Cycloaddition. The Diels-Alder Reaction

Give the structures of both 1,2- and 1,4-adducts resulting from reaction of 1 equivalent of HCl with penta-1,3-diene. 

Perhaps the most striking difference between conjugated and nonconjugated dienes is that conjugated dienes undergo a reaction with alkenes to yield substituted cyclohexene products. For example, buta-1,3-diene and bnt-3-en-2-one give cyclohex-3-enyl methyl ketone. 

This process, named the Diels-Alder cycloaddition reaction after its discoverers, is extremely useful in the laboratory because it forms two carbon-carbon bonds in a single step and is one of the few general methods available for making cyclic molecules. (As the name implies, a cycloaddition reaction is one in which two reactants add together to give a cyclic product.) The 1950 Nobel Prize in Ghemistry was awarded to Diels and Alder in recognition of the importance of their discovery. 

The mechanism of the Diels-Alder cycloaddition is different from that of other reactions we ve studied because it is neither polar nor radical. Rather, the Diels-Alder reaction is a so-called pericyclic process. Pericyclic reactions, which are considerably less common than either polar or radical reactions, take place in a single step by a cyclic redistribution of bonding electrons. The two reactants simply join together through a cyclic transition state in which the two new carbon-carbon bonds form at the same time. 

Of all the pericyclic reactions, the Diels-Alder cycloaddition reaction is the most popular. In the Diels-Alder reaction, a 1,3-diene reacts with a dienophile to form a six-membered ring adduct (3.1). Two new a-bonds and a new rr-bond are formed at the expense of three tt-bonds in the starting materials.  

The Diels-Alder reaction and indeed other pericyclic reactions are concerted processes in which there is no intermediate on the reaction pathway. The mechanisms of such processes can be considered in terms of orbital symmetry concepts. A normal Diels-Alder reaction involves an electron-rich diene and an electron-deficient dienophile, and in such cases the main interaction is that between the highest occupied molecular orbital (HOMO) of the diene and the lowest unoccupied molecular orbital (LUMO) of the dienophile (3.4). The smaller the energy difference between these frontier orbitals, the better these orbitals interact and therefore the more readily the reaction occurs. 

If the reaction is concerted then there should be a high level of stereoselectivity, as is indeed observed. However, this does not rule out a two-step mechanism should rotation about the bonds in the intermediate be slow compared with the rate of ring-closure. In this connection, it is noteworthy that cycloaddition of trans-and c/5-l,2-dichloroethene to cyclopentadiene is completely stereospecific (3.5). A two-step mechanism via a biradical intermediate might have been expected to be sufficiently long-lived to allow some interconversion, resulting in a mixture of products. Addition of dichlorodifluoroethene to cis,cis- and / ran5,/ ra 5-2,4-hexadiene is, however, non-stereospecific and is thought to proceed by a two-step mechanism with a biradical intermediate. 

Attempts to detect biradical intermediates in the Diels-Alder reaction have been unsuccessful and compounds that catalyse singlet-triplet transitions have no influence on the reaction. Similarly, the kinetic effects of para substituents in 1-phenylbutadiene, although large in absolute terms, are considered too small for a rate-determining transition state corresponding to a zwitterion intermediate. 

Whether or not both of the new bonds in the concerted mechanism are formed to the same extent in the transition state is an open question. It is likely that in most cases both bonds begin to form at the same time, although this may occur at different rates, such that one bond is formed to a greater extent than the other. There may be a gradation of mechanisms for different Diels-Alder reactions, extending from a completely concerted mechanism with a symmetrical transition state at one 

This process, named the Diels-Alder cycloaddition reaction ai 

Mtthanl m of the Diels-Alder cycloaddition reaction. The reaction occurs in a single step through a cyclic transition state in which the two new carbon-carbon bonds form simultaneously. 

Kurt Alder (1902-1958) was born in Konigshiitte, Prussia, and moved to Germany after World War I. He received his Ph.D. in 1926 at Kiel working with Otto Diels. He worked first at I. G- farben on the manufacture of plastics but then became professor at the University of Cologne (1940-1958). He shared the 1950 Nobel Prize in chemistry with his mentor, Otto Diels. 

In the Diels-Alder transition state, the two alkene carbons and carbons 1 and 4 of the diene rehybridize from sp2 to sp3 to form two new single bonds. Carbons 2 and 3 of the diene remain sp2-hybridized to form the new double bond in the cyclohexene product. We ll study this mechanism at greater length in Chapter 30 and will concentrate for the present on learning more about the chemistry of the Diels-Alder reaction. 

Thomson O Click Organic interactive to use a web-based palette to predict products from cycloaddition reactions. 

Kurt Alder (1902-1958) was born in Konigshtitte, Prussia, and moved to Germany after World War I. 

1950 Nobel Prize in chejnistiy was awarded to Hiels and Alder in recognition of the importance of their discovery. 

0 876-1954 was born in Hamburg, Germany, and received his Ph.D. at the University of Berlin working with Enii Fischer. He was professor of chemistry both at the University of Berlin (1906-1916) ant at Kiel (1916—1948). His most important discovery was the Diels-Alder reaction, which he developed with one of his research students and for which he received the 1950 Nobel Prize in chemistry. 

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In contrast to oxazole, thiazole does not undergo the Diels-Alder cycloaddition reaction (331). This behavior can be correlated with the more dienic character of oxazole, relative to thiazole, as shown by quantochemical calculations (184). 

In contrast to those unreactive dienes that can t achieve an s-cis conformation, other dienes are fixed only in the correct s-cis geometry and are therefore highly reactive in the Diels-Alder cycloaddition reaction. 1,3-Cyclopentadiene, for example, is so reactive that it reacts with itself. At room temperature, 1,3-cycIopentadiene dimerizes. One molecule acts as diene and a second molecule acts as dienophile in a self Diels-Alder reaction. 

We ve seen that the Diels-Alder cycloaddition reaction is a one-step, peri-cyclic process that occurs through a cyclic transition state. Propose a mechanism for the following reaction ... 

The Diels-Alder cycloaddition reaction (Section 14.4) is a pericvclic process that takes place between a diene (four tt electrons) and a dienophile (two tr electrons) to yield a cyclohexene product. Many thousands of examples of Diels-Alder reactions are known. They often take place easily at room temperature or slightly above, and they are stereospecific with respect to substituents. For example, room-temperature reaction between 1,3-butadiene and diethyl maleate (cis) yields exclusively the cis-disubstituted cyclohexene product. A similar reaction between 1,3-butadiene and diethyl fumarate (trans) yields exclusively the trans-disubstituted product. 

Concerted (Section 30.1) A reaction that Lakes place in a single step without intermediates. For example, the Diels-Alder cycloaddition reaction is a concerted process. 

Dienophile (Section 14.5) A compound containing a double bond that can take part in the Diels-Alder cycloaddition reaction. The most reactive dienophiles are those that have electron-withdrawing groups on the double bond. 

An example of the second type of modification is the application of the Diels-Alder cycloaddition reaction to polders and copol ers containing pendant or backbone furan moieties. The use of bis-dienophiles such as propiolic acid and its esters or bis-maleimides provides a means of crosslinking based on multiple bridging by the double interchain lycloadditions. The thermal reversibility of these reactions allows the return to the original linear structure (thermoplastic material) by simply heating the gel. 

A number of reactions do not seem to belong to any of the above mechanistic types. Such processes are referred to as multicenter reactions. The Diels-Alder cycloaddition reaction of 1,3-butadiene with maleic anhydride is an example (Scheme 5). No charged or odd election intermediates seemingly are involved in this reaction. 

An AMI semiempirical method was used to investigate the Diels-Alder cycloaddition reactions of vinyl sulfenes with buta-1,3-dienes.156 The reactivity and stereoselectivity of vinyl boranes have been reviewed.157 Aromatic methyleneamines undergo reverse-electron-demand Diels-Alder reactions with cyclopentadiene, norbom-ene, and vinyl sulfides.158... 

The Diels-Alder cycloaddition reaction of both cis- and trans-dienyl-2-azetidi-nones with unsymmetrical dienophiles in the presence of Lewis acid catalysts has been reported to give in regio-, stereo-, and remarkably high 7i-facial selectivity novel l,3,4-trisubstituted-2-azetidinone derivatives in good yields (I and II, Fig. 26), [306],... 

While studies of reactions in supercritical fluids abound, only a few researchers have addressed the fundamental molecular effects that the supercritical fluid solvent has on the reactants and products that can enhance or depress reaction rates. A few measurements of reaction rate constants as a function of pressure do exist. For instance, Paulaitis and Alexander (1987) studied the Diels Alder cycloaddition reaction between maleic anhydride and isoprene in SCF CO2. They observed bimolecular rate constants that increased with increasing pressure above the critical point and finally at high pressures approached the rates observed in high pressure liquid solutions. Johnston and Haynes (1987) found the same trends in the... 

Molecular electrostatic potentials have been used to explain the regioselectivity exhibited in the Diels-Alder cycloaddition reactions between 1-trimethylsilyloxy-butadiene and the quinones 5-formyl-8-methyl-1,4-naphthoquinone, 5-methoxy-7-methyl-1,4-phenanthrenequinone, and 5,6,7-trimethyl-1,4-phenanthrenequinone.128 The intramolecular Diels-Alder reaction of masked o-benzoquinones (123) with a variety of dienes provides adducts (124) which rearrange to functionalized ris-decal ins (125) with complete stereocontrol of up to five stereocentres. This methodology ... 

Other examples of reactions closely related to the Diels-Alder cycloaddition reaction are the ene reactions between alkenes with allylic hydrogen atoms (ene) and compounds with a double bond (enophile) [135, 136], and the dye-sensitized photooxygenation of allylic alkenes by singlet oxygen to give allylic hydroperoxides with a shifted double bond [137-139]. 

For example, the rate of the Diels-Alder cycloaddition reaction between 9-(hydroxymethyl)anthracene and A-ethylmaleimide, as shown in Eq. (5-159), is only slightly altered on changing the solvent from dipolar acetonitrile to nonpolar isooctane, as expected for an isopolar transition state reaction cf. Section 5.3.3. In water, however. 

The Diels-Alder cycloaddition reaction of 2,6-dimethyl-1,4-benzoquinone with methyl (ii)-3,5-hexadienoate, carried out in toluene as solvent, gives only traces of the cycloadduct shown in Eq. (5-160), even after seven days. However, when the solvent is changed to water and sodium ( )-3,5-hexadienoate is used as the diene, 77 cmol/mol of the desired cycloadduct is obtained after one hour and esterification with diazomethane [714] f Again, hydrophobic interactions between diene and dienophile in the aqueous medium seem to be responsible for this remarkable and synthetically useful rate acceleration. 

The Diels-Alder cycloaddition reaction of maleic anhydride with isoprene has been studied in supercritical-fluid CO2 under conditions near the critical point of CO2 [759]. The rate constants obtained for supercritical-fluid CO2 as solvent at 35 °C and high pressures (>200 bar) are similar to those obtained using normal liquid ethyl acetate as the solvent. However, at 35 °C and pressures approaching the critical pressure of CO2 (7.4 MPa), the effect of pressure on the rate constant becomes substantial. Obviously, AV takes on large negative values at temperatures and pressures near the critical point of CO2. Thus, pressure can be used to manipulate reaction rates in supercritical solvents under near-critical conditions. This effect of pressure on reacting systems in sc-fluids appears to be unique. A discussion of fundamental aspects of reaction kinetics under near-critical reaction conditions within the framework of transition-state theory can be found in reference [759],... 

Dienes and dienophiles The Diels-Alder cycloaddition reactions proceed more efficiently if the diene is electron rich and the dienophile is electron poor. Steric hindrance at the bonding sites may inhibit or prevent the reaction. Electron-donating groups on the diene facilitate the reaction. The way to make the dienophile electron poor is to add electron-withdrawing groups, such as CN, C=0 and NO2. 

The Diels-Alder cycloaddition reaction occurs most rapidly if the alkene component, or dienophile ("diene lover"), has an electron-withdrawing substituent group. Thus, ethylene itself reacts sluggishly, but propenal, ethyl propenoate, maleic anhydride, benzoquinone, proiicnenitrile, and similar compounds are highly reactive. Note also that alkyncs, such as methyl propynoate, can act as Diels-Alder dienophiles. 

The Diels-Alder cycloaddition reaction between the transient diene 208 and /i-quinonic dienophiles such as /i-benzoquinone or 1,4-naphthoquinone, followed by further aromatization with DDQ, afforded cycloadducts 216 and 217, which were used for the preparation of TTF derivatives (Scheme 26) <1998CC2197, 2000TL2091>. 

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