Ketal tosylates

Enantiomeric forms of proteins are not accessible so that a conceptual reversal of the elution order by switching to the enantiomeric CSP is not feasible. However, in some special ca.ses, the elution order can be influenced by the mobile phase conditions. For example, on an ovomucoid CSP a reversal in elution order of the enantiomers of the ketal tosylate intermediate of azalanstat was observed when the organic modifier was changed from ethanol to acetonitrile. This unusual effect has been attributed to a change in binding domains or recognition sites on the ovomucoid protein as a function of the organic modifier of the mobile phase [ 149. ... 

Interestingly, the reduction (LiAlH/j), or the Grignard reaction (CH3MgI), of the ketal tosylate 376 gave ketal 378 (R=H or CH3) (109). The two oxygens of the ketal function in 376 have each an electron pair oriented antiperi-planar to ease the fragmentation process to give the dioxolenium ion intermediate 377. 

Ketal Tosylates. The second candidate for the acid proliferation is ketal derivatives having a tosylated residue (5). These were synthesized by the ketalization of benzoylacetate, followed by LAH reduction and tosylation (5). Compound 5 (mp 48-50 C) had to be stored in a refrigerator since crystals of 5 were converted into black materials gradually at an ambient temperature upon prolonged storage. The ketal compound (5) was readily converted in the present of an addic spedes into p-keto-tosylate (6) which is subjected to the -elimination to give TsOH in a non-linear maimer (Scheme 2(b)). NMR spectra of a solution of 5 in the presence of TsCH at 100 revealed that e p-keto-tosylate (6) as an intermediate was formed during the reaction (6). 

Figure 4 Photosensitivity curves for poly(te/t-butyl methacrylate) photoactivated by 2 mol% of 8 in the absence (-A-) and in the presence (- -) of 15 mol% of ketal-tosylate (5) as an add amplifier. Post-exposure bake 100 C for 1 min, development 3 wt% of Me4N OH .

Regeneration of Carbonyl and Amino Groups. Excellent yields are obtained in the formation of carbonyl compounds from acetals, ketals, tosyl hydrazones (eq 3), oximes, 2,4-dlnltro-phenylhydrazones, and semicarbazones when reactions are carried out in an acetone/water mixture. 

Deoxy-D-jcylo hexose 6-(dihydrogen phosphate) (21) has also been synthesized (2) the reaction sequence makes use of 3-deoxy l 2,5 6-di-O-isopropylidene D-galactofuranose (16), a compound that can be easily prepared from D-glucose (2, 60). The mono-isopropylidene derivative (17) formed by partial hydrolysis of the di-ketal is converted into the 6-tosylate (18) by reaction with one molar equivalent of p-toluenesulfonyl chloride. From this the epoxide (19) is formed by reaction with sodium methoxide. Treatment of the anhydro sugar with an aqueous solution of disodium hydrogen phosphate (26) leads to the 6-phosphate (20)... 

Fe(OTf)2-catalyzed aziridination of enol silyl ethers with PhlNTs followed by ring opening led to a-N-tosylamido ketones in good yields (Scheme 27) [81]. With silyl ketene ketal (R = OMe) as substrate, the N-tosyl-protected amino acid ester was obtained in 50% yield. In contrast, the copper (I) salt CuClOq was found not effective for this substrate [82]. 

The following abbreviations are used in this and the subsequent tables Ac for acetyl, Pr for propionyl, Bu for butyryl, Bz for benzoyl, Ts for tosyl, My for methylene, Ed for ethylidene, Bd for benzylidene, Fd for furfurylidene. Id for isopropylidene, Me for methyl, Et for ethyl, Be for benzyl, Tr for trityl and Az for azoyl. Where the linkages of acetals and ketals are known, they are shown by different type fonts.)... 

In this reaction, considerable nitration of the tosyl groups was observed. The bicycle 89 was obtained in better yield (36%) from 88 by reaction with trifluoroacetyl nitrate in DCM <1996JOC8897, 1998LJSP5831099>. Swern oxidation of the dihydroxy diazocine 90a led to the oxygen-bridged hydroxyl diazocine 91 by transannular hemi-ketalization (Scheme 16) <1996JOC8897>. 

Acetalization. Pyridinium tosylate catalyzes the reaction of ketones with cthanediol to form ketals (90-95% yield) it also catalyzes the transacetalization of the ketals with acetone (90-95% yield). 

The plant bufadienolide scillarenin (500) has been synthesized. The starting material was 15a-hydroxycortexone (501), which was converted into the diketone ketal (502) by cupric acetate oxidation at C(21), followed by selective ketalization and tosylate elimination. Protection at C(3) as the dienol ether, oxiran formation at C(20) with dimethylsulphonium methylide, and regeneration of the C(3)- and C(21)-oxo-groups by acid hydrolysis then provided (503). Selective reaction at C(21) with the sodium salt of diethyl methoxycarbonyl-methylphosphonate, and boron trifluoride rearrangement of the epoxide ring to the aldehydo-unsaturated ester (504), was followed by enol lactonization to the bufadienolide (505). This was converted, in turn, to scillarenin (500) via the 14,15-bromohydrin, by standard reactions. Unsubstituted bufadienolides have also been prepared by the same method. 

The chemoenzymatic synthesis of a Ps adrenergic receptor agonist was developed by J.Y.L. Chung and co-workers. The key chiral 3-pyridylethanolamine intermediate was prepared via the Neber rearrangement of the ketoxime tosylate derived from 3-acetylpyridine. The oxime formation and the tosylation were carried out in a one-pot process using pyridine as the solvent. The solution of the ketoxime tosylate in ethanol was then cooled to 10 °C and potassium ethoxide was added. After the TsOK salt was removed from the reaction mixture, HCI gas was bubbled through the solution until the pH reached 2 and the 3-pyridylaminomethyl ketal was isolated as its di-HCI salt. 

Selective tosylation. One step of Johnson s synthesis of aldosterone required selective tosylation of the primary alcoholic group of the ketal diol (1) in order that the secondary group could be oxidized to produce the keto tosyiate (2) required for... 

A solution of the ketone (1.23 g, 8.11 mmol), ethylene glycol (1.8 mL, 32 mmol), pyridinium tosylate (0.6 g, 2.4 mmol), and benzene (45 mL) was refluxed for 22 h in a Dean-Stark apparatus. The reaction mixture was cooled, poured into saturated NaHCOj (50 mL), the aqueous layer extracted with hexanes/EtiO (1/1, 2 x 20 mL), and washed with brine (2 x 15 mL). The combined organics were dried (MgSO4), concentrated, and chromatographed to give the ketal (1.59 g, 100%). 

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