Di-tert-butylsilyl Bis(trifluoromethanesulfonate)

Introduction

Di-tert-butylsilyl bis(trifluoromethanesulfonate) is a useful reagent in organic synthesis. It is a colorless to yellow or light brown-yellow liquid with a boiling point of 73–75 °C, it is sensitive towards moisture, corrosive and reacts with hydroxylic solvents. It has been prepared by reaction of di-tert-butylchlorosilane with trifluoromethanesulfonic acid[1] but it is also commercially available. It has been applied in intramolecular cyclizations as a novel promoter for a Boekelheide reaction.[2] It acts as protecting group for 1,3-diols to improve yield and stereoselectivity of organic reactions,[3] for 1,2-diols in a synthesis of dienophiles[4] and 1,4-diols to obtain 3,6-bridged glycosyl donors[5] and to receive natural products.[6] Triethylsilyl ether, isopropylidene ketal would perform the same role as the t-Bu₂Si(OTf)₂; however, their acidic removal could be problematic in some cases.[7] The bridging di-tert-butylsilylene can be cleaved to give the corresponding fullerene polyols.[8] Moreover, this reagent is a valuable material for the synthesis of prodrugs of chemotherapeutics.[9]

Table 1Use of Di-tert-butylsilyl Bis(trifluoromethanesulfonate)

(A) Massaro and co-workers have treated (aminoalkyl)quinoline N-oxide 1 with t-Bu2Si(OTf)2 and triethylamine in dichloromethane to obtain 2-(N-benzylpyrrolidin-2-yl)quinoline 2 by intramolecular Boekelheide reaction.[2] The cyclized product 2 was synthesized in 51% yield, which was increased to 75% by using microwave irradiation.
(B) Di-tert-butylsilyl bis(trifluoromethanesulfonate) is reported to be a useful reagent for the preparation of C3−5-O-silylated 2-deoxythioriboside 4. This product was formed from the corresponding thioglycoside 3 in the presence of 2,6-lutidine in good yield (83%). The C3−5-O-silylated group of compound 4 influences the stereoselectivity during its glycosylation.[3]
(C) The electron-rich dienophile 7 was obtained starting from the commercially available peracetyl fucal 5.[4] Compound 5 was first deprotected and then the hydroxyl groups at C-3 and C-4 of 6 were protected by reaction with di-tert-butylsilyl bis(trifluoromethanesulfonate) under mild conditions. Fucal derivative 7 was used in a highly selective Diels–Alder reaction.
(D) The reaction of 2,4-di-O-benzyl-1-thio derivatives of glucose, mannose and galactose 8–10 with di-tert-butylsilyl bis(trifluormethanesulfonate) in 2,6-lutidine led to 3,6-bridged glycosyl donors 11–16 in moderate yields.[5] A number of other bridging reagents were examined but no products were observed.
(E) The reaction of substituted dibenzofuran with di-tert-butylsilyl bis(trifluoromethanesulfonate) in the presence of a base such as pyridine has given the derivative of dibenzofuran 18. The reaction was applied to obtain aglycone fulicinerine.[6]
(F) Treating compounds 19a–b (2 equiv) with t-Bu2Si(OTf)2 (1 equiv), Guerra and co- workers have afforded the corresponding bis-malonates 20a–b, which they then used for the regioselective bis-functionalization of C60.[8]
(G) Asymmetric bifunctional silyl ether (ABS) prodrugs of chemotherapeutics (camptothecin, dasatinib, and gemcitabine) were obtained in one step by reacting a dichlorodialkyl silane (i-Pr, Et,) or t-Bu2Si(OTf)2 with the pendant alcohol on the chemotherapeutic.[9] This kind of combination of a silyl ether, a chemotherapeutic and a polymerizable monomer ensures protection for the drugs and decreases the rate of degradation.

• References

• 1 Corey EJ, Hopkins PB. Tetrahedron Lett. 1982; 23: 4871
• 2a Boekelheide V, Linn WJ. J. Am. Chem. Soc. 1954; 76: 1286
• 2b Massaro A, Mordini A, Mingardi A, Klein J, Andreotti D. Eur. J. Org. Chem. 2011; 271
• 3 Mata G, Luedtke NW. J. Org. Chem. 2012; 77: 9006
• 4 Richichi B, Imberty A, Gillon E, Bosco R, Sutkeviciute I, Fieschic F, Nativia C. Org. Biomol. Chem. 2013; 11: 4086
• 5 Heuckendorff M, Pedersen CM, Bols M. J. Org. Chem. 2013; 78: 7234
• 6 Bartholomäus R, Dommershausen F, Thiele M, Karanjule NS, Harms K, Koert U. Chem. Eur. J. 2013; 19: 7423
• 7 Bock M, Dehn R, Kirschning A. Angew. Chem. Int. Ed. 2008; 47: 9134
• 8 Guerra S, Trinh Nguyet TM, Schillinger F, Muhlberger L, Sigwalt D, Holler M, Nierengarten JF. Tetrahedron Lett. 2013; 54: 6251
• 9 Parrott MC, Finniss M, Luft JC, Pandya A, Gullapalli A, Napier ME, DeSimone JM. J. Am. Chem. Soc. 2012; 134: 7978