Summary of Metal-Catalyzed Reactions

Summary of Metal-Catalyzed Reactions
Metal-catalyzed coupling reactions are common in organic synthesis to form carbon-carbon bonds and have a vital role in organic synthesis. The following is a compilation of previously posted articles to facilitate learning. Click on the title of the reaction to view the details.
A particularly useful class of metal-catalyzed reactions are those catalyzed by palladium, which provide a unique method of forming carbon-carbon bonds. Advantages of this class of reactions: 1. No other oxidant catalysts need to be added; 2. Only catalytic amounts of palladium catalyst are required. The palladium-catalyzed intercalation reaction is one of the most widely used reactions of this type, and we will focus on it here.
It is well known that in the Grignard reaction the reaction of a singlet magnesium metal with organic halides with sp3 hybridized carbon atoms (alkyl halides) is easier than the reaction of organic halides with sp2 hybridized carbon atoms (aryl and alkenyl halides). In contrast, palladium complexes react more readily with organic halides containing sp2 hybridized carbon atoms. In other words, alkenyl and aryl halides react very easily with Pd(0) in an oxidative addition reaction to produce complex intermediate 1 containing a palladium-carbon б-bond; then, unsaturated compounds (e.g., olefins, conjugated dienes, alkynes, and carbon monoxide, etc.) are inserted between the palladium-carbon bonds; and, finally, the corresponding target compounds are produced by a reduction-elimination or β-hydrogen-elimination reaction. At the same time, the Pd(0) catalyst is regenerated and a new catalytic cycle begins. It can be seen that it is the generation of such complex intermediates containing palladium-carbon б-bonds that makes the subsequent insertion and metal transfer processes possible.

Experimentally, it was demonstrated that the complexes of Pd are relatively easy to undergo oxidative addition reactions with iodides and bromides. Iodides can be reacted without the addition of any phosphine ligand using only Pd(dba)3, Pd(OAc)2 or even Pd/C as catalyst. Whereas the reaction of bromides generally requires a phosphine ligand. However, chlorides are very inert under normal conditions, and reactions can only occur with strong electron-donating ligands with bidentate groups (e.g., dppp) and under very drastic conditions. For example, the palladium-catalyzed reaction of chlorobenzene often involves the addition of Cr(CO)3 in order to activate the Cl-C bond using its strong electron-drawing properties. It should be noted that the use of bases (R3N, NaOAc, KOAc, Na2CO3, K2CO3, etc.) is necessary in order to neutralize the HX acid produced by the reaction.
In addition to the halides, the halide-like compounds R-X = ArCO-Cl, ArSO2-Cl,Ar-N2+X-, R-OP(O)(OR)2, R-OSO2CF3(OTf), R-OSO2Rf (Rf = perfluoroaikyl), R-OSO2F, R-OSO2CH3, and Ar-ArI+ are good leaving groups, which can also undergo oxidative addition reactions with Pd(0) to form aryl and alkenyl palladium complex intermediates. However, the reactivity of these leaving groups for Pd(0) is variable, and some of their compounds tend to react only with certain specific substrates under very specific conditions.
The most useful classes of halides are the aryl trifluoromethanesulfonate esters of phenols and the enol trifluoromethanesulfonate esters derived from carbonyl compounds. Aryl halides and sulfonyl halides form aryl palladium complexes by first undergoing an oxidative addition reaction with Pd(0), immediately followed by the removal of CO and SO2. In addition, the diazonium salt of benzene is the most reactive source for the formation of aryl palladium complexes.
The oxidative addition reaction between alkyl halides and Pd(0) is very slow. Moreover, after the alkyl palladium complex obtained by the oxidative addition reaction of the alkyl halide undergoes β-hydrogen elimination, the reaction stops at this stage and no further insertion or metal transfer processes take place. For alkynyl halides, although there is not much documentation, alkynyl iodides do react with Pd(0) to produce alkynyl palladium complexes.
There are also several classical reactions that are nickel-catalyzed and copper-catalyzed, all of which are described below.

I. Buchwald_Hartwig reaction, Buchwald-Hartwig cross coupling reaction (Buchwald-Hartwig cross coupling)
Buchwald-Hartwig aryl amination reaction is very commonly used to prepare aryl amines from aryl halogenates or aryl sulfonates. The main feature of this reaction is the use of catalytic amounts of palladium and electron-rich ligands to catalyze the reaction. Also strong bases (e.g. sodium tert-butanol) are essential for the catalytic cycle.
II.Cadiot-Chodkiewicz coupling reaction
Monovalent copper is used as a catalyst for the reaction of terminal alkynes and alkynyl halides to form asymmetric diynes.
C. Carbonylative Cross Coupling reaction
Utilizing the characteristic that carbon monoxide can insert the carbon-metal bond, the carbonyl group is introduced in the coupling reaction at the same time to produce esters, amides, ketones, alcohols and other products. It is a very efficient reaction in organic synthesis. It is often used in palladium-catalyzed coupling reactions.
We know that carbon monoxide is easily inserted between carbon-metal bonds. With a palladium catalyst, the reaction of an alkyl halide, carbon monoxide, and an alcohol together produces an ester. Replacing one of the alcohols with an amine will give an amide, replacing the alcohol with a hydrogen source will give an aldehyde, and switching to an organometallic reagent will give a ketone.
Fourth, Castro-Stephens coupling reaction (Castro-Stephens Coupling)
Copper alkynylidene and aryl halide cross-coupling occurs, resulting in disubstituted alkynes and copper halides. This reaction was discovered by C. E. Castro and R. D. Stephens in 1963. It is now known as a modified Sonogashira coupling.
V. Chan-Lam C-X Coupling, Chan-Lam-Evans Coupling (Chan-Lam-Evans Coupling)
Arylation, alkenylation and alkylation of substrates containing NH/OH/SH groups by oxidative cross-coupling with organoborate compounds catalyzed by copper acetate in air under weak alkali conditions.
VI. Cross Dehydrogenative Coupling (CDC)
A cross C-C coupling reaction in which the C-H of two substrates is activated by the action of a hydrogen acceptor (oxidizing agent). If the oxidizing agent is molecular oxygen, the by-product is theoretically water, which makes the reaction excellent green chemistry. Therefore, this reaction is considered to be the ultimate and the most desirable form of reaction if it is realized.
Eglinton coupling
The oxidative coupling of terminal alkynes catalyzed by stoichiometric (or excess) amounts of Cu(OAc)2. This reaction is a variant of the Glaser coupling reaction.
VIII. Eschenmoser Coupling
This is a method of generating vinylogous amides or polyurethanes by alkylation of thioamides.
Fukuyama Coupling Reaction
This is a reaction in which an organic zinc compound and a thioate are coupled with a palladium catalyst to obtain a ketone. This reaction was discovered by Tohru Fukuyama in 1998 [Tetrahedron Letters. 39 (20): 3189-3192], and is the latest discovery of the classical palladium-catalyzed coupling reaction. This reaction is highly chemoselective, with mild reaction conditions and low toxicity of the reagents used. Due to the low reactivity of the organozinc reagent, this reaction has a good functional group tolerance, and ketones, esters, thioethers, aryl bromides, aryl chlorides and aldehydes can be stabilized under this reaction condition.

Fujiwara-Moritani Reaction
A direct olefinization coupling reaction of unmodified benzene rings in the presence of a Pd catalyst. Also an example of catalytic C-H activation. The reaction form is basically comparable to the Heck reaction.
X. Goldberg coupling reaction
Copper or copper salt catalyzed aryl amidation reaction. This reaction was first discovered by Irma Goldberg, a German chemist and wife of Fritz Ullmann. However, this reaction has some disadvantages: (1) the reaction temperature is generally 140℃ or even higher; (2) part of the reaction requires one mole or more of copper to participate in the reaction; (3) generally need to be carried out in highly polar and toxic solvents. In recent years, the use of copper has been scaled down to catalytic amounts using suitable ligands. The reaction does not require the use of expensive Pd metal, which is very advantageous in terms of economy.
XI, Glaser coupling reaction (Glaser Reaction)
Glaser coupling reaction (Glaser coupling), named after the researcher Karl Glaser. Two molecules of the last alkyne in the alkali and copper salts, coupled to a double alkyne. This reaction is the oldest alkyne coupling reaction. Monovalent copper salts are necessary for the reaction, commonly cuprous chloride, cuprous bromide and cuprous acetate. Ammonia is the classical base used to capture the acidic CH proton of the alkyne. The solvent can be water or ethanol. The reaction proceeds via a binuclear, copper complex intermediate containing a bridged alkyne ligand. Oxygen is used for re-oxidation of the copper catalyst.
XII. Heck reaction, Heck reaction
Palladium-catalyzed alkenylation or arylation of olefins. In addition, the halogenated hydrocarbons without β-hydrogen (mainly benzyl halide) can also be Heck reaction, alkylation.
XIII, aromatic heterocyclic Heck reaction
Aromatic heterocyclic as an acceptor in the molecular or intermolecular Heck reaction.
Pictures of Heck reaction involving diazonium salts
Aryl diazonium salts can be the most common reaction is the Sandmeyer reaction can be prepared halogenated aromatic hydrocarbons, aryl phenols or aryl nitrile, in addition to the Balz-Schiemann reaction for the preparation of aryl fluoride, azo coupling reaction for the preparation of azodiaromatic compounds, in 1995, Beller et al. reported that the use of diazonium salts as the substrate for the preparation of aryl alkenylation reaction, which is a very practical way to prepare aryl alkylates, and this is a very useful way to prepare aryl alkylates, which is a good choice. In 1995, Beller et al. reported the use of diazonium salts as substrates for the Heck reaction to prepare aryl alkenes, which is a very practical reaction for the preparation of aryl olefins, such reactions do not require phosphine catalysts and amines, and the conditions are mild.
XV. Examples of Palladium-Catalyzed Hiyama Coupling Reaction, Hiyama Cross Coupling
A palladium-catalyzed cross coupling reaction between an organosilicon reagent and an organohalogen or trifluoromethanesulfonate. An activating reagent in the form of a fluoride (TASF, TBAF) or a base (e.g., sodium hydroxide, sodium carbonate) is often added to the reaction, which would otherwise be difficult to carry out. The catalytic cycle is similar to the Kumada coupling.
The substituent on the silicon must usually be a heteroatom or a phenyl group. If it is a trialkylmethylsilane, it is difficult to form a silicate intermediate, so the coupling reaction is more difficult to carry out. Silicon has the advantage of low toxicity and is a promising reaction.
XVI. Kagan-Molander coupling reaction
In the late 1970s, H. Kagan systematically studied the reduction properties of divalent lanthanide metal iodides, and on the basis of this study, it was found that in the presence of twice the equivalent of samarium diiodide bromoalkanes, iodoalkanes or TsO alkanes react with aldehydes and ketones to produce the corresponding alcohols. The initial reaction conditions were 24 hours at room temperature with tetrahydrofuran as the solvent or a few hours at reflux.Kagan also found that the addition of catalytic amounts of ferric chloride to the reaction significantly reduced the reaction time, and this method was further developed by G.A. Molander. In 1984, G.A. Molander reported for the first time the intramolecular substitution of ω-iodo esters in the presence of samarium diiodide and catalytic amounts of trivalent iron salts, and furthermore the formation of complex polycyclic aliphatic hydrocarbons. Now such reactions are collectively known as Kagan-Molander samarium diiodide mediated coupling.

Seventeen, Kochi-Fürstner coupling reaction (Kochi-Fürstner Cross Coupling)
The coupling reaction of halogenated aromatic hydrocarbons, aryl trifluoromethanesulfonates and aryl sulfonates with Grignard reagent was carried out in the presence of iron catalyst. Chlorinated aromatic hydrocarbons are the best substrates for this reaction. Brominated aromatics and iodinated aromatics preferentially undergo dehalogenation under these conditions.
XVIII. Kumada coupling reaction
Kumada coupling reaction is the first discovery of Pd or Ni-catalyzed coupling reaction in 1972, this reaction is Grignard reagent and alkyl, alkenyl or aryl halogen substitutes coupled to a very economical reaction, the disadvantage is that not all halogenated compounds can be reacted with organic magnesium compounds. kumada coupling in the industry is an important application of the synthesis of styrenic derivatives is the synthesis of asymmetric low-cost reaction. reaction of biaryl compounds.
This reaction, unlike Negishi Coupling, can be reacted directly with Grignard reagents without first being converted to organozinc reagents.
Kumada (cross) coupling reaction (Kumada Coupling; Kumadacoupling), also known as Kumada-Corriu (cross) coupling reaction, Kumada-Tamao-Corriu Coupling (Kumada-Tamao-Corriu Cross Coupling). It refers to the nickel- or palladium-catalyzed cross-coupling reaction of alkyl or aryl Grignard reagents with aryl halides or vinyl halides, aryl trifluoromethanesulfonates, and the like.
XIX, McMurry coupling reaction
The reaction of preparation of olefins from carbonyl groups catalyzed by low-valent titanium [e.g., Ti(0) generated by TiCl3/LiAlH4]. This reaction is a single electron transfer course.
XX. Negishi cross-coupling reaction
A nickel- or palladium-catalyzed cross-coupling reaction between an organozinc reagent and a variety of halogenated or sulfonated esters (aryl, alkenyl, alkynyl, and acyl).
Reactivity is generally good, alkyl (sp3) zinc compounds can also be used, and functional group compatibility is good.
Alternatively, coupling reactions using organoaluminum or organozirconium are also known as root-shore coupling reactions.