Reactions trans-acetalization

Fully acetylated hexopyranoses react with thiols in the presence of Lewis acids, such as BF3-Et20.32,33 The reaction is faster with 1,2-trans acetates than with the corresponding 1,2-cij ones and 1,2-trans products predominate. Alkyl, alkenyl, and aryl thioglycosides are produced by this method. Variations on this method include the use of trimethylsilyl34 or stannyl derivatives35 of the thiols. 

Electrochemical reduction of a,a -dibromoketones affords the unstable cyclo-propanone, which is in equlibrium with the dipolar intermediate 22. The cyclopro-panone hemiacetal is isolated in yields of 40 - 85 % from reaction in acetonitrile and methanol at -20 °C [99], The dipolar form can be trapped in a cycloaddition process with furan [100], Reaction with acetic acid leads to the a-acetoxy-ketone.[101]. Unstable three membered heterocyclic rings are intermediate in the reduction of sulphur and phosphorus linked dibromo compounds 23. In these reactions, the heteroatom is extruded leaving ci - and trans-stilbenes as the isolated products [102,103],... 

While neither cis- nor tran.s-4-tc/t-butylcyciohexanol is a chiral molecule, the stereochemical course of their reactions with acetic anhydride becomes evident when the relative stereochemistry of the ester function is examined for each case. The cis alcohol yields the cis acetate. 

Nucleophilic addition to ir-allylpalladium complexes is known to take place widi a range of nucleophiles. and die mechanism and steieochonistry of diese reactions have been thoroughly investigated over die last few years. - For example, reaction with acetate anion occuis in the presence of benzoqui-none at room temperature in acetic acid solution by initial cis attack at the metal atom and subsequent migration. Alternatively, in die presence of chloride ions, a trans attack takes place to give the pr uct of opposite stereochemistry (Scheme 10). Intramolecular versions of the reaction are known. ... 

Cleavage of epoxides (6, 16-17 8, 10-12). Cleavage of epoxides catalyzed by Woelm neutral alumina is particularly useful in the case of medium-ring epoxides, which are generally rather unreactive and which are liable to undergo transannular reactions. For example, rfs-cyclooctene oxide supported on neutral alumina is converted to tran.s-2-acetoxycyclooctanol in 78% yield by reaction with acetic acid at... 

Scheme 5.1.20 In competition reactions, stannylene acetals derived from isolated c s-diols are less reactive than those from trans-d/o/s ...

There are several ways to prepare cyclic acyloxonium ions. We will only discuss the reaction of antimony pentachloiide with vicinal diacetates and vicinal chloro- or bromo-acetates because this technique has allowed a most interesting reaction in carbohydrate chemistry (reaction 7.9). The acyloxonium cation can react in two ways the so-called kinetic reaction takes place at the most charged site as, for example with H2O and OH, to give the unstable orthoester 7.20 which opens to the cis-hydroxyl ester 7.21. The so-called thermodynamic reaction, with acetate in an acidic medium, choride, and bromide leads to the formation of the trans product 7.22 (X = AcO, Cl, Br). 

In suitable cases such as cis/trans-isomers, the difference in strain energies can be determined from equilibrium constants or heats of hydrogenation. It is apparent from Table 20 that both methods give similar results. The strain energy of the Bredt-olefin 69 has been estimated from the heat of reaction with acetic acid, with the calculated AHR of the corresponding reaction of 2-methyl-2-butene (257a) as standard (219). 

VIII. 3 Total Synthesis Trans-Acetalization Reaction 339... 

This reaction usually works for nonenolizable imines (e.g., A -aryl aldimines) and has the features of readily accessible starting materials, and simple preparation of 3-substituted or unsubstituted 2-azetidinones (i.e., 3-lactams) with direct control of stereoselectivities. It has been reported that the yield of this reaction depends on the activation and the type of zinc. The stereochemistry of /3-lactams depends on the a-substituent of bromoacetates, the solvent, and the alkyl portion of the esters. For example, when the a-substituent is an alkyl group (e.g.. Me, Et, /-Pr, cyclohexyl, r-Bu), the major product has cis geometry, such a trend is especially prevailing for the reaction of acetate with a branched a-substituent (e.g., j-Pr, cyclohexyl, r-Bu) in THF. s For comparison, the reaction of isopropyl acetate in toluene tends to form jS-lactams of trans geometry. In addition, phenyl acetates favor the trans isomers regardless of the solvents. ... 

Nucleophilic substitution reactions of acetates 88 and 90 (Fig. 4.32) indicate that a single substituent at C2 is not the origin of stereoselectivity for acetal 83 (Fig. 4.32). Treatment of the trans acetate 88 with aUyltrimethylsilane in the presence of SnBr4 provided the 1,4-c/s product 89 with 67 33 stereoselectivity (Fig. 4.32). Use of BF30Et2 and Me3SiOTf as the Lewis acid provided similar selectivities. The reaction of the related cis acetate 90 also afforded a mixture of diastereoisomers. Low selectivity with C2 and C4-c/s-substituted five-membered ring oxocarbenium ions has been observed [108]. 

Both the cmifomiational preference of the oxocarbenium ion intermediate and steric interacti(His that arise in the transitimi structure for nucleophilic attack influence the stereochemical outcomes observed with acetates 88 and 90. While the two ground-state cOTiformers of the cation derived from trans acetate 88, namely, 92 and 93, are comparable in energy, developing steric interactions between the approaching nucleophile and the pseudoequatorial methyl of intermediate 93 slightly disfavor the fomiatitHi of 1,4-trans product (Fig. 4.33). The selectivity obtained from the reaction... 

The mechanism in Figure 9.5 also provides a rationalization for some observations of solvent effects in bromine addition reactions. The major product of the reaction of bromine with cyclohexene in methanol is trans-2-bromo-l-methoxycyclohexane. traMS-l,2-Dibromocyclohexane is observed if Br is added to the solution, but the yield of the dibromo adduct approaches 0% as [Br ] approaches 0 M. This result stands in contrast to the 27% of 1,2-dibromo adduct obtained from the corresponding reaction in acetic acid. It appears that the greater polarity of methanol accelerates the dissociation of IIP to DI, and the greater nucleophiliciW of methanol enhances the reaction of solvent with IIP, SSIP, DI, and SSIP. ... 

The differences in reactivities in poly(vinyl alcohol)s between isotactic meso) and syndiotactic (trans acetals [26-28] is another example. In extending this to model compounds, reactions of stereo isomers of pentane-2,4-diol and heptane-1,4,6-triol with formaldehyde take place much faster for the meso than for the dl-diol portions [26-28]. Even more important are the steric effects imposed by restricted rotations. For instance, quatemizations of chloromethylated polyether sulfmies exhibit decreasing rates at high degrees of substitution. This can be attributed to restricted rotations of the polymeric chains, because this phenomenon is not observed with more flexible chloromethylated polystyrene under identical conditions [23, 24]. 

Intramolecular reactions ofallylic acetates with conjugated dienes catalyzed by Pd(0) lead to a 1,4-addition of a carbon and an oxygen to the diene. The reaction, which is formally an isomerization, involves two different 7t-allyl complexes (Scheme 11.5) [49]. Reaction of 28 in the presence of the Pd(0) catalyst Pdjldba), CHClj and LiOAc/HOAc in acetonitrile under reflux produces the cycHzed isomer 31 in 62% yield. The double bond had exclusively ( )-configuration, while the configuration on the ring was a mixture of cis and trans. Oxidative addition of the allylic acetate to the Pd(0) species gives the intermediate it-aUyl complex 29. Subsequent insertion of a diene double bond into the allyl-palladium bond produces another it-allyl intermediate 30, which is subsequently attacked by acetate to give the product 31. 

Esterification with the dineopentyl acetal is very slow (benzoic acid, 80° in benzene, 1 hr —7% yield of ester) and this reagent is used conveniently as a catalyst in the direct esterification of acids and alcohols (benzyl and p-methoxy-benzyl alcohol) where for the alcohol k kneope tyi. Trans-acetalization occurs initially via the reaction (a). 

Trans-acetalization is also useful. Treatment of a ketone with excess 2-ethyl-2-methyl-l, 3-dioxolane in acid gives 2-butanone and the new ketal (Eq. 6.33) [56]. In some cases, a smaller excess of dioxolane is used and the reaction is driven by distilling the 2-butanone as it is formed. 

In 2010, List reported a catalytic enantioselective intramolecular trans-acetalization reaction via Bronsted acid catalysis [37a]. Chiral 0,0-acetals, which are usually synthesized by enzymatic resolutions or metal-catalyzed desymmetri-zations, could now be easily obtained by catalysis with phosphoric acid 107. Alcohols 108 with both aUphatic and aromatic substitutions are suitable substrates, furnishing the tetrahydrofurans 109 in high yields and enantioselectivity (Scheme 36.29). 

Scheme 36.29 Enantioselective intramolecular trans-acetalization reaction.

Basic catalysts other than alkali acetates have been employed in the Perkin reaction thus salicylaldehyde condenses with acetic anhydride in the presence of triethylamine to yield coumarin (tlie lactone of the cis form of o-hydroxy-cinnamio acid) together with some of the acetyl derivative of the trans form (o-acetoxycoumaric acid) ... 

As supporting evidence, rapid isomerization of the ds- and maui-Tr-allylpal-ladium complexes 27 and 28 is catalyzed by Pd(Ph3P)4 in THF even at -15 C to give a 45 55 equilibrium mixture from either 27 or 28[29-31].. Actually, in the intramolecular reaction of soft nucleophiles of 29 and 30, a trans-ds mi.xttire (31 and 32) (1 1) was obtained from /raiw-allylic acetate 29. On the... 

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