Introduction

            The Diels-Alder reaction is considered to be one of the most interesting and useful reactions found in organic chemistry, and is often used for the synthesis of six-membered rings. The discovery of this reaction itself earned its discoverers the Nobel Prize in 1950 “for their discovery and development of diene synthesis”.

            The Diels-Alder mechanism has since been subject to much debate. This article will explore the different proposed mechanisms for the Diels-Alder reaction.

Historical Background

            In 1928, two German Chemists by the names of Otto Diels and Kurt Alder discovered that butadiene reacts vigorously with maleic anhydride to give cis-1, 2, 3, 6-tetrahydrophthalic andhydride.

An inert solvent such as ether or benzene is used to carry out the reaction, and typically the diene and dienophile are mixed in equimolar proportions at STP1. 

The Reaction: A General Overview

            In the Diels-Alder reaction, a double bond (dienophile) adds to a conjugated diene to form an unsaturated six-membered ring. One new pi bond and two new sigma bonds are formed when the dienophile attacks the diene. Here is a simple version of the Diels-Alder reaction:

                                Diene        Dienophile                     six-membered ring

Common dienophiles that are used are –C=C-Z or Z-C=C-Z’, where Z and Z’ may be CHO, COR, COOH, COOR, COCl, COAr, CN, NO2, Ar, CH2Cl, CH2NH2, CH2CN, CH2COOH, halogen or C=C. 2

            Nearly all conjugated dienes will react with appropriate dienophiles. By varying the type of diene and dienophiles, many different types of ring structures can be synthesized.

The Reaction: Stereochemistry

            The cis principle applies to the Diels-Alder reaction (with very, very few exceptions). Here is an example of the stereochemistry of the reactants being conserved in the products.

            The major product of a cyclic diene Diels-Alder reaction is an endo addition, which means that the electron withdrawing group(s) will be on the same side as the double bond of a bicyclic ring, as shown here:

The following figure shows the addition of two cyclo-pentadienes with the two different possibilities of endo and exo addition:

(reference of diagram to endnote 3)

            In order for the Diels-Alder reaction to occur, it is imperative that the diene take on a cisoid conformation during the mechanism. Certain dienes are stuck in the trans conformation. And if the diene remains in the transoid conformation during the mechanism, the reaction will not occur2.

The Mechanism

            Apparently, the exact Diels-Alder mechanism has been the subject of a lot of debate. There are however, three main ideas on how the mechanism occurs, based on the following three studies.

1)      The mechanism is concerted and synchronous.

2)      The mechanism is concerted and asynchronous.

3)      The reaction is stepwise, first with the formation of a rate determining single bond, followed by a faster formation of a second bond.

The following O’Ferral-Jencks diagram illustrates the concerted synchronous, non-concerted asynchronous,  and concerted synchronous Diels-Alder reaction mechanisms.

            The non-concerted and concerted asynchronous mechanisms show diradical intermediates, where as the concerted synchronous mechanisms does not.

            One of these ideas is supported by a kinetic study done by Dewar and Pierini in 1984. This experiment suggests that the reaction is concerted and synchronous.4 This conclusion was confirmed by doing a reverse Diels-Alder reaction involving maleic anhydride with furan, 2-methylfuran and 2,5 dimethylfuran. This experiment was based on the idea that since reactions of unsymmetrical dienes or dienophiles have been shown to have unsymmetrical transition states, there is no evidence to suggest that the same is not true for symmetrical dienes or dienophiles.

            In 2001 Leach and Houk did a study applying density functional theory to the transition states and mechanisms of Diels-Alder reactions involving a variety of nitroso compounds as dienophiles with butadiene and a variety of 1- and 2- substituted dienes. The reaction’s activation and reaction energies as well as its stereoselectivities and regioselectivities were theoretically predicted and then compared to known experimental data. The general mechanism of the Diels-Alder reaction was found to be concerted and asynchronous.5 Here is a diagram from the original article of possible mechanisms involving the reaction between a nitroso compound with butadiene:

            This diagram shows that the pathway on the top is a concerted [4+2] cyclo-addition with that particular transition state that is showed above. The pathway in the middle shows a possible diradical transition state. And the one down below shows a possible zwitterion transition state. The study concluded that diradical and zwitterionic transition states only complete with each other when nitroso compounds with small amounts of nitrogen react with dienes that have substituents that stabilize radicals.

            According to this study, the asynchronicity of these concerned reactions may be due to the lack of symmetry of the nitroso dienophile. This study also concluded that Diels-Alder reactions involving nitroso compounds show a strong preference for endo products, which may be due to the lone pairs of the nitrogen and oxygen being electrostatically repulsed by the electron rich diene.

The Diels-Alder Reaction: Recent Updates

            The Diels-Alder reaction mechanism still remains the topic of much debate because of the uncertainty in whether the mechanism is synchronous, asynchronous, concerted, or non-concerted. Over the past decade or so, theoretical chemists have taken an interest in studying the transition states and energies of activation and entropies and there has been a rapid growth in the synthetic applications of the Diels-Alder reaction.6

References