Diels-Alder adducts as intermediates

Diels-Alder adducts as intermediates—Activation of G-hydrogen s. 19, 766... 

Diels-Alder adducts as intermediates—1,3-Dioxoles s. Hydrogen peroxide/boron fluoride Carboxylic acid esters from ketones s. 18,190... 

Hydrogen peroxide sodium carbonate Quinone monoepoxides Diels-Alder adducts as intermediates... 

Diels-Alder adducts as intermediates Activation of G-hydrogen G-Cyanoethylation of a,y -ethylenealdehydes... 

The proposed reaction mechanism (81) invokes a charge transfer complex which converts to a resonance stabilized diradical. The latter leads to a Diels-Alder adduct as a result of intramolecular coupling. However, when the diradical intermediate is attacked by a free radical, it is opened, and an alternating copolymer results from intermolecular coupling. 

The diketo-ester (1) has 1,4 1,5 and 1,6-dicarbonyl relationships. Both the 1,4 and 1,5 relationships can be disconnected at the branchpoint in the middle of the molecule, to give sensible intermediates such as (3) and (4), but difficult synthons (2) and (5). The 1,6 reconnection requires symmetrical Diels-Alder adduct (6). 

Free intermediate thioaldehydes 598 or 602 and the selenoaldehydes 605 and HMDSO 7 are obtained in THF at 0°C on treatment of aliphatic and aromatic aldehydes with bis(trimethylsilyl)thiane 601 or bis(trimethylsilyl)selenide 604 in the presence of traces of butyllithium, while trapping the sensitive intermediate thio- or selenoaldehydes 602 and 605 with cyclopentadiene or cyclohexadiene to furnish mixtures of endo and exo Diels-Alder adducts such as 603 a and 606 a and 603 b and 603 b [148-150], the exo/endo ratio of which can be controlled [150] (Scheme 5.48). Analogous reaction of ketones such as 2-adamantanone or acetylene ketones with MesSiXSiMes 608 (a. X=S (601) b. X=Se (604)) in the presence of... 

Grieco utilized an aqueous intermolecular Diels-Alder reaction as the key step in forming the AB ring system of the potent cytotoxic sesquiterpene vernolepin. 87 Cycloaddition of sodium ( >3,5-hexa-dienoate with an a-substituted acrolein in water followed by direct reduction of the intermediate Diels-Alder adduct gave the desired product in 91% overall yield (Eq. 12.28). 

The source of alcohol 50 is most probably acid-catalysed hydrolysis of 49 to the nitrosocarbonylbenzene intermediates 51, which, like acid chlorides, react with water to give benzoic acids 52 (Scheme 1 pathway (i)).159 Acylnitroso intermediates 51 were trapped as the Diels Alder adducts 53 in reactions in CH3CN/H20 and in the presence of cyclopentadiene. In CH3CN/10% H280, 53 was enriched in lsO... 

Linz et al.6 report the synthesis of enantiomerically pure cyclosarkomycin 6, a stable crystalline precursor of sarkomycin 5. As described in Scheme 5-3, 6 can be obtained from 8, an asymmetric Diels-Alder adduct of (E )-bromoacry-late. (E)-3-bromoacrylate 9a [the acrylate of (R)-pentolactone 11] and 9b [the acrylate of ( S )-A-methyl hydroxyl succinimide 12] undergo TiCL-mediated Diels-Alder reactions giving 10a or 10b, the endo-product, with high diaster-eoselectivity (Scheme 5-4). With the key intermediate 10a in hand, synthesis of compound 6 is accomplished by following the reaction sequence shown in Scheme 5-5. 

At higher temperatures retro-Diels-Alder reaction may also occur in the opposite sense to addition, as in the reaction of methyl pyrrole-1-carhoxylate with dimethyl acetylenedicarboxylate at 200°, which affords acetylene and the pyrrole triester (56). The decomposition of the suspected intermediate Diels-Alder adduct (11) at 170° has been separately established. Compounds 19 and 20 are intermediates in similar addition-elimination reactions leading to pyrrole-l,3,4-triesters, in which removal of acetylene from the system makes the reaction sequence effectively irreversible. 

Reaction of N-acetyl-lO-bromodibenzazepine 51 with potassium ferf-butoxide yields the reactive intermediate 52 that reacts with N-methyl pyrrole 53 (X = NMe) used as a solvent to produce a mixture of Diels-Alder/retro Diels-Alder adduct 54 with the Michael by-product 55 (X = NMe, Scheme 10 (1994JHC293)). 

Another approach to synthesize stable Diels-Alder adducts of Cjq was introduced by Mullen and co-workers [41—43], The use of o-quinodimefhane derivatives as dienes, prepared in situ, leads to the formation of thermally stable cycloadducts (Scheme 4.5). As with the isobenzofuran addition product [13], a cycloreversion of these adducts would need to overcome the stabilization provided by the aromatic system and would also give the unstable o-quinodimefhane intermediate. A fast ring inversion, at elevated temperatures, of the cyclohexane moiety causes a 2 -symmetry of the cycloadduct, leading to 17 lines for the fuUerenyl carbons in the NMR spectra [41]. 

As already mentioned, treatment of dihalocyclopropanes with bases furnishes cyclopropenes. When nucleophilic reagents are present, these are added to the strained double bond, and the products thus formed correspond to the products of direct nucleophilic substitution of the substrate, i.e. the elimination/addition process is equivalent to an overall substitution. In fact, in some cases the instable chlorocyclopropene intermediates could be trapped as Diels-Alder adducts with cyclopen tadiene. 

When 2-ethylbenzophenone is brominated as described earlier and the crude product treated with A -phenylmaleimide (refluxing CCI4) and dimethyl acetylenedicarboxylate (refluxing CHCI3), the Diels-Alder adducts 98 (mp 183-184°C, 40% presumably endo, when the H-NMR data are compared with those of 88 and 89) and 99 (mp 126.5-127°C, 57%) are isolated again a benzo [cjfuran (87 R = Me, R — Ph, R = H) is assumed to be an intermediate. ... 

Polysubstituted methyl- and phenyl-thiophenes could be oxidized with perbenzoic acid or peracetic acid to the corresponding sulfones electron-withdrawing groups like NO2 hindered the oxidation (63AHC(l)l). Yields of such dioxides have been improved by the use of three equivalents of MCPBA (76SC583). However, with thiophene and 2-methylthiophene as substrates, only the Diels-Alder adducts (145) between the intermediate sulfoxide and the final sulfone could be isolated. 

Thieno[2,3-6]quinoxalines have been prepared by a method which resembles quite closely the ring closure reaction described in Scheme 111. Heating 3-j8-arylvinyl-2-oxo-l,2-dihy-droquinoxalines (389 equation 42) and phosphorus pentasulfide under reflux in pyridine yields 2-arylthieno[2,3-6]quinoxalines (390). Probably a dihydro compound occurs as an intermediate (80Ci(L)536). Attempts to prepare thieno[3,4-6]quinoxaline (392) by dehydration of sulfoxide (391 Scheme 114) were unsuccessful (77JHC541). Again it was possible to trap (392) as a Diels-Alder adduct (e.g. 393) when (391) was refluxed in acetic anhydride... 

In the thermal reaction the [4 + 2] or Diels-Alder adduct is the major product, whereas in the photochemical reaction [2 + 2] cycloadditions dominate. Because the photochemical additions are sensitized by a ketone, C6H5-COCH3, these cycloadditions occur through the triplet state of 1,3-butadiene and, as a result, it is not surprising that these cycloadditions are stepwise, nonstereospecific, and involve diradical intermediates. 

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