Imidazoles, silyl derivatives

Imidazole or pyridine mediated silylation of l,2-0-[l-exo-ethoxy )ethylidene]-oc-D-glucopyranose failed to give a high yield of the 6-silyl ether due to some polymerization and side reactions. Activation of hydroxyl groups via a tributylstannyl intermediate followed by the tetrabutylammonium bromide catalyzed reaction with tert-butyl-chlorodiphenylsilane was more successful [231], the 6-0-silyl derivative being isolated in 87 % yield.. The lability of this protecting group under benzylation with benzyl bromide and sodium hydride at 0 °C has been observed [449]. 

To a soln of Boc-Ser-OBzl (200 mg, 0.68 mmol) and imidazole (116 mg, 1.70 mmol, 2.5 equiv) in dry THE was added TBDPSCl (206 mg, 0.75 mmol, 1.1 equiv) and the soln was stirred overnight at rt. After filtration and removal of the solvent, the silyl derivative was purified by chromatography (silica gel, CH2CI2) to give Boc-Ser(TBDPS)-OBzl as an oil yield 290mg (79%). 

Photochemical Balz-Schiemann reaction of diazonium fluoroborates continues to be the method of choice to prepare fluoro substituted imidazoles. Thus, 4(5)-fluoroimidazole 1565 is prepared from 4(5)-nitroimidazole 1559 in moderate yield by conversion of the nitro group to the diazonium salt followed by irradiation in aqueous tetrafluoroboric acid. Sugar-fluoroimidazole derivatives 1566 and 1567 were prepared using an iV-silyl derivative of 1565 (Scheme 404). 

Silyl derivatives have received much attention, they can be utilized to block diverse polar groups (OH, COOH, SH, NH2, =NH). The amino group is not very reactive in silylation reactions. Silyl derivatives are either trimethyl chlorosilanes (TMS), hexamethyldisilazane (HMDS) in conjunction with TMS, silylamines such as trhnethylsilyl diethylamine and trimethylsilyl imidazole, silyl amides such as A,(9-bistrimethylsilylfluoroacetamide (BSTTFA). Example is given by sterols. Isomers with a hydroxy group in the a position are not separated from the (S isomers but when the OH group is converted into a suitable derivative (e.g., TMS) both isomers are well resolved. 

The proteetion of hydrojg l groups as their silyl-derivatives has been one of the most used protection strategies, from its discoveiy by Corey et due to their simplieity of use, chemoselectivity and facile deprotection. The most used Lewis bases are pyridine, triethylamine, imidazole and recently, DMAP derivatives and DABCO. " ... 

A new and efficient combination for silylation is trimethylsilyl chloride-lithium sulphide. Even hindered hydroxy-groups are silylated at room temperature in neutral conditions, although the mechanism of the process is not yet clear. 4-Dimethylaminopyridine (DMAP) has been shown to be an efficient catalyst for the silylation of alcohols by t-butyldimethylsilyl chloride and to be more selective than the imidazole traditionally used. Two new methods for removal of the t-butyldimethylsilyl group are treatment with boron trifluoride etherate and reaction with aqueous HF in acetonitrile. The O-silyl derivatives of normal carboxylic esters, i.e. keten methyl trialkylsilyl acetals (59), have been investigated in silyl transfer to alcohols (Scheme 31) they have the advantage of... 

Whereas condensation of a-hydroxy ketones such as benzoin and acetoin on heating with formamide [240] or ureas in acetic acid [239, 242] to form imidazoles such as 769 or 770 is a well known reaction, only two publications have yet discussed the amination of silylated enediols, prepared by Riihlmann-acyloin condensation of diesters [241], by sodium, in toluene, in the presence of TCS 14 [241, 242]. Thus the silylated acyloins 771 and higher homologues, derived from Riihl-... 

Diethyl [(2-tetrahydropyranyloxy)methyl]phosphonate is useful in the Wlttig-Horner synthesis of enol ethers, which are intermediates in one-carbon homologations of carbonyl compounds. This procedure is an adaptation of a general method for making dialkyl hydroxymethylphosphonates. An 0-tetra-hydropyranyl derivative also has been made from dibutyl hydroxymethyl -phosphonate, and diethyl hydroxymethylphosphonate has been O-silylated with tert-butylchiorodimethylsilane and imidazole. Another useful congener in this series has been prepared by an Arbuzov reaction of methoxyethoxymethyl (HEM) chloride and triethyl phosphite. 

Analogues of (751) react with derivatives of phosphorus-containing acids to form 1-phosphoryl-imidazoles (90CHE599). The same compound also silylates ketones to give enol silyl ethers and/or siloxyalkylimidazoles (Scheme 107) (87JC271). 

Basically, the synthesized target molecules were achieved in amounts of 200-500 mg with a standard on purity of >95%. The purities of the compounds were routinely checked by analytical HPLC. The core template 1 was prepared by palladium-catalyzed hydrogenation of commercially available glucal 10 followed by deacetylation, according to the literature, which afforded derivative 11 [27] (Scheme 3.2.3). Free hydroxy compound 11 was selectively silylated with two equivalents of TBDMSC1 in the presence of imidazole 12, followed by benzylation and subsequent cleavage of the TBDMS groups 1. 

A two-step silylation has been described for catecholamines [92]. All of the hydroxyl groups are converted into TMS ethers within 2—3 h by reaction with TMS-imidazole in acetonitrile at 60°C, BSA—TMCS (2 1) reagent is added and within the next 2 h all of the primary amino groups are converted into the N,N-di-TMS derivative. Secondary (N-methyl) amino groups do not react under these conditions. A distinct speed-up of the silylation reaction on the addition of a small amount (1%, v/v) of water to the reaction mixture (see Fig. 5.6) and different effects of the solvents are interesting. These derivatives possess excellent chromatographic properties and are well separated on OV-1. 

N-silylated l-cyano-N,N -disnbstitnted formamidines 592 react with DCC to give substituted imidazole derivatives 593. ... 

Hydroxyl (serine) and sulfhydryl groups (cysteine) are also silylated. These derivatives can be used in peptide synthesis by the phosphoryl chloride, imidazole, mixed anhydride, or p-nitrophenyl ester methods. An attractive feature is that the silyl groups are removed merely by treatment with water in the normal workup. Trimethylchlorosilane is not suitable because of the amphoteric nature of the amino acids. 

A-Glycosylimidazoles (related to nucleosides) are of interest in the preparation of novel chemotherapeutic agents, hence selective A -glycosylation techniques are of interest. The palladium-catalyzed addition of vinyl epoxides and allyl acetates to imidazoles provides one such route to imidazole nucleoside analogues <91JCS(Pi)2603, 9UOC4990>. The silyl-Hilbert-Johnson method is another in which the imidazole is silylated, then treated with a suitable peracetylated carbohydrate derivative in the presence of trimethylsilyl triflate catalyst. With 4-carbamoylimidazolium-5-olate, for example, the major product is the l-glycosyl-5-carbamoyl isomer with only low yields of the... 

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