Diels-Alder Reaction

Definition:

The 1,4-addition of the double bond of a dienophile to a conjugated diene to generate a six-membered ring.

Frequency of appearance:

        This bar graph represents all of the online articles that were found to contain this specific name reaction in the title of the article. Tetrahedron letters, Tetrahedron, Synthetic letters, Synthesis, Journal of Organic Chemistry and Journal of the American Chemical Society are represented here. This table by no means represents the periodicity of the name reaction found in the literature.

Original References:

1. Diels, K. Alder, Ann. 460, 98 (1928).
2. Diels, O.; Alder, K.; Lubbert, W.; Naujokas, E.; Querberitz, F.; Rohl, K.; Segeberg, H. Ann., 62, 470, (1929).
3. Diels, O.; Alder, K. Ber. 62, 2081, 2087 (1929).

Recent academic references: Click here for more references

4. http://jbcs.sbq.org.br/jbcs/2001/vol12_n5/03.pdf

5. Synthesis of an orange anthrathiophene pigment isolated from a Japanese bryozoan

• Kelly, T. R., et al. Org. Lett., vol.2, no 15, 2351 (2000).

6. Diels_¯Alder reactions on solid supports

• Jari Yli-Kauhaluoma Tetrahedron, Volume 57, Issue 33, 13 August 2001, Pages 7053-7071

Recent process references:

7. An Experimental Study of the Solvent Effect on Rate and Selectivity in a Concentrated Diels-Alder Reaction

• Sheehan, M.; Sharratt, P.; Org. Process Res. Dev.; 1999; 3(6); 471-475.  

8. Diels-Alder Reactions of Epoxybutene Derivatives and Subsequent Synthetic Manipulations of the Cycloadducts

• Franks, M. A.; Hyatt, J. A.; Welker, M. E.; Org. Process Res. Dev.; 2001; 5(5); 514-518.  

9. Hetero Diels-Alder-Biocatalysis Approach for the Synthesis of (S)-3-[2-{(Methylsulfonyl) oxy}ethoxy]-4-(triphenylmethoxy)-1-butanol Methanesulfonate, a Key Intermediate for the Synthesis of the PKC Inhibitor LY333531

• Caille, J.-C.; Govindan, C. K.; Junga, H.; Lalonde, J.; Yao, Y.; Org. Process Res. Dev.; 2002; 6(4); 471-476.

 

Mechanism: http://www.hut.fi/Yksikot/Orgaaninen/opetus/perisykliset_reaktiot/diels_alder.pdf

Scope and Limitations:

• Reaction is often done under mild conditions (room T to slightly above).
• Yields are increased if dienophile is substituted by electron-withdrawing substituents. ^A
• Reaction is stereospecific (geometry of the starting dienophile is maintained). ^A
• In bicyclic structures the endo product is formed over the exo.
• The diene must be able to assume an s-cis conformation.
• Hetero atom analogs of the diene (e.g., CHR=CR-CR=O, O=CR-CR=O, and RN=CR-CR=NR)
• Hetero atom analogs of the dienophile (e.g., RN=NR, R₂C=NR, and RN=O)

Synonyms:

•   4 + 2 cycloaddition