Acetic acid Lewis acids

The scope of this reaction is similar to that of 10-21. Though anhydrides are somewhat less reactive than acyl halides, they are often used to prepare carboxylic esters. Acids, Lewis acids, and bases are often used as catalysts—most often, pyridine. Catalysis by pyridine is of the nucleophilic type (see 10-9). 4-(A,A-Dimethylamino)pyridine is a better catalyst than pyridine and can be used in cases where pyridine fails. " Nonbasic catalysts are cobalt(II) chloride " and TaCls—Si02. " Formic anhydride is not a stable compound but esters of formic acid can be prepared by treating alcohols " or phenols " with acetic-formic anhydride. Cyclic anhydrides give monoesterified dicarboxylic acids, for example,... 

Suitably protected glycosyl halides or acetates, upon Lewis-acid promoted SN1 heterolysis, generate glycosyl cation intermediates that can react with electron-rich arenes, heteroarenes, Me3SiCN, enoxysilanes, enamines, allyl silanes and stannanes, acetylenyl silanes and stannanes affording C-glycosyl compounds. 

Many such activated acyl derivatives have been developed, and the field has been reviewed [7-9]. The most commonly used irreversible acyl donors are various types of vinyl esters. During the acylation of the enzyme, vinyl alcohols are liberated, which rapidly tautomerize to non-nucleophilic carbonyl compounds (Scheme 4.5). The acyl-enzyme then reacts with the racemic nucleophile (e.g., an alcohol or amine). Many vinyl esters and isopropenyl acetate are commercially available, and others can be made from vinyl and isopropenyl acetate by Lewis acid- or palladium-catalyzed reactions with acids [10-12] or from transition metal-catalyzed additions to acetylenes [13-15]. If ethoxyacetylene is used in such reactions, R1 in the resulting acyl donor will be OEt (Scheme 4.5), and hence the end product from the acyl donor leaving group will be the innocuous ethyl acetate [16]. Other frequently used acylation agents that act as more or less irreversible acyl donors are the easily prepared 2,2,2-trifluoro- and 2,2,2-trichloro-ethyl esters [17-23]. Less frequently used are oxime esters and cyanomethyl ester [7]. S-ethyl thioesters such as the thiooctanoate has also been used, and here the ethanethiol formed is allowed to evaporate to displace the equilibrium [24, 25]. Some anhydrides can also serve as irreversible acyl donors. 

N, P ] and [P, P ] Aldehydes with an a-stereocenter exhibit unusually high diastereofacial preferences for the addition of silyl enol ethers and ketene acetals with Lewis acid assistance (81). Heathcock and Uehling found good levels of facial discrimination in the addition of silyl enol ethers to chiral enones (Scheme 38, Table 11) (82). With the more substituted silyl enol ether, only one diastereomeric addition product is obtained (Eq. [1], Scheme 38). Use of a prostereogenic silyl enol ether allows control over the relative... 

A question of regiochemistry arises with O-silylated dienolates derived from a, -unsaturated aldehydes, ketones and esters. The silylated dienolates of crotonaldehyde and its 3-methyl derivative (108) react with acetals in Lewis acid catalyzed conditions at the y-position. This high regioselectivity has been used in the synthesis of vitamin A acetate (Scheme 41). ... 

Type-Ill cyclizations are initiated by conversion of an acetal, ketal or enol ether into an oxonium ion. Such an activated carbonyl group attacks an olefin intramolecularly in an exo reaction. Mono- and trialkylated double bonds form new C-C bonds regioselectively at the least hindered terminus according to Markovnikov s rule, and in this case endo cyclization products can be produced25. It is worth noting that acetals are also used as initiators in cation olefin cyclizations (see Section 1.5.5.3.)26. Use of activated acetals in Lewis acid catalyzed C-glycoside synthesis is also known 12c 12e. 

Eight- and nine-membered cyclic ethers are also generated via type-III reactions by treating the 5-hexen-l-ol acetals with Lewis acids. 8-endo Cyclization of 5-hexenyl methoxyethoxymethyl ether in the presence of two equivalents of tin(IV) chloride forms a 2 1 mixture of chlorinated and unsaturated 1 -oxycyclooctanes 11 and 1232. Vinylsilane undergoes an 8-endo Prins cyclization. After O-desilylation, oxocene 13, which is used as a precursor in a laurenyne synthesis, is obtained in 37% yield33. 

High yields of seven-membered rings can be achieved by treating ally] acetates with Lewis acids. The dimethylsilyl enol ether exclusively attacks the least alkylated terminus of the initial allyl cation3. 

Ketene silyl acetals undergo Lewis acid catalyzed addition to imines to give /3-amino esters, which can then be cyclized in a second step to give /3-lactams. Chiral substituents, which might control the configuration of the product, can be introduced into R1, R2, R3 or R4. 

The stereochemistry of the reaction of crotylsilanes with acetals under Lewis acid catalysis was studied by Sakurai and coworkers78 (equation 73). It was found that with... 

Weaker catalysts (e.g., tin tetrachloride or titanium tetrachloride25) require the presence of a co-catalyst such as water, tert-butyl alcohol, acetic acid, trichloroacetic acid, or sulfuric acid. The actual polymerization catalyst is then probably the Lewis acid formed. As an example, isobutene reacts only slowly at —80° in hexane containing titanium tetrachloride, but a violent reaction occurs if moist air is led slowly through the mixture. Evans and Meadows26 similarly found that no reaction occurs when completely anhydrous isobutene is kept with anhydrous boron trifluoride for 2 hours at —80° in a flask that was previously dried in a high vacuum at 400° but that immediate reaction occurs if the vessel is dried without being heated in a high vacuum. From the last experiment it can be concluded that a co-catalyst is necessary even with power-... 

Mukaiyama aldol reaction. Chemoselective ionization of a mixed-0,5-acetal by Lewis acid is noted. Thus, it is possible to synthesize 3-alkoxyketones or... 

Aldol condensation. The reaction of A-protected a-amino aldehydes with ketene silyl acetals is jy/i-selective in the presence of (/-PrO)2TiCl2. (V,(V-Disubsti-tuted amides and thioamides behave similarly, although the less acidic Lewis acid (i-PrO)3TiCl is used as catalyst. ... 

The relatively weak leaving group (acetate) is lost from the allylic acetate with Lewis acid catalysis to give a stable allyl cation. This couples with the other (isopentenyl) acetate in a way very similar to the natural process. However, what happens to the resulting cation is not well controlled. Loss of each of the three marked protons gives a different product. In the enzymatic reaction, loss of the proton would probably be concerted with C-C bond formation as a basic group, such as an imidazole of histidine or a carboxylate anion, would be in the right position to remove one of the protons selectively. 

Glycosides. Glycosides can be prepared conveniently by reaction of peracyl derivatives of D-ribofuranose or D-glucopyranose with N,N-dimethylformamide dialkyl acetals under Lewis acid catalysis (equations I and II). Unlike classical methods, this new glycosidation method does not employ the unstable glycosyl halides. 

The first industrial synthesis of ) -carotene by Hoffmann-La Roche followed the Ci9 + C2 + Ci9 principle. With the Ci4-aldehyde from the Vitamin A synthesis as the starting point, the sequence of acetal formation, Lewis acid-catalysed insertion of an enol ether, hydrolysis and elimination of ethanol, produces initially a Cjg-aldehyde. Repetition of this sequence with ethyl 1-propenyl ether gives the Cjg-aldehyde. 

Formaldehyde is a strong electrophile, allowing acetal to polymerize by nucleophilic, anionic, or cationic addition of an alcohol to ketene carbonyl groups. Relatively weak bases such as pyridine initiate anionic addition polymerization cationic addition polymerization is catalyzed by strong acids. When the cyclic trimer trioxane is used as a copolymer to polymerize acetal copolymers, Lewis acids such as boron tiifluoride promote copolymerization. A more fundamental description is polymerization of an aldehyde or ketone -l- alcohol -i- an acid or base catalyst to form hemiac-etal, which further converts to acetal. The hemiacetal reaction is reversible to aldehyde and alcohol. 

Figure 1. C-NMR Spectra of Heptanal Dimethyl Acetal and Lewis Acids at -80 C.

The capnellane (109) has been synthesized, using two dififerent annulation procedures (Scheme 11). The a/b ring junction was formed through consecutive Michael and ene-type reactions by addition of a lithium cuprate to 3-methyl-cyclopent-2-enone and trapping of the enolate anion that is thus formed as the enol acetate (110). Lewis-acid-induced cyclization then formed the ketone (111). 

Preparation by Fries rearrangement of phenyl acetate with Lewis acids aluminium chloride,... 

Acetylation. The most notable use of acetic anhydride is for the acetylation reaction of alcohols, amines, and thiols. Acids, Lewis acids, and bases have been reported to catalyze the reactions. 

Although the chemistry of acetal and ether bonds is quite different, cyclic acetals bear some resemblance to cyclic ethers thus the polymerization of both groups of monomers shows some similarities. Essentially the same groups of initiators that initiate cationic polymerization of cyclic ethers (i.e., strong protonic acids, Lewis acids, or oxonium, carbenium, or oxocar-benium salts) are also effective in the polymerization of cyclic acetals. On the other hand, there are distinct differences. 

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