P-Trichloroacetimidates

In recent times, anomeric trichloroacetimidates have become the most widely used glycosyl donors. They can easily be prepared by a base-catalysed reaction of a lactol with trichloroacetonitrile. When the reaction is performed in the presence of the mild base potassium carbonate, the kinetic p-trichloroacetimidate is formed (Scheme 4.3). Under these conditions, the more reactive (1-alkoxide forms preferentially. It then attacks the trichloroacetonitrile irreversibly. However, when a strong base such as NaH or l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is employed, alkoxide equilibration occurs, with the more stable a-alkoxide predominating. It then goes on to react with the trichloroacetonitrile to give the a-trichloroacetimidate. 

Formation of a P-trichloroacetimidate trichloroacetimidation of 2,3,4,6-tetra-O-benzyl-a/(3-D-galactopyranose under kinetic control [24]. 

Notes and discussion. This procedure is used to form the kinetic P-trichloroace-timidate product in the imidation reaction and is based on the method reported by Schmidt et al. [16]. It utilizes a relatively mild base (potassium carbonate) which is essentially unable to catalyse the reverse imidation reaction. Hence equilibration between a- and P-imidate products is not possible and the kinetic product dominates. It is of note, however, that reactions of this type must be monitored carefully if the yield of the kinetic product is to be maximised. The P-trichloroacetimidate product could be used under SN2-like glycosylation conditions to provide access to a-glycosides [25]. 

A detailed study of trichloroacetonitrile addition to 2,3,4,6-tetra-O-benzyl-D-glucose showed that from the 1-oxide the p-trichloroacetimidate is formed preferentially or even exclusively in a very rapid and reversible addition reaction (Scheme 16). However, this product anomerizes in a slow, base-catalyzed reaction (yia retroreaction, 1-oxide anomerization and renewed addition) practically completely to the a-trichloroacetimidate, with the electron-withdrawing 1-substituent in an axial position as favored by the thermodynamically efficient anomeric effect. " Thus with different bases, for instance K2CO3 and... 

Tetra-0-benzyl-Z)-glucose l-O-a or p-trichloroacetimidate with alcohols in nitrile solvents with TMS triflate as catalyst react at -40° to give 70-90% yields of disaccharides (from primary or secondary alchols) with p a ratios of 8-24 1 by way, it is proposed, of intermediate ions which involve strong association with the solvent. With mannose disaccharides ratios are about 1 1. ... 

Pinto and co-workers [75] have chosen a more traditional approach toward establishing 1,2-thio linkages and ultimately the production of thiokojibiosides and related derivatives. The thiol 187 was coupled to the P-trichloroacetimidate 188 thereby yielding the protected allyl kojibioside 189 [75] (Scheme 37). Interestingly, when the a-trichloroacetimidate 190 was used as donor the thiosophorose derivative 191 was obtained as the major product (191 192, 2.3 1) in a reaction proceeding via the stable orthoester 193. 

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