Orthoester formation

Scheme 4.52 Overcoming orthoester formation in the presence of a base.

Acyl protection should lead, as a consequence of neighboring-group participation and the anomeric effect, exclusively to a products. This has been proved in many experiments (Table XV) with Me3SiOTf as catalyst excellent yields could be obtained in cases where all other methods essentially failed (129). It could be shown that at least some of the reactions proceed via rapid orthoester formation (129), and this intermediate then rearranges under Me3SiOTf catalysis to the desired reaction product. 

ShyG17.18c HygX 258 24783 Dioxygenase or hydroxylase (orthoester formation )... 

When, however, solvolysis is carried out in the absence of an acid acceptor (and, therefore, in acid medium), orthoester formation stops, and simple replacement occurs, with net retention of configuration01 as in (11)— (lla). Under the same conditions, 1,2-dfi halides undergo solvolysis with inversion of configuration01 as in (12)— (12a) therefore, irrespective of whether a 1,2-trana or a 1,2-da halide is the starting material, the result... 

In Reichstein s synthesis15 of convallatoxin (9), 2,3,4-tri-0-acetyl-6-deoxy-a-L-mannosyl bromide (13) (a 1,2-trans halide) was employed. In contrast to the preparation of simple glycosides, the use of silver carbonate did not lead to orthoester formation instead, glycoside formation took... 

Orthoester formation is reviewed by E. Pacsu, Advances in Carbohydrate Chem., 1, 77 (1945). 

The results obtained are shown in Table III (see p. 26). The mutarotation of the product indicated, in each case, that the /3-D-modification predominated for the acetyl sugars formed from reaction with water. The data show that the reaction was only slightly affected by change of solvent or of temperature, and was free of orthoester formation. These facts, and the almost exclusive formation of 1,2-trans products from the 1,2-cis-bromide, was interpreted as evidence that the reaction proceeds by way of the Sw2 mechanism. It was suggested that the increase of O-acetyl-a-D-glucoside formed at 50° (over that at 20°) may be due to racemization through carbonium-ion formation. 

The trichloroacetimidate methodology has been successfully applied to the synthesis of sialyl and asialyl TN epitopes (Scheme 5.9).29 The use of this methodology can lead to predominant orthoester formation with 2-(9-acetyl protected glycosyl donors, but acceptable results can be obtained with 2-azido-glycosyl donors. The complexity of the tetra-saccharide donor probably contributes to the poor chemical yield of this... 

On removal of the six acetyl groups from hexaacetylturanose methyl 1,2-orthoacetate, either by alcoholic ammonia or by a trace of sodium methoxide according to the method of Zempl n and Pacsu, crystalline turanose methyl 1,2-orthoacetate (Vlllb) was obtained. It crystallized from ethanol in the form of tabular crystals with m. p. 137 and [o]d + 114.6 in aqueous solution. Hydrolysis with alkali did not eliminate the remaining acetyl group until the methyl glycosidic group with which it was linked in the orthoester formation had been removed. The instability of the turanose methyl 1,2-orthoacetate in aqueous solution was illustrated by a gradual decrease in rotation in water from [aln +113.3 to a constant value of [a]n +72.7 in sixty-four hours. 

Regarding the orthoester formation in the ketose series, any acetyl-ketosyl halide may give at least a 1,2-orthoester because the acetyl group at position 1 is always free to approach, from the opposite side, the halogen atom at position 2 in either modification of the halide. 

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