In 1928, Otto Diels and Kurt Alder first reported the reaction that would eventually carry their nam — Organic Chemistry Chemistry Question
The Diels–Alder Reaction
In 1928, Otto Diels and Kurt Alder first reported the reaction that would eventually carry their names. The reaction between a conjugated diene and a dienophile provides a cyclohexene, as shown in the simplest example below:
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When the reaction partners are substituted, the possibilities increase as asymmetric centers are formed in the reaction. The Diels–Alder reaction is one of the most useful tools available to a synthetic organic chemist.
E. J. Corey, a professor at Harvard University and recipient of the 1990 Nobel Prize in Chemistry, employed the Diels–Alder reaction in his landmark synthesis of the prostaglandins. Draw the product of the following reaction and place a star (*) next to the chiral centres.
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Model Answer
Starred chiral centers in the bicyclic product:
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(Four chiral centers are starred in the cyclopentane-fused cyclohexene system: the carbon with the -CN group, the carbon with the -Cl group, the carbon with the -CH2OCH3 group, and the bridgehead carbon linking the ring system).
Due to its popularity, many chemists have sought to produce and employ even more useful variants of the reaction. Two of the most straightforward are hetero- and retro- Diels–Alder reactions. In a hetero reaction, one of the carbons in either the diene or dienophile is replaced with a heteroatom (N, O, S, etc.) such that the 6-membered ring of the product is a heterocycle. In the retro-Diels–Alder reaction, a cyclohexene transforms to a diene and olefin.
Both of these reactions appear in the following reaction sequence towards pseudotabersonine:
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Draw the reactive intermediate D, as well as the final product of the reaction E.
Model Answer
Structures of reactive intermediate D and final product E:
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Where D is the reactive azadiene intermediate and E is the pentacyclic framework of pseudotabersonine.
Suggest an “electron-pushing” mechanism for both parts of the transformation.
Model Answer
Mechanism showing curly arrows for electron movement:
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The first step is a retro-Diels-Alder reaction of the starting bicyclic structure to release cyclopentadiene and form the azadiene intermediate D. The second step is an intramolecular Diels-Alder cycloaddition in which the azadiene moiety in D acts as a heterodiene reacting with the pendant alkene to construct product E.
Triazenes are able to provide aromatic rings via a Diels–Alder process. Suggest an electron pushing mechanism for the following reaction. Draw the other two products of the reaction:
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Model Answer
Electron pushing mechanism and structures of the other two products:
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The other two products of the reaction are nitrogen gas (N2) and ethanol (EtOH).
Danishefsky’s diene, named for Samuel Danishefsky of Columbia University, contains acid labile functional groups, which can be selectively removed after the Diels–Alder reaction. Draw the missing structures in the scheme of Danishefsky’s synthesis of disodium prephenate:
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Model Answer
Structures of intermediate X and Y:
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Where X is the initial Diels-Alder adduct formed from Danishefsky's diene and the dienophile, and Y is the cyclohexenone intermediate generated after the selective removal of silyl ether and methoxy groups under acidic conditions.