Stereospecific reactions Diels-Alder reaction

A number of stereospecific intramolecular Diels-Alder reactions of trienones leading to c -fused products have been described. The ketone 34 forms solely compound 35 on treatment with aluminium trichloride at 110°C (equation 25)30. The lower homologue 36 undergoes a spontaneous cyclization to 37 below 20 °C (equation 26)31 and the isomeric ketones 38 and 40 similarly give 3932 and 4133, respectively (equations 27 and 28). 

J. C. Lopez, E. Lameignere, and G. Lukacs, Stereospecificity in Diels-Alder reactions of dienes and dienophiles derived from methyl 4,6-O-benzyIidene-a-D-glucopyranoside, J. Chem. Soc. Chem. Commun. p. 706 (1988). 

Keywords solid-gas reaction, Diels-Alder reaction, maleic anhydride, 1,3-cyclo-hexadiene, quantitative, stereospecific... 

Keywords solid-solid reaction, Diels-Alder reactions, maleic anhydride, fumaro-dinitrile, fumarodinitrile, fulvenes, orthoquinone, 9-methylanthracene, ball mill, stereospecific, stereospecific... 

In a much more complicated piece of work recently disclosed, two stereospecific aldehyde Diels-Alder reactions have been used in preparation of hikosamine derivative 29, a component of the antibacterial compound hizikimycin (Scheme 4-XIII).45k Diene 25 reacted with furfural to give cw-y-pyrone 26, which was transformed in several steps to aldehyde 27. Condensation of 27 with 25 using magnesium bromide as catalyst afforded only adduct 28, presumably via chelated intermediate 27A. Compound 28 was converted in a series of steps to acetylhikosamine 29. The methodlogy described here allowed total synthesis of this unusual sugar having 10 contiguous chiral centers with complete stereocontrol. 

Note that the stereochemistry comes out right. H s a and b are cis because they were cis in the starting quinone and the Diels-Alder reaction is stereospecific in this respect. H is also cis to and H " because the Diels-Alder reaction is stereoselectively endo. These points are described in more detail in Norman p.284-6 and explained in Ian Fleming Frontier Orbitals and Organic Chemical Reactions, Wiley 1976, p. 106-109. How would you make diene A ... 

The Diels-Alder reaction is stereospecific Substituents that are cis in the dienophile remain cis in the product substituents that are trans in the dienophile remain trans m the product... 

Section 10 12 Conjugate addition of an alkene (the dienophile) to a conjugated diene gives a cyclohexene derivative in a process called the Diels-Alder reaction It is concerted and stereospecific substituents that are cis to each other on the dienophile remain cis m the product... 

Cycloaddition involves the combination of two molecules in such a way that a new ring is formed. The principles of conservation of orbital symmetry also apply to concerted cycloaddition reactions and to the reverse, concerted fragmentation of one molecule into two or more smaller components (cycloreversion). The most important cycloaddition reaction from the point of view of synthesis is the Diels-Alder reaction. This reaction has been the object of extensive theoretical and mechanistic study, as well as synthetic application. The Diels-Alder reaction is the addition of an alkene to a diene to form a cyclohexene. It is called a [47t + 27c]-cycloaddition reaction because four tc electrons from the diene and the two n electrons from the alkene (which is called the dienophile) are directly involved in the bonding change. For most systems, the reactivity pattern, regioselectivity, and stereoselectivity are consistent with describing the reaction as a concerted process. In particular, the reaction is a stereospecific syn (suprafacial) addition with respect to both the alkene and the diene. This stereospecificity has been demonstrated with many substituted dienes and alkenes and also holds for the simplest possible example of the reaction, that of ethylene with butadiene ... 

Diels-Alder reactions are almost always stereospecific, which implies that if an intermediate exists, it cannot have a lifetime sufficient to permit rotation or inversion. The prevailing view is that the majority of Diels-Alder reactions are concerted processes, and most current theoretical analyses agree with this view." ... 

The stereochemistry of the 1,3-dipolar cycloaddition reaction is analogous to that of the Diels-Alder reaction and is a stereospecific syn addition. Diazomethane, for example, adds stereospecifically to the diesters 43 and 44 to yield the pyrazolines 45 and 46, respectively. 

Diels-Alder reaction and. 494-495 El reaction and, 392 E2 reaction and, 387-388 R.S configuration and, 297-300 S 1 reaction and, 374-375 S -2 reactions and, 363-364 Stereogenic center, 292 Stereoisomers, 111 kinds of, 310-311 number of, 302 properties of, 306 Stereospecilic, 228, 494 Stereospecific numbering, sn-glycerol 3-phosphate and, 1132 Steric hindrance, Sjvj2 reaction and, 365-366 Steric strain, 96... 

Scheme 8 presents the sequence of reactions that led to the synthesis of the B-ring of vitamin B12 by the Eschenmoser group. An important virtue of the Diels-Alder reaction is that it is a stereospecific process wherein relative stereochemical relationships present in the diene and/or the dienophile are preserved throughout the course of the reaction.8 Thus, when the doubly activated dienophile 12 (Scheme 8) is exposed to butadiene 11 in the presence of stannic chloride, a stereospecific reaction takes place to give compound 27 in racemic form. As expected, the trans relationship between... 

Most Diels-Alder reactions, particularly the thermal ones and those involving apolar dienes and dienophiles, are described by a concerted mechanism [17]. The reaction between 1,3-butadiene and ethene is a prototype of concerted synchronous reactions that have been investigated both experimentally and theoretically [18]. A concerted unsymmetrical transition state has been invoked to justify the stereochemistry of AICI3-catalyzed cycloadditions of alkylcyclohexenones with methyl-butadienes [12]. The high syn stereospecificity of the reaction, the low solvent effect on the reaction rate, and the large negative values of both activation entropy and activation volume comprise the chemical evidence usually given in favor of a pericyclic Diels-Alder reaction. 

In a photochemical cycloaddition, one component is electronically excited as a consequence of the promotion of one electron from the HOMO to the LUMO. The HOMO -LUMO of the component in the excited state interact with the HOMO-LUMO orbitals of the other component in the ground state. These interactions are bonding in [2+2] cycloadditions, giving an intermediate called exciplex, but are antibonding at one end in the [,i4j + 2j] Diels-Alder reaction (Scheme 1.17) therefore this type of cycloaddition cannot be concerted and any stereospecificity can be lost. According to the Woodward-Hoffmann rules [65], a concerted Diels-Alder reaction is thermally allowed but photochemically forbidden. 

To generate molecular libraries, a series of 5-oxo-2-azabicyclo[2.2.2]octane and triaza analogs were prepared via a stereospecific Diels-Alder reaction by reacting Wang-resin-bound diene 35 with a variety of dienophiles [28]. After removing the solid support with a strong acid, adducts 36 were isolated examples of reactions that have furnished the best yields are reported in Scheme 4.6. 

It must be emphasized once again that the rules apply only to cycloaddition reactions that take place by cyclic mechanisms, that is, where two s bonds are formed (or broken) at about the same time. The rule does not apply to cases where one bond is clearly formed (or broken) before the other. It must further be emphasized that the fact that the thermal Diels-Alder reaction (mechanism a) is allowed by the principle of conservation of orbital symmetry does not constitute proof that any given Diels-Alder reaction proceeds by this mechanism. The principle merely says the mechanism is allowed, not that it must go by this pathway. However, the principle does say that thermal 2 + 2 cycloadditions in which the molecules assume a face-to-face geometry cannot take place by a cyclic mechanism because their activation energies would be too high (however, see below). As we shall see (15-49), such reactions largely occur by two-step mechanisms. Similarly. 2 + 4 photochemical cycloadditions are also known, but the fact that they are not stereospecific indicates that they also take place by the two-step diradical mechanism (mechanism... 

The chemical reactions through cyclic transition states are controlled by the symmetry of the frontier orbitals [11]. At the symmetrical (Cs) six-membered ring transition state of Diels-Alder reaction between butadiene and ethylene, the HOMO of butadiene and the LUMO of ethylene (Scheme 18) are antisymmetric with respect to the reflection in the mirror plane (Scheme 24). The symmetry allows the frontier orbitals to have the same signs of the overlap integrals between the p-or-bital components at both reaction sites. The simultaneous interactions at the both sites promotes the frontier orbital interaction more than the interaction at one site of an acyclic transition state. This is also the case with interaction between the HOMO of ethylene and the LUMO of butadiene. The Diels-Alder reactions occur through the cyclic transition states in a concerted and stereospecific manner with retention of configuration of the reactants. 

Diels-Alder reactions are stereospecific with respect to the E- and Z-relationships in both the dienophile and the diene. For example, addition of dimethyl fumarate and dimethyl maleate with cyclopentadiene is completely stereospecific with respect to the cis or trans orientation of the ester substituents. 

An interesting mechanistic issue was raised by Firestone on the aqueous Diels-Alder reaction between 2-methylfuran and maleic acid in water, which is found to be 99.9% stereospecific.80 By adding heavy atom (defined as any below the first complete row of the periodic table) salts to the aqueous media, it was found that addition of heavy but not light atom salts reduced the degree of stereospecificity significantly in the retrodiene reaction. The results suggest that a large portion of the Diels-Alder reaction occurs via diradical intermediates (Scheme 12.2). 

By far the best known (47t + 2n) cycloaddition is the Diels-Alder reaction. This has been discussed to some extent already (p. 197), including the fact that it proceeds rigorously, stereospecifically SYN, with respect to both diene (26) and dienophile (27) ... 

Concerted cycloaddition reactions provide the most powerful way to stereospecific creations of new chiral centers in organic molecules. In a manner similar to the Diels-Alder reaction, a pair of diastereoisomers, the endo and exo isomers, can be formed (Eq. 8.45). The endo selectivity in the Diels-Alder arises from secondary 7I-orbital interactions, but this interaction is small in 1,3-dipolar cycloaddition. If alkenes, or 1,3-dipoles, contain a chiral center(s), the approach toward one of the faces of the alkene or the 1,3-dipole can be discriminated. Such selectivity is defined as diastereomeric excess (de). 

Despite the aromatic character, the arylphospholes could also participate in Diels-Alder reactions to give new type of 7-phosphanorbomenes. These products together with phosphanorbomenes obtained by the regio- and stereospecific dimerization of arylphosphole oxides were useful model compounds in the UV light mediated fragmentation-related phosphorylation of alcohols. A novel mechanism was substantiated. 

The Diels-Alder reaction between DEAZDand 1,4-substituted butadienes occurs rapidly, and the adducts are obtained in high yield, retaining the initial configuration of the diene substituents in the product i.e., diene 100 gives adduct 101 exclusively.155 This is in accord with the expected concerted, stereospecific nature of the Diels-Alder reaction. These initial adducts... 

The reaction is carried out simply by heating a diene or another conjugated system of n bonds with a reactive unsaturated compound (dienophile). Usually the reaction is not sensible to catalysts and light does not affect the course. Depending on the specific components, either carboxylic or heterocyclic products can be obtained. The stereospecificity of the reaction was firmly established even before the importance of orbital symmetry was recognized. In terms of orbital symmetry classification, the Diels-Alder reaction is a k4s + n2s cycloaddition, an allowed process. 

The Diels-Alder reaction (Figure 7.1) is of great value in synthetic organic chemistry. It is a [4 -I- 2] cycloaddition in which a diene (4-tt component) reacts with a dienophile (2-tt component) to provide a six-membered ring. In the reaction six new stereocenters are formed in a single step. The reaction is stereospecific and the absolute configuration of the newly formed asymmetric centers can be controlled efficiently. 

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