Hemiacetals without

Tetrahydro-2H-pyran-2-ol, a model for the xylose ring hemiacetal without other hydroxyl groups, reacted with a monofunctional urea to produce the expected ureide. Continued reaction resulted, as for normal saccharides, in a multitude of products, predominantly aliphatic, in much lower concentration. 

Carb-36.2. Disaccharides without a free hemiacetal group... 

Haworth representation, cyclic monosaccharides, 61-63 Hemiacetal groups disaccharides with, 149-150 without, 148-149 nomenclature, 122-123 oligosaccharides with, 153-154 without, 151-153... 

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 compatibility of Et3B with a hydroxy group is demonstrated by the reaction with cyclic hemiacetals (n = 1 or 2). Here again the reaction proceeds smoothly without using any extra amount of Et3B and provides co-hydroxy bishomoallyl alcohols 44 with an excellent 1,3-asymmetric induction (Eq. 13). 

O-acetylophiocarpine (381) with ethyl chloroformate afforded the C-8—N cleaved urethane 382 in quantitative yield. Sequential treatment of 382 with silver nitrate, PCC, sodium hydroxide, and p-toluenesulfonic acid in ethanol furnished acetal 384, which was reduced with lithium aluminum hydride followed by hydrolysis to afford the hemiacetal 385. Oxidation of 385 with PCC provided (+ )-a-hydrastine (369). Similar treatment of O-acetylepi-ophiocarpine (386) afforded ( )-/J-hydrastine (368) however, in this case, C—N bond cleavage of 386 with ethyl chloroformate proceeded without regioselectivity. 

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. 

Fluoral hydrate and hemiacetals are industrial products. They are stable liquids that are easy to handle, and they react as fluoral itself in many reactions. Thus, in the presence of Lewis acids, they react in Friedel-Crafts reactions. They also react very well with organometallics (indium and zinc derivatives) and with silyl enol ethers.Proline-catalyzed direct asymmetric aldol reaction of fluoral ethyl hemiac-etal with ketones produced jS-hydroxy-jS-trifluoromethylated ketones with good to excellent diastereo- (up to 96% de) and enantioselectivities. With imine reagents, the reaction proceeds without Lewis acid activation. The use of chiral imines affords the corresponding 8-hydroxy ketones with a 60-80% de (Figure 2.49). ° ... 

Inspection of molecular models of the 2,5-anhydroaldohexoses reveals that, when the carbonyl group and the primary alcohol group on C-6 are cis-disposed, as in 2,5-anhydro-a/dehydo-D-glucose (96) for example, the formation of a 1,6-hemiacetal (97) is possible without... 

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... 

Further into the skeleton is another hidden carbonyl group 85 masked as a hemiacetal rather than an acetal. Disconnection there shows up an enol 86 and conversion of the enol into the aldehyde gives the simplest structure we have yet seen 87 without any rings at all. Indeed if we redraw that structure in a more conventional way 88, we can see that it is one continuous piece... 

The stable hemiacetal tetrahydropyranol 94 was used in a Wittig reaction to give the unsaturated ester 95 mostly as the E-isomer. Oxidation, nitroaldol and elimination gave the unsaturated nitro-compound 98. It turns out that the aryl-lithium does conjugate addition without any copper and that it reacts exclusively with the nitroalkene to give 99. 

As noted above, one difficulty which prevents versatile use of levoglucosenone 1 is its sturdy internal acetal functionality. We, therefore, designed12 a levoglucosenone carrying a handle on an appropriate position such as 6-alkoxymethyllevoglucosenone 20 so as to cleave the internal acetal functionality without difficulty. If 20 is available, its acetal linkage may be cleaved after conversion into a halomethyl derivative 21 to give a hemiacetal 22 under reductive conditions (Scheme 6). 

When aldehydes and ketones are dissolved in alcohol without an acid catalyst being present, only the first part of the above mechanism occurs with one alcohol molecule adding to the carbonyl group. An equilibrium is set up between the carbonyl group and the hemiacetal or hemiketal, with the equilibrium favouring the carbonyl compound ... 

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). 

When the hemiaminals A (Figure 9.12, Nu = NR3R4) are formed in a neutral or weakly basic solution, they also have the possibility to react further by an SN1 reaction albeit in a different manner than just described for the corresponding hemiacetals (Nu = OR3) and hemithioacetals (Nu = SR3). The OH group of hemiaminals A is then ejected without prior protonation (i.e., simply as an OH ion). This is possible because an especially well-stabilized carbocation is produced at the same time, that is, the iminium ion C (Nu = NR3R4). It reacts with the second equivalent of the N nucleophile. Proton loss affords the jVW-acetal B (Nu = NR3R4). 

As can be seen from Figure 7.7, carbonyl compounds without electron-withdrawing a-substituents 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 hemiacetalization to occur, the reaction is not drastically disfavored. This... 

A proton has to be transferred from one oxygen atom to the other we have shown ethanol doing this job, with one molecule being protonated and one deprotonated. There is no overall consumption of ethanol in the pro to nation/deprotonation steps, and the order in which these steps happen is not important. In fact, you could reasonably write them in one step as shown in the margin, without involving the alcohol, and we do this in the next hemiacetal-forming reaction below. As with all these carbonyl group reactions, what is really important is the addition step, not what happens to the protons. 

Just as protonated carbonyl groups are much more electrophilic than unprotonated ones, these oxonium ions are powerful electrophiles. They can react rapidly with a second molecule of alcohol to form new, stable compounds known as acetals. An oxonium ion was also an intermediate in the formation of hemiacetals in acid solution. Before reading any further, it would be worthwhile to write out the whole mechanism of acetal formation from aldehyde or ketone plus alcohol through the hemiacetal to the acetal, preferably without looking at the fragments of mechanism above, or the answer below. 

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