In acyclic acetals

In a similar reaction, bromosuccinic acid and thiobenzamide in ethyl-acetate yielded an acyclic intermediate (229), Ri = Ph, R2 = CH2C02H, which by heating in water cyclizes to the thiazole (230), Rj = Ph and R2 = CH2C02H. (260). 

The anomeric effect is also present in acyclic systems and stabilizes conformations that allow antiperiplanar (ap) alignment of the C—X bond with a lone-pair orbital of the heteroatom. Anomeric effects are prominent in determining the conformation of acetals and a-alkoxyamines, as well as a-haloethers. MO calculations (4-3IG) have found 4kcal/mol as the difference between the two conformations shown below for methoxy-methyl chloride. ... 

A vinyl cation is probably an intermediate in the acetolysis of 6-phenyl-5-hexynyl brosylate, 86. At 80°, despite the inductive effect of the triple bond, the rate of acetolysis of 86 is comparable to that of the saturated analog and yields, besides the acyclic acetate 87, 36% of the rearranged acetate 88 (83). The exclusive formation of the five-membered ring rearranged product with none of... 

In contrast to the allyltitaniums derived from acrolein cyclic acetals, such as 1,2-dicyclo-hexylethylene acetal shown in Scheme 9.8, those derived from acrolein acyclic acetals react with ketones and imines exclusively at the y-position. As shown in Eq. 9.29, the reaction with chiral imines having an optically active 1-phenylethylamine moiety proceeds with high diastereoselectivity, thus providing a new method for preparing optically active 1-vinyl-2-amino alcohol derivatives with syn stereochemistry [53], The intermediate allyltita-nium species has also found use as a starting material for a carbozincation reaction [54],... 

Stereoelectronic factors are also important in the conformational dynamics of acyclic acetals [6] (Cosse-Barbi and Dubois, 1986). Here the usual preference for staggered conformations is supplemented by the anomeric effect (Kirby, 1983), which favours the gauche stereochemistry ( = 60°) about both central C-O bonds, mainly because this allows optimal n-rr overlap between an oxygen lone pair and the antibonding (cr ) orbital of the C-0 bond. Thus the pathway for conformational isomerization suggested by... 

In acyclic systems the 1,4-relative stereoselectivity was controlled by the stereochemistry of the diene. Thus, oxidation of (E,E)- and (E,Z)-2,4-hexadienes to their corresponding diacetates affords dl (>88% dl) and mesa (>95% me so) 2,5-diacetoxy-3-hexene, respectively. A mechanism involving a t vans-accto xy pal I adation of the conjugated diene to give an intermediate (rr-allyljpalladium complex, followed by either a cis or trans attack by acetate on the allyl group, has been suggested. The cis attack is explained by a cis migration from a (cr-allyl)palladium intermediate. The diacetoxylation reaction was applied to the preparation of a key intermediate for the synthesis of d/-shikimic acid, 3,... 

The Smith degradation4 involves reduction of the periodate-oxidized polysaccharide with borohydride, followed by mild hydrolysis with acid. (The periodate oxidation has already been treated in Section 111,1, p. 200.) The modified sugar residues contain acyclic acetal groupings, which are hydrolyzed much faster than the glyco-sidic linkages. The product therefore contains small fragments (such... 

Strategies for preparing mixed, acyclic acetals on insoluble supports include the oxidative haloalkoxylation of support-bound enol ethers (Entry 6, Table 6.1) and the acid-catalyzed reaction of alcohols with resin-bound enol ethers [627]. Alternatively, resin-bound a-chloro ethers can be converted to mixed acetals by reaction with alcohols or phenols in the presence of strong bases (KO/Bu, HOfBu, DMF, 5 h) [550,628]. Polystyrene-bound a-(phenylseleno)ethers react with aliphatic alcohols under slightly acidic conditions (NIS, TfOH, DCM/dioxane (1 1), 0°C to 20 °C, 1 h) to yield mixed, acyclic acetals [628],... 

Even though it is difficult to achieve a C-H insertion at methylene sites a to an N-Boc group in acyclic systems, many cyclic amines are excellent substrates for the C-H insertion. The reaction with N-Boc-pyrrolidine (31) is a spectacular example [27]. The Rh2(S-DOSP)4-catalyzed reaction of methyl phenyldiazo-acetate with 31 at -50 °C generates the C-H insertion product 32 in 94% ee and 92% de [Eq. (16)]. 

Conformational analysis explains why the relatively strained 2,6-dioxa-bicyclo[3.2.1]octane skeleton 98 of 3,6-anhydro-D-gluco- and -D-manno-pyranose tends to recyclize rapidly in the presence of methanolic hydrogen chloride into the less-strained 2,6-dioxabicyclo[3.3.0]octane skeleton 99 of the 3,6-anhydrohexofuranose. Obviously, such rearrangement cannot take place with the galacto or talo configurations, and consequently, acyclic acetals are formed.390,391... 

Cyclization of acyclic acetals.3 Reaction of the y-hydroxy-y-vinyl acetal (1) with SnCl4 (1 equiv.) in CH2C12 at -78° provides cw-hydroindenes 2 and 3, which are convenient precursors to the dione 4. 

The formation of intermediate enol ethers has long been recognised to occur in the mechanism of cyclic and acyclic acetal bromination or isotope exchange (54) (Marquet et al., 1961 Marquet and Jacques, 1962 Gaudry and Marquet,... 

Part of the reason for the stability of cyclic hemiacetals concerns entropy. Formation of an acyclic acetal involves a decrease in entropy (AS° negative) because two molecules are consumed for every one produced. This is not the case for formation of a cyclic hemiacetal. Since AG°= AH° -7AS°, a reaction with a negative AS° tends to have a more positive AG° in other words, it is less favourable. 

The reaction of 1,1-enediamines with 1,4-benzoquinone takes a different course132. Acyclic 1,1-enediamines 149 react with 1,4-benzoquinone in refluxing acetic acid to give after workup two products 150 and 151, resulting from dehydration and deamination, respectively (equation 57). Only benzofurans 152 (21-27%) are isolated in the case of enediamines 8 derived from 4-bromoacetophenone. Cyclic 1,1-enediamine 8 (n = 2, R = H) examined in the reaction leads exclusively to a low yield (9%) of the tricyclic indole 153. 

Because of the relative fragility of acyclic acetals, the principal challenge in their use lies in defining the mildest conditions for their hydrolytic removal All of our examples are taken from syntheses in which the liberated carbonyl is prone to further acid-catalysed reactions. However, we begin with an example of selective hydrolysis of only one of three differentially protected carbonyls spanning a mere 6-carbon chain [Scheme 2.47],l(M The acyclic acetal was easily removed in the presence of a dioxolane and a dithiane. 

The usual acid-sensitivity of acyclic acetals was similarly of no avail in the related system studied by Myers and co-workers [Scheme 2.53].111 In this case, treatment of the dimethyl acetal 55.1 with trichloroacetic acid generated an oxonium ion intermediate, that was rapidly and efficiently intercepted with hydrogen peroxide - a reagent which is much more nucleophilic than water. The resultant a-methoxyhydroperoxide 53 was then reductively cleaved under neutral conditions to produce a hemiacetal, which lost methanol to give the desired aldehyde 53.3. 

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