Observations on Iodine-promoted β-Mannosylation [1]

Abstract

The stereoselectivity of iodine-promoted glycosylation with mannosyl sulfoxides gives rise to unexpected β-selectivity with less reactive alcohol acceptors. Less reactive accceptors also give better coupling yields. Comparison of iodine with other promoters highlights differences in reaction rates and stereoselectivities indicative of different reaction mechanisms.

carbohydrates - glycosylations - iodine - stereoselectivity - sulfoxides

References

1 Iodine: a versatile reagent in carbohydrate chemistry XV. For part XIV see: Kartha KPR. Ballell L. Bilke J. McNeil M. Field RA. J. Chem. Soc., Perkin Trans 1  2001,  770 

2

Present address: Kartha K. P. R., National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali 160 062, Punjab, India.

3

Present address: Field R. A., Centre for Carbohydrate Chemistry, School of Chemical Sciences and Pharmacy, University of East Anglia, Norwich NR4 7TJ, UK.

4 Kartha KPR. Cura P. Aloui M. Readman SK. Rutherford TJ. Field RA. Tetrahedron: Asymmetry  2000,  11:  581 

5 Kartha KPR. Field RA. Tetrahedron  1997,  53:  11753 ; and references cited therein

6 Trost BM. Miller CH. J. Am. Chem. Soc.  1975,  97:  7182 

7 Reviewed by: Taylor CM. In Solid Support Oligosaccharide Synthesis and Combinatorial Carbohydrate Libraries   Seeberger PH. Wiley Interscience; New York: 2001.  p.41 

8 Kartha KPR. Kärkkäinen TS. Marsh SJ. Field RA. Synlett  2001,  260 

9 Crich D. J. Carbohydr. Chem.  2002,  21:  667 

10

To date, all attempts to use the corresponding 4,6-O-benzylidenated mannosyl sulfoxide donor, to parallel Crich’s work, [9] have met with cleavage of the benzylidene acetal prior to glycosylation during iodine-promoted reactions. This serves to illustrate the ability of iodine to select between oxygen centers of different basicity (viz acetal or alcohol vs sulfoxide).

11 Alkyl hypoiodites have been known and exploited, particularly in steroid chemistry, for many years. Reviewed by: Kalvoda J. Heusler K. Synthesis  1971,  501 

12a Although glycosyl iodides were long thought to be too labile to be useful in synthesis, the Gervay-Hague lab have demonstrated the stability and popularized the use of this class of compounds. See: Lam SN. Gervay-Hague J. Carbohydr. Res.  2002,  337:  1953 ; and references cited therein

12b The first crystal structure of a glycosyl iodide has recently been reported. See: Bickley J. Cottrell JA. Ferguson JR. Field RA. Harding JR. Hughes DL. Kartha KPR. Law JL. Scheinmann F. Stachulski AV. Chem. Commun.  2003,  1266 ; and references cited therein

13 Spijker NM. van Boeckel CAA. Angew. Chem. Int. Ed. Engl.  1991,  30:  180 

14 Kartha KPR. Field RA. Tetrahedron Lett.  1997,  38:  8233 

15

These studies were conducted with known glycosyl donor 1 [16] and glycosyl acceptors 2, [17] 3, [18] 4 [19] and 5, [20] which were prepared by standard procedures. Typical iodine-mediated glycosylation procedure: A stirred mixture of sulfoxide donor (0.125 mmol), sugar acceptor (0.25 mmol) and 3 Å molecular sieves (50 mg) in dichloromethane (1 mL) containing anhydrous potassium carbonate (0.25 mmol) was cooled (ice/water/salt bath, approx -5 °C) under a nitrogen atmosphere. Iodine (38 mg, 0.15 mmol) was added, and the mixture was stirred overnight (during this period, the reaction mixture was allowed to warm to ambient temperature). The reaction mixture was filtered through Celite with the aid of dichloromethane (20 mL), washed with aqueous Na₂S₂O₃ solution, dried (Na₂SO₄) and concentrated in vacuo. Column chromatography of the resulting residue gave disaccharides as summarised in the Tables. Ratios of product glycosides were determined by ¹H NMR spectroscopy of appropriate signals (H-1, OMe), as permitted by spectral dispersion. Stereochemical assignments were made with the aid of one bond J _C1-H1 coupling constants. [21]

16 Borén HB. Eklind K. Garegg PJ. Lindberg B. Pilotti Å. Acta Chem. Scand.  1972,  26:  4143 

17 Guthrie RD. Jenkins AD. Stehlícek J. J. Chem. Soc. C  1971,  2690 

18 Brimacombe JS. Ching OA. J. Chem. Soc., C  1968,  1642 

19 Kovác P. Glaudemans CPJ. Carbohydr. Res.  1985,  138:  C10 

20 Crich D. Sun SX. Tetrahedron  1998,  54:  8321 

21 Bock K. Pedersen C. J. Chem. Soc., Perkin Trans. 2  1974,  293