The diene

A wide variety of 1,3-dienes can take part in the Diels-Alder cycloaddition reac-tion, including open-chain and cyclic dienes, and transiently formed dienes such as ort/jo-quinodimethanes. Heterodienes, in which one or more of the atoms of the diene is a heteroatom, are also known. Acyclic dienes can exist in a cisoid or a transoid conformation, and an essential condition for reaction is that the diene can adopt the cisoid form. If the diene does not have, or cannot adopt, a cisoid conformation then no Diels-Alder cycloaddition reaction occurs. 

Acyclic conjugated dienes react readily with dienophiles. Butadiene itself reacts quantitatively with maleic anhydride in benzene at 100 °C in 5 h, or more slowly at room temperature, to form cA-l,2,3,6-tetrahydrophthalic anhydride (3.35). 

Fringuelli and A. Taticchi, Dienes in the Diels-Alder Reaction (New York Wiley, 1990). 

Z-Alkyl or aryl substiments in the 1-position of the diene reduce its reactivity by sterically hindering formation of the cisoid conformation through non-bonded interaction with a hydrogen atom at C-4. Accordingly, an A-substituted 1,3-butadiene reacts with dienophiles much more readily than the Z-isomer. Thus Z-1,3-pentadiene gave only a 4% yield of adduct when heated with maleic anhydride at 100 °C, whereas the A-isomer formed an adduct in almost quantitative yield in benzene atO°C. 

Similarly, , -l,4-dimethylbutadiene reacts readily with many dienophiles, but the Z,E-isomer yields an adduct only when the components are heated in benzene at 150°C. Z,Z-l,4-Disubstituted butadienes are uiureactive. 1,1-Disubstituted butadienes also react with difficulty, and with such compounds addition may be preceded by isomerization of the diene to a more reactive species. Thus, in the reaction of 1,1-dimethylbutadiene with acrylonitrile, the diene first isomerizes to 1,3-dimethylbutadiene, which then reacts in the normal way. 

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Polymerization of compounds perfonned with UV light was first reported in the 1970s [86] and was followed by further studies [87, 88 and 89]. Another study was concerned with the deposition and polymerization of multilayers of alcohols and acids incoiyDorating the diene group, -CH=CH-CH=CH-, at the hydrophilic end of the molecule [90]. 

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 ... 

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. 

The last example is an interesting application of the diene synthesis, for the adduct upon dehydrogenation (most simply by the action of oxygen upon its solution in alcoholic potash) yields 2 3-dimethylantbraquinone. 

The mechanism of the diene synthesis appears to involve an electron transfer from the diene to the dienophile, .e., it is initiated by an ionic reaction. The following scheme may represent the addition of 2 3-dimethylbutadiene to maleic anhydride ... 

D-A rxns are sensitive to steric effects of the dienephiles, particularly at the I- and 2-postions. Steric bulk at the I-position may prevent approach of the dienophile while steric bulk at the 2-position may prevent the diene from adopting the s-cis conformation. 

Intramolecular D-A rxn which form large rings are often favorable reactions with the diene and olefin portions act as if they were seperate molecules... 

Preference for endo or exo transition state depends on the substitution of the diene, dieneophile and connecting chain. 

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). 

Diels-Alder reactions can be divided into normal electron demand and inverse electron demand additions. This distinction is based on the way the rate of the reaction responds to the introduction of electron withdrawing and electron donating substituents. Normal electron demand Diels-Alder reactions are promoted by electron donating substituents on the diene and electron withdrawii substituents on the dienophile. In contrast, inverse electron demand reactions are accelerated by electron withdrawing substituents on the diene and electron donating ones on the dienophile. There also exists an intermediate class, the neutral Diels-Alder reaction, that is accelerated by both electron withdrawing and donating substituents. 

Figure 1.2. Endo and exo pathway for the Diels-Alder reaction of cyclopentadiene with methyl vinyl ketone. As was first noticed by Berson, the polarity of the endo activated complex exceeds that of the exo counterpart due to alignment of the dipole moments of the diene and the dienophile K The symmetry-allowed secondary orbital interaction that is only possible in the endo activated complex is usually invoked as an explanation for the preference for endo adduct exhibited by most Diels-Alder reactions.

The mechanism by which Lewis-acids can be expected to affect the rate of the Diels-Alder reaction in water is depicted in Scheme 2.6. The first step in the cycle comprises rapid and reversible coordination of the Lewis-acid to the dienophile, leading to a complex in which the dienophile is activated for reaction with the diene. After the irreversible Diels-Alder reaction, the product has to dissociate from the Lewis-acid in order to make the catalyst available for another cycle. The overall... 

The effect of ligands on the endo-exo selectivity of Lewis-acid catalysed Diels-Alder reactions has received little attention. Interestingly, Yamamoto et al." reported an aluminium catalyst that produces mainly exo Diels-Alder adduct. The endo-approach of the diene, which is normally preferred, is blocked by a bulky group in the ligand. 

Due to the prolonged reaction times in organic solvents, cKmerisation of the diene occurs during the reaction, resulting in contaminated product mixtures after work-up. In contrast the reactions in water yield quantitatively the H-NMR-pure Diels-Alder adducts. 

In a second attempt to obtain more insight into the binding location of the dienophile and now also the diene, we have made use of the influence of paramagnetic ions on the spin-lattice relaxation rates of species in their proximity. Qose to these ions the spin-lattice relaxation rate is dramatically enhanced. This effect is highly distance-dependent as is expressed by Equation 5.7, describing the spin-lattice... 

Analysis The carbene synthon is easy it can be ethyl diazoacetate NiCHCOiEt. The diene can be made by the Wittig reaction from a familiar aUylic bromide (TM 31). 

Comments The diene A is symmetrical so it doesn t matter which double bond is attacked by the carbene. On the other hand, it may be difficult to stop carbene addition to the second double bond. The only control over the stereochemistry will be that the trans compound we want is more stable. Japanese chemists have recently synthesised optically active trans chrysanthemic acid by this route (Tetrahedron Letters. 1977, 2599). 

Now consider strategy b. How would you make the diene acid B, what reagent would you use for the carbene synthon, and how do you rate the chances of this route ... 

Analysis The normal approaeh to the diene looks all right ... 

The carbene synthon might be difficult, but since the olefin is conjugated with a carbonyl group we could try a sulphur ylid as a nucleopliilic carbene equivalent (as in frame 283). Synthesis The diene could be made by this route ... 

The synthesis of vitamin Dj from a sensitive dienone was another etu-ly success of phosphorus ylide synthesis (H.H. Inhoffen, 1958 A). This Wittig reaction could be carried out without any isomerization of the diene. An excess of the ylide was needed presumably because the alkoxides formed from the hydroxy group in the educt removed some of the ylide. 

The wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

In the synthesis of morphine, bis-cyclization of the octahydroisoqtiinolinc precursor 171 by the intramolecular Heck reaction proceeds using palladium trifluoroacetate and 1,2,2,6,6-pentamethylpiperidine (PMP). The insertion of the diene system forms the rr-allylpalladium intermediate 172, which attacks the phenol intramolecularly to form the benzofuran ring (see Section 1.1.1.3). Based on this method, elegant total syntheses of (-)- and (+ )-dihydrocodei-none and (-)- and ( + )-morphine (173) have been achieved[141]. 

In the reaction of aryl and alkenyl halides with 1,3-pentadiene (248), amine and alcohol capture the 7r-allylpalladium intermediate to form 249. In the reactions of o-iodoaniline (250) and o-iodobenzyl alcohol (253) with 1,3-dienes, the amine and benzyl alcohol capture the Tr-allylpalladium intermediates 251 and 254 to give 252 and 255[173-175]. The reaction of o-iodoaniline (250) with 1,4-pen tadiene (256) affords the cyclized product 260 via arylpalladiuni formation, addition to the diene 256 to form 257. palladium migration (elimination of Pd—H and readdition to give 258) to form the Tr-allylpalladium 259, and intramolecular displacement of Tr-allylpalladium with the amine to form 260[176], o-Iodophenol reacts similarly. 

The dienyne 394 undergoes facile polycyclization. Since the neopentylpalla-dium 395 is formed which has no hydrogen /J to the Pd after the insertion of the disubstituted terminal alkene, the cyclopropanation takes place to form the tt-allylpalladium intermediate 396, which is terminated by elimination to form the diene 397(275]. The dienyne 398 undergoes remarkable tandem 6-e. o-dig. 5-cxo-trig. and -exo-trig cyclizations to give the tetracycle 399 exclu-sively(277]. 

The reduction of acyl halides with hydrogen to form aldehydes using Pd catalyst is well known as the Rosenmund reduction[756]. Some acyl chlorides give decarbonyiation products rather than aldehydes under Rosenmund conditions. The diene 890 was obtained by decarbonyiation in an attempted Rosenmund reduction of acetyloleanolic acid chloride (889)[757], Rosenmund reduction of sterically hindered acyl chlorides such as diphenyl- and tnpheny-lacetyl chloride (891) gives the decarbonylated products 892[758],... 

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