TBS-OTf is a very powerful silylating agent, and is capable of protecting primary, secondary, and teriary alcohols.
(excess silyl chloride, dry pyridine, elevated temperatures) were not
aryl silyl ethers was accomplished selectively in the presence of base-sensitive
G.D. K. Kumar, S. Baskaran, J. Org. Chem. Finally, the 2′-TBS groups are removed using tetrabutylammonium fluoride in tetrahydrofuran. Trimethylsilyl ethers are too susceptible to solvolysis for
When the commercially available tert-butyldimethylsilyl chloride
B. Wang, H.-X.
Protection As is always the case in silicon chemistry, the substitution reaction proceeds via pentacoordinated intermediates. The Si–F bond steng 76, 7352-7358. were significantly accelerated by addition of iodine. Sun, Z.-H. Sun, J. Org. We use cookies to help provide and enhance our service and tailor content and ads. The tert-butyldimethylsilyloxy group is ca. Other acid sensitive functionalities may also be affected. treatment with 2-3 eq.
Hf(OTf)4 required for the deprotection of 1°, 2°, 3° alkyl and aryl
The general structure is R R R Si−O−R where R is an alkyl group or an aryl group. Benavidez, M. Gaši, L. Guerrera, B. Zajc,
[1] The TBS group is not 100% stable to the basic conditions used to removed the tert-butylphenoxyacetyl protecting groups, and loss of the TBS group at this stage can lead to phosphodiester chain cleavage and (more seriously) 3′- to 2′-phosphate migration (Figure 4). T. W. Green, P. G. M. Wuts, Protective Groups in Organic Synthesis,
catalyzed by DMF (J. Org. The four butyl groups are installed to increase the solubility of the salt in organic solvents. 1972,
Various tert-butyldimethylsilyl (TBDMS) ethers as well as
M. K. Lakshman, F. A. Tine, T. A. Khandaker, V. Basava, N. B. Agyemang, M. S. A.
conditions show tolerance for acid- and base-sensitive groups. It is imperative that RNA is handled with care to avoid contamination with RNAse enzymes that might otherwise result in degradation.
Figure 7 | TC-protected RNA monomersStructures of 2′-thiomorpholine-4-carbothioate (TC)-protected phosphoramidite monomers, used in solid-phase RNA synthesis. imidazole with 1.2 eq.
Protection As is always the case in silicon chemistry, the substitution reaction proceeds via pentacoordinated intermediates. Wiley-Interscience, New York, 1999, 127-141, 708-711. The first examples of highly selective deprotection of silyl ethers by DIBALH are reported. them to have any utility as protecting groups.
University of Southampton TBDMS ethers of various phenols have been deprotected at room temperature with
General. Protection for the thiol group is important in many areas of organic research, particularly in peptide and protein syntheses that often involve the amino acid cysteine. Another key discovery by E. J. Corey (J. C.-E. Yeom, H. W. Kim, S. Y. Lee, B. M. Kim, Synlett, 2007,
TMS (1) < TES (64) < TBS (20,000) < TIPS (700,000) < TBDPS (5,000,000) • In general, stability towards basic media increases in the following order: TMS (1) < TES (10-100) < TBS~ TBDPS (20,000) < TIPS (100,000) • A study comparing alkoxysilyl vs. trialkylsilyl groups has also been done: P. Hogan • Silyl groups are typically deprotected with a source of fluoride ion. groups such as isopropylidene acetal, OTBDPS, OTHP, Oallyl, OBn, alkene, alkyne,
74, 1781-1784. Ac, Bz, THP, and TBDPS groups using tetrabutylammonium tribromide in methanol. ethers, or sterically hindered aliphatic TBS ethers. [1], TBS-OTf is a very powerful silylating agent, and is capable of protecting primary, secondary, and teriary alcohols. tert-butyldimethylsilyl chloride (TBDMSCl). This method enables
B. Karimi, A. Zamani, D. Zarayee, Tetrahedron Lett., 2004,
Improvements in the synthesis, deprotection and purification of RNA have produced more robust methods that enhance the yield and purity of the final product.
B. Barnych, J.-M. Vatèle, Synlett, 2011,
removal of TBS in the presence of most hydroxyl protecting groups was also
This is in contrast to the other methods described here, all of which require separate deprotection steps for the 2′-OH protecting groups and nucleobase protecting groups. group is ca. Benzyl alcohols and benzyl TBDMS ethers were efficiently oxidized to the
and dimethylformamide as solvent proved to be effective, and resulted in the
tetra-n-butylammonium fluoride (TBAF) in THF at
accomplished. [1][2], 1) Kocienski, P. J.; Protecting Groups, 3rd Edition, 2) Wuts, P. G. M.; Greene, T. W.; Greene's Protective Groups in Organic Synthesis, 4th Edition. The use of 2.5 eq. These
TBS or TBDMS TBS: Corey, JACS, 1972, 6190 (23rd most cited JACS paper) Si O Si O TIPS TBDPS ON: OH R 3SiCl, Imidazole DMF We will discuss general features of protecting groups, for specific examples and exotic methods for attachment or removal, see Greene OSiR 3 N N H R 3Si + via OH R 3SiOTf 2,6-lutidine, CH 2Cl 2 OSiR 3 These transformations are very water sensitive. Figure 3 | Deprotection of the TBS groupMechanism of deprotection of the 2′-tert-butyldimethylsilyl (TBS) group with fluoride.
corresponding carbonyl compounds in high yield with periodic acid catalyzed by
A major advantage is that the RNA can be purified with the 2′-protecting group attached. The oxidation procedure was highly
A selective
This is a particularly severe problem for long oligoribonucleotides as the probability of any given RNA chain containing at least one 5′-2' linkage increases with oligonucleotide length. https://doi.org/10.1016/j.tetlet.2008.06.072. TBDMS ethers can be cleaved selectively in the presence of isopropylidine, Bn,
acid-Lewis base catalyst allows the selective deprotection of aryl silyl ethers
The preparation of synthetic RNA has a number of limitations. R. S. Porto, M. L. A.
proceeds readily in acetonitrile at room temperature in the presence of p-toluenesulfonyl
out in acetonitrile from 24 to 40°C and on rare occasions in DMF from 24 to
Its selectivity enabled us to remove a primary TBS group and a primary TBDPS group in the presence of a secondary TES group. Structure: CAS Number: 18162-48-6 Molecular Weight: 150.72 g/mol Melting Point: 86-89 C Boiling Point: 125 C tert-Butyldimethylsilyl chloride (TBS-Cl) is generally used as a reagent for installing TBS protecting groups.A similar reagent is tert-butyldimethylsilyl trifluoromethanesulfonate ().
Importantly, the acetal group prevents 2′- to 3′-silyl migration in the nucleoside, which can occur with TBS protection, leading (after phosphitylation) to isomeric RNA monomers (Figure 1). S. T. A. Shah, S. Singh, P. J. Guiry, J. Org. It plays an important role in multistep organic synthesis.. The base is usually 2,6-lutidine and the solvent DCM.
1463-1466. of TBDMS-Cl
mild and convenient method tolerates various other protecting groups and does
Soc.
DMF is the most common solvent.
Conversion of TBDMS Ethers to Other Functional Groups. employing a catalytic amount of acetyl chloride in dry MeOH in good yields. yielding method for efficient silylation of primary, secondary, and tertiary
Reaction Mechanism 1. 70, 4520-4523. promise for such applications. Chem., 2009,
in the presence of aryl silyl ethers. Various tert-butyldimethylsilyl ethers are easily removed in excellent