Stereoselective uncatalyzed synthesis of 2,3-unsaturated-4-N-substituted- β-O-glycosides by means of a new D-galactal-derived N-(mesyl)-aziridine

Journal of Organic Chemistry

Volumn 71, Issue 4, 2006, Pages 1696-1699

  Di Bussolo, Valeria ^a   Romano, Maria Rosaria ^a   Favero, Lucilla ^a   Pineschi, Mauro ^a   Crotti, Paolo ^a  

^a UNIVERSITY OF PISA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

D-GALACTAL-DERIVED ALLYLIC AZIRIDINE; O-NUCLEOPHILES;

ALCOHOLS; STEREOCHEMISTRY; SUGARS; SYNTHESIS (CHEMICAL);

NITROGEN COMPOUNDS;

2,3 UNSATURATED BETA O GLYCOSIDE; ALCOHOL; AZIRIDINE DERIVATIVE; BETA O GLYCOSIDE; DEXTRO GALACTAL; GALACTOSE; GLYCOSIDE; MONOSACCHARIDE; N MESYL AZIRIDINE; UNCLASSIFIED DRUG;

ADDITION REACTION; ARTICLE; CATALYSIS; CHEMICAL MODIFICATION; CHROMATOGRAPHY; GLYCOSYLATION; REACTION ANALYSIS; SEPARATION TECHNIQUE; STEREOCHEMISTRY; STEREOISOMERISM; SYNTHESIS;

ALCOHOLS; AZIRIDINES; GALACTOSE; GLYCOSIDES; MONOSACCHARIDES; STEREOISOMERISM;

EID: 33644505774     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo051877p     Document Type: Article

References (28)

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9. On the basis of the absolute configuration of the corresponding C(3) and C(4) aziridine carbons, aziridines 1α and 1β are considered to be derived from D-allal and D-galactal, respectively, which present the same absolute configuration at the same carbons.
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14. 6 with a dried alkaline resin (MP-carbonate) showed the presence of only a limited amount (15%) of aziridine 1β. together with products deriving from its extensive decomposition. The use in this experiment of t-BuOK (1 equiv) as the base led to a complex reaction mixture containing glycoside 13β (10-15%), the product of the addition of t-BuOH, formed in the reaction mixture, to the in situ formed aziridine 1β.
15. The same reaction carried out under standard conditions turned out to be extremely sluggish, to the point that after 36 h at room temperature, the starting azido alcohol 8 was still present (20%). Longer reaction times led only to complex reaction mixtures.
16. 4-EtOH) turned out to be decidedly less stereoselective toward the desired trans-azido alcohol 5.
17. 14
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19. 1H NMR spectrum of the respective crude reaction mixture, reasonably due to the corresponding isomeric α-anomer 13α, 15-17α (less than 1%), respectively.
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24. Theoretical conformational studies, in a vacuum and in the presence of the solvent, carried out for simplicity on the 6-deoxy-N-acetyl aziridine 23, which is structurally related to aziridine 1β, revealed that aziridine 23 exists only in the ring conformation 23′-exo2 with the methyl group equatorial and with a preference (>98%) for the N-acetyl group in the exo position (see the Supporting Information). The results obtained with aziridine 23 can reasonably be extended to aziridine 1β and allow us to consider aziridine 1β as existing only in the corresponding conformation 1β′ (Scheme 6), corresponding to 23′-exo2, as stated in the text. Diagram presented.
25. + has little or no influence on the β-stereoselectivity observed under typical protocol B reaction conditions [see, for comparison, entries 1 (MeOH) and 3 (i-PrOH), Table 1].
26. In conformation 1β″, the corresponding coordination-driven nucleophilic attack on C(1) (route b′) would correspond to a more favored pseudoaxial attack (Scheme 6).
27. In addition to the reasonable presence of both α- and β-anomers 14α (15%) and 14β (45%) (see routes a and b, respectively, and discussion in the text), the unexpected presence of the anti-1,2-adduct 20 (40%) in this reaction could be attributed to the acidity of phenol, which determines, in the reaction mixture, a more pronounced protonation of the aziridine nitrogen with concomitant polarization of the aziridine C(3)-N bond in the direction of the C(3) allylic carbon. Subsequent nucleophilic attack on C(3) by a free, noncoordinated PhOH, necessarily occurring in an anti fashion (route c), leads to the trans-phenoxy sulfonamide 20, as experimentally found. Diagram presented.
28. 3 is larger than the β-stereoselectivity presently obtained with aziridine 1β, under the same conditions.