Protection Benzyl trichloroacetimidate

Reaction of the Benzyl-Protected Glucosyl Trichloroacetimidate la-/ with 0-Nucleophiles... 

For the mono-C-glycosylphenol, the commercially available 2,4,6-trihydroxyacetophe-none was chosen and selectively methylated at C-2 and C-4. The partially protected phenol was glycosylated with the C-benzyl-protected glucosyl trichloroacetimidate in the presence of trimethylsilyl triflate as promoter to give directly a C-(benzyl protected)glycosylphenol. The unprotected hydroxyl group of this compound was converted with benzoyl chloride into a fully protected C-glycoside phenol. Treatment of the benzoate derivative with sodium hydroxide in... 

Acid-Catalyzed Benzylation. Benzyl trichloroacetimidate, Cl3CC(=NH)OBn, reacts with hydroxyl groups under acid catalysis to give the con-esponding benzyl ethers in good yield. The method is particularly useful for the protection of base-sensitive substrates (i.e., alkoxide-sensitive), such as hydroxy esters or hydroxy lactones, as exemplified below. 

The reaction of trichloroacetimidates with silylenol ethers is also well established [221]. Another interesting example, reaction of benzyl-protected galactosyl trichloroacetimidate with a silyl enol ether, which can be considered as a homoalanine carbanion equivalent [224], led to the a-glycoside as expected from previous results [221] it was formed with high stereoselectivity. The p-glycoside could be obtained by base-catalyzed isomerization. Further transformations were performed to obtain the a- and p-C-galactosyl-L-serine derivatives. 

When W-aceCyl-protected sugar amines were under investigation the A -acetyl group was observed to undergo transformation to the O-benzyl imidate in competition with OH benzylation (eq 3). It appears for best yields at least 1 equiv of reagent per OH and NAc group is needed, and subsequent hydrolysis and reacetylation of the amine are necessary to obtain are the originally desired material. Similar problems were encountered with the morpholine derived lactams (eq 4), where mixed products were obtained, but with p-lactams with yV-amide protection (eq 5), t -benzylation with benzyl trichloroacetimidate proceeded smoothly. BTCA has recently been used to convert diketopiperazines into their bis-benzyl imino ethers. ... 

The synthesis and application of 0-glucosyl trichloroacetimidates is focused on 0-benzyl- and 0-acetyl protected derivatives (1,52a) because these two protective groups have proven to be the most valuable in glycoside synthesis. Representative examples of trichloroacetimidate formation are collected in Table I (la- Id). As already outlined (Section III. 1), the glucosyl trichloroacetimidates are obtained in high yields and the diastereoselectivi-... 

Unprotected galactose derivatives may be readily transformed into the trichloroacetimidates 8a-8g, as shown in Table VIII. Again, as demonstrated for the O-benzyl-protected compounds 8a, either the a-trichloroace-timidate 8a-a or the / -trichloroacetimidate 8a -/ may be obtained highly selectively, depending on the base used for the catalysis of the addition to the trichloroacetonitrile. 

Before this acid could be used in lipid A synthesis, its 3-hydroxyl group had to be protected most preferably by benzylation. This was performed as shown in Figure 6. Of the two benzylating procedures, that with trichloroacetimidate described recently by Iversen and Bundle (9) was preferable because of the shorter reaction time needed. Since this hydroxyl group is on the 3-carbon atom of the carboxyl function, strong alkali such as NaOH could not be used as it caused 3-elimination of benzyl alcohol from the product (J ). 

En route to pseudodisaccharide 96 (Scheme 13.13), the 1,2,6-0-diffcrcntiated inositol derivative 94 was used to react with the trichloroacetimidate donor 39 in the presence of TMSOTf, which supplied 95 in an 89% yield (ot/p=4/1) after full deacetylation. The mixture of anomers carried forth to undergo 4, 6 -0-benzyhdine protection, 3 -0-benzylation, and regioselective benzylidine ring opening, rendering the 04 position free. At this point, the mixture of anomers could be separated, and the pseudodisaccharide acceptor 96 was ready for the key glycosylation step. 

Acid-catalysed alkylation of an alcohol with O-alkyl trichloroacetimidate prepared from allyl alcohol and trichloroacetonitrile is readily accomplished Scheme 4.233]440 as previously discussed for the preparation of benzyl and tert-butyl ethers.311 However, these conditions are not compatible with many of the protecting groups employed in oligosaccharide synthesis. For such cases, two methods for 0-allylation under essentially neutral conditions have been devised. The first method takes advantage of the mild conditions and regioselectivity of stannylene alkylations (see section 4.3.3). The method is illustrated by the selective O-allylation of o-lactal, which began with stannylene formation on an 0.8 mole scale [Scheme 4.234].441... 

Similarly, the trichloroacetimidates 6a and 6b rearranged smoothly to the acetimidates 7 under palladium(II) catalysis49. However, exposure of the benzyl-protected derivative 6c to the palladium(II) species only led to partial destruction56 of this compound. 

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