Cycloadditions imino esters

Dipolar cycloaddition of nitrile oxide at the C=N bond of indole imino esters 130, followed by elimination of the alcohol moity gives oxadiazole derivatives 131 (Scheme 1.26) (298). Reaction of N-arylbenzamidines with arenenitrile N-oxides (generated in situ from oximoyl chlorides) produce unstable 5-amino-4,5-dihydro-1,2,4-oxadiazoles which, on aqueous acidic treatment hydrolyze to open-chain N-benzoyloxy-N -arylareneamidines (299). 

In the area of [3 + 2]-cycloadditions (1,3-dipolar cycloadditions), chiral silver catalysts have been utilized extensively for the enantioselective formation of five-membered rings from prochiral substrates. For example, Zhang and co-workers360 have reported the highly enantioselective Ag(i)-catalyzed [3 + 2]-cycloaddition of azomethine ylides to electron-deficient alkenes. Thus, reaction of ct-imino esters 442 with dimethyl maleate in the presence of catalytic amounts of silver(i) acetate and the chiral bisferrocenyl amide phosphine 443 provided the chiral pyrrolidines 444 with high stereoselectivities and chemical yields (Scheme 131). Only the endo-products were isolated in all cases. 

Chiral Auxiliary for Asymmetric Induction. Numerous derivatives of (—)-8-phenylmenthol have been utilized for asymmetric induction studies. These include inter- and intramolecular Diels-Alder reactions, dihydroxylations, and intramolecular ene reactions of a,p-unsaturated 8-phenylmenthol esters. These reactions usually proceed in moderate to good yield with high diastereofacial selectivity. a-Keto esters of 8-phenylmenthol (see 8-Phenylmenthyl Pyruvate) have been used for asymmetric addition to the keto group, as well as for asymmetric [2 -F 2] photoadditions and nucleophilic alkylation. Ene reactions of a-imino esters of 8-phenylmenthol with alkenes provide a direct route to a-amino acids of high optical purity. Vinyl and butadienyl ethers of 8-phenylmenthol have been prepared and the diastereofacial selectivity of nitrone and Diels-Alder cycloadditions, respectively, have been evaluated. a-Anions of 8-phenylmenthol esters also show significant diastereofacial selectivity in aldol condensations and enantiose-lective alkene formation by reaction of achiral ketones with 8-phenylmenthyl phosphonoacetate gives de up to 90%. ... 

For the preparation of optically active P-lactams (154) with relative trans configuration (e.g. for the synthesis of (+)-PS-5 ), the [2 -i- 2] cycloaddition of ester enolates such as (152) and A -trialkylsilyl-imines (153) is an appropriate strategy (Scheme 70).In this case, chirality is introduced by the imino moiety. 

Azomethine ylides are very important 1,3-dipoles, and they are usually used to react with alkenes leading to the formation of the highly substituted pyrrolidine derivatives [17]. A novel and practical process for the 1,3-dipolar cycloaddition of azomethine ylides with alkenes had been reported by j0rgensen and coworkers [18]. They proposed that a dipol-chiral base ion pair would be generated between a-imino ester-metal complex and a cinchona alkaloid, and subsequent cycloaddition with dipolarophile would take place in a stereoselective manner (Scheme 10.13). 

Akiyama et al. reported the Cu(I)-catalyzed enan-tioselective [2 + 2]-cycloaddition of 1-methoxy-allenylsilane 372 with a-imino ester 373 (Scheme 118).182 In the presence of catalytic amounts of [Cu-(MeCN)4]BF4 and (A)-Tol-BINAP the reaction of 2 equiv of 1-methoxyallenylsilanes 372 with a-imino ester 373 afforded azetidine derivatives 374 in good to high yields with high enantioselectivities. 

Enantioselective 1,3-dipolar cycloaddition of imino esters to electron-deficient alkenes is one of the most powerful and atom-economical C-C bond-forming reaction that facilitates the synthesis of a range of structurally and stereochemically rich pyrrolidines [35]. Wang developed the asymmetric 1,3-dipolar cycloaddition of naphthalene-1,4-dione (116) with imino esters 117 catalyzed by the Cu(I) complex of ferrocenyl ligand 115, followed by silica-gel-promoted aromatization [39]. 

Scheme 1.11 Cycloaddition of azomethine ylides derived from imino esters with methyleneindolinones.

In 2010, Arai et al investigated a catalytic asymmetric exo -selective virtual [3 + 2] cycloaddition of imino esters with trans-nitroalkenes. Usually, when... 

Resin-bound maleimide has been used as a dipolarophile in the synthesis of N-substituted pyrrolidines as well (Scheme 11.2). " Cycloaddition with a-imino esters, which were generated from aryl aldehydes and amino acid esters, yielded resin-bound pyrrolidines. The compounds were bound to the acid-cleavable SASRIN resin with an ester linkage and then cleaved from the resin as carboxylic acids with highly diluted trifluoroacetic acid. 

More recently, a study by Lassaletta, Fernandez and co-workers showed that enantioselective NHC-Ag catalysis was not an impossible goal. Hence, the use of polydentate thiolato-NHCs 11-14 afforded good enantioselectivities in the 1,3-dipolar cycloaddition of azomethine ylides with acrylates (Scheme 11.4). ° Ligand 11 systematically produced the highest ee s (up to 80% ee) with a number of imino esters. The authors proposed that a tridentate SCS coordination of these C2-symmetric ligands onto the silver center was key for obtaining the good chiral induction observed in the cycloaddition. 

Rhodium(I)-catalyzed [2 + 2 - - 2] cycloaddition of A(-propargyl maleimide and a 1,6-diyne followed by silver(I) acetate-mediated 1,3-dipolar cycloaddition with imino esters afforded endo cycloadducts in good yields (Scheme 4.39) [43]. 

Using a related cycloaddition protocol, Schreiber found that the chiral P,N-ligand QUINAP (121) exhibited comparable high enantioselectivity in silver-catalyzed dipolar cycloadditions (Equation 6) [98], The highest asymmetric induction was observed for tert-hutyl acrylate (119) with aromatic imino esters such as 118. The process shows a wide substrate scope, as the transformation was tolerant both of a-substitution in 118 and of /3-substitution of the acrylate dipolarophile 119. Carreira has crafted and studied the use of a family of atropisomeric P,N-ligands, as exemplified by 122 [99]. 

Microwave-induced 1,3-dipolar cycloadditions involving azomethine ylides have been widely reported in the literature. Bazureau showed that imidates derived from a-amino esters 120, as potential azomethine ylides, undergo 1,3-dipolar cyclo-additions with imino-alcohols 121 in the absence of solvent under microwave irradiation. This reaction leads to polyfunctionalized 4-yliden-2-imidazolin-5-ones 122 (Scheme 9.36) [87]. 

The reaction of 5(4H)-oxazolones (32) and miinchnones with triphenylvinylphos-phonium bromide (33) provides a mild synthesis of substituted pyrroles (34) (Scheme 11). The cycloaddition-elimination reactions of 5-imino-l,2,4-thiadiazolidin-3-ones with enamines and ester enolates produce 2-iminothiazolidines. " Chiral isomtinchnone dipoles show jr-facial diastereoselectivity with IV-phenyl- or A -methyl-maleimide in refluxing benzene. ... 

Carrie and co-workers studied the cycloaddition of oxime esters derived from methyl cyanoacetate and malonate esters 82 (Scheme 8.20) with diazomethane and some monosubstituted derivatives. Thermally labile 1,2,3-triazolines 83 were obtained when tosyloxy- and benzoyloxyimines were used (141), while methyl acetoxyimino-cyanoacetate (82, X = CN, Y = C02Me, = Ac) gave products derived from both a 1,2,3- and a 1,2,4-triazoline, depending on the stmcture of the diazo compound (142). Not unexpectedly, diazomethane reacted with the corresponding imino-malononitrile (82, X = Y = CN) system at the nitrile function rather than at the C=N bond (143). 

Dipolar cycloaddition reactions between nitrile oxides and aUcenes produce 2-isoxazolines. Through reductive cleavage of the N—O bond of the 2-isoxazohnes, the resulting heterocycles can be readily transformed into a variety of important synthetic intermediates such as p-hydroxy ketones (aldols), p-hydroxy esters, a,p-unsaturated carbonyl compounds, y-amino alcohols, imino ketones and so forth (7-12). 

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