Insertion reaction

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An insertion reaction is a chemical reaction where one chemical entity (a molecule or molecular fragment) interposes itself into an existing bond of typically a second chemical entity e.g.:

Contents

The term only refers to the result of the reaction and does not suggest a mechanism. Insertion reactions are observed in organic, inorganic, and organometallic chemistry. In cases where a metal-ligand bond in a coordination complex is involved, these reactions are typically organometallic in nature and involve a bond between a transition metal and a carbon or hydrogen. [1] It is usually reserved for the case where the coordination number and oxidation state of the metal remain unchanged. [2] When these reactions are reversible, the removal of the small molecule from the metal-ligand bond is called extrusion or elimination.

 

 

 

 

(a)

 

 

 

 

(b)

Examples of type 1,1 (a) and 1,2 (b) resulting geometries for insertion reactions

There are two common insertion geometries— 1,1 and 1,2 (pictured above). Additionally, the inserting molecule can act either as a nucleophile or as an electrophile to the metal complex. [2] These behaviors will be discussed in more detail for CO, nucleophilic behavior, and SO2, electrophilic behavior.

Organic chemistry

Homologation reactions like the Kowalski ester homologation [3] provide simple examples of insertion process in organic synthesis. In the Arndt-Eistert reaction, [4] [5] a methylene unit is inserted into the carboxyl-carbon bond of carboxylic acid to form the next acid in the homologous series. Organic Syntheses provides the example of t-BOC protected (S)-phenylalanine (2-amino-3-phenylpropanoic acid) being reacted sequentially with triethylamine, ethyl chloroformate, and diazomethane to produce the α-diazoketone, which is then reacted with silver trifluoroacetate / triethylamine in aqueous solution to generate the t-BOC protected form of (S)-3-amino-4-phenylbutanoic acid. [6]

Homologation of N-boc-phenylalanine.png

Mechanistically, [7] the α-diazoketone undergoes a Wolff rearrangement [8] [9] to form a ketene in a 1,2-rearrangement. Consequently, the methylene group α- to the carboxyl group in the product is the methylene group from the diazomethane reagent. The 1,2-rearrangement has been shown to conserve the stereochemistry of the chiral centre as the product formed from t-BOC protected (S)-phenylalanine retains the (S) stereochemistry with a reported enantiomeric excess of at least 99%. [6]

A related transformation is the Nierenstein reaction in which a diazomethane methylene group is inserted into the carbon-chlorine bond of an acid chloride to generate an α-chloro ketone. [10] [11] An example, published in 1924, illustrates the reaction in a substituted benzoyl chloride system: [12]

Nierenstein1924.png

Perhaps surprisingly, α-bromoacetophenone is the minor product when this reaction is carried out with benzoyl bromide, a dimeric dioxane being the major product. [13] Organic azides also provide an example of an insertion reaction in organic synthesis and, like the above examples, the transformations proceed with loss of nitrogen gas. When tosyl azide reacts with norbornadiene, a ring expansion reaction takes place in which a nitrogen atom is inserted into a carbon-carbon bond α- to the bridge head: [14]

Azidenorbornadieneinsertion.png

The Beckmann rearrangement [15] [16] is another example of a ring expanding reaction in which a heteroatom is inserted into a carbon-carbon bond. The most important application of this reaction is the conversion of cyclohexanone to its oxime, which is then rearranged under acidic conditions to provide ε-caprolactam, [17] the feedstock for the manufacture of Nylon 6. Annual production of caprolactam exceeds 2 billion kilograms. [18]

BeckmannRearrangement3.svg

Carbenes undergo both intermolecular and intramolecular insertion reactions. Cyclopentene moieties can be generated from sufficiently long-chain ketones by reaction with trimethylsilyldiazomethane, (CH3)3Si–CHN2:

Alkylidene carbene.svg

Here, the carbene intermediate inserts into a carbon-hydrogen bond to form the carbon-carbon bond needed to close the cyclopentene ring. Carbene insertions into carbon-hydrogen bonds can also occur intermolecularly:

Carbene intermolecular insertion.svg

Carbenoids are reactive intermediates that behave similarly to carbenes. [19] One example is the chloroalkyllithium carbenoid reagent prepared in situ from a sulfoxide and t-BuLi which inserts into the carbon-boron bond of a pinacol boronic ester: [20]

CarbenoidApplication.png

Organometallic chemistry

Many reactions in organometallic chemistry involve insertion of one ligand (L) into a metal-hydride or metal-alkyl/aryl bond. Generally it is the hydride, alkyl, or aryl group that migrates onto L, which is often CO, an alkene, or alkyne.

Carbonylations

The insertion of carbon monoxide and alkenes into metal-carbon bonds is a widely exploited reaction with major industrial applications. [21] [22]

Nucleophilic insertion and rearrangement of a square planar complex Square Planar.png
Nucleophilic insertion and rearrangement of a square planar complex

Such reactions are subject to the usual parameters that affect other reactions in coordination chemistry, but steric effects are especially important in determining the stereochemistry and regiochemistry of the reactions. The reverse reaction, the de-insertion of CO and alkenes, are of fundamental significance in many catalytic cycles as well.

Widely employed applications of migratory insertion of carbonyl groups are hydroformylation and the carbonylative production of acetic acid. The former converts alkenes, hydrogen, and carbon monoxide into aldehydes. The production of acetic acid by carbonylation proceeds via two similar industrial processes. More traditional is the rhodium-based Monsanto acetic acid process, but this process has been superseded by the iridium-based Cativa process. [23] [24] By 2002, worldwide annual production of acetic acid stood at 6 million tons, of which approximately 60% is produced by the Cativa process. [23]

The catalytic cycle of the Cativa process Cativa-process-catalytic-cycle.png
The catalytic cycle of the Cativa process

The Cativa process catalytic cycle, shown above, includes both insertion and de-insertion steps. The oxidative addition reaction of methyl iodide with (1) involves the formal insertion of the iridium(I) centre into the carbon-iodine bond, whereas step (3) to (4) is an example of migratory insertion of carbon monoxide into the iridium-carbon bond. The active catalyst species is regenerated by the reductive elimination of acetyl iodide from (4), a de-insertion reaction. [23]

Olefin insertion

The insertion of ethylene and propylene into titanium alkyls is the cornerstone of Ziegler-Natta catalysis, the commercial route of polyethylene and polypropylene. This technology mainly involves heterogeneous catalysts, but it is widely assumed that the principles and observations on homogeneous systems are applicable to the solid-state versions. Related technologies include the Shell Higher Olefin Process which produces detergent precursors. [25] the olefin can be coordinated to the metal before insertion. Depending on the ligand density of the metal, ligand dissociation may be necessary to provide a coordination site for the olefin. [26]

Migratory insertion of an alkene into a metal hydride. The middle image depicts the transition state. Notice that the less substituted carbon becomes bonded to the metal, at least usually. The reverse reaction is called beta-hydride elimination. Beta-hydrideElim&TS.png
Migratory insertion of an alkene into a metal hydride. The middle image depicts the transition state. Notice that the less substituted carbon becomes bonded to the metal, at least usually. The reverse reaction is called beta-hydride elimination.

Other insertion reactions in coordination chemistry

Many electrophilic oxides insert into metal carbon bonds; these include sulfur dioxide, carbon dioxide, and nitric oxide. These reactions have limited practical significance, but are of historic interest. With transition metal alkyls, these oxides behave as electrophiles and insert into the bond between metals and their relatively nucleophilic alkyl ligands. As discussed in the article on Metal sulfur dioxide complexes, the insertion of SO2 has been examined in particular detail.

More insertion reactions in organic chemistry

Electropositive metals such as sodium, potassium, magnesium, zinc, etc. can insert into alkyl halides, breaking the carbon-halide bond ( halide could be chlorine, bromine, iodine ) and forming a carbon-metal bond. This reaction happens via a SET mechanism ( single-electron-transfer mechanism ). If magnesium reacts with an alkyl halide, it forms a Grignard reagent, or if lithium reacts, an organolithium reagent is formed. Thus, this type of insertion reactions has important applications in chemical synthesis.

Insertion reactions of magnesium and lithium OrgG.jpg
Insertion reactions of magnesium and lithium

Related Research Articles

<span class="mw-page-title-main">Carboxylic acid</span> Organic compound containing a –C(=O)OH group

In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group attached to an R-group. The general formula of a carboxylic acid is R−COOH or R−CO2H, with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic acids occur widely. Important examples include the amino acids and fatty acids. Deprotonation of a carboxylic acid gives a carboxylate anion.

<span class="mw-page-title-main">Organometallic chemistry</span> Study of organic compounds containing metal(s)

Organometallic chemistry is the study of organometallic compounds, chemical compounds containing at least one chemical bond between a carbon atom of an organic molecule and a metal, including alkali, alkaline earth, and transition metals, and sometimes broadened to include metalloids like boron, silicon, and selenium, as well. Aside from bonds to organyl fragments or molecules, bonds to 'inorganic' carbon, like carbon monoxide, cyanide, or carbide, are generally considered to be organometallic as well. Some related compounds such as transition metal hydrides and metal phosphine complexes are often included in discussions of organometallic compounds, though strictly speaking, they are not necessarily organometallic. The related but distinct term "metalorganic compound" refers to metal-containing compounds lacking direct metal-carbon bonds but which contain organic ligands. Metal β-diketonates, alkoxides, dialkylamides, and metal phosphine complexes are representative members of this class. The field of organometallic chemistry combines aspects of traditional inorganic and organic chemistry.

<span class="mw-page-title-main">Alkylation</span> Transfer of an alkyl group from one molecule to another

Alkylation is a chemical reaction that entails transfer of an alkyl group. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene. Alkylating agents are reagents for effecting alkylation. Alkyl groups can also be removed in a process known as dealkylation. Alkylating agents are often classified according to their nucleophilic or electrophilic character. In oil refining contexts, alkylation refers to a particular alkylation of isobutane with olefins. For upgrading of petroleum, alkylation produces a premium blending stock for gasoline. In medicine, alkylation of DNA is used in chemotherapy to damage the DNA of cancer cells. Alkylation is accomplished with the class of drugs called alkylating antineoplastic agents.

<span class="mw-page-title-main">Organolithium reagent</span> Chemical compounds containing C–Li bonds

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<span class="mw-page-title-main">Bamford–Stevens reaction</span>

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<span class="mw-page-title-main">Nierenstein reaction</span>

The Nierenstein reaction is an organic reaction describing the conversion of an acid chloride into a haloketone with diazomethane. It is an insertion reaction in that the methylene group from the diazomethane is inserted into the carbon-chlorine bond of the acid chloride.

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In organometallic chemistry, a migratory insertion is a type of reaction wherein two ligands on a metal complex combine. It is a subset of reactions that very closely resembles the insertion reactions, and both are differentiated by the mechanism that leads to the resulting stereochemistry of the products. However, often the two are used interchangeably because the mechanism is sometimes unknown. Therefore, migratory insertion reactions or insertion reactions, for short, are defined not by the mechanism but by the overall regiochemistry wherein one chemical entity interposes itself into an existing bond of typically a second chemical entity e.g.:

<span class="mw-page-title-main">Doyle–Kirmse reaction</span> Reaction in organic chemistry

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A Fischer carbene is a divalent organic ligand in an organometallic compound. In a Fischer carbene, the carbene ligand is a σ-donor π-acceptor ligand. Because π-backdonation from the metal centre is generally weak, the carbene carbon is electrophilic.

References

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  2. 1 2 J.J. Alexander (1985). Hartley and Patai (ed.). The chemistry of the metal-carbon bond, vol. 2. John Wiley & Sons.
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  5. ↑ Ye, T.; McKervey, M. A. (1994). "Organic Synthesis with α-Diazo Carbonyl Compounds". Chem. Rev. 94 (4): 1091–1160. doi:10.1021/cr00028a010.
  6. 1 2 Linder, M. R.; Steurer, S.; Podlech, J. (2002). "(S)-3-(tert-Butyloxycarbonylamino)-4-phenylbutanoic acid". Organic Syntheses . 79: 154.; Collective Volume, vol. 10, p. 194
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  8. ↑ Meier, H.; Zeller, K.-P. (1975). "The Wolff Rearrangement of α-Diazo Carbonyl Compounds". Angew. Chem. Int. Ed. 14 (1): 32–43. doi:10.1002/anie.197500321.
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  14. ↑ Reed, D. D.; Bergmeier, S. C. (2007). "A Facile Synthesis of a Polyhydroxylated 2-Azabicyclo[3.2.1]octane". J. Org. Chem. 72 (3): 1024–1026. doi:10.1021/jo0619231. PMID   17253828.
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  17. ↑ Eck, J. C.; Marvel, C. S. (1939). "ε-Benzoylaminocaproic acid". Organic Syntheses . 19: 20.; Collective Volume, vol. 2, 1943, p. 76
  18. ↑ Ritz, J.; Fuchs, H.; Kieczka, H.; Moran, W. C. (2000). "Caprolactam". Ullmann's Encyclopedia of Industrial Chemistry. Weinheim: Wiley-VCH. doi:10.1002/14356007.a05_031. ISBN   3527306730.
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  23. 1 2 3 Jones, J. H. (2000). "The Cativa Process for the Manufacture of Acetic Acid" (PDF). Platinum Metals Rev. 44 (3): 94–105. Archived from the original (PDF) on 2015-09-24. Retrieved 2010-12-22.
  24. ↑ Sunley, G. J.; Watson, D. J. (2000). "High Productivity Methanol Carbonylation Catalysis using Iridium - The Cativa Process for the Manufacture of Acetic Acid". Catalysis Today. 58 (4): 293–307. doi:10.1016/S0920-5861(00)00263-7.
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  26. ↑ Kissin, Y. V. (2008). "Synthesis, Chemical Composition, and Structure of Transition Metal Components and Cocatalysts in Catalyst Systems for Alkene Polymerization". Alkene Polymerization Reactions with Transition Metal Catalysts. Amsterdam: Elsevier. pp. 207–290. ISBN   978-0-444-53215-2.
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