Inverse procedure, trichloroacetimidates

In addition, the fulvestrant could be glycosylated effectively at its 17-OH position with pivaloylated glycosyl trichloroacetimidates, which suppressed the competing transacylation side reaction and led to improved yields of the desired glycosides (Scheme 3.48d) [503]. In this synthesis, the inverse procedure (i.e. addition of a trichloroacetimidate donor to a mixture of an acceptor and a promoter) was found to be superior for glycosylations. Very recently, a stepwise synthesis of branched... 

The high reactivity of glycosyl trichloroacetimidate can lead to side reactions or even decomposition of the donor before reaction with the acceptor. To improve yield and the stereocontrol of the reaction, the so-called inverse glycosylation procedure is often used. In this case the glycosyl acceptor and the catalyst are dissolved together followed by the addition of the glycosyl donor. 

This procedure enables direction of the reaction toward the formation of either the a ox p anomer. Control is achieved during attachment of the trichloroacetimi-date group to the anomeric position of the sugar. If the reaction is performed in the presence of NaH, 96 % of the trichloroacetimidated product (9) is obtained with an aip ratio of 96 4. In the presence of Na2C03, 80 % of the product is obtained with an alp ratio of 25 75. Substitution of the trichloroacetimidate by the alkyl group occurs with inversion of the configuration. 

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