Preparation of trichloroacetimidates

Formation of an a-trichloroacetimidate trichloroacetimidation of 4,6-di-O-acetyl-2-0-benzoyl-3-0-chloroacetyl-a/ 3-D-glucopyranose under thermodynamic control [21]. 

Anhydrous dichloromethane (100 cm, distilled from calcium hydride) 

Round-bottomed flask (250 cm ) with rubber septum and magnetic stirrer bar Magnetic stirrer 

Source of dry argon (or nitrogen) as inert gas Syringe (5 cm ) and needle Microsyringe (250 p, ) and needle Rotary evaporator Column chromatography equipment 

Formation of a p-trichloroacetimidate trichloroacetimidation of 2,3.4,6-tetra-O-benzyl-o/p-D-galactopyranose under kinetic control [24]. 

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Scheme 3 The preparation of trichloroacetimidates and their glycosidation reaction [10].

Cramer, F., Pawelzik, K., Baldauf, H. J. Imido esters. I. Preparation of trichloroacetimidic acid esters. Chem. Ber. 1958, 91, 1049-1054. 

For the preparation of trichloroacetimidates used in glycoside synthesis (see Section 10.3.2), the anomeric position must be selectively deacetylated. This is possible starting from the j3-anomer by treatment with hydrazine acetate (Excoffier et al. 1975). Thus, compound 5,3 can be prepared from 5.2 by this method. 

Preparation of Trichloroacetimidates. The imidates derived from the addition of alcohols to trichloroacetonitrile have become important and versatile intermediates in synthetic chemistry. Consequently the principal synthetic use of trichloroacetonitrile has been in the formation of these useful trichloroacetimidate intermediates. The imidates are most often prepared by simple addition of a sodium or potassium alkoxide to the electron-deficient trichloroacetonitrile (eq l). In certain cases, slight modifications of the above procedure are utilized. The product imidates are isolable and, despite their propensity to rearrange, can in some instances be purified by distillation or chromatography. Typically the addition reaction is sufficiently clean to use the imidates without further purification. ... 

In the synthesis of analogues of calicheamicin 71 and esperamicin Ajb, Moutel and Prandi employed the glycosyla-tion of a nitrone with a trichloroacetimidate as a key step - /3-N-O glycosidic bond formation. Preparation of the nitrone begins with the alkylation of the known alcohol 69 <1992CC1494> with 1,4-dibromobutane in the presence of sodium hydride. Subsequent aminoalkylation, amine protection with 9-fluorenylmethoxycarbonyl (Fmoc), and reduction with NaBHsCN were followed by nitrone 70 formation with 4-methoxybenzaldehyde (Scheme 8) <2001J(P1)305>. 

Condensation [270] of the chloride (370) with the allyl lactoside (397) as described above for the preparation of (392) gave a 6 % yield of the P-linked iV-acetylneuraminic acid derivative (on the 3 -hydroxyl group) and none. of the a-linked material. The product was acetylated and deallylated to give (398) and this was converted into the trichloroacetimidate (399) which was condensed with the 3-O-benzoylceramide to give the P-iV-acetyl-neuraminyl derivative of hematoside ( epi-hematoside ). 

New resins more suitable for the preparation of libraries have recently been reported [17]. Polystyrylboronic acid can be prepared with high loading capacity even more importantly, a solvent mixture of acetone and water can be used to reduced the amount of impurities after the cleavage step. Polystyrylboronic acid has proven to be especially useful for coupling of thioglycosides, for which trichloroacetimidates give only modest results. 

An anomeric acetyl group can be removed selectively by treatment with hydrazine acetate or ammonium carbonate in DMF (Scheme 2.15c).46 The latter transformations are of great importance for the preparation of glycosyl donors such as anomeric trichloroacetimidates. 

Intramolecular substitutions offer a convenient and stereoselective method for the introduction of amino functionalities. A strategy for the preparation of vicinal m-hydroxy amino moieties entails the halocy-clisation of allylic trichloroacetimidates.77 Conversion of the hydroxyl of unsaturated sugar derivatives into a trichloroacetimidate, followed by Ar-bromosucciniinide (NBS) or JV-iodosuccinimide (NIS) mediated intramolecular cyclisation, gives bromo- and iodo-oxazoline derivatives (Scheme 3.13a). The oxazoline can be hydrolysed with mild acid to unmask the amino functionality, and the halogen can be removed by treatment with tributyltin hydride. 

The next section describes briefly the procedures for the preparation of anomeric halides, trichloroacetimidates and thioglycosides and their modes of activation. 

Almost all types of leaving groups have been explored in sialyl donors with, until recently, two notable exceptions the venerable imidates and the sulfoxides. While the preparation of stable, isolable sialyl trichloroacetimidates has still to be demonstrated, the recent innovation of the Biao Yu group—the (V-phenyltrifluoroacctimidatcs—has proven equal to the task and has provided access to new potent class of sialyl donors [27], Stable sulfoxides of sialyl thioglycosides have also been described recently and employed as glycosyl donors on activation with triflic anhydride (Tf20) [28], The S-benzoxazolyl (.S -Box) thiosialosides constitute another recent addition to the armory of sialyl donors [29, 30],... 

The Overman rearrangement, a thermal [3,3]-sigmatropic rearrangement of allylic trichloroacetimidates, is an attractive procedure for the preparation of ally] amines from allyl alcohols (Eq. (4)) [7]. 

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