Cycloadditions Diels-Alder

Diels-Alder cycloadditions are among the most useful and valuable synthetic reactions. A large variety of electron-deficient olefins as well as acetylenes interact with diverse dienes resulting in cyclic products. 

The strongly polarized C = C bond of alkynyliodonium salts, along with their propensity for Michael additions, predicts that they should be good 1,3-dipolarophiles. Indeed, reaction of arylethynyliodonium tosylates with arenenitrile oxides, 127, gives a mbtture of cycloadducts, 128 and 129, in 62-80% yields [91] [Eq. (59)]. Similarly, Me3SiC=CIPh OTf and various diazocarbonyl compounds, 130, result [92] in cycloadducts 131 [Eq. (60)]. Likewise, alkynyliodonium salts react with methyl and phenyl azide to give low yields of triazines, 132, as adducts [Eq. (61)]. 

It is evident that alkynyliodonium salts represent a highly versatile, new class of valuable, functionalized acetylenes. Although they have only been available for a dozen years, they provide an added dimension to acetylene transformations. Due to the superb leaving ability of 

SCHEME 12.10 Diels-Alder reactions with furans. 

SCHEME 12.11 Controlling regiochemistry in aryne-furan Diels-Alder reactions. 

In order to control the regiochemistry of the aiyne-furan cycloadditions, removable silicon tethCTs have been used and this methodology has been applied in total synthesis. This concept is exemplified with the regioselective preparation of naphthol 18 (Schane 12.12) [20]. 

SCHEME 12.14 Diels-Alder cycloadditions with all-caibon cyclic dienes. 

Other Dienes. Naphtho-fused oxindole derivatives 23 have been accessed by an aiyne Diels-Alder reaction using methyleneindolines as dienes. The proposed mechanism involves a [4+2] cycloaddition followed by isomerization and further dehydrogenation. These results represent the 

---

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. 

---