Hemiacetal acylation

Kusumoto and coworkers have found that the treatment of hemiacetal 1 with trifluoro- or trichloroacetic anhydride 94 (1 equiv) and trimethylsilyl perchlorate (0.2 equiv) selectively provides the corresponding anomeric ester intermediate 91 [152], Hemiacetal acylation occurs even in the presence of the alcohol acceptor. With Lewis acid assistance, the glycosyl ester intermediate is displaced to provide disaccharide products in good yields. This transformation allowed the synthesis of disaccharides 98 (81%) and 99 (91%). In some cases, acetic anhydride has been used as the electrophilic activator of hemiacetal donors and the reaction with thiol acceptors yields S-linked glycosides [153,154],... 

The effect of a substituent may be substantially modified by fast, concurrent, reversible addition of the nucleophile to an electrophilic center in the substituent. Ortho- and para-CS.0 and pam-CN groups have been found by Miller and co-workers to have a much reduced activating effect on the displacement of halogen in 2-nitrohaloben-zenes with methoxide ion [reversible formation of hemiacetal (143) and imido ester anions (144)] than with azide ion (less interaction) or thiocyanate (little, if any, interaction). Formation of 0-acyl derivatives of 0x0 derivatives or of A-oxides, hydrogen bonding to these moieties, and ionization of substituents are other examples of reversible and often relatively complete modifications under reaction conditions. If the interaction is irreversible, such as hydrolysis of a... 

Aldehydes and ketones can be converted to ethers by treatment with an alcohol and triethylsilane in the presence of a strong acid or by hydrogenation in alcoholic acid in the presence of platinum oxide. The process can formally be regarded as addition of ROH to give a hemiacetal RR C(OH)OR", followed by reduction of the OH. In this respect, it is similar to 16-14. In a similar reaction, ketones can be converted to carboxylic esters (reductive acylation of ketones) by treatment with an acyl chloride and triphenyltin hydride. " ... 

Polysubstituted 3-thiofiirans which are receiving a great interest as flavour and odour chemicals have been obtained by mono-//J5osubstitution and ortho-metallation from 3,4-dibromofuran <96T4065>. Dihydrofuran is used in a new synthesis of ketones from acids via acyl hemiacetals (Scheme 8, <96JOC6071>). 

A more general route to 4-acetoxy-l,3-dioxanes utilizes the reductive acylation of l,3-dioxane-4-ones [46] (Scheme 21). l,3-Dioxane-4-ones 126 are prepared from the corresponding -hydroxy carboxylic acids. Low temperature reduction with DIBALH generates a diisobutylaluminum hemiacetal (127) which undergoes acylation in situ with AC2O in the presence of pyridine and DMAP. This method allows for the preparation of a wide range of 4-acetoxy-l,3-dioxanes, without the problem of a-epimerization. This method also represents a general approach to acylic a-acetoxy ethers, which are themselves useful synthetic intermediates [47,48]. 

The pKj, value (2.43) of the hydration constant of the cyanidin was found to be lower than the pKj, values of glycosylated and acylated cyanidins, meaning lower resistance of the anthocyanidin to hydration. The stability of nonacylated 3,5-diglucosides was lower compared to the 3-glucoside because the 5 position markedly lowered the hydration constant due to decreased electron density of the pyrilium ring that favors nucleophilic attack by water, enhancing hemiacetal formation. ... 

Hemiacetals and O-Acyl/Carbonyl Derivatives 95 Daniel A. Ryan, David Y. Gin Introduction 95... 

This chapter outlines the development, achievements and limitations of glycosyla-tion methods that rely on Cl-hemiacetal donors and Cl-O-acyl donors. These are among the simplest glycosyl donors to prepare in standard O-glycosylation reactions. As such, developments in the use of these donors constitute valuable advances in the field of synthetic carbohydrate chemistry. 

A typical procedure calls for reaction of the hemiacetal donor with dicydohexyl carbodiimide and copper(I) chloride (0.1 equiv) at 80 °C, followed by an addition of the acceptor and continued heating. As an early demonstration of this protocol, oc-riboside 86 was prepared in moderate yield but with exclusive stereoselectivity [141]. Further measures were required for the glycosylation of monosaccharide acceptors, such as addition of p-toluenesulfonic add (0.1 equiv) to promote the formation of disaccharide 87 [144]. The method was more suitably applied to the synthesis of O-acyl glycopeptides, as evidenced by the formation of 88 in 60% yield [143,144]. Various peptides with non-nudeophilic side chains were found to be amenable to this stereoselective reaction. The [3-selectivity was suggested to arise from a preponderance of the a-isourea intermediate 85 in the activation step. 

Generally, carbonyl derivatives have to be protected during synthesis. In the case of carbohydrate synthesis, this is frequently done through the intramolecular formation of hemiacetals, followed by alkylation or acylation. In the first instance, glycosides are formed. Light-sensitive glycosides were discussed in Section 11,2. 

The mechanism of the acid-catalysed breakdown of hemiorthoesters Electron releasing substituents when attached to the pro-acyl carbon have a smaller effect on fcH+ for the breakdown of hemiorthoesters than of orthoesters (see p. 67 above) which suggest that these two classes of compounds react by different mechanisms and that the transition state for breakdown of the hemiorthoesters has less carbocationic character. Jencks and his coworkers (Funderburk et al., 1978) proposed mechanism (5) for the breakdown of hemiacetals and a similar mechanism (6) can be written for the breakdown of hemiorthoesters. This would explain (i) the general acid catalysis observed... 

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