Lewis acid-promoted anomerization

The conversion of anomerically linked enol ethers 29 into either the cis- or trans-substituted pyranyl ketones with high diastereoselectivity and yield involves a Lewis acid-promoted O —> C rearrangement (Scheme 19) <00JCS(P1)2385>. Under similar conditions, homoallylic ethers 30 ring open and the oxonium ions then recyclise to new pyran derivatives 31. Whilst the product is a mixture of alkene isomers, catalytic hydrogenation occurs with excellent diastereoselectivity (Scheme 20) <00JCS(P1)1829>. 

Esterification and transesterification using TiIV compounds are useful methods for functionalization of ester moieties under mild conditions. In the transformation of carboxylic acids to esters, a catalytic amount of TiCl(OTf)3 is effective (Scheme 30).110 Titanium alkoxides, such as Ti(OEt)4 or Ti(0 Pr)4, easily promote transesterification of alkoxy groups to other ones—even to more hindered groups.111 Anomerization of glycosides to Q-isomers using a Tilv-bascd Lewis acid is an important method for controlling the product structure.112... 

Epimerization of / -glucosides to the corresponding a anomers is promoted by the group IV metal halides (MX4, M = Ti, Zr, Hf Eq. 4). The proposed mechanism for this anomerization includes the Lewis acid-mediated fission of the endo-cycWc C-O bond (Fig. 8). The rate and extent of the anomerization are in the order Ti > Zr > Hf, and the best result is obtained by use of TiBr4 (20 mol %) and MgBr2-OEt2 (100 mol %) [14]. 

Acid or Lewis-acid catalyzed self-condensation reactions of 1,2-anhydro sugars were studied for the synthesis of polysaccharides [438]. Polysaccharides of relatively low molecular weights (< 10,000) were obtained, and the anomeric configurations could be varied depending on the promoter and temperature [439]. 

An anomeric acetate is efficiently displaced by a thiol under the influence of an acidic catalyst, and this is probably presently the most used and efficient way to produce thioglycosides of simple mercaptans, especially on a large scale. The standard procedure is to react a peracetylated aldose dissolved in dichloromethane with a slight excess of thiol using a hard Lewis acid as promoter, which generally gives a high yield of mainly the 1,2-trans product ( Scheme i) [11]. 

Step 1 Silver ion acts as a Lewis acid to promote loss of bromide from the anomeric carbon giving a carbocation. 

The stereocontrol of the Strecker reaction (eq. 10) can be explained by steric, stereoelectronic and complexing effects of the carbohydrate. The delocalization of the C=N-tc-electron pair into the ring-C-0-a -orbital should favour the conformation I of the aldimines 25, as is demonstrated by a strong NOE between the aldimine and the anomeric proton. The constellation of the polar complexing groups at the carbohydrate framework obviously promotes the attack of the Lewis-acid catalyst at the front-site of the molecule (formula... 

The analogous anomeric N-piperidine derivatives could be activated not only by thiophilic promoters (MeOTf and DMTST) but also by AgOTf and various Lewis acids, e.g. SnCU and FeCb, to allow orthogonal couplings with thioglycosides and the building of thioglycoside donor blocks (Scheme 26) [143]. 

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