[16961-83-4] · F6H2Si · Fluorosilicic Acid · (MW 144.09)
(a fluoride source with both protic and Lewis acid properties providing efficient cleavage of silicon-oxygen bonds, e.g. silyl ether deprotection)
Physical Data: d 1.220 g cm-3 for a 25% aq solution.
Form Supplied in: 25% aq solution, clear and colorless. Upon dehydration, this reagent decomposes giving HF and SiF4.
Handling, Storage, and Precautions: fluorosilicic acid is toxic and very corrosive. Like HF, this compound attacks glass and therefore must be stored in plastic containers. Use the same precautions as for aq HF solutions. Use in a fume hood.
Fluorosilicic acid is a superior reagent for Si-O bond cleavage applications.1 One of the common reagents used for desilylation is Hydrofluoric Acid; however, significant problems can accompany its use. Standard protocols utilizing HF specify a large excess of the reagent, leading to low pH conditions which can decompose acid-sensitive substrates.2 Hydrofluoric acid also lacks selectivity in removing silyl ethers. For example, a substrate which incorporates both a t-butyldimethysilyl (TBDMS) ether and a triisopropylsilyl (TIPS) ether will undergo cleavage of both protecting groups with little difference in cleavage rates. Of course, this is not problematic if the goal is to remove both groups; however, it is often desirable to remove one group selectively while retaining the other.
For the deprotection of silyl ethers, aq H2SiF6 is superior to aq HF. Fluorosilicic acid is a more potent cleaving agent than HF, allowing its use in stoichiometric or even catalytic quantities (eqs 1 and 2). The lower acid concentrations result in milder reaction conditions that are compatible with several acid labile moieties (see below).
Fluorosilicic acid also has the unique ability to differentiate effectively between TBDMS and TIPS ethers, as seen in the competitive deprotection experiment in eq 3. The presence of bulky cosolvents, such as t-butanol, which serve as ligands to silicon, further enhance selectivity at the expense of reaction rate. The reaction time can be reduced by increasing the amount of H2SiF6; however, the accompanying increase in acid concentration precludes the use of acid-labile substrates.
The optimal compromise between selectivity, reaction rate, and acid concentration is achieved by using a 90:10 acetonitrile-t-butanol solvent system. Under these conditions, selectivity is only slightly degraded and the reaction rate is relatively fast, so the amount of reagent can be reduced to 0.25 equiv (eq 4). Due to the lower acid concentration, certain acid labile groups are tolerated. In competitive deprotection experiments, Bn-O-TBDMS is deprotected in the presence of another acid labile protecting group (an example is shown in eq 5 for THP): MEM and MOM groups are 100% retained; THP (86%) and benzylidine derivatives (77%) are partially retained. An acetonide derivative is retained only to the extent of 16%.
The effects of increasing the steric bulk of the substrate at carbon were also probed. Compounds (1)-(4) (eq 6) were paired and used in competitive deprotection reactions, providing the results reported in Table 1. Excellent selectivity was observed in the deprotection of primary TBDMS vs. tertiary TBDMS, and secondary TBDMS vs. tertiary TBDMS derivatives. On the other hand, selectivity was only fair for primary TBDMS vs. secondary TBDMS, and secondary TBDMS vs. secondary TIPS ethers. As observed before, t-butanol provided greater selectivity than t-BuOH-MeCN solvent mixtures.
Anthony S. Pilcher & Philip DeShong
University of Maryland, College Park, MD, USA