Diels-Alder/domino reaction

The strained undecacyclic pagodane framework was obtained in a series of 14 one-pot operations with an overall yield up to 24% from commercial isodrin. The key steps are (i) a benzene-benzene [6 -I- 6]photocycloaddition, and (ii) a domino Diels-Alder reaction. 

A domino Diels-Alder reaction (the term was chosen from the well-known game) is a one-pot process involving two or more Diels-Alder reactions carried out under the same reaction conditions without adding additional reagents or catalyst such that the second, third, etc., cycloaddition is the consequence of the functionality generated in the previous reaction. A historical example is illustrated in Equation 1.28 [60]. This type of transformation is sometimes named tandem or cascade, but these terms seem less appropriate for describing a time-resolved transformation. 

In further studies, the group of Dailey [6] also investigated the domino Diels-Alder reaction of tetraenes of type 4-18 with dicyanoacetylene 4-15, which led exclusively to product 4-19 in good yield (Scheme 4.4). 

Domingo and coworkers [11] have contributed an important theoretical input for the understanding of domino reactions. An interesting example is the domino Diels-Alder reaction of 4-33 and 4-34, in which the products 4-37 and 4-38 could be formed via 4-35 and 4-36, respectively (Scheme 4.7). Visnick and Battiste [12] had shown that, at room temperature, only cycloadduct 4-37 is formed, whereas with heat 4-38 is obtained quantitatively. This is in line with the calculations showing that TS5 is higher in energy than TS4 (74.5 and 55.3 kj mol"1, respectively) on the other hand, cycloadduct 4-38 is more stable (-92.9 kj mol"1) than cycloadduct 4-37 (-78.7 kj mol"1), which explains the formation of 4-38 under thermodynamic control. Calculations have also been performed for the bisfuran system 4-28a [13]. 

In contrast to the lack of examples of the domino Diels-Alder reaction/l,3-dipolar cycloaddition, the combination of a Diels-Alder reaction with a sigmatropic rearrangement has been used intensively. 

SCHEME 8. Competition between pincer and domino Diels-Alder reactions in the synthesis of pagodane precursurs92... 

Dailey and colleagues109 employed a domino Diels-Alder reaction to synthesize the complex hexacycle 146. The intermolecular reaction of tetracycle 143 with maleic anhydride 144 afforded a single adduct (145) which immediately underwent an intramolecular Diels-Alder reaction to give 146 (equation 42). This reaction is similar to a reaction performed previously by Prinzbach and colleagues110. Prinzbach observed that when alkynes were used as dienophiles, either domino or pincer Diels-Alder reactions occurred. In the latter type, the triple bond reacts with both diene units. 

The domino cycloaddition-iV-acyliminium ion cyclization cascade has been extensively reviewed. Tandem reactions combining Diels-Alder reactions and sigma-tropic rearrangement reactions in organic synthesis have been extensively reviewed. The tandem Diels-Alder reaction between acetylenedicarboxaldehyde and N,N -dipyrrolylmethane has been extensively studied at the RHT/3-21G and RHF/6-31G levels.The molecular mechanism of the domino Diels-Alder reaction between hexafluorobut-2-yne and A,A -dipyrrolylmethane has been studied using density functional theory. 

On the other hand, a C-5 cyclopentadiene moiety induced almost no face discrimination on addition of dimethyl acetylenedicarboxylate to 9,10-dihydrofulvalene (266) (Scheme 63). Products (268) and (270) result from a tandem inter- ntra-molecular Diels-Alder reaction (domino Diels-Alder reactions). 

One step in the synthesis of dodecahedrane (Section 4.11) invoived reaction of the tetraene A with dimethyiacetyiene dicarboxylate (B) to afford two compounds having moiecuiar formuia C16H16O4. This reaction has been caiied a domino Diels-Alder reaction. Identify the two products formed. 

Simple variations on this synthesis are summarized in Table 5. The last example in this table involves a domino Diels-Alder reaction in which two sequential [27t + drt] cycloaddition processes converted 5,5 -bicyclopentadienyl (6) to the pentacyclic product 7 which was converted to the diazene 8 in the normal manner. 

The diester 87 with the same tetracyclic skeleton as 83 had previously been prepared by Paquette et al. via a domino Diels-Alder reaction of 5,5 -bicyclo-pentadienyl 84 with dimethyl acetylenedicarboxylate (Scheme 20) [73]. The key precursor 84 was obtained by iodine-induced oxidative coupling of the copper cyclopentadienide derived from the sodium derivative. The diester 85 formed along with 86 was transformed into a bissilyl bisenol ether by reductive cleavage of the central bond in the succinate moiety with sodium in the presence of trimethylsilyl chloride. Subsequent hydrolysis of the bisenol ether - actually a bisketene acetal - gave the dienic tetraquinacenedicarboxylate 87. This compound served as the key intermediate in the first synthesis of dodecahedrane 88 [74]. 

Wyvratt, M. Paquette, L. A. "Domino Diels Alder Reactions. II. A Four-Step Conversion of Cyclopentadienide to Triquinacene" Tetrahedron Lett. 1974, 2433-2436... 

The dibenzo compound 168 was inert toward acetone-sensitized excitation, probably because the triplet energy for the isolated chromophoric xylene units is too high, whereas irradiation of 168 with monochromatic 254 nm hght slowly gave a ca. 7 3 equilibrium mixture of 168 and the [6 + 6]-photo-addition product 169. The key step for the successful synthesis of Pagodane, the CjqHjo polyquinane, is this type of benzo/benzo [6 + 6]-photocycloaddition and a domino Diels-Alder reaction. 

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