Azomethine ylide

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Azomethine ylide Azomethine ylide 2.svg
Azomethine ylide

Azomethine ylides are nitrogen-based 1,3-dipoles, consisting of an iminium ion next to a carbanion. They are used in 1,3-dipolar cycloaddition reactions to form five-membered heterocycles, including pyrrolidines and pyrrolines. [1] [2] [3] These reactions are highly stereo- and regioselective, and have the potential to form four new contiguous stereocenters. Azomethine ylides thus have high utility in total synthesis, and formation of chiral ligands and pharmaceuticals. Azomethine ylides can be generated from many sources, including aziridines, imines, and iminiums. They are often generated in situ, and immediately reacted with dipolarophiles.

Contents

Structure

The resonance structures below show the 1,3-dipole contribution, in which the two carbon atoms adjacent to the nitrogen have a negative or positive charge. [1] The most common representation of azomethine ylides is that in which the nitrogen is positively charged, and the negative charge is shared between the two carbon atoms. The relative contributions of the different resonance structures depend on the substituents on each atom. The carbon containing electron-withdrawing substituents will have a more partial negative charge, due to the ability of the nearby electron-withdrawing group to stabilize the negative charge.

Resonance structures Azomethine ylide resonance.png
Resonance structures

Three different ylide shapes are possible, each leading to different stereochemistry in the products of 1,3-dipolar cycloaddition reactions. W-shaped, U-shaped, and S-shaped ylides are possible. [1] The W- and U-shaped ylides, in which the R substituents are on the same side, result in syn cycloaddition products, whereas S-shaped ylides result in anti products. In the examples below, where the R3 substituent ends up in the product depends on the substituent's steric and electronic nature (see regioselectivity of 1,3 dipolar cycloadditions). The stereochemistry of R1 and R2 in the cycloaddition product is derived from the dipole. The stereochemistry of R3 is derived from the dipolarophile—if the dipolarophile is more than mono-substituted (and prochiral), up to four new stereocenters can result in the product.

Azomethine ylide shapes Azomethine ylide shapes.png
Azomethine ylide shapes

Generation

From aziridines

Azomethine ylides can be generated from ring opening of aziridines. [4] [5] In accordance with the Woodward–Hoffmann rules, the thermal four-electron ring opening proceeds via a conrotatory process, whereas the photochemical reaction is disrotatory.

Ring opening of aziridine to form azomethine ylide. Aziridine opening.png
Ring opening of aziridine to form azomethine ylide.

In this ring opening reaction, there is an issue of torquoselectivity. Electronegative substituents prefer to rotate outwards, to the same side as the R substituent on the nitrogen, whereas electropositive substituents prefer to rotate inwards. [6]

Note that with aziridines, ring opening can result in a different 1,3-dipole, in which a C–N bond (rather than the C–C bond) breaks. [7]

By condensation of aldehyde with amine

Azomethine ylide from condensation Azomethine ylide from condensation.png
Azomethine ylide from condensation

One of the easiest methods of forming azomethine ylides is by condensation of an aldehyde with an amine. If the amine contains an electron-withdrawing group on the alpha carbon, such as an ester, the deprotonation occurs readily. A possible disadvantage of using this method is that the ester ends up in the cycloaddition product. An alternative is to use a carboxylic acid, which can easily be removed during the cycloaddition process by decarboxylation. [8]

From imines and iminiums

Deprotonation of iminium to form azomethine ylide. Deprotonation of iminium.png
Deprotonation of iminium to form azomethine ylide.

Azomethine ylides can also be formed directly by deprotonation of iminiums.

By N-metallation

Formation of azomethine ylides by N-metallation. Azomethine ylide from imine.png
Formation of azomethine ylides by N-metallation.

The metal reagents used in this reaction include lithium bromide and silver acetate. [1] In this method, the metal coordinates to the nitogen in order to activate the substrate for deprotonation. Another way to form azomethine ylides from imines is by prototropy and by alkylation.

From münchnones

Ylides can be formed from münchnones, which are mesoionic heterocycles, and act as cyclic azomethine ylides. [9]

Formation of azomethine ylide from munchnone. Azomethine ylide from munchnone.png
Formation of azomethine ylide from munchnone.

1,3-dipolar cycloaddition reactions

General cycloaddition reaction of azomethine ylide with alkene. Azomethine ylide cycloaddition.png
General cycloaddition reaction of azomethine ylide with alkene.

As with other cycloaddition reactions of a 1,3-dipole with a π-system, 1,3-dipolar cycloaddition using an azomethine ylide is a six-electron process. According to the Woodward–Hoffmann rules, this addition is suprafacial with respect to both the dipole and dipolarophile. The reaction is generally viewed as concerted, in which the two carbon-carbon bonds are being formed at the same time, but asynchronously. However, depending on the nature of the dipole and dipolarophile, diradical or zwitterionic intermediates are possible. [10] The endo product is generally favored, as in the isoelectronic Diels–Alder reaction. In these reactions, the azomethine ylide is typically the HOMO, and the electron-deficient dipolarophile the LUMO, although cycloaddition reactions with unactivated π-systems are known to occur, especially when the cyclization is intramolecular. [11] For a discussion of frontier molecular orbital theory of 1,3-dipolar cycloadditions, see 1,3-dipolar cycloaddition#Frontier molecular orbital theory.

Azomethine ylide cyclization example. Azomethine ylide cycloaddition rxn.png
Azomethine ylide cyclization example.

1,3-Dipolar cycloaddition reactions of azomethine ylides commonly use alkenes or alkynes as dipolarophiles, to form pyrrolidines or pyrrolines, respectively. A reaction of an azomethine ylide with an alkene is shown above, and results in a pyrrolidine. [12] This kind of reactions can be used to synthesis Ullazine. [13] While dipolarophiles are typically α,β-unsaturated carbonyl compounds, there have been many recent advances in developing new types of dipolarophiles. [14]

When the dipole and dipolarophile are part of the same molecule, an intramolecular cyclization reaction can lead to a polycyclic product of considerable complexity. [1] If the dipolarophile is tethered to a carbon of the dipole, a fused bicycle is formed. If it is tethered to the nitrogen, a bridged structure results. The intramolecular nature of the reaction can also be useful in that regioselectivity is often constrained. Another advantage to intramolecular reactions is that the dipolarophile need not be electron-deficient—many examples of cyclization reactions with electron-rich, alkyl-substituted dipolarophiles have been reported, including the synthesis of martinellic acid shown below.

Stereoselectivity of cycloadditions

Unlike most 1,3-dipolar cycloaddition reactions, in which the stereochemistry of the dipole is lost or non-existent, azomethine ylides are able to retain their stereochemistry. This is generally done by ring opening of an aziridine, and subsequent trapping by a dipolarophile before the stereochemistry can scramble.

Like other 1,3-dipolar cycloaddition reactions, azomethine ylide cycloadditions can form endo or exo products. This selectivity can be tuned using metal catalysis. [15] [16]

Enantioselective synthesis

Enantioselective cycloaddition of azomethine ylides using chiral catalysts was first described in a seminal work by Allway and Grigg in 1991. [17] This powerful method was further developed by Jørgensen and Zhang. These reactions generally use zinc, silver, copper, nickel, and calcium complexes.

Using chiral phosphine catalysts, enantiomerically pure spiroindolinones can be synthesized. The method described by Gong, et al. leads to an unexpected regiochemical outcome that does not follow electronic effects. This is attributed to favorable pi stacking with the catalyst. [18]

Other reactions

Electrocyclizations

Conjugated azomethine ylides are capable of [1,5]- and [1,7]-electrocyclizations. [19] An example of a [1,7]-electrocyclization of a diphenylethenyl-substituted azomethine ylide is shown below. This conrotatory ring-closing is followed by a suprafacial [1,5]-hydride shift, which affords the rearomatized product. The sterics and geometry of the reacting phenyl ring play a major role in the success of the reaction. [20]

1,7 electrocyclization of azomethine ylide Ylide 1,7 electrocyclization.png
1,7 electrocyclization of azomethine ylide

The compounds resulting from this type of electrocyclization have been used as dienes in Diels–Alder reactions to attach compounds to fullerenes. [21]

Use in synthesis

Total synthesis of martinellic acid

Step of martinellic acid synthesis using azomethine ylide. Synthesis of Martinellic acid.svg
Step of martinellic acid synthesis using azomethine ylide.

A cycloaddition of an azomethine ylide with an unactivated alkene was used in total synthesis of martinellic acid. The cycloaddition step formed two rings, including a pyrrolidine, and two stereocenters. [22]

Total synthesis of spirotryprostatin B

Step of spirotryprostatin synthesis using azomethine ylide. Application of azomethine ylide in the synthesis of spirotryprostatin.tif
Step of spirotryprostatin synthesis using azomethine ylide.

In the synthesis of spirotryprostatin B, an azomethine ylide is formed from condensation of an amine with an aldehyde. The ylide then reacts with an electron-deficient alkene on an indolinone, resulting in formation of a spirocyclic pyrrolidine and four contiguous stereocenters. [23]

Synthesis of benzodiazepinones

Synthesis of benzodiazepinones from azomethine ylide cyclizations Benzodiazepinones from azomethine ylides.png
Synthesis of benzodiazepinones from azomethine ylide cyclizations

Cyclization of an azomethine ylide with a carbonyl affords a spirocyclic oxazolidine, which loses CO2 to form a seven-membered ring. These high-utility decarboxylative multi-step reactions are common in azomethine ylide chemistry. [24]

Related Research Articles

In organic chemistry, the Diels–Alder reaction is a chemical reaction between a conjugated diene and a substituted alkene, commonly termed the dienophile, to form a substituted cyclohexene derivative. It is the prototypical example of a pericyclic reaction with a concerted mechanism. More specifically, it is classified as a thermally-allowed [4+2] cycloaddition with Woodward–Hoffmann symbol [π4s + π2s]. It was first described by Otto Diels and Kurt Alder in 1928. For the discovery of this reaction, they were awarded the Nobel Prize in Chemistry in 1950. Through the simultaneous construction of two new carbon–carbon bonds, the Diels–Alder reaction provides a reliable way to form six-membered rings with good control over the regio- and stereochemical outcomes. Consequently, it has served as a powerful and widely applied tool for the introduction of chemical complexity in the synthesis of natural products and new materials. The underlying concept has also been applied to π-systems involving heteroatoms, such as carbonyls and imines, which furnish the corresponding heterocycles; this variant is known as the hetero-Diels–Alder reaction. The reaction has also been generalized to other ring sizes, although none of these generalizations have matched the formation of six-membered rings in terms of scope or versatility. Because of the negative values of ΔH° and ΔS° for a typical Diels–Alder reaction, the microscopic reverse of a Diels–Alder reaction becomes favorable at high temperatures, although this is of synthetic importance for only a limited range of Diels-Alder adducts, generally with some special structural features; this reverse reaction is known as the retro-Diels–Alder reaction.

An ylide or ylid is a neutral dipolar molecule containing a formally negatively charged atom (usually a carbanion) directly attached to a heteroatom with a formal positive charge (usually nitrogen, phosphorus or sulfur), and in which both atoms have full octets of electrons. The result can be viewed as a structure in which two adjacent atoms are connected by both a covalent and an ionic bond; normally written X+–Y−. Ylides are thus 1,2-dipolar compounds, and a subclass of zwitterions. They appear in organic chemistry as reagents or reactive intermediates.

The 1,3-dipolar cycloaddition is a chemical reaction between a 1,3-dipole and a dipolarophile to form a five-membered ring. The earliest 1,3-dipolar cycloadditions were described in the late 19th century to the early 20th century, following the discovery of 1,3-dipoles. Mechanistic investigation and synthetic application were established in the 1960s, primarily through the work of Rolf Huisgen. Hence, the reaction is sometimes referred to as the Huisgen cycloaddition. 1,3-dipolar cycloaddition is an important route to the regio- and stereoselective synthesis of five-membered heterocycles and their ring-opened acyclic derivatives. The dipolarophile is typically an alkene or alkyne, but can be other pi systems. When the dipolarophile is an alkyne, aromatic rings are generally produced.

Bamford–Stevens reaction

The Bamford–Stevens reaction is a chemical reaction whereby treatment of tosylhydrazones with strong base gives alkenes. It is named for the British chemist William Randall Bamford and the Scottish chemist Thomas Stevens Stevens (1900–2000). The usage of aprotic solvents gives predominantly Z-alkenes, while protic solvent gives a mixture of E- and Z-alkenes. As an alkene-generating transformation, the Bamford–Stevens reaction has broad utility in synthetic methodology and complex molecule synthesis.

Chiral auxiliary

A chiral auxiliary is a stereogenic group or unit that is temporarily incorporated into an organic compound in order to control the stereochemical outcome of the synthesis. The chirality present in the auxiliary can bias the stereoselectivity of one or more subsequent reactions. The auxiliary can then be typically recovered for future use.

Johnson–Corey–Chaykovsky reaction Chemical reaction in organic chemistry

The Johnson–Corey–Chaykovsky reaction is a chemical reaction used in organic chemistry for the synthesis of epoxides, aziridines, and cyclopropanes. It was discovered in 1961 by A. William Johnson and developed significantly by E. J. Corey and Michael Chaykovsky. The reaction involves addition of a sulfur ylide to a ketone, aldehyde, imine, or enone to produce the corresponding 3-membered ring. The reaction is diastereoselective favoring trans substitution in the product regardless of the initial stereochemistry. The synthesis of epoxides via this method serves as an important retrosynthetic alternative to the traditional epoxidation reactions of olefins.

Prato reaction

The Prato reaction is a particular example of the well-known 1,3-dipolar cycloaddition of azomethine ylides to olefins. In fullerene chemistry this reaction refers to the functionalization of fullerenes and nanotubes. The amino acid sarcosine reacts with paraformaldehyde when heated at reflux in toluene to an ylide which reacts with a double bond in a 6,6 ring position in a fullerene via a 1,3-dipolar cycloaddition to yield a N-methylpyrrolidine derivative or pyrrolidinofullerene or pyrrolidino[[3,4:1,2]] [60]fullerene in 82% yield based on C60 conversion.

1,3-dipole

In organic chemistry, a 1,3-dipolar compound or 1,3-dipole is a dipolar compound with delocalized electrons and a separation of charge over three atoms. They are reactants in 1,3-dipolar cycloadditions.

The Nazarov cyclization reaction is a chemical reaction used in organic chemistry for the synthesis of cyclopentenones. The reaction is typically divided into classical and modern variants, depending on the reagents and substrates employed. It was originally discovered by Ivan Nikolaevich Nazarov (1906–1957) in 1941 while studying the rearrangements of allyl vinyl ketones.

Aziridines

Aziridines are organic compounds containing the aziridine functional group, a three-membered heterocycle with one amine (-NR-) and two methylene bridges. The parent compound is aziridine, with molecular formula C
2H
4NH. Several drugs feature aziridine rings, including mitomycin C, porfiromycin, and azinomycin B (carzinophilin).

Isoindoline is a heterocyclic organic compound with the molecular formula C8H9N. The parent compound has a bicyclic structure, consisting of a six-membered benzene ring fused to a five-membered nitrogen-containing ring. The compound's structure is similar to indoline except that the nitrogen atom is in the 2 position instead of the 1 position of the five-membered ring. Isoindoline itself is not commonly encountered, but several derivatives are found in nature and some synthetic derivatives are commercially valuable drugs, e.g. pazinaclone.

Horsfiline Chemical compound

Horsfiline is an oxindole alkaloid found in the plant Horsfieldia superba, which is used in traditional herbal medicine. It has analgesic effects and has been the subject of research both to produce it synthetically by convenient routes and to develop analogues and derivatives which may have improved analgesic effects.

Staudinger synthesis Form of chemical synthesis

The Staudinger synthesis, also called the Staudinger ketene-imine cycloaddition, is a chemical synthesis in which an imine 1 reacts with a ketene 2 through a non-photochemical 2+2 cycloaddition to produce a β-lactam3. The reaction carries particular importance in the synthesis of β-Lactam antibiotics. The Staudinger synthesis should not be confused with the Staudinger reaction, a phosphine or phosphite reaction used to reduce azides to amines.

Nitrile ylides also known as nitrilium ylides, or nitrilium methylides are generally reactive intermediates. With a few exceptions, they cannot be isolated. However, a structure has been determined on a particularly stable nitrile ylide by X-ray crystallography. Another nitrile ylide has been captured under cryogenic conditions.

The nitrone-olefin (3+2) cycloaddition reaction is the combination of a nitrone with an alkene or alkyne to generate an isoxazoline or isoxazolidine via a [3+2] cycloaddition process. This reaction is a 1,3-dipolar cycloaddition, in which the nitrone acts as the 1,3-dipole, and the alkene or alkyne as the dipolarophile.

The term bioorthogonal chemistry refers to any chemical reaction that can occur inside of living systems without interfering with native biochemical processes. The term was coined by Carolyn R. Bertozzi in 2003. Since its introduction, the concept of the bioorthogonal reaction has enabled the study of biomolecules such as glycans, proteins, and lipids in real time in living systems without cellular toxicity. A number of chemical ligation strategies have been developed that fulfill the requirements of bioorthogonality, including the 1,3-dipolar cycloaddition between azides and cyclooctynes, between nitrones and cyclooctynes, oxime/hydrazone formation from aldehydes and ketones, the tetrazine ligation, the isocyanide-based click reaction, and most recently, the quadricyclane ligation.

Montréalone

Montréalone is a mesoionic heterocyclic chemical compound. It is named for the city of Montréal, Canada, which is the location of McGill University, where it was first discovered.

Alkene carboamination

Alkene carboamination is the simultaneous formation of C–N and C–C bonds across an alkene. This method represents a powerful strategy to build molecular complexity with up to two stereocenters in a single operation. Generally, there are four categories of reaction modes for alkene carboamination. The first class is cyclization reactions, which will form a N-heterocycle as a result. The second class has been well established in the last decade. Alkene substrates with a tethered nitrogen nucleophile have been used in these transformations to promote intramolecular aminocyclization. While intermolecular carboamination is extremely hard, people have developed a strategy to combine the nitrogen and carbon part, which is known as the third class. The most general carboamination, which takes three individual parts and couples them together is still underdeveloped.

Ferulic acid decarboxylase Decarboxylase enzymes

Ferulic acid decarboxylases (Fdc) are decarboxylase enzymes capable of the reversible decarboxylation of aromatic carboxylic acids such as ferulic acid and cinnamic acid. Fdc's are fungal homologues of the E.coli UbiD enzyme which is involved in ubiquinone biosynthesis. This places Fdc within the wider UbiD enzyme family, representing a distinct clade within the family Presence of fdc1 and the associated pad1 genes were shown to be required for the decarboxylation of phenylacrylic acids in Saccharomyces cerevisiae.

An organic azide is organic compounds containing the azide (N3) functional group. Because of the hazards associated with their use, few azides are used commercially although they exhibit interesting reactivity for researchers. Low molecular weight azides are considered especially hazardous and are avoided. In the research laboratory, azides are precursors to amines. They are also popular for their participation in the "click reaction" and in Staudinger ligation. These two reactions are generally quite reliable, lending themselves to combinatorial chemistry.

References

  1. 1 2 3 4 5 Coldham, Iain; Hufton, Richard (2005). "Intramolecular Dipolar Cycloaddition Reactions of Azomethine Ylides". Chemical Reviews. 105 (7): 2765–2809. doi:10.1021/cr040004c. PMID   16011324.
  2. ↑ Padwa, Albert; Pearson, William H.; Harwood, L. M.; Vickers, R. J. (2003). "Chapter 3. Azomethine Ylides". Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry Toward Heterocycles and Natural Products. Chemistry of Heterocyclic Compounds: A Series of Monographs. Vol. 59. pp. 169–252. doi:10.1002/0471221902.ch3. ISBN   9780471387268.
  3. ↑ Adrio, Javier; Carretero, Juan C. (2011). "Novel dipolarophiles and dipoles in the metal-catalyzed enantioselective 1,3-dipolar cycloaddition of azomethine ylides". Chemical Communications. 47 (24): 6784–6794. doi:10.1039/c1cc10779h. PMID   21472157.
  4. ↑ Dauban, Philippe; Guillaume, Malik (2009). "A Masked 1,3-Dipole Revealed from Aziridines". Angewandte Chemie International Edition. 48 (48): 9026–9029. doi:10.1002/anie.200904941. PMID   19882612.
  5. ↑ Huisgen, Rolf; Scheer, Wolfgang; Huber, Helmut (1967). "Stereospecific Conversion of cis-trans Isomeric Aziridines to Open-Chain Azomethine Ylides". Journal of the American Chemical Society . 89 (7): 1753–1755. doi:10.1021/ja00983a052.
  6. ↑ Banks, Harold D. (2010). "Torquoselectivity Studies in the Generation of Azomethine Ylides from Substituted Aziridines". Journal of Organic Chemistry. 75 (8): 2510–2517. doi:10.1021/jo902600y. PMID   20329779.
  7. ↑ Cardoso, Ana L.; Pinho e Melo, Teresa M. V. D. (2012). "Aziridines in Formal [3+2]Cycloadditions: Synthesis of Five-Membered Heterocycles". European Journal of Organic Chemistry (33): 6479–6501. doi:10.1002/ejoc.201200406.
  8. ↑ Huie, Edward (1983). "Intramolecular [3+2]cycloaddition routes to carbon-bridged dibenzocycloheptanes and dibenzazepines". Journal of Organic Chemistry. 48 (18): 2994–2997. doi:10.1021/jo00166a011.
  9. ↑ Padwa, Albert; Gingrich, Henry L.; Lim, Richard (1982). "Regiochemistry of intramolecular munchnone cycloadditions: preparative and mechanistic implications". Journal of Organic Chemistry. 47 (12): 2447–2456. doi:10.1021/jo00133a041.
  10. ↑ Li, Yi; Houk, Kendall N.; González, Javier (1995). "Pericyclic Reaction Transition States". Accounts of Chemical Research. 20 (2): 81–90. doi:10.1021/ar00050a004.
  11. ↑ Heathcock, Clayton H.; Henke, Brad R.; Kouklis, Andrew J. (1992). "Intramolecular 1,3-Dipolar Cycloaddition of Stabilized Azomethine Ylides to Unactivated Dipolarophiles". Journal of Organic Chemistry. 57 (56): 7056–7066. doi:10.1021/jo00052a015.
  12. ↑ Streiber, S. L. (2003). "Catalytic asymmetric [3+2]cycloaddition of azomethine ylides. Development of a versatile stepwise, three-component reaction for diversity-oriented synthesis". Journal of the American Chemical Society. 125 (34): 10174–10175. doi:10.1021/ja036558z. PMID   12926931.
  13. ↑ R. Berger, M. Wagner, X. Feng, K. Müllen. “Polycyclic aromatic azomethine ylides: a unique entry to extended polycyclic heteroaromatics”. 2014. 436–441.doi: 10.1039/C4SC02793K
  14. ↑ Adrio, Javier; Carreter, Juan C. (2011). "Novel dipolarophiles and dipoles in the metal-catalyzed enantioselective 1,3-dipolar cycloaddition of azomethine ylides". Chemical Communications. 47 (24): 6784–6794. doi:10.1039/c1cc10779h. PMID   21472157.
  15. ↑ Zhang, Xumu; Raghunath, Malati; Gao, Wenzhong (2005). "Cu(I)-Catalyzed Highly Exo-selective and Enantioselective [3+2]Cycloaddition of Azomethine Ylides with Acrylates". Organic Letters. 7 (19): 4241–4244. doi:10.1021/ol0516925. PMID   16146397.
  16. ↑ Fukuzawa, Shin-ichi; Oura, Ichiro; Shimizu, Kenta; Ogata, Kenichi (2010). "Highly Endo-Selective and Enantioselective 1,3-Dipolar Cycloaddition of Azomethine Ylide with α-Enones Catalyzed by a Silver(I)/ThioClickFerrophos Complex". Organic Letters. 12 (8): 1752–1755. doi:10.1021/ol100336q. PMID   20232852.
  17. ↑ Allway, Philip; Grigg, Ronald (1991). "Chiral cobalt(II) and manganese(II) catalysts for the 1,3-dipolar cycloaddition reactions of azomethine ylides derived from arylidene imines of glycine". Tetrahedron Letters. 32 (41): 5817–5820. doi:10.1016/S0040-4039(00)93563-9.
  18. ↑ Gong, Liu-Zhu; Chen, Xiao-Hua; Wei, Qiang; Luo, Shi-Wei; Xiao, Han (2009). "Organocatalytic Synthesis of Spiro[pyrrolidin-3,3′-oxindoles] with High Enantiopurity and Structural Diversity". Journal of the American Chemical Society. 131 (38): 13819–13825. doi:10.1021/ja905302f. PMID   19736987.
  19. ↑ Nedolya, N. A.; Trofimov, B. A. (2013). "[1,7]-Electrocyclization reactions in the synthesis of azepine derivatives". Chemistry of Heterocyclic Compounds. 49 (1): 152–176. doi:10.1007/s10593-013-1236-y. S2CID   96192354.
  20. ↑ Nyerges, Miklós (2006). "1,7-Electrocyclization reactions of stabilized α,β:γ,δ-unsaturated azomethine ylides". Tetrahedron. 16 (24): 5725–5735. doi:10.1016/j.tet.2006.03.088.
  21. ↑ Nierengarten, Jean-François (2002). "An unexpected Diels–Alder reaction on the fullerene core rather than an expected 1,3-dipolar cycloaddition". Chem. Commun. (7): 712–713. doi:10.1039/B201122K. PMID   12119686.
  22. ↑ Snider, B. B.; Ahn, Y.; O'Hare, S. M. (2001). "Total synthesis of (±)-martinellic acid". Organic Letters. 3 (26): 4217–4220. doi:10.1021/ol016884o. PMID   11784181.
  23. ↑ Williams, Robert (2003). "Concise, Asymmetric Total Synthesis of Spirotryprostatin A". Organic Letters. 5 (17): 3135–3137. doi:10.1021/ol0351910. PMID   12917000.
  24. ↑ Ryan, John H. (2011). "1,3-Dipolar cycloaddition-decarboxylation reactions of an azomethine ylide with isatoic anhydrides: formation of novel benzodiazepinones". Organic Letters. 13 (3): 486–489. doi:10.1021/ol102824k. PMID   21175141.
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