Dimethyl Diels-Alder

We chose benzyli dene acetone (4.39, Scheme 4.11) as a model dienophile for our studies. The uncatalysed Diels-Alder reaction of this compound with cyclopentadiene is slow, justifying a catalytic approach. Reaction of 4.39 with paraformaldehyde and dimethyl amine under acidic conditions in an aqueous ethanol solution, following a literature procedure, produced the HCl salt of 4.42 (Scheme 4.11). The dienophile was liberated in situ by adding one equivalent of base. 

As illustrated in Scheme 8.1, both 2-vinylpyrroles and 3-vinylpyiroles are potential precursors of 4,5,6,7-tetrahydroindolcs via Diels-Alder cyclizations. Vinylpyrroles are relatively reactive dienes. However, they are also rather sensitive compounds and this has tended to restrict their synthetic application. While l-methyl-2-vinylpyrrole gives a good yield of an indole with dimethyl acetylenedicarboxylate, ot-substitiients on the vinyl group result in direct electrophilic attack at C5 of the pyrrole ring. This has been attributed to the stenc restriction on access to the necessary cisoid conformation of the 2-vinyl substituent[l]. 

Most examples of Diels-Alder reactions reported for both 2-vinyl and 3-vinylindoles involve typical electrophilic dienophiles such as benzoquinone, A"-phenylmaleimide and dimethyl acetylenedicarboxylate (see Table 16.1). T hese symmetrical dienophiles raise no issues of rcgiosclectivity. While there arc fewer examples of use of mono-substituted dienophiles, they appear to react... 

Give the structure of the Diels-Alder adduct of 1 3 cyclohexadiene and dimethyl... 

The Diels-Alder addition to 1,3-dienes is particularly interesting because of the exceptional ease with which it takes place, eg, see equation 1 in which l,2-dimethyl-4,4,5,5-tetracyanocyclohexene [69155-29-9] is formed. 

Dicyanoacetylene, 2-hiitynedinitri1e, is obtained from dimethyl acetylenedicarboxylate by ammonolysis to the diamide, which is dehydrated with phosphoms pentoxide (44). It bums in oxygen to give a flame with a temperature of 5260 K, the hottest flame temperature known (45). Alcohols and amines add readily to its acetylenic bond (46). It is a powerhil dienophile in the Diels-Alder reaction it adds to many dienes at room temperature, and at 180°C actually adds 1,4- to benzene to give the bicyclo adduct (7) [18341 -68-9] C QHgN2 (47). 

The reactions of pyrroles with dimethyl acetylenedicarboxylate (DMAD) have been extensively investigated. In the presence of a proton donor the Michael adducts (125) and (126) are formed. However, under aprotic conditions the reversible formation of the 1 1 Diels-Alder adduct (127) is an important reaction. In the case of the adduct from 1-methylpyrrole, reaction with a further molecule of DMAD can occur to give a dihydroindole (Scheme 48) (82H(19)1915). 

Other methods for the preparation of cyclohexanecarboxaldehyde include the catalytic hydrogenation of 3-cyclohexene-1-carboxaldehyde, available from the Diels-Alder reaction of butadiene and acrolein, the reduction of cyclohexanecarbonyl chloride by lithium tri-tcrt-butoxy-aluminum hydride,the reduction of iV,A -dimethylcyclohexane-carboxamide with lithium diethoxyaluminum hydride, and the oxidation of the methane-sulfonate of cyclohexylmethanol with dimethyl sulfoxide. The hydrolysis, with simultaneous decarboxylation and rearrangement, of glycidic esters derived from cyclohexanone gives cyclohexanecarboxaldehyde. 

In the case of 1,3-diphenylisoindole (29), Diels-Alder addition with maleic anhydride is readily reversible, and the position of equilibrium is found to be markedly dependent on the solvent. In ether, for example, the expected adduet (117) is formed in 72% yield, whereas in aeetonitrile solution the adduet is almost completely dissociated to its components. Similarly, the addition product (118) of maleic anhydride and l,3-diphenyl-2-methjdi.soindole is found to be completely dissociated on warming in methanol. The Diels-Alder products (119 and 120) formed by the addition of dimethyl acetylene-dicarboxylate and benzyne respectively to 1,3-diphcnylisoindole, show no tendency to revert to starting materials. An attempt to extrude carbethoxynitrene by thermal and photochemical methods from (121), prepared from the adduct (120) by treatment with butyl-lithium followed by ethyl chloroform ate, was unsuccessful. 

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. 

Pyrano[3,4-i]indol-3-one (329) enters the Diels-Alder reaetion with methoxy-butenone as an eleetron-rieh olefin [92JCS(P1)415]. After deearboxylation of the primary adduet330,2-aeetyl-3-methoxy-l, 9-dimethyl-2,3-dihydroearbazole (331) eliminates methanol to form 2-aeetyl-l,9-dimethylearbazole (332) [92JCS (Pl)415]. 

It was found that the introduction of a sulfonyl substituent considerably enhances the furanone reactivity in Diels-Alder reaction. Thus, (55)-5-(reacted with cyclopentadi-ene at room temperature in benzene with complete conversion to the adduct 212. Also, the reaction of 211 with 2,3-dimethyl-1,3-butadiene was readily performed in refluxing benzene to give the adduct213 in 98% yield (Scheme 57) (91TL7751). 

A Diels-Alder type [4+2] cycloadditions of 4,5-dihydropyridazine, prepared in situ from its trimer, with 2-methyl- and 2,3-dimethyl-1,3-butadienes (65, R = H, Me R = Me) afforded a complex reaction mixture, from which 6-methyl- and 6,7-dimethyl-3,4,4n,5-tetrahydro-8//-pyrido[l,2-ftjpyridazines (66, R = H, Me R =Me) could be isolated (97CEJ1588). With 1,3-butadiene (65, R = R =H) only a mixture of endo and exo isomers 67 and 68 (R = R =H) was obtained. 

The influence of alkyl substituents on the asynchronous transition-state structure of the BF3-catalyzed carbo-Diels-Alder reaction of a,/ -unsaturated aldehydes with 1,1-dimethyl-l,3-butadiene derivatives has been investigated by Dai et al. [13]. 

A Dimethyl butynedioate undergoes a Diels-Alder reaction with (2 ,4 )-hexadiene. Show the structure and stereochemistry of the product. 

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