Diels-Alder pathway

Estrone (54, Chart 6) contains a full retron for the o-quinonemethide-Diels-Alder transform which can be directly applied to give 55. This situation, in which the Diels-Alder transform is used early in the retrosynthetic analysis, contrasts with the case of ibogamine (above), or, for example, gibberellic acid (section 6.4), and a Diels-Alder pathway is relatively easy to find and to evaluate. As indicated in Chart 6, retrosynthetic conversion of estrone to 55 produces an intermediate which is subject to further rapid simplification. This general synthetic approach has successfully been applied to estrone and various analogs. ... 

J 469 There is evidence that the mechanism of the last step more likely resembles the Diels-Alder pathway than the ring expansion pathway Bianchini, C. Caulton, K.G. Chardon, C. Eisenstein, O. Folting, K. Johnson, T.J. Meli, A. Peruzzini, M. Raucher, D.J. Streib, W.E. Vizza, F. J. Am. Chem. Soc., 1991, 113, 5127. 

Isochromones lose carbon dioxide on heating via retro-Diels-Alder pathway to result in o-quinodimethanes (equation 81)1241,129. An isochromone route to podophyllotoxin derivative has been described (equation 82)130. Diels-Alder adducts of a-pyrone readily extrude carbon dioxide on thermal activation to furnish cyclohexadienes, which are useful substrates in tandem Diels-Alder reactions (equation 83)131. 

Retro-Diels-Alder reactions can be used to regenerate dienes or alkenes from Diels-Alder protected cyclohexene derivatives under pyrolytic conditions144. Most of the synthetic utility of this reaction comes from releasing the alkene by diene-deprotection. However, tetralin undergoes cycloreversion via the retro-Diels-Alder pathway to generate o-quinodimethane under laser photolysis (equation 89)145. A precursor of lysergic acid has been obtained by deprotection of the conjugated double bond and intramolecular Diels Alder reaction (equation 90)146. 

The Diels Alder pathway illustrated above belongs to what is called the grafting to method, which consists of attaching a defined polymer chain through transformation of an appropriate end group. 

With one exception, naphthalen-l,4-imines with a double bond between C-2 and C-3 are not known to dissociate thermally by either possible retro-Diels-Alder pathway (the reverse of reactions described in Section III, A, 1 and 2), and the enthalpy requirements for the formation of a benzyne or an acylic acetylene are doubtless unfavorable. However, the mass spectra of compounds 93-99 reveal one important fragmentation of the molecular ions to be loss of dimethyl acetylene-dicarboxylate, and another fragmentation pathway involves the formation of nitrilium ions MeC=NR and PhC=NR from 93-95 and 96-99, respectively. ... 

Using a diene, the reaction can proceed through the ene pathway as above, or through the hetero-Diels-Alder pathway. For example, the condensation of 2,3-dimethyl-1,3-butadiene 103 with glyoxylate esters 99, 104, and 105 can proceed to form either a hetero Diels-Alder cycloadduct 106 or an ene product 107 (Fig. 9.35). 

As before, the homopolymer forming reaction involved the generation of an o-quinoidimethane from benzocyclobutene which in turn reacted with the double bond of a maleimide functionality on a second monomer to give chain extended AB material via a Diels-Alder pathway. The polymers prepared to date using this type of approach have been shown to have excellent thermal and mechanical properties and have been considered as potential candidates for use as matrix resins for advanced composites. This area has been investigated by the researchers at both the Air Force Wright Laboratories and the Dow Chemical Co. 

There is evidence that the mechanism of the last step more likely resembles the Diels-Alder pathway than the ring expansion pathway Bianchini et al. J. Am. Chem. Soc. 1991,113, 5127. 

Since then, the transient generation of 4 through the retro Diels-Alder pathway has been used a number of times for synthetic purposes. Decomposition of 36 in the presence of dimethyl fumarate gave 37 (mp 66°C) with dimethyl maleate 38 (mp 105°C) and 39 (mp 146-147°C) were obtained (ratio, 38/39 = 2 Decomposition of 19 in the presence of 40 (R = H)... 

Epoxynitrone (742) can be transformed to a positively charged heterodiene (743) using CF3S03SiMe3 or CF3S03Si(Bu )Me2 as electrophilic reagents (79HCA205). The diene adds to isolated double bonds to afford oxazines such as (744) via an inverse electron demand Diels-Alder pathway. Subsequent addition of cyanide to the iminium salt leads to a stable derivative (745) which can be converted through its mesylate (746) to an a-methylene y-lactone (747) on base treatment followed by acid hydrolysis (Scheme 171). 

Sarkar and coworkers reported a route from which heterocyclic analogs of 1-arylnaphthalene lignans were synthesized via a sequential Pummerer-Diels-Alder pathway, featuring furo[3,4-c]pyridines as intermediates. An example is depicted below <03JOC6919>. 

There are two different modes of cyclizations in hetero [4+2] cycloadditions involving Danishefsky s diene 1) concerted (pericyclic) and 2) stepwise. When carbonyl compounds are reacted with Danishefsky s diene, the stepwise pathway is often referred to as the Mukaiyama aldol reaction pathway. The concerted process is called the Diels-Alder pathway. The mode of cyclization in the case of Lewis acid catalyzed reactions depends on the Lewis acid itself and whether it is present in stoichiometric or catalytic amounts. The Mukaiyama aldol pathway has been... 

This thioaldehyde could be trapped by 1,3-dienes in good yields. With cyclopentadiene, a 7 3 endo exo kinetic stereoisomer mixture was obtained. Heating either pure isomer in toluene afforded a 3 7 endo exo equilibrium mixture via a retro-Diels-Alder pathway. 

Benzoxazolo[3,4-a]pyridinium salts (116) are known to give cycloadditions of the [4-1-2] and [3 -I- 2] type with alkenes and alkynes. The primary adducts were readily converted to alternative heterocyclic systems (121) and (122) which were usually the isolated major products (Scheme 24) <79JOCill, 82JOC3098>. The formation of oxazoles from the reaction of alkynic aldehydes with (116) was claimed to result from the Diels-Alder pathway with the carbonyl group acting as the dienophile <93JCS(P1)1839>. 

A multicomponent reaction of phosphonate 154, nitriles 155, aldehydes, and isocyanates 156 with base afforded N-3 functionalized DHPMs 157 via a Homer-Emmons/aza Diels-Alder pathway (Scheme 59) (03JCS(CC)2594). 

Steinhagen H, Corey EJ (1999) A convenient and versatile route to hydroquinolines by inter-and intramolecular aza-Diels-Alder pathways. Angew Chem Int Ed 38 1928-1931... 

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