Unsaturated hemiacetal

In the retrosynthetic plan (Scheme 14), the key step was based on the crucial supposition that the truns-fused bicyclic hemiacetal Dill would undergo a reversible ring tautomerization with the monocyclic system DII, the skeletal and functionalization of which are well correlated with both actinobolin 1 and bactobolin 2 (vide infra). Further retrosynthesis of Dill led to unsaturated hemiacetal DIV which is reminiscent of a 2,3-unsaturated pyranose (i.e., a pseudo glycal) [46], and thence to lactone DV. The construction of the unsaturated bicyclic lactone therefore constituted the first plateau of this synthesis. 

Enol Ethers. Treatment of testosterone acetate with 2,2-dimethoxypropane/DMF/TsOH converts this material into the enol ether (eq 9). In this case, enol ether formation is attributed to loss of water directly from the unsaturated hemiacetal. 

The methyl enol ether 37 is oxidized to the a,/3-unsaturated aldehyde 39 via hemiacetal 38. Unsaturated aldehyde 39, elongated one carbon from the aldehyde 36, is prepared by the Wittig reaction of 36 to give 37, and application of this reaction[ 88]. 

If the carbonyl and the hydroxyl group are in the same molecule, an intramolecular nucleophilic addition can take place, leading to the formation of a cyclic hemiacetal. Five- and six-membered cyclic hemiacetals are relatively strain-free and particularly stable, and many carbohydrates therefore exist in an equilibrium between open-chain and cyclic forms. Glucose, for instance, exists in aqueous solution primarily in the six-membered, pyranose form resulting from intramolecular nucleophilic addition of the -OH group at C5 to the Cl carbonyl group (Figure 25.4). The name pyranose is derived from pyran, the name of the unsaturated six-membered cyclic ether. 

Reaction of 1,2-glycol systems, such as in the hemiacetal sesquiterpene 1751, with Me3SiCl/NaI in acetonitrile for 5 min at ambient temperature affords more than 80% of the corresponding olefin 1752 [15, 16] (Scheme 12.4). On reacting active methylene groups such as in ethyl acetoacetate or acetylacetone with benzal-dehyde in the presence of TCS14/Nal in acetonitrile, the intermediate unsaturated ketones 1753 and 1755 are reduced to ethyl 2-benzylacetoacetate 1754 [17] or 2-benzylacetylacetone 1756 [18] in 82% and 80% yield, respectively. 

Such a secondary photoreaction can be avoided by trapping the unsaturated aldehyde, e.g. as a hemiacetal. This principle is demonstrated in the synthesis of a furanoid sesquiterpene (2.6)210). 

Hydroformylation of unsaturated amines offer a convenient synthetic access to cyclic AT.O-hemiacetals. If performed in the presence of alcohols or orthoesters AT,O-acetals are formed. With additional N-nucleophiles N,N-acetals are obtained. These compounds are synthetically attractive building blocks and were therefore used as a key step in the synthesis of various natural products [27,35]. Thus the synthesis of (+)-prosopinine starting from enantiopure (T)-scrinc leads to a cyclic N,O-acetal functionality with the required functionality for the attachment of the side chain (Scheme 6) [36]. 

Dehydrations have been observed to be caused by water-accepting reagents. Thus cyclic hemiacetal 259 was dehydrated with oxalic acid to 2,2,4-trimethyl-2//-pyran (260) in a 50% yield289 (for similar examples see Section IV,G,1 and IV,G,4). The dehydration of easily accessible hemi-acetals 263 to appropriate condensed 4//-pyrans, e.g., 263a - 27 and 263b - 264, proceed smoothly in an acidic medium.59,290 Similarly, dehydration 28 - 27 has been mentioned in Section III,A. A more complex dehydration agent consisting of phthalimide, triphenylphosphine, and diethyl azodicar-boxylate was used for the transformation of stereoisomeric unsaturated monosaccharides 261 to 2//-pyran 262 (15 to 26%).291... 

Reduced furan rings occur in many important anhydrides, lactones, hemiacetals and ethers. Maleic anhydride is frequently used as a dienophile in Diels-Alder reactions and it is a component of alkyd resins. Several unsaturated y-lactones are natural products, while the furanose sugars are cyclic hemiacetals. 

Below this GA concentration, the relative content of each monomeric structure was found to be virtually constant regardless of the GA concentration, and also pH (pH2- 8), in contrast to the temperature which has marked effect on it On the other hand, above this concentration, considerable amount of polymerized structures exist in GA solution, which are closely related with cyclic hemiacetal structure, that is, again not related with a, 0- unsaturated structure. The conversion velocity between the monomeric and polymerized structures is quite slow, compared to that between the monomeric structures. The chemistry of GA in concentrated aqueous solution will be discussed in detail elsewhere. 

The functions of flavoprotein enzymes are numerous and diversified.151-1533 A few of them are shown in Table 15-2 and are classified there as follows (A) oxidation of hemiacetals to lactones, (B) oxidation of alcohols to aldehydes or ketones, (C) oxidation of amines to imines, (D) oxidation of carbonyl compounds or carboxylic acids to a,(3-unsaturated compounds,... 

Unsaturated 1,5-diones are in the correct oxidation state for direct conversion to pyrylium salts and in fact they cyclize spontaneously under strongly acidic conditions. The reaction is thought to involve three steps initial enolization is followed by ring closure to the hemiacetal and subsequent rapid dehydration to the pyrylium salt (Scheme 247). 

The related synthesis of benzopyrylium salts involves the condensation of salicylaldehydes with methyl ketones in a basic medium, which affords the unsaturated ketone (642). Cyclization occurs on treatment with acid. The same benzopyrylium salt is formed rapidly and in high yield if the condensation is effected under acidic conditions (Scheme 252) (73BSF3421). It has been proposed that the latter synthesis proceeds via an aldol condensation accompanied by the formation of a hemiacetal, followed by dehydration. 

The hemiacetal exists as an equilibrium mixture of cyclic compound 20 and its open counterpart (21), but an aldehyde addition reaction can occur only with the acyclic form A Wittig reaction of the stabilized ylide leads to an a. (3-unsaluraied ester that has the configuration with respect to the double bond. This reaction occurs under neutral conditions, so 1,4-addition of the alcohol to the a.p-unsaturated ester is avoided.6 A subsequent DIBAH reduction leads to ally lie alcohol 6 in a reaction that ordinarily shows complete 1,2-selectivit. ... 

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. 

After conjugate addition of the hydroperoxide anion to the chelated a,p-unsaturated lactone, the resulting enolate counterattacks the proximal [3-hydroperoxide group to form an epoxide. The latter then ring-expands to create another enolate, which captures a proton from water. The product hemiacetal finally undergoes ring-opening and saponification to produce 9 (Scheme 6.5). 

Alkenyl and aryl substituents stabilize the C=0 double bond of carbonyl compounds even more than alkyl substituents. This is due to their pi electron-donating (+M) effect, which allows one to formulate additional zwitterionic resonance forms for carbonyl compounds of this type. Thus, no hydrates, hemiacetals, oligomers, or polymers can be derived from unsaturated or aromatic aldehydes. 

Synthetically even more versatile trifunctional intermediates result from the addition of carbonyl compounds onto methyl 2-siloxycyclopropanecarboxylates 92). Benzo-phenone, titanium tetrachloride, and 162, for instance, provide an excellent yield of the a-hydroxyalkylated y-oxoester 174, which predominates in the equilibrium with its cyclic hemiacetal 176 (y-lactol). It can undergo elimination to the unsaturated ester 175, but as Scheme 7 illustrates, 174/176 can also serve as the starting material to several highly substituted furan(one) derivatives. 

Peroxymonosulfuric acid (Caro s acid, H2S05) and its salts may be used to oxidize aldehydes. Although early results were poor compared with the use of organic peracids, good yields of esters have been obtained when reactions are carried out in the presence of alcohols.225 Unsaturated and aromatic aldehydes undergo analogous reactions. It is believed that hemiacetal formation occurs in these reactions, and that it is this species which is oxidized, rather than the aldehyde. 

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