Diels-Alder reaction

from Wikipedia, the free encyclopedia

The Diels-Alder reaction is a chemical reaction in which bonds between carbon atoms are established. It was named after its discoverers Otto Diels and Kurt Alder from Kiel , who were awarded the Nobel Prize in 1950 for their work .

In this reaction, a ring of six carbon atoms is formed, with a conjugated diene and a substituted alkene being linked. The substituted alkene is also called a dienophile ; in order to achieve an acceptable yield, the diene and dienophile must have special electronic properties. The special importance of the Diels-Alder reaction is that CC bonds can be built up with high stereoselectivity . Diels-Alder reactions play a particularly important role in the synthesis of natural substances (including the formation of steroids such as the female sex hormone estradiol ). The atom economy of the Diels-Alder reaction is consistently excellent.

General

The Diels-Alder reaction is a [4 + 2] cycloaddition . This means that 4 or 2 π electrons of the two molecules are involved in the reaction. A typical example is the reaction of maleic anhydride with 1,3-butadiene .

The reaction of 1,3-butadiene with ethene with the formation of cyclohexene , which is often shown as an example in this context, can only be understood as a schematic , because without electron-withdrawing substituents on the dienophile, its lowest, unoccupied orbital ( LUMO ) is energetically too high to withstand highest occupied orbital ( HOMO ) of the diene to enter into binding interaction.

This leads to a concerted rearrangement of three π-electron pairs, which form two new σ-bonds between a dienophile and a diene as well as a double bond in the resulting Diels-Alder product. The reaction can be initiated both thermally and photochemically.

The stereochemistry of the reaction can be understood by applying the Woodward-Hoffmann rules .

mechanism

A Diels-Alder reaction proceeds according to the following mechanism:

Reaction mechanism of the Diels-Alder reaction

The p orbitals of diene and dienophile overlap in the transition state in such a way that new chemical bonds are formed. The arrows are to be understood here only schematically and do not represent any interactions between electrophilic and nucleophilic centers.

Orbital model of the rather rare Diels-Alder reaction with inverse electron demand

Kinetic consideration

The reaction rate can be increased considerably by introducing functional groups on the diene and / or dienophile (combination of an electron-poor diene and electron-rich dienophile (inverse electron requirement) or an electron-rich diene and electron-poor dienophile (normal electron requirement)). The stereochemical arrangement of these functional groups in the product ( cis or trans ) depends on the type of reaction (thermal or photolytic; conrotatory or disrotatory ring closure) and the electron density of the reactants . Predictions are possible based on the energetic position of the respective HOMO / LUMO orbitals ( MO theory ).

Stereochemistry and endo rule

Endo - (left) and exo form (right) of the dimer of cyclopentadiene

The formation of an exo and an endo product is basically conceivable. The thermodynamically (because sterically) more favorable variant is the exo product, in which the dienophile is "folded away" from the diene. For the transition state of addition of the diene to the dienophile, it is generally assumed that the endo transition state is preferred because of secondary orbital interactions. A final explanation is still pending. Kinetic control of the reaction (e.g. by means of a low temperature, which suppresses or slows down the reversible reaction) promotes the preferential formation of the endo product.

Chemistry of service

The diene component in the Diels-Alder reaction can be both open-chain and cyclic and have many different substituents. The only restriction is that the open-chain diene must be in the s-cis configuration for the reaction . However, this is achieved through an equilibrium between the s-cis and s-trans isomers . Under normal conditions, the s-trans modification is predominant; since the s-cis form is withdrawn from the equilibrium, it shifts according to the principle of Le Chatelier . Cyclic dienes are almost always in the s-cis configuration because the ring can no longer flip over to s-trans . You are exceptionally reactive. An example of this is cyclopentadiene ; despite the lack of electron-withdrawing or electron-donating substituents, it also reacts with itself to form dicyclopentadiene .

Chemistry of Dienophiles

In a typical Diels-Alder reaction, the dienophile has an electron-withdrawing group conjugated to the double bond. Dienophiles can be activated by Lewis acids .

For example, cyclopentadiene will not react with cyclohexenone in ethyl acetate unless a Lewis acid activates the reaction. α, β-unsaturated carbonyl compounds can deactivate the Lewis acid.

If aldehydes , ketones , imines , thioketones or other compounds with hetero atoms are used as dienophiles , one also speaks of hetero-Diels-Alder reactions .

Retro-Diels-Alder reaction

Some Diels-Alder reactions are reversible. The breakdown of a Diels-Alder adduct into the starting components is known as the retro-Diels-Alder reaction . One example is the thermal decomposition of the dimeric cyclopentadiene in the presence of an iron catalyst.

In mass spectrometry , electron impact ionization can lead to fragmentation, also known as the retro-Diels-Alder reaction . The mechanism of this reaction is not concerted, but radical.

literature

  • Francesco Fringuelli, Aldo Taticchi: Dienes in the Diels-Alder Reaction. Wiley, New York 1990, ISBN 0-471-85549-9 .
  • Nguyên Trong Anh: The Woodward-Hoffmann rules and their application. Chemie, Weinheim 1972, ISBN 3-527-25430-7 .

Web links

Commons : Diels-Alder reaction  - collection of pictures, videos and audio files

Individual evidence

  1. ↑ O. Diels, K. Alder: Syntheses in the hydroaromatic series . In: Justus Liebig's Annals of Chemistry . 460, No. 1, 1928, pp. 98-122. doi : 10.1002 / jlac.19284600106 .
  2. ↑ Otto Diels, Kurt Alder: Syntheses in the hydroaromatic series. III. Communication: Synthesis of terpenes, camphor, hydroaromatic and heterocyclic systems. Collaborated by Messrs. Wolfgang Lübbert, Erich Naujoks, Franz Querberitz, Karl Röhl, Harro Segeberg. In: Justus Liebig's Annals of Chemistry. 470, No. 1, 1929, pp. 62-103, doi: 10.1002 / jlac.19294700106 .
  3. ↑ Otto Diels, Kurt Alder: Syntheses in the hydroaromatic series, IV. Part: About the addition of maleic anhydride to arylated dienes, trienes and fulvene (edited by Paul Pries). In: Reports of the German Chemical Society (A and B Series). 62, No. 8, 1929, pp. 2081-2087, doi: 10.1002 / cber.19290620829 .
  4. ↑ Otto Diels, Kurt Alder: Syntheses in the hydroaromatic series, V. Communication: About Δ4-Tetrahydro-o-phthalic acid (Comment on the communication from EH Farmer and FL Warren: Properties of conjugated double bonds (VII). In: Reports of the German chemical Society (A and B Series). 62, No. 8, 1929, pp. 2087-2090, doi: 10.1002 / cber.19290620830 .
  5. ↑ Milton C. Kloetzel: The Diels-Alder Reaction with Maleic Anhydride. In: Organic reactions. 4, No. 1, 1948, pp. 1-59, doi: 10.1002 / 0471264180.or004.01 .
  6. ↑ HL Holmes: The Diels-Alder Reaction Ethylenic and Acetylenic Dienophiles. In: Organic Reactions. 4, No. 2, 2004, pp. 1007-1019, doi: 10.1002 / 0471264180.or004.02 .
  7. ^ Henri B. Kagan, Olivier Riant: Catalytic asymmetric Diels Alder reactions. In: Chemical Reviews. 92, No. 5, 1992, pp. 1007-1019, doi: 10.1021 / cr00013a013 .
  8. ^ KC Nicolaou, Scott A. Snyder, Tamsyn Montagnon, Georgios Vassilikogiannakis: The Diels-Alder Reaction in Total Synthesis. In: Angewandte Chemie International Edition. 41, No. 10, 2002, pp. 1668-1698, doi : 10.1002 / 1521-3773 (20020517) 41:10 <1668 :: AID-ANIE1668> 3.0.CO; 2-Z .
  9. ^ Charles E. Mortimer, Ulrich Müller: Chemistry: the basic knowledge of chemistry . 9th edition. Georg Thieme Verlag, Stuttgart 2007, ISBN 978-3-13-484309-5 , p. 539 ( limited preview in Google Book search).
  10. ↑ Jonathan Clayden, Nick Greeves, Stuart Warren: Organic Chemistry . 2nd Edition. Springer Spectrum, Berlin / Heidelberg 2013, ISBN 978-3-642-34715-3 , p. 970 .
  11. ↑ SA Kozmin, S. He, VH Rawal ,: [4 + 2] cycloaddition of 1-dimethylamino-3-tert-butyldimethylsiloxy-1,3-butadiene with methyl acrylate: 4-hydroxymethyl-2-cyclohexen-1-one Template: link text check / apostrophe In : Organic Syntheses . 78, 2002, p. 160, doi : 10.15227 / orgsyn.078.0160 ; Coll. Vol. 10, 2004, p. 442 ( PDF ).
  12. ↑ EB Hershberg, JR Ruhoff: 1,3-Butadiene In: Organic Syntheses . 17, 1937, p. 25, doi : 10.15227 / orgsyn.017.0025 ; Coll. Vol. 2, 1943, p. 102 ( PDF ).
  13. ↑ Mauricio Gomes Constantino, Valdemar Lacerda Júnior, Gil Valdo José Da Silva: Niobium Pentachloride Activation of Enone Derivatives: Diels-Alder and Conjugate Addition Products. In: Molecules . Volume 7, No. 5, 2002, pp. 456-464, doi: 10.3390 / 70500456 (free full text).