Protective groups dioxolanes

In addition to their use as protecting groups, dioxolanes have been employed as intermediates. One example is a ring expansion of cyclopentanones via Grob fragmentation of the acetal (eq 14). A novel synthesis of glycerol from formaldehyde and ethylene glycol involves dioxolane intermediates. ... 

The prevalence of diols in synthetic planning and in natural sources (e.g., in carbohydrates and nucleosides) has led to the development of a number of protective groups of valuing stability to a substantial array of reagents. Dioxolanes and diox-anes are the most common protective groups for diols. The ease of formation follows the order ... 

In some cases the formation of a dioxolane or dioxan -can result in the generation of a new stereogenic center, either with complete selectivity or as a mixture of the two possible isomers. Since the new center is removed on deprotection, it should not seriously complicate the use of those protective groups that generate a new stereogenic center. 

The 1,3-dioxolane group is probably the most widely used carbonyl protective group. For the protection of carbonyls containing other acid-sensitive functionality, one should use acids of low acidity or pyridinium salts. In general, a molecule containing two similar ketones can be selectively protected at the less hindered carbonyl, assuming that neither or both of the carbonyls are conjugated to an al-kene. ... 

A review discusses the condensation of aldehydes and ketones with glycerol to give 1,3-dioxanes and 1,3-dioxolanes. The chemistry of 0 0 and 0 S acetals has been reviewed, and a recent monograph discusses this area of protective groups in a didactic sense. ... 

The carbonyl group can be deprotected by acid-catalyzed hydrolysis by the general mechanism for acetal hydrolysis (see Part A, Section 7.1). A number of Lewis acids have also been used to remove acetal protective groups. Hydrolysis is promoted by LiBF4 in acetonitrile.249 Bismuth triflate promotes hydrolysis of dimethoxy, diethoxy, and dioxolane acetals.250 The dimethyl and diethyl acetals are cleaved by 0.1-1.0 mol % of catalyst in aqueous THF at room temperature, whereas dioxolanes require reflux. Bismuth nitrate also catalyzes acetal hydrolysis.251... 

Dioxacycloalkanes are cyclic acetals that are used frequently as protective groups. Substituted derivatives have been synthesized to achieve easy removal. Simplest of all, the 4-phenyl-1,3-dioxolane has not been used commonly because cleavage needs electrolytic conditions. A mild hydrogenolysis method was developed in 1997 to make this protective group more popular (Scheme... 

D-Ribono-1,4-lactone (1) readily condenses with acetone, under acidic catalysis with mineral acids or anhydrous copper sulfate, to give 2,3-0-isopropylidene-D-ribono-1,4-lactone (16a), which was employed for the synthesis of 5-deoxy and 5-0-substituted derivatives of D-ribono- 1,4-lactone and D-ribitol (24). Acid removal of the 1,3-dioxolane protecting group gave products having probable inhibitory activity of arabinose 5-phosphate isomerase (25). Other applications of 16a for the synthesis of natural products will be discussed later. 

Other acetal-type protecting groups (tetrahydrofurfuryl ethers, methoxymethyl ethers, 1,3-dioxolanes) are also considered to be incompatible with oxidising agents. 

Alkylation of a-lithio-iV,/V-dimethylhydrazones with 2-(iodomethyl)-l,3-dioxolane provides masked 7-hydrazonoaldehydes. Cyclization occurs after acid-catalyzed removal of the dioxolane protecting group and the /V-unsubstituted pyrrole can be obtained by hydrogenolysis of the N,N-dimethylamino substituent (Scheme 41) (88JHC1135). 

Only short comments will be given for other acetal derivatives that are less popular Chart 1 presents a list of formulae of cyclic acetals, mainly, those with five- and six-membered rings (1,3-dioxolanes and 1,3-dioxanes). Seven-membered ring acetals are omitted because they are scarcely represented in carbohydrate chemistry. The special case of spiroacetah and cydohexane-l,2-diacetal-protecting groups, which have been reported recently, will be presented in Part K. 

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). 

The presence or absence of the dioxolane protecting group in dienes dictates whether they participate in normal or inverse-electron-demand Diels-Alder reactions.257 The intramolecular inverse-electron-demand Diels-Alder cycloaddition of 1,2,4-triazines tethered with imidazoles produce tetrahydro-l,5-naphthyridines following the loss of N2 and CH3CN.258 The inverse-electron-demand Diels-Alder reaction of 4,6-dinitrobenzofuroxan (137) with ethyl vinyl ether yields two diastereoisomeric dihydrooxazine /V-oxide adducts (138) and (139) together with a bis(dihydrooxazine A -oxide) product (140) in die presence of excess ethyl vinyl ether (Scheme 52).259 The inverse-electron-demand Diels-Alder reaction of 2,4,6-tris(ethoxycarbonyl)-l,3,5-triazine with 5-aminopyrazoles provides a one-step synthesis of pyrazolo[3,4-djpyrimidines.260 The intermolecular inverse-electron-demand Diels-Alder reactions of trialkyl l,2,4-triazine-4,5,6-tricarboxylates with protected 2-aminoimidazole produced li/-imidazo[4,5-c]pyridines and die rearranged 3//-pyrido[3,2-[Pg.460]

Acetals and ketals protect two hydroxyls at a time by forming either a 1,3-dioxane or a 1,3-dioxolane ring (Scheme 2.12). The most common ketal and acetal protecting groups are isopropylidene or acetonide and the benzylidene-type groups with... 

Protecting group acetal (dioxolane) Structure Protects ketones, aldehydes From nucleophiles, bases Protection H(r °H Deprotection water, H+cat. 

The exocyclic double bond was made by Wittig reaction on the deprotected ketone aqueous acetic acid removed the dioxolane protecting group). This product had all the characteristics of natural sesquifenchene, confirming its true structure. 

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