Iodine/Triethylsilane as a Convenient Promoter System for the Activation of Disarmed Glycosyl Trichloro- and N-(Phenyl)trifluoroacetimidates

Abstract

Disarmed glycosyl trichoro- and N-(phenyl)trifluoroacetimidates can be efficiently activated by the combined reagent system I₂/Et₃SiH in the fast and high yielding glycosylation of primary and secondary saccharidic acceptors.

carbohydrates - glycosylations - iodine - neighboring-group effects - triethylsilane

References

For recent reviews:

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6 For an alternative use of I₂ in the generation of anhydrous HI: Chervin SM. Abada P. Koreeda M. Org. Lett.  2000,  2:  369 

7 For the use of triethylsilane in the formal addition of HI to alkenes: Barluenga J. Gonzalez JM. Campos PJ. Asensio G. Angew. Chem., Int. Ed. Engl.  1985,  24:  319 

8

Use of acetonitrile as the solvent resulted in lower glycosylation yields due to concomitant side reactions of the donor. On the other hand, in dichloromethane the reactions occurred very sluggishly.

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10

This donor was prepared as an anomeric mixture (α/β, 2:1) by reacting the corresponding 1-hydroxyl sugar [3] with N-(phenyl)trifluoroacetimidoyl chloride in the presence of diisopropylethylamine (overnight stirring in CH₂Cl₂ at r.t., yield 88%). The use of K₂CO₃ as the base (as reported in ref. [11] ) resulted in a very sluggish reaction.

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13 Typical Procedure: Donor 4 (31 mg, 0.056 mmol) and acceptor 5 (16 mg, 0.043 mmol) were dissolved in CH₂Cl₂ (600 µL) in the presence of freshly activated acid washed 4Å molecular sieves (purchased from Fluka). The mixture was cooled at 0 °C (ice bath) and a solution of I₂ in MeCN (0.36 M, 120 µL, 0.043 mmol) and a solution of Et₃SiH in MeCN (0.06 M, 35 µL, 0.002 mmol) were added. After 30 min the temperature was allowed to raise to r.t. After one additional hour the mixture was diluted with CH₂Cl₂ and washed with an aq solution of NaHCO₃ containing sodium thiosulfate. The organic phase was concentrated and the residue was chromatographed on a short silica gel column eluted with 7:3 hexane/EtOAc. This purification afforded 27 mg of disaccharide 11 (yield 85%)

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15

Treatment of per-O-acetyl-β-d-glucose with I₂ and triethylsilane (1.2 mol each) in refluxing CH₂Cl₂ for 20 min resulted in the high yielding synthesis of the corresponding α-glycosyl iodide in analogy to the alternative system (RSH/I₂) reported in ref. [6] .