Alder Cycloadditions

Diels-Alder Cycloadditions.—The range of functionalized diene systems, displaying regioselective behaviour in the Diels-Alder reaction, continues to expand. Notable new additions include l-phenylseleno-2-trimethylsilyloxy-4-methoxybuta-l,3-diene (82) and the isomers 1- and 2-methyl-l,3-bis(trimethylsilyloxy)buta-l,3-dienes (84) and (85). The diene (82) is readily derived from l-methoxy-3-trimethylsilyloxybuta-1,3-diene (81) and provides a direct route to the synthetically valuable 4-acylcyclohexa-2,5-dienones (83), whereas dienes (84) and (85) react with activated dienophiles (e.g. RCH=CHC02Et) in good yield, leading to keto-esters of the type (86) on hydrolysis. 

In an alternative approach to (83) Danishefsky and his co-workers have achieved what is effectively the same transformation by reaction of the diene (81) directly with dienophiles of the general type (87) (R = H or alkyl, R = alkyl or O-alkyl). Pyrolytic elimination of the phenylsulphinyl group occurs during the addition, and subsequent hydrolysis then furnishes thb dienone (83). 

Thermolysis of the photoadducts of alkoxyolefins and cyclic jS-diketone enol acetates or /3-chloroenones leads to cyclobutene derivatives capable of undergoing conrotatory ring opening. The method provides ready access to dienes which are 

Diels-Alder Cycloadditions.—Recent interest in the synthetic potential provided by the Diels-Alder reaction has largely centred about the intramolecular variant of the reaction and the Lewis-acid-catalysed reaction. Another area of activity has been the development of new and more versatile dienes which might not only display enhanced regiospecificity in the cycloaddition but also introduce usable functionality in the adducts. Amongst the several dienes investigated this year, 

Oppolzer and co-workers have extended their very elegant investigations of the synthesis of novel N-heterocycles via the intramolecular Diels-Alder reaction, and have shown that whereas the transformation (122) -s- (123)/(124) is non-stereospecific, the corresponding bis-cinnamyl derivative (125) produces almost entirely the m-adduct (126). 

The synthetic potential provided by the intramolecular variant of the Diels-Alder reaction is further illustrated in key steps in the synthesis of tetracyclic diterpenoids possessing bridged bicyclic [3,2,l]octane units, (127) (128), and 

Oppolzer, R. Achini, E. Pfenninger, and H. P. Weber, Hetv. Chim. Acta, 1976, 59, 1186. 

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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). 

The Diels-Alder cycloaddition is one example of a pencyclic reaction, which is a one step reaction that proceeds through a cyclic transition state Bond formation occurs at both ends of the diene system and the Diels-Alder transition state involves a cyclic array of six carbons and six tt electrons The diene must adopt the s cis conformation m the transition state... 

The product of a Diels-Alder cycloaddition always contains one more ring than was present m the reactants The dienophile maleic anhydride contains one ring so the product of Its addition to a diene contains two... 

Let us now examine the Diels-Alder cycloaddition from a molecular orbital perspective Chemical experience such as the observation that the substituents that increase the reac tivity of a dienophile tend to be those that attract electrons suggests that electrons flow from the diene to the dienophile during the reaction Thus the orbitals to be considered are the HOMO of the diene and the LUMO of the dienophile As shown m Figure 10 11 for the case of ethylene and 1 3 butadiene the symmetry properties of the HOMO of the diene and the LUMO of the dienophile permit bond formation between the ends of the diene system and the two carbons of the dienophile double bond because the necessary orbitals overlap m phase with each other Cycloaddition of a diene and an alkene is said to be a symmetry allowed reaction... 

Its Strained triple bond makes benzyne a relatively good dienophile and when benzyne IS generated in the presence of a conjugated diene Diels-Alder cycloaddition occurs... 

The transition state for the first step of the Claisen rearrangement bears much m common with the transition state for the Diels-Alder cycloaddition Both involve a con certed six electron reorganization... 

Miscellaneous Reactions. Some hydantoin derivatives can serve as precursors of carbonium—immonium electrophiles (57). 5-Alkoxyhydantoins are useful precursors of dienophiles (17), which undergo Diels-Alder cycloadditions under thermal conditions or in the presence of acid catalysis (58). The pyridine ring of Streptonigrine has been constmcted on the basis of this reaction (59). 

Polyimides have been synthesized by Diels-Alder cycloaddition of bismaleimides and substituted biscydopentadienones (81,82). The iatermediate tricychc ketone stmcture spontaneously expeU carbon monoxide to form dihydrophthalimide rings, which are readily oxidized to imides ia the presence of nitrobenzene. 

The diene undergoes Diels-Alder cycloaddition with dienophiles. Polyimides have been synthesized from various imide-containing benzocyclobutenes and dienophiles (83—85). 

The synthesis of natural products containing the quinonoid stmcture has led to intensive and extensive study of the classic diene synthesis (77). The Diels-Alder cycloaddition of quinonoid dienophiles has been reported for a wide range of dienes (78—80). Reaction of (2) with cyclopentadiene yields (79) [1200-89-1] and (80) [5439-22-5]. The analogous 1,3-cyclohexadiene adducts have been the subject of C-nmr and x-ray studies, which indicate the endo—anti—endo stereostmcture (81). 

Reaction of the azocine (212 R = Me) with DMAD yields the fused 1-azetine (213) by Diels-Alder cycloaddition to the bicyclic valence tautomer (211 R = Me) (71JOC435, 71JA152). 

Diels-Alder cycloaddition reactions, 2, 350 tautomerism, 2, 27, 152, 347 Isoquinoline, 4-hydroxy-alkylation, 2, 349 sulfonation, 2, 321... 

Recall from Section 7.13 that a stereospecific reaction is one in which each stereoisomer of a particular starting material yields a different stereoisomeric form of the reaction product. In the examples shown, the product from Diels-Alder cycloaddition of 1,3-butadiene to c/s-cinnamic acid is a stereoisomer of the product from trans-cinnamic acid. Each product, although chiral, is formed as a racemic mixture. 

An alternative approach to thionitrosoarenes involves the reaction of amines with SCla. This method has also been adapted to the production of selenonitrosoarenes ArN=Se by using the selenium(If) synthon PhSOaSeCl as the Se source (Scheme 10.2). It is likely that SeCla, generated in situ in THF, could also be used in this process. The Diels-Alder cycloaddition of ArN=Se species with dimethylbutadiene gives 1,2-selenazine derivatives in low yields. 

As it happens, the frontier orbital interactions in the Diels-Alder cycloaddition shown above are like those found in the middle drawing, i.e., the upper and lower interactions reinforce and the reaction proceeds. The cycloaddition of two ethene molecules (shown below), however, involves a frontier orbital interaction like the one on the right, so this reaction does not occur. 

Both of the reactions, radical combination and Diels-Alder cycloaddition, cause new bonds to be made. Bond making normally releases energy. Why then are the barriers for the two reactions so different (Hint Consider the nel bond making/bond breaking in the two reactions.)... 

LUMO energies for free and complexed acrylonitrile are. 103 and. 089 au (65 and 56 kcal/mol), respectively. On the basis of orbital energies, would you expect BF3 to enhance, retard, or leave unchanged the rate of Diels-Alder cycloaddition ... 

UV irradiation. Indeed, thermal reaction of 1-phenyl-3,4-dimethylphosphole with (C5HloNH)Mo(CO)4 leads to 155 (M = Mo) and not to 154 (M = Mo, R = Ph). Complex 155 (M = Mo) converts into 154 (M = Mo, R = Ph) under UV irradiation. This route was confirmed by a photochemical reaction between 3,4-dimethyl-l-phenylphosphole and Mo(CO)6 when both 146 (M = Mo, R = Ph, R = R = H, R = R" = Me) and 155 (M = Mo) resulted (89IC4536). In excess phosphole, the product was 156. A similar chromium complex is known [82JCS(CC)667]. Complex 146 (M = Mo, R = Ph, r2 = R = H, R = R = Me) enters [4 -H 2] Diels-Alder cycloaddition with diphenylvinylphosphine to give 157. However, from the viewpoint of Woodward-Hoffmann rules and on the basis of the study of UV irradiation of 1,2,5-trimethylphosphole, it is highly probable that [2 - - 2] dimers are the initial products of dimerization, and [4 - - 2] dimers are the final results of thermally allowed intramolecular rearrangement of [2 - - 2] dimers. This hypothesis was confirmed by the data obtained from the reaction of 1-phenylphosphole with molybdenum hexacarbonyl under UV irradiation the head-to-tail structure of the complex 158. 

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