq. (6.4). 

Iwasawa et al. [21] also reported chelation-assisted reactions in an article entitled Rhodium(I)-Catalyzed Direct Carboxylation of Arenes with CO2 via Chelation-Assisted C-H Bond Activation, in which the cyclometalation reactions proceed easily and form cyclometalation intermediates. The metal atoms are active centers in their intermediates. Hence, the active metal atom reacts easily with inert carbon dioxide to give carboxylic acid derivatives. Examples include the cyclometalation of 2-phenylpyridine as a substrate in the presence of a rhodium intermediate. Carbon dioxide can be inserted into the rhodium-phenyl carbon bond, and a methyl ester is formed with TMSCH2N2 from a rhodium carboxylate, as shown in Eq. (6.5). The reaction mechanism is proposed as shown in Scheme 6.2 [21]. 

Ortho C-H Bond Activation Regioselective Oxidative Cycloaddition of Aromatic Amides to Alkynes. Cyclometalation reactions with nickel phosphine COD complexes used an amido nitrogen atom as the coordinating atom. The insertion and cyclization with alkynes is then proposed to proceed via the cyclometalation nickel intermediate as an active center to give the six-membered isoquinolone derivatives shown in Eq. (6.6). In 2013, Chatani et al. [22] also reported on these chelation-assisted transformations in details as the review articles. 

The mechanisms of the two steps in cyclometalation reactions are shown in Eq. (6.7). The first step is metal activation, and the second is the chelate effect. Recently, numerous articles have been pubhshed on agostic interactions, C-H activations (C-H bond activations), C-X activations (C-X bond activations), chelation-assisted reactions, and C-H functionalizations (C-H bond functionalizations). However, many of these articles are concerned with cyclometalation reactions. It is considered that, in the first stage, the metal activation in cyclometalation reactions is related to agostic interactions, C-H activations, and C-X activations and that, in the second stage, the chelate effect is related to chelation-assisted reactions and C-H functionalizations. 

Scheme 6.3 Easy cyclometalation reactions with a benzylamine proceed via agostic interaction as shown in agostic intermediate 6.6 Equation (6.4) Chelation-Assisted Carbon-Halogen Bond Activation by a Rhodium(I) Complex ...

Other terms related to the cyclometalation reactions described above, that is, C-H activations (C-H bond activations), C-X activations (C-X bond activations), chelation-assisted reactions, and C-H functionalizations (C-H bond functionalizations), are employed as title words in article titles, as shown in the following sequence. 

Chelate-Assisted Oxidative Coupling Reaction of Arylamides and Unactivated AUcenes Mechanistic Evidence for Vinyl C-H Bond Activation Promoted by an Electrophilic Ruthenium Hydride Catalyst... 

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