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79851492989
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To compare the relative nucleophilicity of azide versus bromide ions in the Mg(ClO4)2-mediated bromolysis of epoxide acetate (±)-1b, the reaction was carried out with NaBr (to correlateNaN3), which was shown to be as good as LiBr. These observations support the fact that bromide ion is much more nucleophilic than azide under the studied conditions, with the former consuming the epoxide (±)-1b in 1 h at 0-25 °C (Table 4, entry 1while the latter takes 8 h at 80 °C (Table 2, entry 5)
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To compare the relative nucleophilicity of azide versus bromide ions in the Mg(ClO4)2-mediated bromolysis of epoxide acetate (±)-1b, the reaction was carried out with NaBr (to correlateNaN3), which was shown to be as good as LiBr. These observations support the fact that bromide ion is much more nucleophilic than azide under the studied conditions, with the former consuming the epoxide (±)-1b in 1 h at 0-25 °C (Table 4, entry 1while the latter takes 8 h at 80 °C (Table 2, entry 5).
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87
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4, HOAc, or TMSClunder a variety of solvents (DMF, acetone, water, and aqueous solutions), but the several methodologies tested gave poor results
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4, HOAc, or TMSClunder a variety of solvents (DMF, acetone, water, and aqueous solutions), but the several methodologies tested gave poor results.
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0001238829
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79851491997
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Interestingly, preferential formation of aziridine acetate was observed even when acetonitrile with high water content was used as the reaction medium. This observation implies that, under the studied conditions, the intermediate iminophosphorane (see refs 10c and 15edid not suffer hydrolysis, which might lead to the corresponding γ-amino ester and ultimately to the γ-lactam (±)-16a-anti by spontaneous cyclization (see Scheme 8)
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Interestingly, preferential formation of aziridine acetate was observed even when acetonitrile with high water content was used as the reaction medium. This observation implies that, under the studied conditions, the intermediate iminophosphorane (see refs 10c and 15edid not suffer hydrolysis, which might lead to the corresponding γ-amino ester and ultimately to the γ-lactam (±)-16a-anti by spontaneous cyclization (see Scheme 8)
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91
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79851502352
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The relative stereochemistry of the ring substituents in the aziridines was determined by 1H NMR on the basis of literature reports. For instance, the coupling constants observed for the methyne protons in the isomeric anti-.0-4.0 Hzand syn-aziridines (6.5-7.2 Hzwere of similar magnitudes as the model compounds found in the literature
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The relative stereochemistry of the ring substituents in the aziridines was determined by 1H NMR on the basis of literature reports. For instance, the coupling constants observed for the methyne protons in the isomeric anti-.0-4.0 Hzand syn-aziridines (6.5-7.2 Hzwere of similar magnitudes as the model compounds found in the literature
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94
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79851485335
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Treatment of the ß-amino-γ-azido ester (±)-13-anti with tosyl chloride and a base yielded theN-tosylamino (±)-14-anti, thus confirming that the two azido esters have the same anti configuration (see the Experimental Section)
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Treatment of the ß-amino-γ-azido ester (±)-13-anti with tosyl chloride and a base yielded theN-tosylamino (±)-14-anti, thus confirming that the two azido esters have the same anti configuration (see the Experimental Section).
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79851493743
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Published patents (see ref 10d and EP 0947505A2 CAS 131:271805)
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Published patents (see ref 10d and Mitsuhashi, S.; Sumi,K.;Moroi, T.; Sotoguchi, T.; Miura, T. Eur.Pat.Appl. EP 0947505A2, 1999 (CAS 131:271805)
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describe the hydrogenation of ethyl γ-azido-ß- hydroxybutanoate followed by treatment of the corresponding γ-amino ester intermediate (see the analogous methyl ester in Figure 1, R=H;W=OHwith either strong bases or acids to achieve cyclization to ß-hydroxy γ-lactam, an important intermediate for the synthesis of carbapenem antibiotics
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describe the hydrogenation of ethyl γ-azido-ß- hydroxybutanoate followed by treatment of the corresponding γ-amino ester intermediate (see the analogous methyl ester in Figure 1, R=H;W=OHwith either strong bases or acids to achieve cyclization to ß-hydroxy γ-lactam, an important intermediate for the synthesis of carbapenem antibiotics
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However, in our case, mild palladium-catalyzed hydrogenation of ethyl γ-azido-ß-hydroxybutanoate (prepared by reduction of the corresponding ketone with NaBH4 as described in Experimental Section), furnished the ß-hydroxy γ-lactam in ~75% yield after 1 h at 25 °C without any additive
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However, in our case, mild palladium-catalyzed hydrogenation of ethyl γ-azido-ß-hydroxybutanoate (prepared by reduction of the corresponding ketone with NaBH4 as described in Experimental Section), furnished the ß-hydroxy γ-lactam in ~75% yield after 1 h at 25 °C without any additive.
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In contrast to the other γ-lactams synthesized here, which are all crystalline solids, (±)-23-anti is a low-melting point solid that was purified by chromatography and further transformed to ß-tosylamino γ-lactam (±)-24- anti by direct tosylation, thus proving the structural relationship between them (see the Experimental Section)
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In contrast to the other γ-lactams synthesized here, which are all crystalline solids, (±)-23-anti is a low-melting point solid that was purified by chromatography and further transformed to ß-tosylamino γ-lactam (±)-24- anti by direct tosylation, thus proving the structural relationship between them (see the Experimental Section).
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