Hemiacetalization reaction

Fig. 6.25. Simplified mechanism of two degradation reactions between peptides and reducing sugars occurring in solids, a) Maillard reaction between a side-chain amino (or amido) group showing the formation of an imine (Reaction a), followed by tautomerization to an enol (Reaction b) and ultimately to a ketone (Reaction c). Reaction c is known as the Amadori rearrangement (modified from [8]). b) Postulated mechanism of the reaction between a reducing sugar and a C-terminal serine. The postulated nucleophilic addition yields an hemiacetal (Reaction a) and is followed by cyclization (intramolecular condensation Reaction b). Two subsequent hydrolytic steps (Reactions c and d) yield a serine-sugar conjugate and the des-Ser-peptide...

The intra-molecular hemiacetalization reaction, corresponding to cyclization, may also take place on the alcohol function on carbon 4, rather than carbon 5, to produce a five-link cycle such as furan. This reaction produces /S-D-glucofuranose instead of /S-D-glucopyranose (Figure 3.5). 

Fig. 3.2. Intra-molecular hemiacetalization reaction with formation of two stereoisomers, a- and S-D-glucopyranose...

Scheme 7.54 Enantioselective synthesis of furofuranes by cascade oxa-Michael/aldol/ hemiacetalization reaction.

The imididazolidinone 180 (10-20 mol%, Fig. 4.35) catalyzed the homo-aldol dimerization process of an aldehyde and also the cross-aldol reaction between eno-lizable aldehydes (5, source of nucleophile, 10 equiv.) and aromatic aldehydes (2, electrophile). For both cases, the yields were high (58-90%), the anti-diastereo-selectivity was moderated (60-86% de) and the enantioselectivity was excellent (91-97% ee). To prevent a hemiacetal reaction of the initial aldol product 29 with another equivalent of aldehyde, the reaction was quenched by a methanolysis process to form the corresponding dimethyl acetal [259]. 

SCHEME 16.28. Enantioselective domino aldol/oxa-Michael/hemiacetalization reaction. 

Formaldehyde is a strong electrophile, allowing acetal to polymerize by nucleophilic, anionic, or cationic addition of an alcohol to ketene carbonyl groups. Relatively weak bases such as pyridine initiate anionic addition polymerization cationic addition polymerization is catalyzed by strong acids. When the cyclic trimer trioxane is used as a copolymer to polymerize acetal copolymers, Lewis acids such as boron tiifluoride promote copolymerization. A more fundamental description is polymerization of an aldehyde or ketone -l- alcohol -i- an acid or base catalyst to form hemiac-etal, which further converts to acetal. The hemiacetal reaction is reversible to aldehyde and alcohol. 

Spiro 2-hydroxytetrahydro-2H-pyrans 12 result from the asymmetric organocatalytic Michael—hemiacetalization reaction of... 

Most simple hemiacetals, like gem-6io s, are not isolable. However, the cyclic versions of these compounds often are. Consider combining the carbonyl and hydroxyl components of the hemiacetal reaction in Figure 16.37 within the same molecule (Fig. 16.38). Now hemiacetal formation is an intramolecular process. If the ring size is neither too large nor too small, the hemiacetals are often more stable than the open-chain molecules. 

Dianionic Synthon for Trimethylenemethane. Reagent (1), upon metalation with tin(II) fluoride can be used as a dianionic synthon for trimethylenemethane (eq 5). This versatile synthon, in conjunction with bis-electrophiles such as (4), has been used to synthesize rings that range in size from flve to eight members. An intramolecular hemiacetalization reaction followed by cyclization of the allylsilane makes possible the formation of seven- and eight-membered rings (eq b). ... 

It already has been mentioned (Chapter 2) that the cyanohydrin reaction of adding hydrogen cyanide to carbohydrates played an important role in the elucidation of the configurational structures of the carbohydrates. The reaction increases the length of the carbohydrate chain by one carbon but, unfortunately, forms two epimeric products that must be separated. Sometimes one of the two products is produced in much larger amounts than the other, facilitating the separation, but sometimes also providing the unwanted product. The nitrile products can be converted into the aldonic acids by hydrolysis with sodium hydroxide. The aldonic acid can be converted into the lactone by treatment with sulfuric acid. The lactone can then be reduced by sodium borohydride to the hemiacetal (reaction 4.41). 

After successfully achieving the asymmetric synthesis of spiro-3,4-dihydropyrans via chiral tertiary amine-catalyzed domino Michael-hemiacetalization reaction of... 

SCHEME 2.54 Cyclic -oxo aldehyde-involved domino Michael-hemiacetalization reaction. 

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