Annelation Diels-Alder

Select one compound from (37) - (40) for synthesis by each of the methods of this chapter Robinson annelation, Diels-Alder reaction, total reduction of aromatics, and Birch reduction. 

Inverse Diels-Alder reaction as synthetic tool in the synthesis of annelated heterocycles 95F419. 

These results show that inverse Diels-Alder reactions of pyrimidines open an easy access to a number of differently substituted pyridines and especially to compounds, in which the carbocyclic ring and the heterocyclic rings are annelated on the b position of pyridine. An interesting illustrating example... 

The Diels-Alder methodology can also be applied in the synthesis of tricyclic heterocycles, as was demonstrated by reactions of 2-(2-trimethylsilylethynylphenyl-X)pyrimidines (X = 0, S, NCOMe, CHj, CO). They are converted in good yield on heating at 160°C into tricyclic annelated pyridines (89T6511) (Scheme 37). A similar reaction was found with the 2-(2-allylphenoxy)pyrimidines affording azaxanthenes (79H665) (Scheme 37). 

Due to the two electron-donating groups in the bicyclic product 150 and the unhydrolyzed precursor of 148, they should be quite reactive dienes in Diels-Alder reactions. However, such [4+2] cycloadditions were observed only for the cyclohexane-annelated cyclopentadienes 151b, which equilibrate with the more reactive isomers 154 by 1,5-hydrogen shifts (Scheme 33). The [4+2] cycload-... 

Double intramolecular /zcfcro-Diels-Alder reaction of 1,3-diynil-bis-a,)S-unsaturated hydrazones 139 and 140 is a good example of a thermal multiple Diels-Alder reaction and is a particularly attractive route to annelated pyridines [123]. The initial cycloadduct readily aromatizes by the loss of dimethylamine (Scheme 2.52) under thermal reaction conditions. 

In supramolecular chemistry [31] iterative synthesis is frequently used for the construction of ribbon and belt shaped molecules [32]. The repeated Diels-Alder reaction is suitable for the preparation of beltenes, collarenes and cycla-cenes containing partially or fully unsaturated annelated six-membered rings. They are potential molecular receptors for appropriate substrates. Stoddart et al. synthesized the cyclacene 18 by Diels-Alder cyclization of the bisdiene 15 and the bisdienophil 16 [33] (Fig. 10). 

The initially generated o-diallenylarene 273 electrocydizes to the annelated o-xyly-lene 274, which can either ring close to a naphtho[fo]cyclobutene or be trapped with a dienophile to yield the Diels-Alder adduct 275. Instead of the terminal hydrogen atom, the ethynyl functions can also carry alkyl and aryl substituents. 

Bicyclopropylidenes with two larger rings annelated at both cyclopropyl moieties are sufficiently well documented (Table 1). But compounds in which the larger ring bridges the two ends of a bicyclopropylidene are usually more highly strained and, as a consequence, not as easily accessible. The first such compounds 89 and 91 were obtained by Diels-Alder reaction of the bis(cyclo-propenyl) derivative 90 with dimethyl acetylenedicarboxylate (DMAD) and te-... 

The enedione (15), a tetracyclic intermediate on a synthetic route to fusidic acid, has been synthesized from the a-methylene-ketone (16) (Scheme 2). The first step, involving a Diels-Alder reaction with a substituted acrylate (17), provides a new versatile annelation procedure. Further modification of (15) by a route worked out on model systems (see Vol. 4, p. 318) afforded the tetracyclic enone (24) with the desired trans-syn-trans geometry (Scheme 3). This compound (24) has also been prepared by degradation of fusidic acid. Attempts to introduce the C-11 oxygen function necessary for the synthesis of fusidic acid have not been very... 

Preparation the linear tropone-annelated benzo [c] furans 371 (X = O) by direct condensation of dialdehyde 370 (X = O) with acetone, 1-phenyl-acetone, and 1,3-diphenylacetone, in alkaline medium was—in contrast to the corresponding benzo [c]thiophene (X = S)—unsuccessful. Interestingly, this condensation has been brought about with the Diels-Alder adduct 372 subsequent heat yields 371 (X = O), a rare case where V-phenylmaleimide is used as a protective group. Compounds 371 react with V-phenylmaleimide even at room temperature to give adducts 373. 

Since the reaction of a /3-dicarbonyl compound with an a,/3-unsaturated aldehyde gives a 2i/-pyran (640) in a single step, Diels-Alder reaction as above provides a new route for aryl annelation (Scheme 146). 

Annelation (see Cycloaddition reactions, Diels-Alder reactions, Ring-forming reactions)... 

Salicylate annelatiun.1 A new method involves conversion of a cyclohexanone llllo the annelated 3-carbomethoxy-2-pyrone by reaction of the enolate with dimethyl iliclhoxyincthylcnemalonate2 to form a 3-carbomethoxy-2-pyrone. This product undergoes a facile Diels-Alder reaction with 1,1-dimethoxyethylene with loss of C02 anil ( II, OII to give a salicylate... 

The first step is an intramolecular Diels-Alder reaction. The regioselectivity of this transformation may be explained as follows The reaction can yield annelated products of type 34 by cyclization in a quasi ortho sense or bridged products of type 36 by cylization in a... 

Nitrosonium terafluoroborate initiates the cation radical-mediated imino-Diels-Alder reaction of IV-arylimines with IV-vinylpyrrolidinones to give cw-4-(2-oxopyr- (g) rolidin-l-yl)tetrahydroquinolines.175 Also, 2,4,6-triphenylpyrylium tetrafluoroborate catalyses the Diels-Alder addition of IV-arylimines with IV-vinylpyrrolidinone and IV-vinylcarbazole to yield the corresponding 2-oxopyrrolidin-l-yl- and carbazole-9-yl-tetrahydroquinolines.176 The tricyclic core (151) of the batzelladine alkaloids has been prepared by a diastereoselective 4 + 2-annelation of the vinylcarbodiimide (150)... 

N-Substituted benzotriazole intermediate (77) is an excellant synthon for the synthesis of 2-ethoxy-2-vinylcyclopropanecarboxylate esters (78) [95JOC6], 1-Propargylbenzotriazole was reacted with bromoacetophenone to provide the novel 2-(benzotriazolomethyl)furan (80) in 60% yield [95JOC638]. Annelated N-aminotriazoles, on oxidation, are a good source of cyclic alkynes as illustrated for the reaction of aminotriazolotropone (80) with 4-phenyloxazole to generate the furyl[3,4-cf]tropone (82) from a Diels-Alder intermediate with facile loss of benzonitrile [94TL8421 ]. 

Another annellation reaction starts from a,a -dibromo-o-xylene, an activated olefin and zinc.63 This reaction, according to the authors proceeds by a Diels-Alder cycloaddition via the o-xylylene (Scheme 15.10), and was employed in carbohydrate chemistry to prepare anthracyclinones analogues.64 No reaction occurs without sonication. Instead of a cycloaddition, another explanation can be postulated, consisting first of addition of a mono-organozinc reagent to the activated olefin, followed by alkylation of the resulting enolate by the second benzylic bromide. 

Annelations via Diels-Alder reaction were employed by Katz and coworkers to develop exceedingly efficient methods for multi-gram scale syntheses of [n]heli-cenes with n up to 7. Efficient resolutions were carried out via functionalization with the camphanate ester derivatives and then separation of diastereomers by column chromatography (> 98% de). This synthetic approach may be illustrated by the synthesis of enantiopure [7]thiahelicene 10 [65]. Notably, the Diels-Alder diannelation and aromatization gives racemic 10 in 95 % yield. Resolution with camphanate tetraester provides enantiopure 11 (Fig. 15.4). 

In a study of annelation reactions of 4-alkynylcyclobutenones <91JOC6104>, thermolysis of a 4-alkynyl-4-(propargyloxy)cyclobutenone was observed to give a high yield of a quinone methide as evidenced by the formation of a hetero-Diels-Alder product in the presence of butoxyethene as a... 

The use of cycloaddition reactions for the synthesis of partially reduced heterocyclic systems was shown to be an attractive approach to dihydrobenzimidazoles, dihydroquinazolines, and dihydro-//n-benzopurines (Scheme 14) <86JOC6i6>. The dihydroxylation of the Diels-Alder adduct dimethyl 3,6-dihydrophthalate (128) with 0s04 and NMO followed by protection of the diol as the iso-propylidene derivative afforded compound (129). Saponification, dehydration with ethoxyethyne, and rearrangement with TMS—N3 effected conversion to the substituted tetrahydroisatoic anhydride (130), and subsequent treatment with formamidine acetate yielded compound (131). The substituents at the 6,7-positions of compound (131) were not amenable, however, for annelation of an imidazole. 

Cyclocondensation routes also provide access to pyrimidines. 2,3-Disubstituted pyrido[2,3-/i]-quinazolin-4(3//)-ones are obtained via cyclocondensation of 5-aminoquinoline-6-caiboxylic acid with acid chlorides <02SC235>. 5,6,8-Trialkyl-7-methoxy-2-aminoquinazolines are obtained from 1,3-dimethoxybenzenes via cyclocondensation of intermediate dihydrobenzenes with guanidine carbonate <02TL3295>. Diastereoselective intramolecular hetero Diels-Alder cyclization of a pyrazole carboxaldehyde condensed onto 1,3-dimethylbarbituric acid (101) gave polycyclic heterocycle 102 <02T531>. An efficient one-step synthesis of cyclobutene-annelated pyrimidinones 103 from methyl 2-chloro-2-cyclopropylideneacetate and amidines has been... 

Other novel and noteworthy investigations concerning Diels-Alder reactions of nitroso dienophiles are on the one hand directed to novel accesses to these dienophiles [358] on the other hand, synthetical approaches to nortropanes [359, 360], pyrrolocastanospermine analogs [361] and novel annelated indoles [362] have been developed basing on this powerful preparative tool. 

---