Chelation-assisted reaction

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)). 

In the former reaction regioisomers are possibly formed, so regioselectivity cannot be controlled. Chelation-assisted reactions, on the other hand, occur regioselec-tively, usually at the position ortho to the directing group. 

The first example of silylation of C-H bonds in arenes with hydrosilanes was reported by Curtis [2]. Later, silylation of C-H bonds with triethylsilane using a rhodium catalyst was reported (Scheme 3) [3, 4], The reaction of arenes with bis(hydrosilane) using a platinum catalyst involves a bis(silyl)platinum species in the coupling reaction (Scheme 3) [5]. In these non-chelation-assisted reactions possible regioisomers should be formed. 

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. 

Most reactions among cyclometalation reactions are orthometalation reactions. These reactions are used for the synthesis of orthometalation products or derivatives of orthometalation products. Pfefifer et al. [19] named these synthetic reactions chelation-assisted reactions in 2002. 

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]. 

Chatani et al. [22] reported on another chelation-assisted reaction, moreover, in an article entitled Nickel-Catalyzed Chelation-Assisted Transformations Involving... 

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. 

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. 

Third, articles employing chelation-assisted reactions as title words are shown in Eqs. (6.42)-(6.51). 

Recently, organosynthetic applications for cyclometalation reactions have been expanding remarkably. Many recent articles include agostic interactions, C-H bond activations, C-X (C-F, C-Cl, C-Br, C-I, C-C, C-O, C-Si, etc.) bond activations, chelate-assisted reactions, and C-H bond functionalizations in their titles. These articles have reported on syntheses of derivatives of cyclometalation products or cyclometalation intermediates. 

It is considered that the reason why cyclometalation reactions for producing organometallic intramolecular-coordination flve-membered ring compounds proceed extremely easily is that the reactions first proceed through metal activation initiated by the coordination of lone electron pair, such as N, P, O, or S, to a metal atom. This is followed by y-C-H agostic interactions, C-H activation, and the chelate effect in this order (Eq. (6.7)). A recent report entitled Chelation-Assisted Reactions (Eqs. (6.42)-(6.51)) provides evidence that the chelate effect is a strong activation source for cyclometalation reactions. 

Titanium Phosphorous Containing Chelates. The reaction of a mixture of mono (alkyl) diacid orthophosphate, di(alkyl)monoacid orthophosphate, and TiCl in a high boiling hydrocarbon solvent such as heptane, with nitrogen-assisted evolution of Hberated HCl, gives a mixture of titanium tetra(mixed alkylphosphate)esters, (H0)(R0)0=P0) Ti(0P=0(0R)2)4 in heptane solution (100). A similar mixture can be prepared by the addition of two moles of P2O5 to mole of TiCl in the presence of six moles of alcohol ... 

A chelation-assisted Pd-catalyzed Cope rearrangement was proposed in the reaction of phenanthroline to generate isoquinolinone derivatives (Eq. 12.78).177 The use of aqueous media and ligands enables a double-Heck reaction on a substrate favoring alkene insertion over (J>-hydride elimination. 

Other Group 10 metal complexes, such as Pd2(dba)3 and Pt(cod)2, were tested for chelate-assisted oxidative addition of 55. Use of Pd2(dba)3 in the reaction of 55... 

A mechanism has been proposed for this, and related transformations, involving a chelation assisted C-H bond functionalization. Following hydride addition to the solvent, acetone, and a transmetallation reaction, reductive elimination yields the ketimine. Hydrolysis of the latter affords the ketone (Equation (131)).114 114a... 

The alkylation of the sp3 C-H bonds adjacent to a heteroatom becomes more practical when the chelation assistance exists in the reaction system. The ruthenium-catalyzed alkylation of the sp3, C-H bond occurs in the reaction of benzyl(3-methylpyridin-2-yl)amine with 1-hexene (Equation (30)).35 The coordination of the pyridine nitrogen to the ruthenium complex assists the C-H bond cleavage. The ruthenium-catalyzed alkylation is much improved by use of 2-propanol as a solvent 36 The reaction of 2-(2-pyrrolidyl)pyridine with ethene affords the double alkylation product (Equation (31)). 

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). 

An alternative synthetic route to platinum(II) thiolates is by the oxidative addition of the S—S bond to platinum(O). When the sulfur atom has phenyl or electron-withdrawing substituents such as CF3, this reaction is a useful one to synthesize the thiolato platinum(II) complexes (equation 503).1703-1705 Simple alkyl disulfides such as Me2S2 and Et2S2 do not form stable dithiolato complexes of platinum(II) by S—S addition to Pt(PPh3)3, but if chelation can occur, chelate-assisted oxidative addition can induce S—S cleavage (equation 504).30 An unusual cyclic thiolato complex is obtained by the decarbonylative cleavage of a C—S bond (equation 505).1707... 

Spectrophotometrically, we could detect no reaction between 1 and AsCHO. This result demonstrates that the identity of the neutral donor component of the bifunctional substrate is crucial for the success of our methodology. This observation substantiates the mechanism outlined in Scheme 2 for the chelate assisted oxidative addition reaction. 

For catalytic C-H bond transformation, there are two types of reaction. One involves non-chelation-assisted C-H bond cleavage, the other is chelation-assisted. 

As mentioned above, three types of reaction are used for silylation of C-H bonds. In this section, we describe the reaction pathway of chelation-assisted silylation of C-H bonds with hydrosilanes (reaction 1). 

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 high regioselectivity, one of the most reliable procedures is chelation-assistance, which involves coordination of a heteroatom to a metal. A representative example of regioselective silylation is the Ru3(CO)12-catalyzed reaction of aryloxa-... 

Scheme 1. The proposed reaction pathway of the ruthenium-catalyzed C-H/olefin coupling by means of the chelation-assistance.

This chelation-assisted C-H/olefin and C-H/acetylene coupling can be applied to a variety of aromatic compounds with a directing group such as ester, aldehyde, imine, azo, oxazolyl, pyridyl, and nitrile [7]. In this section, we describe the coupling reactions of aromatic carbonyl compounds with olefins using a transition metal catalyst. 

Takahashi, A., Hirose, Y., Kusama, H., and Iwasawa, N. (2008) Chelation-assisted electrocyclic reactions of 3-alkenyl-2,2 -bipyridines an efficient method... 

Selective addition of alkenes and alkynes to aromatic compounds has also been performed by ruthenium-catalyzed aromatic C-H bond activation. Carbon-carbon bond formation occurs at the ortho positions of aromatic compounds, assisted by the neighboring functional group chelation. The reaction, catalyzed by RuH2(CO)(PPh3)3, was efficient with aromatic and heteroaromatic compounds, with various functional groups, and a variety of alkenes and alkynes [ 121 ] (Eq. 90). Activation of vinylic C-H bonds can occur in a similar manner. 

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