Page 859 - Advanced Organic Chemistry Part A - Structure and Mechanisms, 5th ed (2007) - Carey _ Sundberg

The presence of a t-butyl substituent on both C(2) and C(3), however, prevents 843
attainment of the s-cis conformation, and D-A reactions of 2,3-di-(t-butyl)-1,3-
butadiene have not been observed. 16 SECTION 10.2
The Diels-Alder Reaction

10.2.2. Substituent Effects on Reactivity, Regioselectivity and Stereochemistry

There is a strong electronic substituent effect on the D-A cycloaddition. It
has long been known that the reaction is particularly efficient and rapid when the
dienophile contains one or more EWG and is favored still more if the diene also
contains an ERG. Thus, among the most reactive dienophiles are quinones, maleic
anhydride, and nitroalkenes. ,ß-Unsaturated esters, ketones, and nitriles are also
effective dienophiles. The D-A reaction between unfunctionalized alkenes and dienes
is quite slow. For example, the reaction of cyclopentadiene and ethene occurs at around
17

200 C. These substituent effects are illustrated by the data in Table 10.1. In the case
of the diene, reactivity is increased by ERG substituents. Data for some dienes are
given in Table 10.2. Note that ERG substituents at C(1) have a larger effect than those
at C(2). Scheme 10.2 gives some representative examples of dienophiles activated by
EWG substitution.
It is significant that if an electron-poor diene is utilized, the preference is
reversed and electron-rich alkenes, such as vinyl ethers and enamines, are the best
dienophiles. Such reactions are called inverse electron demand Diels-Alder reactions,
and the reactivity relationships are readily understood in terms of frontier orbital
theory. Electron-rich dienes have high-energy HOMOs that interact strongly with
the LUMOs of electron-poor dienophiles. When the substituent pattern is reversed
and the diene is electron poor, the strongest interaction is between the dienophile
HOMO and the diene LUMO. The FMO approach correctly predicts both the relative
reactivity and regioselectivity of the D-A reaction for a wide range of diene-dienophile
combinations.

Table 10.1. Relative Reactivity toward Cyclopentadiene in the
Diels-Alder Reaction
Dienophile Relative rate a
Tetracyanoethene 43 000 000
1,1-Dicyanoethene 450 000
Maleic anhydride 56 000
p-Benzoquinone 9 000
Z-1,2-Dicyanoethene 91
E-1,2-Dicyanoethene 81
Dimethyl fumarate 74
Dimethyl maleate 0 6
Methyl acrylate 1 2
Cyanoethene 1 0
o
a. From second-order rate constants in dioxane at 20 C, as reported by J. Sauer,
H. Wiest, and A. Mielert, Chem. Ber., 97, 3183 (1964).

16 H. J. Backer, Rec. Trav. Chim. Pays-Bas, 58, 643 (1939).
17
J. Meinwald and N. J. Hudak, Org. Synth., IV, 738 (1963).