Diels-Alder type cleavage

These data show that villamine is a 2,7-dihydropleiocarpamine derivative. The thermal cleavage to pleiocarpamine (196) and macroline (215) is considered to be of the retro-Diels-Alder type. 

Bisdeoxyflavoskyrin (34), obtained by the Diels-Alder-type dimerization reaction of dihydrochrysophanol (46), was subjected to base treatment by keeping it in pyridine for three weeks with occasional warming. The solution turned yellow and showed a pale yellow fluorescence. Bisdeoxyrugulosin (47) was obtained in low yield (less than 10%). This conversion involves C-O bond cleavage followed by oxidation of the hydroquinone moiety and then Michael-type condensation between two monomeric moieties. The partially hydrogenated bisanthraquinone 48 is the direct substrate of the... 

Amino alcohols are also good substrates for aziridination under Mitsunobu conditions. The rfs-1,4-amino alcohols 48, obtained by reductive cleavage of the nitrogen-oxygen bonds of the hetero Diels-Alder adducts 47, underwent syn-SN2 -type displacement on treatment with PPh3 and DEAD to give cyclic vinylaziridines 49 (Scheme 2.15) [27]. 

Examples of the oxidative cleavage/bis-hetero-Diels-Alder domino sequence of compounds of type 7-124 to give acetals of type 7-125 are listed in Scheme 7.34. This shows that the reaction is high-yielding and can be carried out under rather mild conditions. 

The enhanced reaction in ethanol is attributed to weakening of the tight, intramolecular hydrogen bond which is believed to facilitate photoenolization of 2-hydroxybenzophenone. t>-Hydroxybutyrophenone undergoes photoenolization in preference to Type II cleavage.25 The enol of o-benzylbenzo-phenone (2) forms a Diels-Alder adduct with dimethyl acetylenedicarboxylate, indicating that reaction with a reactive substrate is possible.30... 

Finally, a thia Diels-Alder reaction representing a less common cycloaddition type in natural product synthesis shall be discussed. Thus, Vedejs et al. have included such a cycloaddition into an elegant strategy aimed at the synthesis of macrocyclic [ll]-cytochalasans such as zygosporin E 7-76 [536-538]. Thus, release of the thioaldehyde 7-73 from its phenacyl sulfide precursor in the presence of the silyloxydiene 7-74 yielded 7-75 as 2 1 mixture with its C20 epimer. Fortunately, equilibration of this mixture raised the ratio up to 10 1. Several subsequent steps yielded the tetracyclic intermediate 7-77 cleavage of its thioether moiety then liberated the 11-membered macrocycle present e.g. in zygosporin E 7-76 (Fig. 7-16). 

A type 2 intramolecular /V-acylnitroso Diels-Alder reaction of hydroxamic acid 177 followed by catalytic hydrogenation of the double bond was employed for the synthesis of substituted bridged bicyclic derivative 178, as a single diastereomer (Scheme 75 <2002OL2637>). Cleavage of the N-O bond was performed by reduction with Na(Hg) amalgam and provided m-3,7-disubstituted azocane 9, as a single isomer in 80% yield. 

Methods for the reductive cleavage of the N—O bond in hydroxylamines have assumed increasing importance in synthesis because it is a key step in routes based on cycloaddition of nitrones and nitroso compounds. Inter- and intra-molecular cycloadditions of nitrones lead to the formation of tetrahydroisox-azoles (Scheme 25) these compounds are then converted into amino alcohols by reductive cleavage of the N—-O bonds. This type of reaction sequence has been exploited in the synthesis of a number of alkaloids.Nitroso compounds, particularly those activated by electron-withdrawing substituents, act as dienophiles in the Diels-Alder reaction (Scheme 26) and the cycloadducts can be used as synthetic intermediates by cleaving the N—O bonds. 

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