DEAD, cycloaddition

Dodd and co-workers (5) reported the first known synthesis of 11//-indolizino[8,7-h]indoles by the cycloaddition reaction of a nonstabilized ylide 21 and diethylacetylene dicarboxylate (DEAD). The azomethine ylide, formed by the alkylation of the 3,4-dihydro-p-carboline (22) with trimethylsilyl methyl triflate to the triflate salt, followed by in situ desilyation with cesium fluoride, underwent cycloaddition with DEAD at low temperature. The expected major cycloadduct 23 was isolated, along with quantities of a minor product 24, presumed to have been formed by initial reaction of the ylide with 1 equiv of DEAD and the intermediate undergoing reaction with a further equivalent of DEAD before cyclization. Dodd offers no explanation for the unexpected position of the double bond in the newly generated five-membered ring, although it is most likely due to post-reaction isomerization to the thermodynamically more stable p-amino acrylate system (Scheme 3.5). 

Avalos and co-workers (220-228) extensively investigated the 1,3-dipolar cycloaddition chemistry of 2-aminothioisomiinchnones with both acetylenic and olefinic dipolarophiles. For example, sugar derivatives of the mesoionic imi-dazo[2,l-Z7]thiazolium-3-olate system react regioselectively with a variety of acetylenic dipolarophiles [DMAD, diethyl azodicarboxylate (DEAD), methyl propiolate, ethyl phenylpropiolate] to give the corresponding imidazo[l,2-a]pyr-idin-4-ones (e.g., 323) following sulfur extrusion from the not isolable cycloadducts (220). Similarly, these thioisomtinchnones react with diethyl azodicarboxylate and arylisocyanates in the expected fashion (221), and also with aryl aldehydes to form episulfides (222). 

Anderson and co-workers86 used the cycloaddition of acetylenic esters to 19a and 19 (R = COPh) in the synthesis of the antimitotic agent Verrucarin E (28). The pyrrole 19a and DMAD gave 35% of 21a, whereas 19 (R = COPh) gave 67% of 21 (R = COPh) and 23% of recovered starting material 1-benzoylpyrrole gave 54% of 29 with DEAD. Further transformations produced the natural product. 

The intermolecular Diels-Alder reactions of 1,3-dithioles (163) with DMAD and DEAD produced the first 7//-thieno[2,3-c]thiopyran-7-thiones (164) and 47/-thieno [3.2-c]thiopyran-4-thiones (165), the structures of which were confirmed by X-ray diffraction. Further work on the mechanism of the cycloaddition and subsequent rearrangement is in progress (Scheme 46).191... 

The use of pyran intermediates for the synthesis of these ring systems has presented few examples. The [4 + 2] cycloaddition of 5-ethenyl-3,4-dihydro-2//-pyrans with DEAD yields compounds (500) <86CB3204>. Reaction of the esters (501) with hydrazine hydrate gave the pyranodiazines (502) <86MI 716-01). 

In a study of the diene-transmissive Diels-Alder reactions <90BCJ284>, cycloaddition of a substituted 1,4-dihydrothiadiazine and maleic anhydride or A-(p-methoxyphenyl)maleimide gave substituted bicyclo[4.4.0]dec-10-enes (107) in good yield (Equation (59)) <90BCJ284>. The starting thiadiazine is itself a Diels-Alder adduct of an a,(l a, / -unsaturated thioketone and dead. 

Cycloaddition. An unusual transformation at the conclusion of a stephacidin-A synthesis involves a cycloaddition that is prosecuted by BuyP-DEAD. 

Reports of 1,2,3,5-thiatriazines are rare. However, the cycloaddition of a thiodiazabutadiene (59) with DEAD yields such a product (60) in 90% yield (Equation (9)) <89TL6923>. 

There is only a single example of this ring system in recent literature and that is one obtained from the cycloaddition of 30 with diethyl azodicarboxylate (DEAD) (Scheme 30) <1996CC1705>. 

We quickly came to a conclusion that this imique reactivity of azodicarboxylates on water was a fairly general phenomenon. For example, the cycloaddition of diethyl azodicarboxyiate (DEAD, 41) with quadricyciane also shows a large magnitude of on water acceleration (Fig. 11.11). The ene reaction of DEAD with /3-pinene (43) is also considerably faster on water - product formation is complete within 3 h, as compared to 1.5 days for the solventless reaction. 

We also monitored the progress of many of these reactions by NMR in order to get a more accurate measure of rate acceleration. Accordingly, the cycloaddition of quadricyclane with DEAD (49% solution in toluene) was examined both on water and in the absence of any other solvent (Fig. 11.12). A clear rate difference is observed between the two reactions, indicating that the on water effect is operative even when a nonpolar solvent comprises part or most of the organic phase. ... 

A related method with a resin-bound miinchnone intermediate was applied to the synthesis of 1,2,4-triazoles. Cycloaddition of resin-bound miinchnones with the N=N double bond of the dipolarophilic diethyl diazocarboxylate (DEAD) or 4-phenyl-4//-1,2,4-triazohne-3,5-dione gave resin-bound 1,2,4-triazoles. Traceless cleavage of the products from the 2-methoxy-substituted resin was achieved with 30% trifluoroacetic acid (Scheme 11.22). ... 

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