Acetals and Thioacetals

The C-4 carbon in phthiocerol A has been assigned the 5-configuration. Acetals and Thioacetals.—A catalytic dehydrator for rapid acetal synthesis has been described a combination of an acid ion-exchange resin and a drying agent is used. Ingenious use is made of molecular sieves in a related 

Deluzarche, A. Maillard, P. Rimmelin, F. Schue, and J. M. Sommer, Chem. Comm., 

Steroidal alcohols, masked as their tetrahydropyranyl ethers, benzyl ethers or bismethylenedioxy-derivatives, can be deprotected by the trityl carbonium ion in a hydride-transfer process. This method of regeneration should be equally applicable to other protected groups such as amines and carboxylic acids. 

Whereas lithium aluminium hydride-aluminium trichloride reduction of monothioacetals effects carbon-oxygen cleavage to give hydroxythioethers. 

Full details have been published for the preparation of the valuable carbonyl synthon, 1,3-dithian. 

By losing water rather than ethanol from the protonated hemiacetal, we seem to have reached an impasse—we can t just drop off an ethyl cation to go back to the ketone. However, if we compare 14.22 with the protonated carbonyl compound, 14.23, electronically, they are quite similar. So we would expect that 14.20 could be attacked by a nucleophile in the same 

FIGURE 14.25 Dean-Stark Thiols react with carbonyls in the same way as do alcohols. Using the reaction of alcohols as your apparatus. guide, write a mechanism for the reaction in the following, of 2-hexanone  

Note that thioacetals are not easily deprotected using aqueous Bronsted acids sulfur is much less easily protonated than oxygen. The normal conditions for thioacetal hydrolysis employ catalysis. 

You might have thought that the alkyne could also be hydrated under conditions of aqueous acid, but it was possible to adjust conditions to select for the sequence shown. 

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C. Moreau, J. Lecomte, S. Mseddi, and N. Zmimita, Stereoelectronic effects in hydrolysis and hydrogenolysis of acetals and thioacetals in the presence of heterogeneous catalysts, J. Mol. Catal. A Chem., 125 (1997) 143-149. 

Chinese researchers reported a synthetic route to photochrome 16 (Scheme 7), in which the aldehyde functions are then transformed into cyclic acetals and thioacetals, methylol and dicyanoethylene groups (07T5437, 08T2576). Scheme 7 also gives (at the bottom) symmetrical photochrome 17 (where R are ferrocenyl substituents), which does not exhibit fluorescence in the initial state, but shows fluorescence in the cyclic form and which is also synthesized starting from dialdehyde 16 (08AFM302). 

TABLE 6.5. RATIOS OF 4- AND 5-REGIOISOMERS 19 AND 20 IN CYCLOADDITIONS TO a,P-UNSATURATED ACETALS AND THIOACETALS"... 

The catalyst exhibited high enantiomer selectivity in the reaction of the six-membered cyclic acetate roc-lab with KSAc on a 2.5 mmol scale. This led to the isolation of the thioacetate 19aa with 97% ee in 48% yield and the acetate ent-lab with >99% ee in 43% yield (entry 8). The reaction came to a practically complete halt after 51% conversion of the substrate. In order to determine the selectivity factor S, the kinetic resolution of roc-lab was repeated and the ee values of the acetate and thioacetate were monitored over the whole course of the reaction (Fig. 

One of the most reactive electrophilic alkenes is l,l-dicyano-2,2-bis(trifluoromethyl)ethene which undergoes cycloadditions with enol ethers, thioenol ethers, ketene acetals and thioacetals even at temperatures as low as — 78 °C. The cyclobutancs are formed as the sole products of the reaction.37-38 The reactions arc regiospecific and highly stereoselective even though evidence for zwitterionic intermediates have been obtained. 

Ketene acetals and thioacetals can be used as ketene equivalents in cyclobutanone synthesis in situations where ketene to alkene cycloadditions are inefficient such as in the case of electron-deficient alkenes.14 Although thermal cycloadditions of ketene acetals and thioacetals with electron-deficient alkenes have been observed (see Section 1,3.2.1.), such cycloadditions proceed more efficiently and under milder conditions with metal catalysts. Efficient cycloadditions between ketene dimethyl acetal and alkenes substituted by a single electron-withdrawing group have been reported.15... 

Ketcnc equivalents, such as ketene acetals and thioacetals, can be used in cycloadditions to electron-deficient alkenes (see Sections 1.3.2.1. and 1.3.2.2.). In an example of a fumaric acid diester fitted with two chiral alcohol auxiliary groups, the aluminum(III)-catalyzed cycloaddition of 1,1-dimethoxyethene with di-(—)-menthyl fumarate (9) proceeds with > 99% diastereomeric excess. Intermediate 10 can be readily converted to cyclobutanone derivatives.17, 18... 

Table 3. Cyclopropanone acetals and thioacetals from carbene additions...

Further Experiments on the Oxidation of Sugar Acetals and Thioacetals by Aceto-bacter suboxydans, D. T. Williams and J. K. N. Jones, Can. J. Chem., 45 (1967) 741-744. 

In the presence of M0CI5, acetals and thioacetals act as electrophiles towards tri-methylstyrylsilanes [45,46], WCle and TiCU can also be used in this reaction but they are less efficient (Sch. 4) [45]. 

The words acetal and thioacetal are written after the name of the parent sugar as in D-glucose dimethyl acetal 4.33 and D-glucose dimethyl dithioacetal 434. 

Steric interactions dramatically increase the free energy difference for acetates and thioacetates. For example, AG° is respectively 9.3 and 4.9 kcal mol-1 for methyl acetate and methyl thioacetate, compared to AG° = 2.1 and 1.3 kcal moT1 for methyl formate and methyl thioformate respectively. In turn, the barrier to rotation remains the same order of magnitude with AGtE z = 12.4 (methyl acetate) and 10.1 kcal mol-1 (methyl thioacetate). 

Organoyttrium catalysts have been utilized to effect the cyclization of dienes under reductive conditions [39]. Excellent selectivity is achieved in these reactions between two monosubstituted alkenes leading to a single regioisomeric product (Eq. 40), and the diastereoselectivity is consistent with the simple chair transition structure model (Fig. 7). Both acetals and thioacetals are tolerated (Eq.41), whereas nitriles, esters, and sulfones preclude product formation (Eq.42). 

Captodative alkenes 67 can be dialkylated, for example, by addition of iso-butyronitrile radical derived from thermal decomposition of AIBN under the same conditions as those which lead to polymerization of other acrylic alkenes. For example, a-morpholino-acrylonitrile (67, c = CN, d = N(CH2CH2)20) leads to 69, in 71% yield (Scheme 12) [4a]. With a-/-butylthio-acrylonitrile (67, c = CN, d = SC(CHj)3), the same process leads to 70 in 88% yield [7]. The adduct radical 68 is highly stabilized, and is in equilibrium with dimer 70. The reaction is quite general, and has been applied to other captodative alkenes (c = CN, COR, CO2R and d = NR2, OR, SR) together with various sorts of radical partners, derived from alkanes, alcohols, thiols, thioethers, amines, amides, ketones, aldehydes, acetals and thioacetals [44, 45]. 

DDQ, a reagent typically used to deprotect p-methoxybenzyl ethers (see section 4.3.4), has been used for the deprotection of acetals and thioacetals. The use of 0.1-0.4 equivalents of DDQ in acetonitrile-H20 (9 1) cleaves isopropylidene groups at room temperature to 80 C without affecting p-toluenesulfonyl, benzoyl, benzyl, or acetate groups. Monosubstituted dioxolanes [Scheme 3.17] are more readily hydrolysed than bicyclic, spirocyclic, and disubstituted systems and 1,3-dioxanes are more labile than 1,3-dioxolanes. Removal of dithioacetals requires 2 equivalents of DDQ at 80 C. 

Glycosides, Simple Acetals, and Thioacetals, M. L. Wolfrom and Alva Thompson, in The Carbohydrates, W. Pigman, Ed., Academic Press, Inc., New York, 1957, pp. 188-240. 

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