1,3-Anionic cycloadditions

In a different type of procedure, 3 + 2 cycloadditions are performed with allylic anions. Such reactions are called 1,3-anionic cycloadditions.For example, a-... 

Organoelement Group Assisted 1,3-Anionic Cycloadditions 2.1 Scope of 1,3-Anionic Cycloadditions... 

Dithiol-2-imines, formation in 1,3-anionic cycloaddition reactions of a,/3-unsaturated thiolates 87UK267. 

Anionic cycloaddition reactions of a,j8-unsaturated selenolates and tellurolates in the synthesis of selenophene, tellurophene, and 1,3,4-sele-nadiazine derivatives 87UK267. 

If an ethyne (162) is used as starting material and the reaction is carried out without the presence of CXj (X = S or Se), the cycloaddition will take place as a 1,3-anionic cycloaddition between the ketene-intermediate and the acetylide, resulting in formation of a mixture of the (Z)- and ( )-fulvenes (163) (Scheme 39) <8izoR667,90BCJ835,93CL1469>. See also Scheme 49. 

C02Me R = Me or Ph) are formed from7V-(tosylmethyl)iminesTosCH2N=C-(OMe)R and electron-deficient olefins R CH=CHR in a base-catalysed 1,3-anionic cycloaddition, followed by elimination of toluene-p-sulphonic acid... 

With electron-deficient acetylenes, the dithioate anions can be involved in the reactions of both 1,3-anionic cyclo- and nucleophilic additions [550], The reactions of 1,3-anionic cycloaddition are typical provided that the central atom of [S-C-S] has aromatic substituents ensuring the anion stabilization [551,552], For instance, potassium pyrrole-l-carbodithioate selectively reacts (acetonitrile, -30°C, CH3COOH) with dimethyl ester of acetylenedicarboxylic acid to form rapidly polymerizing 2-(pyrrol-l-yl)-4,5-dimethoxycarbonyl-l,3-dithiol (Scheme 2.80) [552,553]. 

Azaallyl anion cycloadditions (13, 163).4 Nonstabilized 2-azaallyl anions (1) are readily generated by transmetallation of N-(trialkylstannyl)methylimines, prepared as shown in equation I, with a base such as butyl- or methyllithium. The... 

Carbonyl or cyano groups, of proven value in Diels-Alder reactions and 1,3-dipolar cycloadditions, are unsuitable for anionic cycloadditions owing to the pronounced nucleophilic and basic character of the anionic reagents. Instead of cycloaddition nucleophilic attack of these groups or deprotonation of the substrates would occur. This means that aromatic residues are indispensible which are practically unremovable after the cycloaddition and, unlike the carbonyl group, hardly unsuitable for subsequent synthetic steps. 

Organoelement groups like the phenylthio- or diphenylarsanyl group can be removed reductively from alkyl residues very well by Raney-Nickel (Scheme 8). But the transfer of this splitting reaction to our products of anionic cycloadditions - pyrrolidine derivatives - led to difficulties because, as demonstrated in Scheme 8, in addition to the splitting of the element carbon bond ring opening or aromatization occured. 

This cycloaddition can be performed with either the amino acid, the aldehyde, or the electron-poor alkene linked to the support. Intramolecular azaallyl anion cycloadditions have been used to prepare polycyclic systems on solid phase (Entries 5 and 7, Table 15.5). 

Azaallyl anion cycloadditions. Imines bearing one or more aryl groups are converted by LDA into 2-azaallyl anions. These anions undergo cycloaddition not only with activated alkenes,2 but can also undergo intramolecular cycloaddition with a double bond to form as-fused bicyclic pyrrolidines.3... 

The intramolecular anionic cycloaddition proceeded rapidly at — 78°C after transmetallation with n-BuLi. The resulting A-lithiopyrrolidine was A-alkylated with methyl iodide to give a 1 5 mixture of 13 and 14 in which 14 predominated. Without purification, the isopropylidene group was cleaved from the unpurified mixture of 13 and 14, and the resulting... 

Another method involves anionic cycloaddition of triethylammonium salts of dithioacids or dithiocarbonates to dimethyl acetylenedicarboxylate to produce the 1,3-dithioles (302) (81ZOR1788, 80ZOR2616). Also dithiocarboxylic esters react with dimethyl acetylenedicarboxylate giving substituted 1,3-dithioles (303) (80ZOR2047,79ZOR1106). 

Anionic cycloaddition of methyl isocyanoacetatc to diethoxyacetonitrile gives methyl 5-diethoxymethylimidazole-4-carboxylate in high yield. The reaction is quite general for nitriles which are sufficiently activated by —I or —M effects, thus aliphatic nitriles do not react. The reactions are also strongly dependent on the base and solvent employed. Whereas n-butyllithium in THF at —70°C is unsuccessful in effecting the above transformation, potassium hydride in dielyme works very well, giving an 82% yield (Scheme 4.2.11) [33]. 

Imidazole-4-carboxylates have been made from amidines derived from or-ainino acids (see Section 2.2.1 and Table 2.2.1), by Claisen rearrangement of the adduct formed when an arylamidoxime reacts with a propiolate ester (see Section 2.2.1 and Scheme 2.2.6), from a-aminocarbonyls with cyanates or thiocyanates (see Section 4.1 and Table 4.1.1), from a-oximino- 6-dicarbonyl compounds heated with an aUcylamine (see Section 4.1 and Scheme 4.1.7), and by anionic cycloaddition of an alkyl isocyanoacetate to diethoxyacetonitrile (see Section 4.2 and Scheme 4.2.11 see also Scheme 4.2.12). A further useful approach is to use an appropriate tricarbonyl compound with an aldehyde and a source of ammonia (see Chapter and Scheme 5.1.1). Irradiation of 1-alkenyltetrazoles bearing an ester substituent may have applications (see Section 6.1.2.3). 

Several examples have appeared in the literature in which this linker has been employed in combinatorial chemistry strategies. Thus, it has been used in a Pd-mediated three-component coupling strategy for the solid-phase synthesis of tropane derivatives [46], in the solid-phase synthesis of aspartic acid protease inhibitors [47], in the attachment of cholic acid as a template for a combinatorial approach [48] and, more recently, in the solid-phase synthesis of pyrrolidines via 2-aza allyl anion cycloadditions with alkenes [49]. 

Intramolecular 2-aza-allyl anion cycloaddition was employed for the synthesis of the crinine-type alkaloids ( )-crinine (135) 142a) and (-)-amabiline (145) 142c) and has been reported to provide potential precursors of 6a-epi-pretazettine (314) and 6a-ep/-precriwelline (methoxy epimer of 314) 142b). 

Similarly, the anionic cycloaddition of methyl isocyanoacetate to diethoxyacetonitrile gives methyl... 

For our anthracycline synthesis, the anionic cycloaddition reaction of the homophthalic anhydrides and quinone dienophiles, leading to the aglycone skeletons of anthracyclines, plays a key role. Table 1 shows the results of the cycloaddition reactions of the homophthaUc anhydrides with quinone... 

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