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A. Bartoszewicz et al. / Tetrahedron 64 (2008) 8843–8850
methylimidazole and iodine, was developed. The reactions can be
carried out in various organic solvents (e.g., THF, acetonitrile,
methylene chloride, and pyridine), at room temperature, and are
compatible with the presence of common functional groups. The
procedure is experimentally simple, high yielding, and expands
range of synthetic methods available for silylation of complex or-
ganic compounds. Application of N-methylimidazole together with
iodine resulted in significant shortening of the silylation time, both
for primary and secondary alcohols. The silylation occurred 5–30
times faster than that under standard conditions when imidazole
was used as a nucleophile catalyst and DMF as a solvent. The re-
action pathway was studied in depth and a mechanistic role of
iodine was elucidated by 1H NMR spectroscopy. It was found that
a base used for the reaction had to have nucleophilic properties,
and that iodine increased concentration of a reactive silyl-nucleo-
phile adduct in the reaction mixture.
chromatography (CH2Cl2/MeOH 100:0/95:5, Table 6 entries 1, 3,
and 7; pentane/AcOEt 10:0/9:1, Table 6 entries 2, 4–6, and 8–
14). The synthesized compounds were fully characterized by 1H
and 13C NMR spectroscopies and HRMS analysis (see the Sup-
plementary data for details).
Acknowledgements
Financial support from the Swedish Research Council is grate-
fully acknowledged.
Supplementary data
Supplementary data associated with this article can be found in
4. Experimental part
4.1. General
References and notes
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4.2. A general procedure for preparative silylation of alcohols
listed in Table 6
23. Since we did not observe simultaneously signals from the TBDMS-OTf and
those of the corresponding silylpyridinium intermediate, we could not exclude
a possibility that these two species existed in a rapid equilibrium. However,
since the observed signals were sifted significantly to the high field, the pos-
tulated adduct probably was formed in large amount.
An alcohol (1.0 mmol), N-methylimidazole (3.0 mmol), and
iodine (2.0–3.0 mmol) were dissolved in an appropriate, anhy-
drous solvent (3 mL, Table 6), and to these, a silyl chloride
(1.1 mmol) was added. The reaction mixture was stirred at room
temperature until complete disappearance of the starting mate-
rial (TLC analysis). The solvent was then evaporated, the residue
dissolved in ethyl acetate and washed with concd aqueous
Na2S2O3. The organic phase was dried over anhydrous Na2SO4
and evaporated. The products were purified by silica gel column
24. Olah, G. A.; Klumpp, D. A. Synthesis 1997, 744–746.
25. The reaction times for silylation of nucleosides 1 and 2 in the presence of
N-methylimidazole and I2 in THF and in acetonitrile in Table 2 are practically
the same despite significant differences in concentrations of the reactive in-
termediate generated in these two solvents. A probably reason for this behavior
can be rather poor solubility of the nucleosides in acetonitrile (heterogeneous
reaction), comparing to a very good solubility in THF, what could slow down
the silylation rate in the former solvent.