Transketalization reaction

Acyclic monothio acetals and ketals can be prepared directly from a carbonyl compound or by transketalization, a reaction that does not involve a free carbonyl group, from a 1,3-dithiane or 1,3-dithiolane. They are cleaved by acidic hydrolysis or Hg(II) salts. 

Butylethylidene and 1-phenylethylidene ketals were prepared selectively from the C4-C6, 1,3-diol in glucose by an acid-catalyzed transketalization reaction [e.g., Me3CC(OMe)2CH3, TsOH/DMF, 24 h, 79% yield PhC(OMe)2Me, TsOH, DMF, 24 h, 90% yield, respectively]. They are cleaved by acidic hydrolysis AcOH, 20°, 90 min, 100% yield, and AcOH, 20°, 3 days, 100% yield, respectively. Ozonolysis of the /-butylmethylidene ketal affords hydroxy ester, albeit with poor regiocontrol, but a more sterically differentiated derivative may give better selectivity, as was observed with the ethylidene ketal. ... 

Dioxazoles 146 are readily prepared by transketalization of 2,2-diethoxypropane, where both the NH and OH moieties are protected in a non-protic form (Scheme 68). The dioxazoles 146 are stable to a wide variety of reaction conditions and readily revert back to the hydroxamic acids 145 and isopropyl ester 147 (145/147 50/1) by treatment with Nafion-H in 2-propanol. The method is applicable to primary, secondary, tertiary and aromatic hydroxamic acids, and the acidity of the protons adjacent to the dioxazole allows R-functionalization. 

Shorter reaction times result in incomplete transketalization. 

A variant of the preceding strategy was applied to the total syntheses of ( )-elwesine (439), ( )-epielwesine (449), and ( )-oxocrinine (415) (Scheme 39) 200). This approach featured a new methodology for the construction of substituted tetrahydrobenzazepine ring systems that was based on a two-step Tscher-niac-Einhom-like aromatic amidoalkylation as exemplified by the conversion of 443 to 444. To this end, the unsaturated nitrile 440 was allowed to react with nitromethane in the presence of Triton B, and the intermediate nitro compound was converted to the acetal 441 by reaction with methanolic sodium methoxide followed by concentrated sulfuric acid in dry methanol. Transketalization of 441... 

An improved synthesis of 1,4,2-dioxazolines from hydroxamic acids 119 and 2,2-diethoxypropane in the presence of camphorsulfonic acid as an acidic catalyst via a transketalization reaction has been reported (Scheme 23)... 

Butyl- and 1 -phenylethylidene ketals were prepared selectively from the C4-C6, 1,3-diol in glucose by an acid-catalyzed transketalization reaction [e.g.,... 

Acid-catalyzed reaction of lb with acetone and simultaneous azeotropic removal of water provides diethyl (27 ,3i )-2,3-0-isopropylidenetartrate 3 in 82—83% yield after distillative purification [3]. However, it has been reported that upon application of this method in petroleum ether as solvent, significant racemate formation was observed [4]. The preferred method for the preparation of 3 involves a transketalization reaction of lb with 2,2-dimeth-oxypropane under acidic catalysis. The yield is nearly quantitative with no loss of optical integrity [5]. 

The last step of the synthesis of —)-frontalin is presented in Scheme 5.37. Lactone and the ester group in 9 are reduced to Ce triol, where two vicinal OH groups are protected as ketal 10. This permits selective oxidation of the terminal OH group to aldehyde 11, which in the Grignard reaction afforded sec alcohol 12. Oxidation of this alcohol under conditions used for the oxidation of 10 to 11 afforded ketone 13. In the last step, acid-catalyzed transketalization afforded (-yfrontalin TM 5.16 where a (5/ ) stereogenic center is generated under asymmetric induction. 

The reaction of a ketone with diols or diketones with polyols yields polyacetals by the direct reaction or by the transketalization using methyl or ethyl ketals with polyols. 

In 1951, Orth [6] prepared polyketals using 1,4-cyclohexanedione and, in 1962, Cohen and Laven [7] reported on the ketal prepared by the transketalization reaction of the ethyl ketal of 2,5-hexanedione with pentaerythritol [Eq. (34)]. 

The synthesis of the 19-nor analog (83) of Sarett s ketone also takes place via nonaromatic intermediates, being carried out in accordance with Scheme 63 [663, 664]. The cyclic diene (77) required for the synthesis was obtained from the ethyl enol ether of 1,3-cyclohexanedione (76) by the Normant reaction and transketalization with ethylmethyldioxolan. Conden-... 

---