Trimethylsilyl Perchlorate1

[18204-79-0]  · C3H9ClO4Si  · Trimethylsilyl Perchlorate  · (MW 172.66)

(nucleoside synthesis;1 selective cleavage of t-Boc group;2 disiloxane3 formation and general silylation characteristics4,5)

Alternate Name: TMSP.

Physical Data: bp 35-38 °C/14 mmHg.

Preparative Method: prepared by a silver salt-trimethylsilane anion exchange (eq 1).6 Not commercially available.

Purification: distillation under reduced pressure.

Handling, Storage, and Precautions: explosive; fumes when exposed to air. Use in fume hood.

Catalytic Synthesis of Nucleosides from Silylated Heterocycles and 1-O-Acyl or 1-O-Alkyl Sugars.1

Trimethylsilyl perchlorate, prepared in situ, acts as a strong Lewis acid suitable as a Friedel-Crafts catalyst in the reaction of silylated heterocycles, like uracil (1), with 1-O-acyl or 1-O-alkyl sugars such as 1-O-acetyl-2,3,5-tri-O-benzoyl-b-D-ribofuranose (2). This Friedel-Crafts reaction produces the nucleoside 4-O-silylated ribosyl benzoate (3) (eq 2).

Since trimethylsilyl perchlorate is produced by the reaction, it can be used catalytically. Workup of these Friedel-Crafts reactions is effected by NaHCO3/CH2Cl2. The use of this reagent as the catalyst is an improvement over the past nucleoside synthesis which employed Tin(IV) Chloride, where isolation and purification were complicated by the formation of emulsions and colloids. This rate of nucleoside formation is also greatly enhanced by an increase in temperature. Trimethylsilyl perchlorate can be effectively substituted with Trimethylsilyl Trifluoromethanesulfonate. Yields ranged from 60-90%.

Selective Acidic Cleavage of the t-Butoxycarbonyl Group.2

Trimethylsilyl perchlorate enables selective cleavage of t-Boc groups in the presence of the benzyloxycarbonyl (Z) group and t-butyl esters. This difficult selective cleavage is executable at rt over a 5 min period in benzene, CH2Cl2, or benzene/acetonitrile with 1.0 equiv of trimethylsilyl perchlorate as the promoter. Yields are quantitative (Table 1).

Disiloxane Formation3 and Silylations.

(Me3Si)3CSiMe2OH, a sterically hindered silanol, gives the disiloxane (Me3Si)3CSiMe2OSiMe3 in 87% yield, when treated with 4.5 equiv of trimethylsilyl perchlorate in benzene at room temperature for 10 min (eq 3). The same result may be effected with Iodotrimethylsilane, N,O-Bis(trimethylsilyl)acetamide, or Methyllithium followed by Chlorotrimethylsilane.

The above disiloxane formation is an example of a silylation. The active nucleophilic species and kinetics of different silylations have been studied. The ideal silylation mixture should consist of a polar solvent to stabilize salts, a highly electrophilic silane, such as trimethylsilyl perchlorate, trimethylsilyl iodide, or trimethylsilyl trifluoromethanesulfonate, a strong nucleophile, such as N-Methylimidazole, 4-Dimethylaminopyridine, or Hexamethylphosphoric Triamide and a proton acceptor like Triethylamine.4 It has also been shown that trimethylsilyl perchlorate forms bis(trimethylsilyl)imidazolium salts which are postulated to be active intermediates in other silylation reactions.5

1. Vorbruggen, H.; Krolikiewicz, K. AG 1975, 14, 421.
2. Vorbruggen, H.; Krolikiewicz, K. AG 1975, 14, 818.
3. Eaborn, C.; Safa, K. D. JOM 1982, 234, 7.
4. Bassindale, A. R.; Stout, T. TL 1985, 26, 3403.
5. Bassindale, A. R.; Lau, J. C. Y.; Stout, T.; Taylor, P. G. JCS(P2) 1986, 227.
6. (a) Eaborn, C. JCS 1955, 2517. (b) Wannagat, U.; Liehr, W. AG 1957, 69, 783.

James S. Panek & Robert M. Garbaccio

Boston University, MA, USA

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