DielsAlder Reaction u DielsAlder reaction A cycloaddition reaction

Diels-Alder Reaction u Diels-Alder reaction: A cycloaddition reaction of a conjugated diene and certain types of double and triple bonds. • dienophile: Diene-loving. • Diels-Alder adduct: The product of a Diels-Alder reaction. 24 -1

Diels-Alder Reaction • Alkynes also function as dienophiles. • Cycloaddition reaction: A reaction in which two reactants add together in a single step to form a cyclic product. 24 -2

Diels-Alder Reaction • We write a Diels-Alder reaction in the following way: • The special value of D-A reactions are that they: 1. form six-membered rings. 2. form two new C-C bonds at the same time. 3. are stereospecific and regioselective. Note the reaction of butadiene and ethylene gives only traces of cyclohexene. 24 -3

Diels-Alder Reaction • The conformation of the diene must be s-cis. 24 -4

Diels-Alder Reaction Steric Restrictions • (2 Z, 4 Z)-2, 4 -Hexadiene is unreactive in Diels-Alder reactions because nonbonded interactions prevent it from assuming the planar s-cis conformation. 24 -5

Diels-Alder Reaction • Reaction is facilitated by a combination of electronwithdrawing substituents on one reactant and electron -releasing substituents on the other. 24 -6

Diels-Alder Reaction 24 -7

Diels-Alder Reaction • The Diels-Alder reaction can be used to form bicyclic systems. 24 -8

Diels-Alder Reaction • Exo and endo are relative to the double bond derived from the diene. 24 -9

Diels-Alder Reaction • For a Diels-Alder reaction under kinetic control, endo orientation of the dienophile is favored. 24 -10

Diels-Alder Reaction • The configuration of the dienophile is retained. 24 -11

Diels-Alder Reaction • The configuration of the diene is retained. Check that this is endo. 24 -12

Diels-Alder Reaction u Mechanism • No evidence for the participation of either radical of ionic intermediates. • Chemists propose that the Diels-Alder reaction is a concerted pericyclic reaction. u Pericyclic reaction: reaction A reaction that takes place in a single step, without intermediates, and involves a cyclic redistribution of bonding electrons. u Concerted reaction: All bond making and bond breaking occurs simultaneously. 24 -13

Diels-Alder Reaction • Mechanism of the Diels-Alder reaction 24 -14

Aromatic Transition States u Hückel criteria for aromaticity: The presence of (4 n + 2) pi electrons in a ring that is planar and fully conjugated. u Just as aromaticity imparts a special stability to certain types of molecules and ions, the presence of (4 n + 2) electrons in a cyclic transition state imparts a special stability to certain types of transition states. • Reactions involving 2, 6, 10, 14. . electrons in a cyclic transition state have especially low activation energies and take place particularly readily. 24 -15

Aromatic Transition States, Examples • Decarboxylation of -keto acids and -dicarboxylic acids. • Cope elimination of amine N-oxides. 24 -16

Aromatic Transition States • the Diels-Alder reaction • pyrolysis of esters (Problem 22. 42) u We now look at examples of two more reactions that proceed by aromatic transition states: • Claisen rearrangement. • Cope rearrangement. 24 -17

Claisen Rearrangement u Claisen rearrangement: A thermal rearrangement of allyl phenyl ethers to 2 -allylphenols. 24 -18

Claisen Rearrangement 24 -19

Cope Rearrangement u Cope rearrangement: A thermal isomerization of 1, 5 -dienes. 24 -20

Cope Rearrangement Example 24. 8 Predict the product of these Cope rearrangements. 24 -21

Synthesis of Single Enantiomers • We have stressed throughout the text that the synthesis of chiral products from achiral starting materials and under achiral reaction conditions of necessity gives enantiomers as a racemic mixture. • Nature achieves the synthesis of single enantiomers by using enzymes, which create a chiral environment in which reaction takes place. • Enzymes show high enantiomeric and diastereomeric selectivity with the result that enzyme-catalyzed reactions invariably give only one of all possible stereoisomers. 24 -22

Synthesis of Single Enantiomers u How do chemists achieve the synthesis of single enantiomers? u The most common method is to produce a racemic mixture and then resolve it. How? • the different physical properties of diastereomeric salts. • the use of enzymes as resolving agents. • chromatographic on a chiral substrate. 24 -23

Synthesis of Single Enantiomers • In a second strategy, asymmetric induction, induction the achiral starting material is placed in a chiral environment by reacting it with a chiral auxiliary Later it will be removed. • E. J. Corey used this chiral auxiliary to direct an asymmetric Diels -Alder reaction. • 8 -Phenylmenthol was prepared from naturally occurring enantiomerically pure menthol. 24 -24

Synthesis of Single Enantiomers • The initial step in Corey’s prostaglandin synthesis was a Diels-Alder reaction. • By binding the achiral acrylate with enantiomerically pure 8 -phenylmenthol, he thus placed the dienophile in a chiral environment. • The result is an enantioselective synthesis. 24 -25

Synthesis of Single Enantiomers • A third strategy is to begin a synthesis with an enantiomerically pure starting material. • Gilbert Stork began his prostaglandin synthesis with the naturally occurring, enantiomerically pure Derythrose. • This four-carbon building block has the R configuration at each stereocenter. • With these two stereocenters thus established, he then used well understood reactions to synthesize his target molecule in enantiomerically pure form. 24 -26