Of hemiacetal

Steps 4-5 Conversion of hemiacetal to carbocation These steps are analogous to the formation of carbocations m acid catalyzed reactions of alcohols... 

You learned in Section 17 8 of the relationship among hemiacetals ketones and alcohols the for mation of phenol and acetone is simply an example of hemiacetal hydrolysis The formation of the hemiacetal intermediate is a key step in the synthetic procedure it is the step in which the aryl—oxygen bond is generated Can you suggest a reasonable mechanism for this step" ... 

During the discussion of hemiacetal formation in d ribose in the preceding section you may have noticed that aldopentoses have the potential of forming a six membered cyclic hemiacetal via addition of the C 5 hydroxyl to the carbonyl group This mode of ring closure leads to a and p pyranose forms... 

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... 

Relaxation kinetics. In the course of a study of hemiacetal formation with a phenol nucleophile, an equation was given for the relaxation time in the system ... 

This is supported by the observation that 0-labelled alcohol is cleaved to unlabelled /-butanol. Wiberg has given other examples of this type of cleavage, and has dealt with other complications such as further oxidation of products, formation of hemiacetals, etc. 

The precatalysts, Pt(IV) or Pt(II) salts, were found to be reduced in a series of steps by excess P(CH20H)5 to give Pt[P(CH20H)5]4, which in aqueous solution exists in equilibrium with the five-coordinate cationic hydride [PtL4H][OH] [L = P(CH20H)3]. Since reaction mixtures are basic [rationalized by the formation of hemiacetals from P(CH20H)3 and formaldehyde], the major Pt species present during catalysis is ze-... 

When alcohols are added to the reaction mixture, unsymmetrical ether products may be obtained. Starting with a mixture of aldehydes can also give rise to the formation of unsymmetrical ethers. These ether products are formed under conditions different from those used in the formation of ethers directly from alcohols. Thus, it is postulated that the reaction sequence that leads from the carbonyl substrate to the ether involves the intermediate formation of hemiacetals, acetals, or their protonated forms and alkoxycarbenium ions, which are intercepted and reduced to the final ether products by the organosilicon hydrides present in the reaction mix. The probable mechanistic scheme that is followed when Brpnsted acids are present is outlined in Scheme 2.311-327 328... 

Scheme 3.1 Electrophilic activation of hemiacetals for dehydrative glycosylation.

Silicon presents an attractive option among eledrophilic activating and dehydrating agents of hemiacetals because of the wide commercial availability of eledrophilic silicon sources. The two main classes of silicon electrophiles used, namely silyl halides and silyl sulfonates, have been demonstrated to promote a variety of glycosylations including some examples of oligosaccharide synthesis. 

In addition to the silicon-based in situ activation of hemiacetal donors, there has been a significant body of work that uses electrophilic silicon activation of preformed C-l silyl hemiacetal donors [54—67]. However, this work is outside the scope of this discussion. 

In an extension beyond hetaryl onium salt promoted hemiacetal activation, Ishido and coworkers have reported the carbodiimide activation of hemiacetals [141]. In the method (Scheme 3.13), the hemiacetal donor 1 is treated with a carbodiimide electrophile 83 and copper(I) chloride to provide glycosyl isourea intermediate 85. Highly susceptible to hydrolysis, the isourea 85 was not isolated but could be detected by 13C NMR and IR spectroscopy [142,143], Accordingly, the reaction between intermediate 85 and the glycosyl acceptor (NuH) provides glycoside product 3, along with urea by-product 84. 

Another mode of carbon-based activation of hemiacetals relies on carbonyl-centered electrophiles 89 (Scheme 3.14). These reagents have demonstrated the highest efficiency for disaccharide synthesis among electrophilic carbon activating agents. In the event, the hemiacetal 1 is activated with electrophile 89 for in situ... 

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],... 

Despite the high utility of glycosyl fluorides as stand-alone glycosyl donors, there has been only one example of a direct dehydrative glycosylation whereby hemiacetal activation proceeds through a glycosyl fluoride intermediate. Hirooka and Koto have detailed the use of diethylaminosulfur trifluoride (DAST) for dehydrative glycosylations with hemiacetal donors (Scheme 3.16) [160]. Treatment of a mixture of hemiacetal 1 and alcohol acceptor (R OH) with DAST 108 (2 equiv) at 0°C provides the... 

A mixture of hemiacetal donor (1 mmol), glycosyl acceptor (1.2 equiv), methoxyacetic acid (0.1 equiv) and Yb(OTf)3 (0.1 equiv) in dichloromethane (40 ml) was... 

Synthesis of glycosyl phosphates by exposure of hemiacetals to 81 activated derivatives of phosphoric acid... 

Synthesis of glycosyl phosphates by reaction of hemiacetals with activated phosphoric acid derivatives... 

Although addition of activated phosphoramidite to hemiacetals of manno-pyranoses under thermodynamic control has been reported to deliver exclusively a-phosphates in some cases,43 anomeric mixtures with preponderance of a-anomer have been reported in other examples.10,44 Since formation of phosphorotetrazolidite is a rate-limiting step of the process, initial activation of phosphoramidite followed by addition of nucleophilic hemiacetal should accelerate condensation and favour the formation of the thermodynamic a-product. Indeed, reaction of hemiacetal 101 with dibenzyl phosphorotetrazolidite assured exclusive a-selectivity of the resulting glycosyl phosphate 102.43 The accumulation in the reaction mixture of mildly acidic 1H-tetrazole, which is liberated upon reaction of tetrazolidite with hydroxylic component, could also favour predominant formation of the a-phosphate (Scheme 18, A). Conventional hydrogenolysis afforded the a-mannosyl phosphate 103. 

The addition of organometallic reagents to the carbonyl group of conveniently substituted aldonolactones constitutes a viable chain-extension method. The reaction leads to the formation of hemiacetals of glyculoses, 1-methylene sugars, and C-glycosyl compounds, which are precursors of, or occur as subunits of, a variety of natural products. 

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. 

Primary alcohols 121 undergo an efficient oxidative dimerization by [IrCl(coe)2]2 under air, without any solvent, to form esters 122 in fair to good yields (Equation 10.30) [54]. The reaction is initiated by the in situ generation of an Ir-hydride complex via hydrogen transfer from alcohols to afford aldehydes, followed by the dehydrogenation of hemiacetals derived from alcohols and aldehydes by action of the Ir-complex to afford esters. 

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