Diels Alder Reaction of dienes and dienophiles
Description: The Diels Alder reaction converts a diene and an alkene (usually electron-poor, called a “dienophile”) into a six-membered ring containing an alkene (cyclohexene).
Notes: X here is usually an electron withdrawing group such as a ketone, ester, or CN.
Notes: Example 1 shows a simple Diels-Alder.
Example 2 shows the reaction with a cyclic diene, to form a bicyclic compound.
Example 3 shows how stereochemistry on the dienophile is conserved (the groups cis to each other on the double bond will end up cis on the ring). That is to say that the reaction is stereospecific.
Examples 4 and 5 show that the groups on the “outside” of the diene end up on the same side of the ring to each other.
Example 6 shows what happens when we have substitution on both the diene and the dienophile. A mixture of diastereomers is formed, called the “endo” and the “exo” products. Generally speaking the “endo” product is favored.
Example 7 shows an alkyne being used as a dienophile.
Examples 8 and 9 show what happens when we have electron donating groups attached to the diene. We always line up the more “electron-rich” carbon of the diene with the more “electron-poor” carbon of the dienophile.
Mechanism: The mechanism of this reaction is concerted meaning that all the bond forming and bond-breaking happens at the same time. The reaction proceeds in a 1-step cycloaddition (Step 1, arrows A, B and C).
Notes: The arrows could just as correctly been drawn proceeding in a clockwise fashion. The end result is the same.
(Advanced) References and Further Reading
This one reaction has spawned a massive amount of research due to its versatility. The papers listed here are representative, but barely scratch the surface of the work that has been done in this area.
- Synthesen in der hydroaromatischen Reihe
Otto Diels and Kurt Alder
Lieb. Ann. Chem. 1928, 460 (1), 98-122
This reaction is named after its discovers, Diels and Alder, who received the Nobel Prize in Chemistry in 1950 for this work. In this paper, they claim their territory in applying their reaction in total synthesis, stating “We explicitly reserve for ourselves the application of the reaction developed by us to the solution of such problems”.
- The mechanism of the Diels-Alder reaction
R. B. Woodward, Thomas J. Katz
Tetrahedron 1959, 5 (1), 70-89
Prof. R. B. Woodward was a legendary figure in organic chemistry, and this paper describes various theories as to the mechanism of the Diels-Alder reaction.
- Diels-alder reactions with inverse electron demand. II. The reaction of benzamidine with π-deficient heteroaromatic compounds
P. Figeys, A. Mathy
Tet. Lett. 1981, 22 (15), 1393-1396
The normal Diels-Alder reaction proceeds best when the diene is electron-rich and the dienophile electron-poor. However, in certain cases, the opposite polarity is possible, and these reactions are known as inverse electron-demand Diels-Alder reactions.
- The Diels–Alder Reaction in Total Synthesis
C. Nicolaou, Scott A. Snyder, Tamsyn Montagnon, Georgios Vassilikogiannakis
Angew. Chem. Int. Ed. 2002, 41 (10), 1668-1698
Prof. K. C. Nicolaou (Rice) is a current leader in natural product total synthesis, and this review covers the applications of the Diels-Alder reaction in this area.
- Hydrophobic acceleration of Diels-Alder reactions
Darryl C. Rideout and Ronald Breslow
Journal of the American Chemical Society 1980, 102 (26), 7816-7817
This publication by Prof. Breslow (Columbia) is significant as it describes an unsual rate acceleration of the Diels-Alder reaction when carried out in water. This is ascribed to the hydrophobic effect, an entropic effect that forces the reactants closer together.
- Useful diene for the Diels-Alder reaction
S. Danishefsky and T. Kitahara
Journal of the American Chemical Society 1974, 96 (25), 7807-7808
This paper describes the synthesis and utility of a functionalized and reactive diene for Diels-Alder reactions. This diene is now commonly known as “Danishefsky’s diene” after its creator, Prof. S. Danishefsky (now at Columbia U.). [Worth noting that Danishefsky’s doctoral supervisor, Prof. Peter Yates, made an important advance in reporting Lewis acid catalysis of the Diels-Alder ]
- New Strategies for Organic Catalysis: The First Highly Enantioselective Organocatalytic Diels−Alder Reaction
Kateri A. Ahrendt, Christopher J. Borths, and David W. C. MacMillan
Journal of the American Chemical Society 2000, 122 (17), 4243-4244
Enantioselective Diels-Alder reactions are also possible and are an active area of research. This paper by Prof. Dave MacMillan (now at Princeton) shows how one can use organocatalysis to achieve an enantioselective Diels-Alder reaction via a chiral iminium ion intermediate.
- Conservation of orbital symmetry
Roald Hoffmann and Robert B. Woodward
Accounts of Chemical Research 1968, 1 (1), 17-22
This is an extremely important paper. Conservation of orbital symmetry allows one to predict the stereochemistry of pericyclic reactions (such as the Diels-Alder reaction). This paper is a great introduction to the topic by its creators and introduces relevant terms (suprafacial, antarafacial, synrotatory, conrotatory, etc.). Prof. Hoffmann received the Nobel Prize in Chemistry in 1981 for this work, and would undoubtedly have shared it with Prof. Woodward that year (which would have been Woodward’s second Nobel) if he had not passed away untimely the previous year.
- ENANTIOSELECTIVE, CATALYTIC DIELS-ALDER REACTION: (1S-endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE
S. Pikul and E. J. Corey
Org. Synth. 1993, 71, 30
This procedure by Nobel Laureate Prof. E. J. Corey (Harvard) demonstrates an asymmetric Diels-Alder reaction by means of a chiral Al catalyst.