1 aldehyde protection dioxolanes

An interesting approach to the central eight-membered ring of ceroplastol I is based on an intramo-lecnlar Homer-Wadsworth-Emmons reaction employing a diethyl 7-formylalkylphosphonate. The C-7 aldehyde, protected as a 1,3-dioxolane, is obtained in 20% yield by a Michael addition of an alkenyllithium to 2-(diethoxyphosphinyl)cyclopentenone in THF at -78°C. Hydrolysis of the acetal nsing HjO and TsOH in reflnxing acetone yields 89% of the phosphonylated ketoaldehyde (Scheme, 5.56). ... 

The most commonly used protected derivatives of aldehydes and ketones are 1,3-dioxolanes and 1,3-oxathiolanes. They are obtained from the carbonyl compounds and 1,2-ethanediol or 2-mercaptoethanol, respectively, in aprotic solvents and in the presence of catalysts, e.g. BF, (L.F. Fieser, 1954 G.E. Wilson, Jr., 1968), and water scavengers, e.g. orthoesters (P. Doyle. 1965). Acid-catalyzed exchange dioxolanation with dioxolanes of low boiling ketones, e.g. acetone, which are distilled during the reaction, can also be applied (H. J. Dauben, Jr., 1954). Selective monoketalization of diketones is often used with good success (C. Mercier, 1973). Even from diketones with two keto groups of very similar reactivity monoketals may be obtained by repeated acid-catalyzed equilibration (W.S. Johnson, 1962 A.G. Hortmann, 1969). Most aldehydes are easily converted into acetals. The ketalization of ketones is more difficult for sterical reasons and often requires long reaction times at elevated temperatures. a, -Unsaturated ketones react more slowly than saturated ketones. 2-Mercaptoethanol is more reactive than 1,2-ethanediol (J. Romo, 1951 C. Djerassi, 1952 G.E. Wilson, Jr., 1968). 

Dioxolanes haye been prepared from a carbonyl compound and an epoxide (e.g., ketone/SnC, CCI4, 20°, 4 h, 53% yield or aldehyde/ Et4N Br, 125-220°, 2-4 h, 20-85% yield ). Perhalo ketones can be protected by reaction with ethylene chlorohydrin under basic conditions (K2CO3, pentane, 25°, 2 h, 85% yield or NaOH, EtOH—H2O, 95% yield ). 

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. ... 

Conversion to acetals is a very general method for protecting aldehydes and ketones against nucleophilic addition or reduction.245 Ethylene glycol, which gives a cyclic dioxolane derivative, is frequently employed for this purpose. The dioxolanes are usually prepared by heating a carbonyl compound with ethylene glycol in the presence of an acid catalyst, with provision for azeotropic removal of water. 

Aldehydes and ketones have been protected as acetals and dioxolanes using orthoformates, 1,2-ethanedithiol or 2,2-dimethyl-l,3-dioxolane by Hamelin and coworkers. This acid-catalyzed reaction proceeds in the presence of p-toluenesulfonic acid (p-TsOH) or KSF clay under solvent-free conditions (Scheme 6.2). The yields ob-... 

Since 1895, when Emil Fischer1 described the reaction of aldehydes and ketones with glycoses, an impressive part of the chemistry of carbohydrates has dealt with acetals, and especially cyclic acetals (mainly 1,3-dioxolanes and 1,3-dioxanes). There are probably relatively few studies on the synthetic chemistry of monosaccharides that do not describe at least one acetal of a carbohydrate, be it for routine protection, or for use in an original synthesis. At least, in this Series, three articles have appeared on the cyclic acetals of the aldoses and aldosides2,3 and of the ketoses4, one article dealt with acetals of tetri-... 

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). 

Although Z-alkene isosteres have been obtained from Wittig alkenation reactions of a-amino aldehydes using triphenyl[3-(trimethylsilyl)prop-2-ynylidene]phosphorane (Section 10.5.2.1.2.1), this stereoisomer was always obtained in minor amounts. Z-Selective alkena-tions were obtained using ylides containing dioxolane-protected aldehydes 42 or orthoester-protected carboxylic acid functions. 58 No experimental data were published, however. 

A synthetic procedure 33 has been developed for the preparation of boronic acids with a protected aldehyde side chain, 2-(l,3-dioxolan-2-yl)ethyl, which is readily converted into boroOrn peptides similar to 30. Peptides containing boroLys were prepared by a series of reactions analogous to those used for the preparation of 30 except 4-bromobut-l-ene was used as starting material in place of 3-bromoprop-l -ene 36 ... 

The combination of TMSOTf, dimethyl sulphide and l,2-bis(trimethylsilyloxy)ethane provides a method91 for the selective dioxolanation of ketones in the presence of aldehydes, via intermediate protection of the aldehyde as its silyloxysulphonium salt (equation 19). 

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

The protection of formaldehyde or other aldehydes as acyclic dithioacetals, sulfanylethers, sulfonylethers, thiosulfoxides, diselenoacetals, aminothioacetals and aminals, as well as cyclic dithioacetals, dioxolanes, oxazolidines and imidazolidines, allows the preparation of different type of protected acyllithium derivatives IV-XI by deprotonation (see... 

Our final example is a base-labile 4-(phenylsulfonyl)methyl-l,3-dioxolane protecting group for aldehydes and ketones.4 Protection is carried out by the reaction of diol 17,1 (obtained by dihydroxylation of ally phenyl sulfone) with a carbonyl compound in the presence of pyridinium p-toluene sulfonate [Scheme 2.17], Cleavage is accomplished by treatment with DBU. /erf-Butyldimethylsilyl ethers, p-toluenesulfonate esters, tetrahydropyranyl ethers, carboxylic esters and benzoates are well tolerated. A disadvantage to the use of 17.1 is the introduc-... 

Another valuable feature of the Noyori dioxolanation is the preference for protection of a saturated ketone in the presence of an a, p-unsaturated ketone or aldehyde as illustrated in Scheme 2,29.67 However, the preference is subject to steric effects because dioxolanation of the a, P-unsaturated carbonyl of the Wieland-Miescher ketone [Scheme 230] occurs selectively (see Scheme 2,22) and there is a further bonus the double bond did not rearrange out of conjugation as it is wont to do under certain traditional acid-catalysed conditions (see below).6 ... 

---