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Synlett 2018; 29(15): 2043-2045
DOI: 10.1055/s-0037-1610648
letter
© Georg Thieme Verlag Stuttgart · New York

Length Matters: One Additional Methylene Group in a Reactant is Able to Affect the Reactivity Pattern and Significantly Increase the Product Yield

Elena V. Stepanova
a   N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, Leninsky prosp. 47, Moscow 119991, Russian Federation   Email: leonid.kononov@gmail.com
b   Research School of Chemistry & Applied Biomedical Sciences, National Research Tomsk Polytechnic University, Lenin Avenue 30, Tomsk 634050, Russian Federation
,
Nikita M. Podvalnyy
a   N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, Leninsky prosp. 47, Moscow 119991, Russian Federation   Email: leonid.kononov@gmail.com
,
Polina I. Abronina
a   N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, Leninsky prosp. 47, Moscow 119991, Russian Federation   Email: leonid.kononov@gmail.com
,
Leonid O. Kononov  *
a   N. D. Zelinsky Institute of Organic Chemistry of the Russian Academy of Sciences, Leninsky prosp. 47, Moscow 119991, Russian Federation   Email: leonid.kononov@gmail.com
› Author AffiliationsThis work was financially supported by the Russian Science Foundation (Project No. 16-13-10244).
Further Information

Publication History

Received: 05 April 2018

Accepted after revision: 29 June 2018

Publication Date:
02 August 2018 (online)

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Abstract

The outcome of the nucleophilic opening of 3-O-benzoyl-β-d-arabinofuranose 1,2,5-orthobenzoate with 4-(ω-chloroalkoxy)phenols (SnCl4, CH2Cl2, –25 °C) unusually strongly depends on the length of the methylene chain of the nucleophile. The presence of one extra methylene group in the molecule of 4-(3-chloropropoxy)phenol [as compared to 4-(2-chloroetoxy)phenol] results in four-fold reduction in the reaction time and five-fold increase in the yield of a selectively protected monosaccharide glycoside with a hydroxy group at C-5, which is a valuable building block for the synthesis of oligoarabinofuranosides related to mycobacterial arabinans. Possible reasons and consequences of this finding are discussed.

Key words

mycobacterial arabinans - oligosaccharides - glycosylation - orthoesters - phenols - reactivity pattern - substituent effects - solution structure

Supporting Information

    Supporting information (NMR spectra of compounds 3a, 3b, 4a, and 4b as well as copies of TLCs of reaction mixtures) for this article is available online at https://doi.org/10.1055/s-0037-1610648.
  • Supporting Information

Primary Data

    Spectrometer files (FIDs and associated files) for the 1H, 13C, COSY, HSQC, and HMBC NMR spectra of compound 3b for this article are available online at https://doi.org/10.1055/s-0037-1610648 and can be cited by using the following DOI: 10.4125/pd0100th.
  • Primary Data
 

  • References and Notes

  • 1 New address: University of Zurich, Institute of Physiology, Winterthurerstraße 190, 8057 Zürich, Switzerland.
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  • 9 Typical Glycosylation Procedure 3-O-Benzoyl-β-d-arabinofuranose 1,2,5-orthobenzoate (1)7b, c(200 mg, 0.588 mmol) and phenol 2a or 2b (2.94 mmol)8 were dried in vacuo, and anhydrous CH2Cl2 (4 mL) was added. The reaction mixture was cooled to –25 °C and 1 M solution of SnCl4 (68 μL, 68 μmol) in CH2Cl2 was slowly added to the resulting mixture with a syringe. The reaction mixture was stirred at –25 °C (for 4 h in the case of 2a and for 1 h in the case of 2b) until total consumption of 1 (Rf 0.58, light petroleum/EtOAc 3:1). The reaction mixture was diluted with saturated NaHCO3 (15 mL), allowed to warm to r.t., and then CH2Cl2 (40 mL) was added. The organic layer was separated, washed with 5% NaOH (4×50 mL), dried with Na2SO4, filtered, and concentrated under reduced pressure. The residue was separated by silica gel column chromatography (light petroleum/EtOAc 3:1 → 1:3) to give monosaccharide glycoside 3a6h (43 mg, 14%) or 3b (237 mg, 77%) along with oligosaccharide glycosides 4a (m ≥ 2, 85%)6b,f or disaccharide derivative 4b (m = 2, 13%), respectively (see Supporting Information for more details). 4-(3-Chloropropoxy)phenyl 2,3-di-O-benzoyl-α-d-arabinofuranoside (3b) Colorless oil, [α]D 25 +29.7 (c 1.0, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 2.23 (tt~q, 2 H, J = 6.1 Hz, C H 2CH2Cl), 3.75 (t, 2 H, J = 6.4 Hz, CH2Cl), 3.96–4.05 (m, 2 H, H-5), 4.09 (t, 2 H, J = 5.8 Hz, OC H 2CH2), 4.50 (ddd~dt, 1 H, J = 3.8, 4.6 Hz, H-4), 5.57 (dd, 1 H, J = 4.6, 1.2 Hz, H-3), 5.80 (d, 1 H, J = 1.2 Hz, H-2), 5.83 (s, 1 H, H-1), 6.87 (d, 2 H, J = 9.1 Hz, OC6H4O), 7.06 (d, 2 H, J = 9.1 Hz, OC6H4O), 7.40–7.55 (m, 4 H, Bz), 7.56–7.69 (m, 2 H, Bz), 7.99–8.18 (m, 4 H, Bz) ppm. 13C NMR (75 MHz, CDCl3): δ = 32.3 ( C H2CH2Cl), 41.5 (CH2Cl), 62.2 (C-5), 64.9 (O C H2CH2), 77.6 (C-3), 81.9 (C-2), 84.4 (C-4), 104.9 (C-1), 115.5, 118.4 (OC6H4O), 128.5, 128.6, 129.0, 129.1, 129.9, 130.0, 133.62, 133.66 (Bz), 150.2 (C-1 OC6H4O), 154.4 (C-4 OC6H4O), 165.3, 166.2 (CO) ppm. HRMS (ESI): m/z [M + Na]+ calcd for C28H27ClO8Na: 549.1285; found: 549.1287.
  • 10 Under the conditions used, 2b is soluble at –25 °C, while 2a forms a suspension even at room temperature.
  • 11 One of the reviewers suggested that the relative reactivity of monosaccharide products 3a and 3b towards orthoester 1 could also be important for the success of oligomerization. Clearly, higher reactivity of 3a in comparison with that of 3b might contribute to the observed preferential formation of oligomeric products 4a in the reaction of 1 with 2a. In such a case one has to justify the putative lowered of reactivity of 3b, which is different from 3a by only one methylene group. Note, however, that glycosides 3a and 3b are both readily soluble in CH2Cl2 unlike the parent phenols 2a and 2b (see note 10). In our opinion, this high solubility of 3a and 3b makes this scenario hardly possible.
  • 12 Kononov LO. RSC Adv. 2015; 5: 46718
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