Hemiacetal formation from

Possible factors influencing these results were that an almost equimolar (4R and 4S) equilibration had been caused by the strongly basic SDMA during the reduction of 156, but the hemiacetal formation from 157 to 158 proceeded more readily for the [(R)-phenylphosphinyl]pen-tofuranoses 158, because there is less steric congestion between the P-phenyl and the 2-and 3-hydroxyl groups in the precursors of 158. 

Fig. 9.2. Base-catalyzed (top) and acid-catalyzed (bottom) hemiacetal formation from carbonyl compounds and alcohols.

What you have learned in Section 9.1.1 about electronic substituent effects explains why intermolecular hemiacetal formation from the electron-deficient carbonyl compounds methyl glyoxalate (A) and ninhydrin (B) take place quantitatively ... 

Fig. 9.6. Stereochemistry of the hemiacetal formation from D-glucose in an aqueous solution at 20 °C (in the formulas, the carbon skeleton of 5-valerolactol is black—which emphasizes the relationship to the reaction from Figure 9.5— whereas the extra substituents as well as the bonds leading to them are red).

Non-specific solute-solvent interactions are reviewed elsewhere in this Volume (p. 83). However certain interactions that are chemical in nature and can be studied by n.m.r. will be mentioned. These include the hydration of pyruvic acid and hydration and hemiacetal formation from carbonyl compounds. 

It had now become clear that if we wished to successfully methylenate the C(l)-carbonyl of 40, we would have to prevent cyclic hemiacetal formation from occurring. A synthetic retreat was therefore beaten, and a triethylsilyl (TES) group was positioned on the C(4)-OH of 63 (Scheme 15). Nucleophilic displacement of the tosyloxy unit now afforded the iodopyranoside 65, and Vasella reductive ring cleavage delivered the desired aldehyde 66 in 85% yield. 

In our new antithetic plan (Scheme 21), Weinreb s oxazolidinone 77 would remain a key synthetic objective. However, the Hoveyda-Grubbs reaction would now be applied to the diene 88. The new route would also block 0(4) of the vinyl aldehyde precursor with a TES ether to prevent hemiacetal formation from occurring. The crucial Vasella... 

Hemiacetal formation from formaldehyde and methanol has been studied by intrinsic reactivity analysis at the B3LYP/6-311-l-l-G(d,p) level and the beneficial combined assistance of watermolecules and Brpnsted acids has been quantified. Theoretical study of hemiacetal formation from methanol with derivatives of CH3CHO (X = H, F, Cl, Br, and I) has shown that the energy barrier can be reduced by a catalytic molecule (MeOH or hemiacetal product)." ... 

Generating Haworth formulas to show stereochemistry m furanose forms of higher aldoses is slightly more complicated and requires an additional operation Furanose forms of D ribose are frequently encountered building blocks m biologically important organic molecules They result from hemiacetal formation between the aldehyde group and the C 4 hydroxyl... 

This is a further example of a carbonyl-electrophile complex, and equivalent to the conjugate acid, so that the subsequent nucleophilic addition reaction parallels that in hemiacetal formation. Loss of the leaving group occurs first in an SNl-like process with the cation stabilized by the neighbouring oxygen an SN2-like process would be inhibited sterically. It is also possible to rationalize why base catalysis does not work. Base would simply remove a proton from the hydroxyl to initiate hemiacetal decomposition back to the aldehyde - what is needed is to transform the hydroxyl into a leaving group (see Section 6.1.4), hence the requirement for protonation. 

Further, and just to stress that this is not new or novel chemistry, let us go back and compare imine formation with acetal formation from hemiacetals (see Section 7.2). 

The approach to polyketide synthesis described in Scheme 5.2 requires the relatively nontrivial synthesis of acid-sensitive enol acetals 1. An alternative can be envisioned wherein hemiacetals derived from homoallylic alcohols and aldehydes undergo dia-stereoselective oxymercuration. Transmetallation to rhodium could then intercept the hydroformylation pathway and lead to formylation to produce aldehydes 2. This proposal has been reduced to practice as shown in Scheme 5.6. For example, Yb(OTf)3-cata-lyzed oxymercuration of the illustrated homoallyhc alcohol provided organomercurial 14 [6]. Rhodium(l)-catalyzed hydroformylation of 14 proved successful, giving aldehyde 15, but was highly dependent on the use of exactly 0.5 equiv of DABCO as an additive [7]. Several other amines and diamines were examined with variation of the stoichiometry and none proved nearly as effective in promoting the reaction. This remarkable effect has been ascribed to the facilitation of transmetallation by formation of a 2 1 R-HgCl DABCO complex and the unique properties of DABCO when both amines are complexed/protonated. 

The much lower thermodynamic stability of hemiorthoesters compared to hemiacetals is illustrated by comparing the equilibrium constant for the formation of [121] from the corresponding hydroxyester, 5 x 10-7 to 1 x 10" 6 (Table 17) with that for the formation of hemiacetal [123] from the corresponding hydroxyaldehyde [122] which is 8.1 in 75 25 dioxan-water... 

Exercise 15-16 Hemiacetal formation is catalyzed by both acids and bases, but acetal formation is catalyzed only by acids. Write the steps involved in the formation of 1-methoxyethanol from ethanal in methanol containing sodium methoxide ... 

Since rapid conversion of hemiacetal to acetal requires more acidic conditions than does formation of the hemiacetal, it is possible to measure the rate of hemiacetal production without complication from the second stage of the reaction.52 As might be expected, the hemiacetal formation displays characteristics similar to those of hydration general acid and general base catalysis are observed.53... 

Lactols are easily transformed into lactones in TEMPO-mediated oxidations.49 When the oxidation of a diol leads to a hydroxyaldehyde that is able to equilibrate with a hemiacetal, the latter is further oxidized to a lactone.50 Interestingly, as TEMPO-mediated oxidations can be very selective in favouring oxidations of less hindered alcohols, lactone formation from diols can be very regioselective.500... 

As can be seen from Figure 9.1, carbonyl compounds without electron-withdrawing a-sub-stituents do not react intermolecularly with alcohols to form hemiacetals to any significant extent. However, while for such carbonyl compounds there is too little driving force for hemi-acetalization to occur, the reaction is not drastically disfavored. This explains why this type of compound undergoes almost complete hemiacetal formation provided it takes place intramolecularly and leads to a nearly strain-free five- or six-membered cyclic hemiacetal— a so-called lactol (Figure 9.4). What makes the difference is that only in the intramolecular hemiacetal formation is no translational entropy lost (because the number of molecules moving about independently of each other does not decrease). 

Draw the structural formulae of both pyranose forms which would result from ring closure (hemiacetal formation) ofD-idose. What is the relationship between these structures and the corresponding pyranose forms derived from L-idose Check your answer by determining the configuration of the chirality centres according to the RIS nomenclature. 

The sugar fructose is an isomer of glucose. Like glucose, fructose forms a cyclic hemiacetal, but in this case the ring is five membered rather than six membered. Show the structure for the hemiacetal formed from fructose and show a mechanism for its formation in acidic solution. 

An interesting, though apparently unique, example of the formation of a furopyrimidine is that of the hemiacetal (237) from the pyrimidinecarboxaldehyde (236) (Equation (79)) <9lJOC56lO>. 

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