Acetal formation cyclic acetals synthesis

Another interesting example of the acetal formation is the synthesis of brevicomin (2), a cyclic acetal, by the palladium-catalyzed intrarttolecular oxidatirm and acetal formation of 6,7-d ydroxy-l-nonene (equation 3). - ... 

The known adduct (385) of furan and vinylene carbonate, previously used for the synthesis of some cyclitols,256,257 has been transformed into DL-ribose derivatives. After hydroxylation of 385 and subsequent formation of the isopropylidene derivative, the carbonate group was removed by treatment with barium hydroxide, and the resulting diol was cleaved by oxidation with permanganate. Dicarboxyl-ic acid 386 gave, upon treatment with acetic anhydride, cyclic anhydride 387. The reaction of 387 with azidotrimethylsilane produced... 

Ethylene glycol in the presence of an acid catalyst readily reacts with aldehydes and ketones to form cyclic acetals and ketals (60). 1,3-Dioxolane [646-06-0] is the product of condensing formaldehyde and ethylene glycol. Applications for 1,3-dioxolane are as a solvent replacement for methylene chloride, 1,2-dichloroethane, 1,1,1-trichloroethane, and methyl ethyl ketone as a solvent for polymers as an inhibitor in 1,1,1-trichloroethane as a polymer or matrix interaction product for metal working and electroplating in lithium batteries and in the electronics industry (61). 1,3-Dioxolane can also be used in the formation of polyacetals, both for homopolymerization and as a comonomer with formaldehyde. Cyclic acetals and ketals are used as protecting groups for reaction-sensitive aldehydes and ketones in natural product synthesis and pharmaceuticals (62). 

Synthesis of oxathionanes from tu-bromo ketone 108, which is formally a [5+4]-type cyclization, requires Lewis acid-catalyzed cyclic acetal intermediate formation. It was further transformed into the corresponding oxathionanes 109 and 110 using a two-step reductive procedure (Scheme 18, Section 14.10.5.6.1) <20020L3047>. 

Carbohydrate chemistry has provided a rich mine of information on the stability, selective formation, and selective cleavage of cyclic acetals and reviews devoted wholly to the synthesis and reactivity of carbohydrate acetals should be consulted for a more detailed coverage of the subject. The Royal Society of Chemistry publishes annual reviews in its Specialist Periodical Reports series entitled Carbohydrates that gives extensive accounts of recent protecting group developments. 

An intramolecular version of this Claisen rearrangement was used for the synthesis of a natural 10-membered lactone, phoracantholide J (8). The synthesis involves preparation of 6 by known reactions. Treatment of 6 with C MsSeBr in the presence of Hiinig s base gives the cyclic acetal 7 as a mixture of diastereoisomers in 71% yield. Decomposition of the selenoxide results in the rearranged y,B-unsaturated lactone 8 as the major product. The ready formation of a 10-membered ring is noteworthy because yields of rings of this size are low on lactonization of 0-hydroxy acids. 

PROBLEM 17.10 Acetal formation is a characteristic reaction of aldehydes and ketones, but not of carboxylic acids. Show how you could advantageously use a cyclic acetal protecting group in the following synthesis ... 

This ease of synthesis of cyclic acetals makes them appropriate for the preparation of certain well-defined, mono-substituted esters of different origin. 2,3 4,5-Di-0-isopropylidene-/8-D-fructopyranose has been used for the synthesis of certain phosphoramidate compounds. The acetal is dissolved in 20 ml of toluene and refluxed for 6 to 8 hours in the presence of phosphoramidic chloride. The sirupy l-[iV,W-bis-(2-chloroethyl)phos-phoramidic chloride] (5) is then used for the preparation of other derivatives, such as the phosphoramidate itself. Hydrolysis with ethanolic hydrogen chloride removes the isopropylidene groups and results in the formation of ethyl /3-D-fructopyranoside l-[iV,JV-bis-(2-chloroethyl)phosphoramidate]. 

The ring synthesis of the tetrahydro-1,3-azoles is simply the formation of N,N-, N,0-or A, S-analogues of aldehyde cyclic acetals the ring synthesis of the 4,5-dihydro-heterocycles requires an acid oxidation level in place of aldehyde. A good route to the aromatic systems is therefore the dehydrogenation of these reduced and partially reduced systems. Nickel peroxide, " manganese(IV) oxide, copper(II) bromide/ base, and bromotrichloromethane/diazabicycloundecane have been used. The example shown uses cysteine methyl ester with a chiral aldehyde to form the tetrahydrothiazole. 

Additional examples of synthetic application of periodic acid as an oxidant include the oxidative iodination of aromatic compounds [1336-1341], iodohydrin formation by treatment of alkenes with periodic acid and sodium bisulfate [1342], oxidative cleavage of protecting groups (e.g., cyclic acetals, oxathioacetals and dithioacetals) [1315, 1343], conversion of ketone and aldehyde oximes into the corresponding carbonyl compounds [1344], oxidative cleavage of tetrahydrofuran-substituted alcohols to -y-lactones in the presence of catalytic PCC [1345] and direct synthesis of nitriles from alcohols or aldehydes using HsIOe/KI in aqueous ammonia [1346],... 

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