Anomeric acetates

Keywords Acetal, Anomeric effect, Diastereoselectivity, Glycosylation, Ion pair. Kinetic isotope effect, Stereoelectronic effects... 

The oxidation of the cyclic enol ether 93 in MeOH affords the methyl ester 95 by hydrolysis of the ketene acetal 94 formed initially by regioselective attack of the methoxy group at the anomeric carbon, rather than the a-alkoxy ketone[35]. Similarly, the double bond of the furan part in khellin (96) is converted ino the ester 98 via the ketene acetal 97[l23],... 

Glycosides m which the anomeric carbon is part of an acetal function are not reducing sugars and do not give a positive test... 

Bu3SnOMe, CICH2CH2CI, 1 h, 77% yield.These conditions selectively cleave the anomeric acetate of a glucose derivative in the presence of other acetates. 

The anomeric effect is also present in acyclic systems and stabilizes conformations that allow antiperiplanar (ap) alignment of the C—X bond with a lone-pair orbital of the heteroatom. Anomeric effects are prominent in determining the conformation of acetals and a-alkoxyamines, as well as a-haloethers. MO calculations (4-3IG) have found 4kcal/mol as the difference between the two conformations shown below for methoxy-methyl chloride. ... 

In cyclic systems such as 1, the dominant conformation is the one with the maximum anomeric effect. In the case of 1, only conformation lA provides the preferred antiperiplanar geometry for both oxygens. Antiperiplanar relationships are indicated by including lone pairs in the oxygen orbitals. Other effects, such as torsional strain and nonbonded repulsion, contribute to the conformational equilibrium, of course. Normally, a value of about 1.5 kcal/mol is assigned to the stabilization due to an optimum anomeric interaction in an acetal. 

Many examples of reactivity effects that are due to the anomeric effect have been identified. For example, Cr03 can oxidize some pyranose acetals, leading eventually to ketoesters. 

Structurally, 0-glycosides are mixed acetals that involve the anomeric position of furanose and pyranose forms of carbohydrates. Recall the sequence of intermediates in acetal formation (Section 17.8) ... 

The anomeric carbon in a cyclic acetal is the one attached to two oxygens. It is the carbon that conesponds to the car bonyl carbon in the open-chain form. The symbols a and p refer to the configuration at the anomeric carbon. 

Section 25.13 Glycosides are acetals, compounds in which the anomeric hydroxyl group has been replaced by an alkoxy group. Glycosides are easily prepared by allowing a carbohydrate and an alcohol to stand in the presence of an acid catalyst. 

Bu2SnO, benzene BnBr, DMF, heat, 80% yield. This method has also been used to protect selectively the anomeric hydroxyl in a carbohydrate derivative. The replacement of Bu2SnO with Bu2Sn(OMe)2 improves the process procedurally. The use of stannylene acetals for the regioselective manipulation of hydroxyl groups has been reviewed. ... 

When the reaction was run in CH3CN, migration of the EtS group to the 2-position was observed. This is attributed to episulfonium salt formation, with the resultant addition of acetate at the anomeric position. ... 

LiEt3BH, THF, —78°, 2 h, 98% yield. An anomeric acetate can be selectively cleaved in the presence of a secondary acetate. 

H2NNH2, MeOH, 92% yield. An anomeric acetate was cleaved selectively in the presence of an axial secondary acetate. ... 

The 3-deoxyhexoses were obtained crystalline after separation on a column of cellulose, a rather tedious operation recently separation of these sugars by fractional crystallization has been reported (41). From the major unsaturated ester 27, 3-deoxy-D-ribo- and -arabino-hexose were shown to have been produced respectively in the ratio 66 34, and from ester 28 in the ratio 24 76. Saturation of the enol grouping of the esters 27 and 28 gives, therefore, the 1,2-cis products preferentially. However, some hydrogenolysis of the anomeric acetate group accompanies simple saturation of the double bond and poses another separation problem. 

Esterification is normally carried out by treating the carbohydrate with an acid chloride or acid anhydride in the presence of a base (Sections 21.4 and 21.5). All the —OH groups react, including the anomeric one. For example, /3-o-glucopyranose is converted into its pentaacetate by treatment with acetic anhydride in pyridine solution. 

Recently, 2,6-dioxabicyclo[2.2.1 Jheptane 33 and 2,7-dioxabicyclo[2.2.1 Jheptane 34 were synthesized, and their rates of acidic solvolysis were compared293. Table 1 summarizes the data, along with those for relevant bicydic acetals determined in a similar manner. Tremendous differences in reactivity among these compounds are noteworthy. The approximate relative reactivities under these conditions spun more than five powers of ten. These differences are attributable to ring strain and anomeric... 

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