What is the Diels Alder Reaction?

The Diels–Alder reaction is the reaction between a conjugated diene and an alkene (dienophile) to form unsaturated six-membered rings. Since the reaction involves the formation of a cyclic product via a cyclic transition state, it is also referred to as a "cycloaddition". The Diels–Alder reaction is an electrocyclic reaction, which involves [4+2]‑cycloaddition of 4 π-electrons of the conjugated diene and 2 π-electrons of the dienophile (an alkene or alkyne). The reaction involves the formation of new σ-bonds, which are energetically more stable than the π-bonds. This reaction has great synthetic importance and was discovered by two German chemists, Otto Diels and Kurt Alder in 1928. They were awarded the Nobel Prize in 1950.1

The Diels Alder Reaction showing the forming of new σ-bonds

The hetero-Diels–Alder reaction is a variant of this reaction and is useful for the synthesis of six-membered heterocyclic rings. In this reaction, either the diene or the dienophile contains a heteroatom, usually nitrogen or oxygen.1

Precautions

Please consult the Safety Data Sheet for information regarding hazards and safe handling practices.

Materials
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Applications for Diels Alder Reaction

The Diels–Alder reaction is useful for the synthesis of:

  • Novel Diels−Alder reactions of arynes with functionalized acyclic dienes have been reported for the synthesis of useful cis-substituted dihydronaphthalene building blocks.2
Novel Diels−Alder reactions of arynes with functionalized acyclic dienes.
  • Natural and unnatural polycarbocycles and polyheterocycles.3
  • Substituted (tetrahydro)quinolines and diverse N-polyheterocycles, including some alkaloids, which contain pyrroloquinoline or cyclopentaquinoline ring systems.4
  • Pyrano[3,2-c]quinolines and indeno[2,1-c]quinolones.5
  • Symmetrically substituted 1,8-diaza-9,10-anthraquinone derivatives.6
  • Oxazaborolidine derived from N-tosyl (αSR)-β-methyltryptophan has been employed as the catalyst for the enantioselective Diels-Alder reaction of 2‑bromoacrolein and furan. This reaction leads to the synthesis of chiral 7‑oxabicyclo[2.2.1]heptene derivatives.7
Diels Alder Reaction, Synthesis of Chiral
  • Functionalized 4-(R)-1,2-bis(trimethylsilyl)benzenes.8
  • Functionalized oxabicyclic alkenes.9

Recent Research and Trends

  • Intra- and intermolecular imino Diels–Alder reactions (Povarov reactions) of N-aryl imines and diverse electron-rich alkenes have been studied.4
  • Ultrasonic irradiation promoted the Diels–Alder reaction of substituted furans with reactive dienophiles such as dimethyl acetylenedicarboxylate (DMAD) and dimethyl maleate afforded functionalized oxabicyclic alkenes in good yields.9
Diels Alder Reaction-04r
  • The Diels–Alder reaction of graphite and tetracyanoethylene has been used for the mechanical exfoliation of graphite into graphene adducts.10
  • Cross-linked hydrogels have been prepared using Diels-Alder “click” reaction without employing a catalyst.11
  • The asymmetric Diels–Alder reaction between N-acryloyloxazolidinone and cyclopentadiene has been catalyzed by heterogeneous copper(II)-bis(oxazoline)-based polymer immobilized ionic liquid phase (PIILP) systems.12
  • Chiral oxazaborolidine−aluminum bromide complexes are potential catalysts for enantioselective Diels–Alder reactions.13
  • Halocycloalkenones have been investigated as potent dienophiles in inter- and intramolecular Diels–Alder cycloadditions.14
  • The chemical thermodynamics of Diels–Alder addition reactions of a series of acenes (anthracene, 9,10-dimenthylanthracene, tetracene and pentacene) to C60 fullerene has been analyzed.15

References

1.
Fringuelli F, Taticchi A. 2001. The Diels?Alder Reaction. http://dx.doi.org/10.1002/0470845813
2.
Dockendorff C, Sahli S, Olsen M, Milhau L, Lautens M. 2005. Synthesis of Dihydronaphthalenes via Aryne Diels?Alder Reactions:  Scope and Diastereoselectivity. J. Am. Chem. Soc.. 127(43):15028-15029. http://dx.doi.org/10.1021/ja055498p
3.
Smith MB. 2011. Organic Synthesis.
4.
Kouznetsov VV. 2009. Recent synthetic developments in a powerful imino Diels?Alder reaction (Povarov reaction): application to the synthesis of N-polyheterocycles and related alkaloids. Tetrahedron. 65(14):2721-2750. http://dx.doi.org/10.1016/j.tet.2008.12.059
5.
Babu G, Perumal PT. 1998. Convenient synthesis of pyrano[3,2-c]quinolines and indeno[2,1-c] quinolines by imino Diels-Alder reactions. Tetrahedron Letters. 39(20):3225-3228. http://dx.doi.org/10.1016/s0040-4039(98)00397-9
6.
Pérez JM, López-Alvarado P, Avendaño C, Menéndez J. 2000. Hetero Diels?Alder Reactions of 1-Acetylamino- and 1-Dimethylamino-1-azadienes with Benzoquinones. Tetrahedron. 56(11):1561-1567. http://dx.doi.org/10.1016/s0040-4020(00)00058-2
7.
Corey E, Loh T. 1993. Catalytic enantioselective diels-alder addition to furan provides a direct synthetic route to many chiral natural products. Tetrahedron Letters. 34(25):3979-3982. http://dx.doi.org/10.1016/s0040-4039(00)60594-4
8.
Reus C, Liu N, Bolte M, Lerner H, Wagner M. 2012. Synthesis of Bromo-, Boryl-, and Stannyl-Functionalized 1,2-Bis(trimethylsilyl)benzenes via Diels?Alder or C?H Activation Reactions. J. Org. Chem.. 77(7):3518-3523. http://dx.doi.org/10.1021/jo3002936
9.
Wei K, Gao H, Li WZ. 2004. Facile Synthesis of Oxabicyclic Alkenes by Ultrasonication-Promoted Diels?Alder Cycloaddition of Furano Dienes. J. Org. Chem.. 69(17):5763-5765. http://dx.doi.org/10.1021/jo049210a
10.
Ji Z, Chen J, Huang L, Shi G. High-yield production of highly conductive graphene via reversible covalent chemistry. Chem. Commun.. 51(14):2806-2809. http://dx.doi.org/10.1039/c4cc09144b
11.
García-Astrain C, Algar I, Gandini A, Eceiza A, Corcuera, Gabilondo N. 2015. Hydrogel synthesis by aqueous Diels-Alder reaction between furan modified methacrylate and polyetheramine-based bismaleimides. J. Polym. Sci. Part A: Polym. Chem.. 53(5):699-708. http://dx.doi.org/10.1002/pola.27495
12.
Doherty S, Knight JG, Ellison JR, Goodrich P, Hall L, Hardacre C, Muldoon MJ, Park S, Ribeiro A, de Castro CAN, et al. An efficient Cu(ii)-bis(oxazoline)-based polymer immobilised ionic liquid phase catalyst for asymmetric carbon?carbon bond formation. Green Chem.. 16(3):1470-1479. http://dx.doi.org/10.1039/c3gc41378k
13.
Liu D, Canales E, Corey EJ. 2007. Chiral Oxazaborolidine?Aluminum Bromide Complexes Are Unusually Powerful and Effective Catalysts for Enantioselective Diels?Alder Reactions. J. Am. Chem. Soc.. 129(6):1498-1499. http://dx.doi.org/10.1021/ja068637r
14.
Ross AG, Townsend SD, Danishefsky SJ. 2013. Halocycloalkenones as Diels?Alder Dienophiles. Applications to Generating Useful Structural Patterns. J. Org. Chem.. 78(1):204-210. http://dx.doi.org/10.1021/jo302230m
15.
Cataldo F, García-Hernández DA, Manchado A. 2015. Chemical Thermodynamics Applied to the Diels?Alder Reaction of C60Fullerene with Polyacenes. Fullerenes, Nanotubes and Carbon Nanostructures. 23(9):760-768. http://dx.doi.org/10.1080/1536383x.2014.997354