Diels -Alder Reactions

The Diels-Alder cycloaddition of various dienes (mostly belonging to 1-vinyl cyclohexenes) with o-quinone proceeds very under ultrasound 

Intramolecular Diels-Alder and Alder Ene Reactions, Springer, New York (1984) 

SL 1 (vinylallenes as dienes), 186 (substituent and solvent effects) (1990) 873 (1995) (RCONO) 

Inverse electronic demand Diels-Alder reaction 

Example 3, Catalytic asymmetric inverse-electron-demand Diels—Alder reaction  

Heterocycl. Chem. 1989,1, 30-64. (Review). 

Inverse electronic demand Diels—Alder reaction 

Example 1, Catalytic asymmetric inverse electronic demand Diels-Alder reaction  

In addition to [2+2] photoadditions, thermal [4+2] cycloadditions (Diels-Alder reactions) are also remarkably accelerated in the cavity of cage 2. The reaction of 

Diels-Alder reaction) and (b) optimized structure of ternary complex 2-23-30 (before the reaction). 

Correlation diagram may also be constructed to predict feasibility of Diels-Alder reaction which isTi s-f-Ji s cycloaddition. Results have been found in conformity with observed fact that reaction is thermally feasible. In Diels-Alder reaction only m-plane of symmetry is conserved. Symmetry properties and correlation diagram for Diels-Alder reaction is given below (Fig. 5.6). 

Diels-Alder reaction involves /i, j/2, V3 and ]/4 orbitals of 1, 3-butadiene andrt and71 orbitals of ethylene as reactants m.os andCj, CT2,7t, 7i, a3,04 orbitals of cyclohexene which are product molecular orbitals. When these molecular orbitals are arranged in the increasing order of their energies alongwith their symmetries, ground state molecular orbitals of reactants correlate with the ground state molecular orbitals of their product, therefore, reaction is thermally allowed but photochemically forbidden on account of the fact that first excited state of reactant does not correlates with first excited state of product (Fig. 5.6). 

The first part of this chapter deals with the effects of high pressure on cycloaddition reactions, particularly the Diels-Alder reaction, which is the most important cycloaddition reaction. The second part will illustrate applications of pressure to nucleophilic substitutions, condensations and other reactions (miscellaneous reactions), such as Mannich, Heck, ene, SeAr, Wittig, Horner-Wadsworth Emmons and multicomponent Strecker reactions. 

Descriptions of high-pressure equipment needed to perform the experiments are discussed in detail by Matsumoto and Acheson.  

The synthetic approach to aklavinone, the aglycone of aclacinomycin A, developed by Li and Wu, is an interesting example of a pressure-promoted cycloaddition reaction. A thermal reaction between p-benzoquinone (1) and the 

The reactions are carried out either in water or under high pressure - the best yields are achieved with the latter. 

The reactions with ( )-piperylene occur e c/o-diastereoselectively an inverse diastereoselectivity is observed with X = CO2H. Extensive decarboxylation of the cycloadducts occurs in the reactions carried out in water. 

The octahedral coordination cage D described by Fujita and co-workers has been applied as a nanoreactor for bimolecular Diels-Alder reactions in water. Suspending 9-(hydroxymethyl)anthracene 7 and A-cyclohexylmaleimide 8a in an aqueous solution of 

In the Diels-Alder transition state, the two alkene carbons and carbons 1 and 4 of the diene rehybridize from sp to sp to form two new single bonds, while carbons 2 and 3 of the diene remain sp -hybridized to form the new double bond in the cyclohexene product. We ll study this mechanism in more detail in Section 30.5 but will concentrate for the present on learning about the characteristics and uses of the Diels-Alder reaction. 

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, propenenitrile, and similar compoimds are highly reactive. Note also that alkynes, such as methyl propynoate, can act as Diels-Alder dienophiles. 

One of the most useful features of the Diels-Alder reaction is that it is stereospecific, meaning that a single product stereoisomer is formed. Furthermore, the stereochemistry of the dienophile is retained, if we carry out the cycloaddition with methyl cis-2-hutenoate, only the cis-substituted cyclohexene product is formed. With methyl trans-2-butenoate, only the trans-substituted cyclohexene product is formed. 

Another stereochemical feature of the Diels-Alder reaction is that the diene and dienophile partners orient so that the endo product, rather than the alternative exo product, is formed. The words endo and exo are used to indicate relative stereochemistry when referring to bicyclic structures like substituted norbornanes (Section 4.9). A substituent on one bridge is said to be endo if it is syn (cis) to the larger of the other two bridges and is said to be exo if it is anti (trans) to the larger of the other two bridges. 

Endo products result from Diels-Alder reactions because the amount of orbital overlap between diene and dienophile is greater when the reactants lie directly on top of one another so that the electron-withdrawing substituent on the dienophile is underneath the diene double bonds. In the reaction of 1,3-cyclopenta-diene with maleic anhydride, for instance, the following result is obtained  

In the mid-1980s, Hoffman and co-workers described a simple synthesis of racemic mikanecic acid via in situ Diels-Alder dimerization of the diene generated from t-butyl 2-bromomethylbut-2-enoate. The first example of a Diels-Alder reaction of a MBH adduct was the dimerization of 2-hydroxy-alkyle-nones and the previously mentioned addition to anthracene. The appKcation of the MBH adducts as hetero dienes or precursors of dienes, and dienophiles for the Diels-Alder cycloaddition reactions was then initiated and expanded by the group of Hoffman. In a series of reports, Hofftnan and co-workers have described the in situ Diels-Alder dimerization of various dienes (157), generated via stereoselective dehydration with MsCl-DABCO-DMAP of the corresponding MBH adducts The elimination of water from MBH adducts always resulted 

The first enantioselective synthesis of mikanecic acid, ( + )-162, a terpene dicarboxyhc add was achieved by Basavaiah et via a double stereo-differentiating asymmetric Diels Alder reaction involving the same molecule as chiral diene and chiral dienophile generated in situ. Treatment of MBH adduct with MsQ/NEts afforded the chiral dienes 161, through a Diels-Alder reaction of the in situ generated chiral l,3-butadiene-2-carboxylate 160. Hydrolysis of the diesters then afforded the desired mikanecic acid 162 (25-74% ee) in good 

EWG = S02Ph 156b, EWG = C02Me 156c, EWG = COMe 

Compared with a previously cumbersome synthesis of 2,3-dimethoxy-carbonyl-1,3-butadiene (164) from either 2,3-butanedione (four steps, 23% 

Supercritical carbon dioxide (SC-CO2) is an environmentally benign solvent that is providing a viable alternative to the traditional organic solvents. A Diels-Alder reaction between n-butyl acrylate and cyclopentadiene was investigated with the Lewis acid catalyst scandium tris (trifluoromethanesuffonate), primarily due to its solubility in SC-CO2 (Eq. 10-12)  

By varying the pressure of the solvent, endoiexo selectivity was maximized at 24 1, a significant improvement over selectivity achieved in conventional solvents (11 1). Green chemistry benefits of a less hazardous solvent, reduced energy usage, 

The selective hydrogenation of an imsaturated cyclic ketone can be carried out suc-cessfiiUy widi Pd catalyst in supercritical CO2 (Eq. 10-13)  

A variety of reactions can be carried out in an aqueous enviromnent given the right choice of catalyst. Water is an extremely attractive solvent choice. Allylation of 1,3-dicarbonyl compounds, for example, is efficiently promoted in water using an indium catalyst (Eq. 10-14). 

Metal mediated reactions in water have foimd applications in cychzation, ring expansion, and isomerization reactions. 

In the synthesis of (-l-)-Minfiensine by MaeMillan and coworkers, a novel Diels-Alder/amine cyclisation sequenee is aehieved using n with TBA (tri-bromoacetic acid) as the coeatalyst, allowing the synthesis of the complex tetracyclic pyrrolindoline core of the target molecule (87% yield, 96% ee), with low loadings possible (5 mol%). Similarly, MacMillan and coworkers have described the short nine-step synthesis of (—)-Vincorine, in which they employ the catalyst II and HBF4 as a cocatalyst for the formation of three stereocentres with the correet absolute and relative stereochemistry. The combination of an intermolecular Diels-Alder reaction with an iminium cyclisation cascade allowed formation of the tetracyclic alkaloid core in one step (70% yield, 95% ee).  

The asymmetric Mannich reaction has been widely studied, particularly in organocatalysis, with the MaeMillan eatalyst employed in the synthesis of various natural products. Koley and coworkers have described the synthesis of hydrojylactams sueh as ( )-epilupinine using an asymmetric 

In addition to aromatic substrates, the MacMillan catalyst has been shown to be applicable for the all lation of ben lic substrates, as seen in the five-step synthesis of bisabolane sesquiterpene (R)-(—)-curcumene by Cozzi and coworkers. Using I as the HCl salt, the a-allg lated product was generated with excellent enantiocontrol (after reduction 95% yield, 94% ee). This route also allowed for the synthesis of a related compound, (/ )-(—)-erogorgiaene.  

However, the two-step one-pot procedure resulted in purer products and was therefore adopted. The products were formed in acceptable to good yields. 

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C, b.p. 170 C (decomp.), has a characteristic odour. It is the Diels-Alder product of cyclopentadiene reacting with itself, the exo-form being formed most rapidly but the endo-form is thermodynamically favoured. At temperatures above ISO C a retro-Diels-Alder reaction occurs and cyclopentadiene monomer is regenerated see diene reactions. 

Diels-Alder reaction is the 1,4-addition of an alkene or alkyne (dienophile) across a conjugated diene. An example is the addition of pro-penal to buta-l,3-diene to give A -tetrahy-... 

CH = CH — CH = CH — are said to have conjugated double bonds and react somewhat differently from the other diolefins. For instance, bromine or hydrogen is often added so that a product of the type -CHBr-CH=CH-CHBr- is formed. Also, these hydrocarbons participate in the Diels-Alder reaction see diene reactions). They show a tendency to form rubber-like polymers. Hydrocarbons not falling into these two classes are said to have isolated double... 

C-jHg. A slightly coloured liquid, b.p. 90 C, obtained by a Diels-Alder reaction between cyclopcntadiene and ethyne at approximately 150°C. At temperatures in excess of 450°C it rearranges to cycloheptatriene (tropilidene). 

An intense purple crystalline solid m.p. 219-220 C. One of the few monomeric cyclo-pentadienone derivatives, most of which spontaneously undergo self Diels-Alder type dimerization. Used as a diene in many studies of various aspects of the Diels-Alder reaction. ... 

Diederich F, Jonas U, Gramlich V, Herrmann A, Ringsdorf H and Thilgen C 1993 Synthesis of a fullerene derivative of benzo[18]crown-6 by Diels-Alder reaction complexation ability, amphiphilic properties, and x-ray crystal structure of a dimethoxy-1,9-(methano[1, 2]benzomethano)fullerene[60] benzene clathrate Helv. Chim. Acta 76 2445-53... 

Chemists usually learn about reactions according to fiinctional groups for example, How can I make an aldehyde and what reactions are known for aldehydes " This is clearly not a very good starting point for classifying reactions. The poor state of affairs in the definition of reaction types is further quite vividly illustrated by the fact that many chemical reactions are identified by being named after their inventor Diels-Alder reaction, Michael addition, Lobry-de Bruyn-van Ekenstein rear-... 

As an example, we shall discuss the Diels-Alder reaction of 2-methoxybuta-l,3-diene with acrylonitrile. Figure 3-7 gives the reaction equation, the correlation diagram of the HOMOs and LUMOs, and the orbital coefficients of the correlated HOMO and LUMO. 

Tran orm-based or long-range strategies The retrosynthetic analysis is directed toward the application of powerful synthesis transforms. Functional groups are introduced into the target compound in order to establish the retion of a certain goal transform (e.g., the transform for the Diels-Alder reaction, Robinson annulation, Birch reduction, halolactonization, etc.). 

Suprafacial attack of me ethene molecule on anotlier (left) is not permitted by the Woodward-Hoffmann id the alternative antarafacial mode of attack is sterically unfavourable. Suprafacial attack is however permitted Diels-Alder reaction between butadiene and ethene (right). 

Fig. 5.35 Geometry predicted by CASSCF ab initio calculations of the two possible transition structure geometries for the Diels-Alder reaction between ethene and butadiene. (Figure adapted from Houk KN, J Gonzalez and Y Li 1995. Pericyclic Reaction Transition States Passions and Punctilios 1935-1995. Accounts of Chemical Research 28 81-90.)...

W C, A Tempcz)rrk, R C Hawley and T Hendrickson 1990. Semianalytical Treatment of Solvation for Molecular Mechanics and Dynamics. Journal of the American Chemical Society 112 6127-6129. ensson M, S Humbel, R D J Froese, T Matsubara, S Sieber and K Morokuma 1996. ONIOM A Multilayered Integrated MO + MM Method for Geometry Optimisations and Single Point Energy Predictions. A Test for Diels-Alder Reactions and Pt(P(t-Bu)3)2 + H2 Oxidative Addition. Journal of Physical Chemistry 100 19357-19363. 

Since the octatetrene contains two CH CH-CH CH units, it will readily combine with two molecules of maleic anhydride and other adducts by the Diels-Alder reaction (p. 292). 

The Diels-Alder Reaction consists in the direct combination of a compound containing a conjugated diene system u ith a reagent which possesses a double or triple bond activated bj suitable adjacent groups. Examples of such reagents are maleic anhydride, p-benzoquinone, acraldehyde and acetylene dicarboxylic esters. Combination always occurs at the 1,4 positions of the diene system ... 

The Diels-Alder Reaction usually occurs readily it is of great value (a) for diagnosing the presence of a conjugated diene grouping, (6) for synthetic purposes in the preparation of cyclic systems. 

Compounds containing a double or triple bond, usually activated by additional unsaturation (carbonyl, cyano, nitro, phenyl, etc.) In the ap position, add to the I 4-positions of a conjugated (buta-1 3-diene) system with the formation of a ax-membered ring. The ethylenic or acetylenic compound is known as the dieTwphile and the second reactant as the diene the product is the adduct. The addition is generally termed the Diels-Alder reaction or the diene synthesis. The product in the case of an ethylenic dienophile is a cyctohexene and in that of an acetylenic dienophile is a cyctohexa-1 4-diene. The active unsaturated portion of the dienophile, or that of the diene, or those in both, may be involved in rings the adduct is then polycyclic. 

Benzilic acid rearrangement Benzoin reaction (condensation) Blanc chloromethylation reaction Bouveault-Blanc reduction Bucherer hydantoin synthesis Bucherer reaction Cannizzaro reaction Claisen aldoi condensation Claisen condensation Claisen-Schmidt reaction. Clemmensen reduction Darzens glycidic ester condensation Diazoamino-aminoazo rearrangement Dieckmann reaction Diels-Alder reaction Doebner reaction Erlenmeyer azlactone synthesis Fischer indole synthesis Fischer-Speior esterification Friedel-Crafts reaction... 

This chapter introduces the experimental work described in the following chapters. Some mechanistic aspects of the Diels-Alder reaction and Lewis-acid catalysis thereof are discussed. This chapter presents a critical survey of the literature on solvent ejfects on Diels-Alder reactions, with particular emphasis on the intriguing properties of water in connection with their effect on rate and selectivity. Similarly, the ejfects of water on Lewis acid - Lewis base interactions are discussed. Finally the aims of this thesis are outlined. 

This thesis contributes to the knowledge of catalysis in water, us it describes an explorative journey in the, at the start of the research, unh odded field of catalysis of Diels-Alder reactions in aqueous media. The discussion will touch on organic chemistry, coordination chemistry and colloid chemistry, largely depending upon the physical-organic approach of structural variation for the elucidation of the underlying mechanisms and principles of the observed phenomena. 

The remainder of this chapter will provide the necessary background, from which the incentive of catalysing Diels-Alder reactions in water and the aims of the study will become apparent. 

In the Diels-Alder reaction (in older literature referred to as the diene synthesis ) a six-membered ring is fonned through fusion of a four-tt component, usually a diene and a two-7C component, which is commonly referred to as the dienophile (Scheme 1.1). 

Scheme 1.1. Schematic representation of the Diels-Alder reaction. The versatility of the reaction is illustrated by the fact that heteroatoms are allowed at any of the positions a-f. Structures A and B indicate two regioisomeric products.

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