Trimethylsilyl thiazole

Addition of t-C4H9—CH=0 (at —80 °C) to the suspension of 2-lithiothiazole gives a clear solution. Aqueous work up, followed by extraction with Et20, drying over K2C03, concentration of the (unwashed) extracts in vacuo gives the carbinol, m.p. 84 °C, in -95% yield. 

The ratio 0.11 0.10 with respect to BuLi and Me3SiCl is a good guarantee that no acid is produced during the addition of water, which might cause removal of the silyl group. 

Solubility insol H2O very sol CH2CI2, diethyl ether, THF. 

Preparative Method although 2-(trimethylsilyl)thiazole (1) is commercially available, it can be easily prepared on a multigram scale from 2-bromothiazole, n-butyUithium, and chloro-trimethylsilane as shown in eq 1.  

Handling, Storage, and Precautions is stable upon storage under an inert atmosphere in a refrigerator. Nevertheless, it should be freshly distilled for best results. Irritating to the eyes, respiratory system, and skin. Wear suitable protective clothing, gloves and eye/face protection. Use in a fume hood. 

General Discussion. 2-(Trimethylsilyl)thiazole (1) reacts with various C-electrophiles such as azolium halides (eq 2), ketenes (eq 3), acyl chlorides (eq 4), 7 ketones, and aldehydes (eq 5) under mild conditions to give the corresponding 2-substituted thiazoles in very good isolated yields. No catalysts are required in these carbodesilylation reactions. 

A list of General Abbreviations appears on the front Endpapers 

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The silyloxazole 34 undergoes addition to chiral aldehydes under mild conditions and although the stereoselectivity is poorer than for 2-trimethylsilyl-thiazole (see Section III,G), the opposite diastereomer of the product 35 is obtained (85TL5477). 

Good to excellent diastereoselectivities have been reported when 2-(trimethylsilyl)thiazole (3), an effective equivalent of an aldehyde group, is used as nucleophile24,27. Thus, addition to TV-Boc-protected amino aldehydes in dichloromethane at — 30 C afforded mixtures of amino alcohols in comparatively good yields with reasonable syn selectivity. However, the stereoselectivity decreased substantially when the reaction was carried out in tetrahydrofuran at 25 °C. 

Method A (in CH,C1,) To a stirred solution of 1 mmol of the aldehyde 1 in 3 mL oT CH2C.l2 is added dropwise a solution ori.5 mmol of 2-(trimethylsilyl)thiazole (3) in 3 mL ofCH2Cl2 at —30 °C. After stirring for 20 h, the solvent is evaporated in vacuo, and the residue is treated with 1 M TBAF (1.5 mmol) in 10 mL of l HK After stirring for 1 h. the solvent is removed under vacuum, and sat. aq NaHC03 is added. The solution is extracted with EtOAc, and the extract is dried over anhyd Na2S04 then the solvent removed under reduced pressure. The residue is chromatographed on a short silica gel column (petrolcum/cthcr/EtOAc, 7 3). 

Synthesis of (S,S)-3-Amino-2,4-dihydroxybutanal via Addition of 2-(Trimethylsilyl)thiazole to L-Serinal. 

A. Dondoni and P. Merino 21 DIASTEREOSELECTIVE HOMOLOGATION OF D-(R)-GLYCERALDEHYDE ACETONIDE USING 2-(TRIMETHYLSILYL)-THIAZOLE 2-O-BENZYL-3,4-ISOPROPYLIDENE-D-ERYTHROSE... 

Dondoni pioneered the use of 2-(trimethylsilyl)thiazole (71) as a formyl anion equivalent for the homologation of aldehydes. Extension of this reaction to ketones would be very useful, but has thus far been restricted to tritluoromethyl cases. However, it has now been widened to include several a, a -alkoxy ketones, as demonstrated in a new route to branched-chain monosaccharides. Aldehydes catalyse the reaction, although the scope is still limited electrophilic aldehydes, such as 2-fluorobenzaldehyde, promote the addition of (71) to electrophilic ketones. 

Trimethylsilyl)thiazole (2-TST) is prepared according to the Organic Syntheses procedure 2 it is also commercially available (Acros Chimica or Aldrich Chemical Company, Inc.). The commercial product was purified by distillation prior to use. 

This procedure describes an example of the "aldehyde route". The addition of 2-(trimethylsilyl)thiazole (2-TST) to aldehydes occurs readily and does not require the presence of a fluoride ion source.10 The resulting secondary alcohol is as a rule isolated in very good yield. The sense of the diastereofacial selectivity of the addition reaction to chiral a-amino aldehydes can be controlled by differential protection of the... 

Trimethylsilyl)thiazole Thiazole, 2-(trimethyIsilyI)- (10) (79265-30-8) (S)-2- [(4S)-N-tert-Butoxycarbonyl-2,2-dimethyl-1,3-oxazolidin-4-yl]hydroxymethyl)-1,3-thiazole 3-Oxazolidinecarboxylic acid, 4-(hydroxy-2-thiazolylmethyl)-2,2-dimethyl-, 1,1-dimethylethyl ester, [(S-(R, R )]- (12) (115822-48-5)... 

In the case of 2-(trimethylsilyl)thiazole (83TL2901) the acylation of nitrogen and desilylation at C-2 are likely to be concerted giving rise directly to a A-acylthiazolium 2-ylide which then evolves to the 2-acylthiazole by a multi-step process (Scheme 41). This hypothesis is supported by a mechanistic study of the reaction of the same silylated thiazole with aldehydes (93JOC3196). 

A. Medici, G. Fantin, M. Fogagnolo, and A. Dondoni, Reactions of 2-(trimethylsilyl)thiazole with acyl chlorides and aldehydes. Synthesis of new thiazol-2-yl derivatives, Tetrahedron Lett. 24 2901 (1983) A. Dondoni, G. Fantin, M. Fogagnolo, A. Medici, and P. Pedrini, Synthesis of (trimethylsilyl)thiazoles and reactions with carbonyl compounds. Selectivity aspects and synthetic utility, J. Org. Chem. 53 1748 (1988). 

A. Dondoni, A. W. Douglas, and 1. Shinkai, Spirodioxolane intermediates in the reaction of 2-(trimethylsilyl)thiazole with aldehydes. Support for the 2-ylide mechanism, J. Org. Chem. 56 3196 (1993). 

A. Dondoni and P. Merino, Diastereoselective homologation of D-(ft)-glyceraldehyde acetonide using 2-(trimethylsilyl)thiazole 2-0-benzyl-3,4,-0-isopropylidene-D-erythrose, Org. Synth. 72 21 (1993) The procedure has been checked by A. I. Meyers and G. P. Brengel, Colorado State University, USA. 

A. Dondoni, J. Orduna, and P. Merino, Construction of all 0-alkoxy D-tetrose and D-pentose stereoisomers from 2,3-0-isopropylidene-D-glyceraldehyde using 2-(trimethylsilyl)thiazole as a formyl anion equivalent. Synthesis p. 201 (1992). 

N. K. Khare, R. K. Sood, and G. O. Aspinall, Diastereoselectivity in the synthesis of D-g/ycero-D-aldoheptoses by 2-(trimethylsilyl)thiazole homologation from hexodialdo-1,5-pyranose derivatives, Can. J. Chem. 72 237 (1994). 

On the other hand, several nucleophilic reagents and catalysts have been found capable of promoting the ring expansion of 4-formyl p-lactams, and/or their imine derivatives, to afford open chain acyl thiazole or succinimide derivatives. For example, treatment of 4-formyl p-lactam 199 with 2-(trimethylsilyl)thiazole,... 

A novel N(l)-C(4) cleavage of azetidin-2-one 320 or 321 forming a-alkoxy-7-keto amides 322 has been observed by addition of 2-(trimethylsilyl)thiazole to cis- or /ra r 4-formylazetidin-2-ones (Equation 111) <20040L1765>. 

The halogen dance reaction is also applied to the synthesis of the 5-substituted 4-bromo-2-chlorothiazole derivatives 89 <07SL3016>. Treatment of 5-bromo-2-chlorothiazole with 1.2 equiv. of LDA at -80 °C brings about full conversion to the halogen dance product 88, which is trapped with various electrophiles to give the 5-substituted thiazoles 89. For example, 4-bromo-5-trimethylsilyl-thiazole is obtained in 71% yield when 5-bromo-2-... 

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