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Volumn 76, Issue 3, 2011, Pages 948-962

Nucleophilic ring-opening of epoxide and aziridine acetates for the stereodivergent synthesis of β-Hydroxy and β-Amino γ-Lactams

Author keywords

[No Author keywords available]

Indexed keywords

ASYMMETRIC SYNTHESIS; AZIRIDINES; CHEMICAL EFFICIENCY; CHIRAL EPOXIDES; FUNCTIONALIZED; HETEROCYCLES; NUCLEOPHILIC RING-OPENING; REDUCTIVE CYCLIZATION; STEREODIVERGENT SYNTHESIS; STEREOSELECTIVE SYNTHESIS;

EID: 79851479427     PISSN: 00223263     EISSN: 15206904     Source Type: Journal    
DOI: 10.1021/jo102267h     Document Type: Article
Times cited : (31)

References (118)
  • 32
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    • (2004) Tetrahedron , vol.60 , pp. 2701-2743
    • Hu, X.E.1
  • 41
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    • Lu, P. Tetrahedron 2010, 66, 2549-2560.
    • (2010) Tetrahedron , vol.66 , pp. 2549-2560
    • Lu, P.1
  • 65
    • 79851501184 scopus 로고    scopus 로고
    • 4of the corresponding ß,γ-unsaturated carboxylic acids see the Experimental Section)
    • 4of the corresponding ß,γ-unsaturated carboxylic acids see the Experimental Section).
  • 85
    • 79851492989 scopus 로고    scopus 로고
    • 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)
    • 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).
  • 87
    • 79851474125 scopus 로고    scopus 로고
    • 4, HOAc, or TMSClunder a variety of solvents (DMF, acetone, water, and aqueous solutions), but the several methodologies tested gave poor results
    • 4, HOAc, or TMSClunder a variety of solvents (DMF, acetone, water, and aqueous solutions), but the several methodologies tested gave poor results.
  • 90
    • 79851491997 scopus 로고    scopus 로고
    • 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)
    • 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)
  • 91
    • 79851502352 scopus 로고    scopus 로고
    • 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
    • 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
  • 94
    • 79851485335 scopus 로고    scopus 로고
    • 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)
    • 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).
  • 100
    • 79851498952 scopus 로고    scopus 로고
    • 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
    • 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
  • 102
    • 79851490559 scopus 로고    scopus 로고
    • 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
    • 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.
  • 105
    • 79851489754 scopus 로고    scopus 로고
    • 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)
    • 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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