Displacement methyl enol ether

These results clearly show that the potential energy surface can contain a series of minima. The fact that selectivity in re-attack by the F ions can be observed indicates that the differences between the energy barriers for the secondary reactions control the distribution of the final products. The multistep character of these processes is further illustrated by the reactions observed when enolate anions are used as reactant ions. The ambident enolate anions may react with methyl pentafluorophenyl ether at the carbon or the oxygen site. If they react with the carbon site at the fluorine-bearing carbon atoms, then the molecule in the F ion/molecule complex formed contains relatively acidic hydrogen atoms so that proton transfer to the displaced F ion may occur. An example is given in (47) where the enolate anion, generated by HF loss, is not observed. An intramolecular nucleophilic aromatic substitution occurs instead and leads to a second F ion/ molecule complex. The F" ion in this complex then re-attacks the substituted benzofuran molecule formed, either by proton transfer or SN2 substitution. 

Treatment of 1,3-dicarbonyl compounds with DBP in a methoxide/methanol system affords 2-alkyl-4-[(phenylsulfonyl)methyl]furans, where reaction proceeds by Initial addition-elimination on the vinyl sulfone moiety. In contrast, silyl enol ethers in the presence of silver tetrafluoroborate resulted in products derived from Sn2 displacement at the allylic site.11 Anions derived from 1,3-dicarbonyls substituted at the C-2 position are found to induce a complete reversal in the mode of ring closure.12 The major products obtained are 3-[(phenylsulfonyl)methyl]-substituted cyclopentenones. The internal displacement reaction leading to the furan ring apparently encounters an unfavorable Ai -interaction in the transition state when a substituent group is present at the 2-position ol the dicarbonyl compound. This steric Interaction is not present in the transition state leading to the cyclopentenone ring. 

The same year, Gerlach described a synthesis of optically active 1 from (/ )- ,3-butanediol (7) (Scheme 1.2). The diastereomeric esters produced from (-) camphorsulfonyl chloride and racemic 1,3-butanediol were fractionally recrystallized and then hydrolized to afford enantiomerically pure 7. Tosylation of the primary alcohol, displacement with sodium iodide, and conversion to the phosphonium salt 8 proceeded in 58% yield. Methyl-8-oxo-octanoate (10), the ozonolysis product of the enol ether of cyclooctanone (9), was subjected to Wittig condensation with the dilithio anion of 8 to give 11 as a mixture of olefin isomers in 32% yield. The ratio, initially 68 32 (E-.Z), was easily enriched further to 83 17 (E Z) by photolysis in the presence of diphenyl disulfide. The synthesis was then completed by hydrolysis of the ester to the seco acid, conversion to the 2-thiopyridyl ester, and silver-mediated ring closure to afford 1 (70%). Gerlach s synthesis, while producing the optically active natural product, still did not address the problem posed by the olefin geometry. 

The UV spectrum of 5-phenyl-3 hydroxythiophene is very similar to that of its methyl ether in alcoholic solution, indicating that it exists largely in the enol form in this solvent. The same coincidence of the wavelength maxima was also obtained for 5-phenyl-2-hydroxy-thiophene and its methyl ether. In chloroform solution, the maxima were shifted toward longer wavelengths, suggesting that the tautomeric equilibrium in this solvent is displaced more toward the keto form. ... 

Considerable work has been devoted to the search for agents devoid of the sedative effect that accompanied some of the earlier antihistamines. One stratagem for achieving that comprises adding a function that will diminish the likelihood that the dmg will cross the blood-brain barrier. The antistamine emedastine (41-3), for example, incorporates a terminal ether that can be potentially metabolized to a carboxylic acid. Alkylation of the imidazole (41-1), available from imidazol-2-one by reaction with phosphoms oxychloride, with the chloroether (41-2) leads to a reaction on nitrogen to afford (41-3). Displacement of the enol chloride in that intermediate with A-methyl-l-4-diazepine (41-4) leads to emedastine (41- 5) [43]. 

The chemistry involved in nucleophilic aromatic substitution is well reflected in the reactions of a variety of nucleophiles with methyl penta-fluorophenyl ether (Ingemann et al 1982a). For most of the nucleophiles such as alkoxide, thiolate, enolate and (un)substituted allyl anions, the dominant reaction channel is the attack upon the fluoro-substituted carbon atoms, as is the case for OH-. The latter ion reacts approximately 75% by attack upon the fluoro-substituted carbon atoms and the remaining 25% by Sn2 (20%) and ipso (5%) substitution as summarized in (41). In the attack upon the fluorinated carbon atoms, the interesting observation is made that a F- ion is displaced via an anionic o-complex to form a F- ion/molecule complex, which is not observed to dissociate into F- as a free ionic product. 

Two distinct mechanisms have been proposed. In the first, the formation of free enolates by nucleophilic attack of F at silicon was supported by a study180 of the interaction of tris(diethylamino)sulphonium (TAS) difluorotrimethylsilicate and the enol trimethylsilyl ether of benzyl methyl ketone. An equilibrium mixture appears to be produced (equation 17), which may be displaced in the direction of the TAS enolate by removal of the volatile fluorotrimethylsilane. 

The alcohol was protected as its TMS ether, and the C-15,16 alkene stereospecifically dihydroxylated to give compound 50. The diol was then converted to its cyclic sulfate derivative according to the Sharpless protocol.29 Attempted base-catalyzed elimination of the sulfate to introduce the C-14,15 alkene was plagued by side-reactions involving epoxide formation by displacement of the sulfate by the adjacent TMS ether, perhaps aided by enolization of the methyl ketone. Instead, displacement of the sulfate by iodide ion occurred uneventfully to provide 51 as its tetrabutylammonium salt. 

Regiospecific syntheses of kermesic add were developed both based primarily on the Diels-Alder reaction. In the first (ref. 215) methyl diacetylacetate was converted to to the enol methyl ether which was silylated to give 4-methoxy-3-methoxycarbonyl-2-trimethylsiloxypenta-2,5-diene (A). Diels-Alder addition to 2,6-dichloronaphthazarin afford, after methylation and nucleophilic displacement of... 

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