[2916-68-9] · C5H14OSi · 2-(Trimethylsilyl)ethanol · (MW 118.28)
(protecting reagent for carboxyl, phosphoryl, hydroxyl, and amino groups)
Physical Data: bp 50-52 °C/10 mmHg, 71-73 °C/35 mmHg; d 0.825 g cm-3.
Form Supplied in: colorless liquid; 99% purity; widely available.
Preparative Methods: three methods of preparation have been reported: (a) from the treatment of ethyl bromoacetate with Zinc followed by the reaction with Chlorotrimethylsilane1 and subsequent reduction of the resultant Ethyl Trimethylsilylacetate with Lithium Aluminum Hydride2,3 or Borane-Tetrahydrofuran4 (eq 1); (b) from the hydroboration/oxidation5,6 or oxymercuration/demercuration7 of Vinyltrimethylsilane (eq 2); and (c) most conveniently, by the reaction of the Grignard reagent formed from (Chloromethyl)trimethylsilane with Paraformaldehyde (eq 3).8
Handling, Storage, and Precautions: corrosive; irritant.
A variety of methods are available for the protection of carboxylic acids as 2-(trimethylsilyl)ethyl esters.9 2-(Trimethylsilyl)ethyl esters are stable to conditions used in peptide synthesis. Deprotection of the ester is readily accomplished by treatment with Tetra-n-butylammonium Fluoride (TBAF).9 Hemisuccinates have been prepared indirectly under nonacidic conditions by monoprotection of succinic anhydride as 2-(trimethylsilyl)ethyl esters followed by esterification (eq 4) and then selective deprotection of the resultant diester (eq 5).10
Transesterification of methyl esters to 2-(trimethylsilyl)ethyl esters under mild and neutral conditions takes place in the presence of Titanium Tetraisopropoxide (eqs 6-8).11 Deprotection of the 2-(trimethylsilyl)ethyl ester in the presence of an O-TBDMS protected secondary hydroxyl group has been achieved (eq 9).11b An alternative method for the transesterification uses 1,8-Diazabicyclo[5.4.0]undec-7-ene/Lithium Bromide and 2-(trimethylsilyl)ethanol.12
Protection of hydroxyl groups as 2-(trimethylsilyl)ethyl ethers13a and 2-(trimethylsilyl)ethyl carbonates13b (eq 10) has been utilized as illustrated below. The 2-(trimethylsilyl)ethyl carbonate group can be cleaved under mild conditions using TBAF in dry THF (eq 11).13b
Methods for the protection of pyranosides and furanosides as 2-(trimethylsilyl)ethyl glycosides (eq 12) and deprotection using dry Lithium Tetrafluoroborate in MeCN have been developed (eq 13).14
2-(Trimethylsilyl)ethanol has been used as a protecting group in phosphate monoester synthesis and involves the use of 2-(trimethylsilyl)ethyl dichlorophosphite (eq 14).15 Bis[2-(trimethylsilyl)ethyl] N,N-diisopropylphosphoramidite has been prepared from dichloro(diisopropylamino)phosphine and 2-(trimethylsilyl)ethanol and used as a phosphitylating agent in the synthesis of phosphotyrosine containing peptides (eq 15).16
2-(Trimethylsilyl)ethoxycarbonyl (Teoc) groups have been used to protect amine functionalities (eq 16).17 Using a mixture of tetra-n-butylammonium chloride and KF.2H2O deprotects the Teoc group.18 N-Debenzylation and concurrent protection as N-Teoc results when tertiary N-benzylamines are treated with 2-(Trimethylsilyl)ethyl Chloroformate.19
A new method for the synthesis of imidazolones involves the replacement of the C-2 nitro group of N-protected dinitroimidazoles by nucleophilic addition of the sodium salt of 2-(trimethylsilyl)ethanol (eq 17).20
Reaction of 2-(trimethylsilyl)ethyl benzenesulfenate with halides in the presence of TBAF yields phenyl sulfoxides (eq 18).21 2-(Trimethylsilyl)ethyl benzenesulfenate is prepared by the reaction of Benzenesulfenyl Chloride and the lithium salt of 2-(trimethylsilyl)ethanol.
Jayachandra P. Reddy
Indiana University, Bloomington, IN, USA