Prototropic reactions activation

There is of course ample evidence that acid-base catalysis in solvents of low dielectric constant does not necessarily involve a concerted process. Such a process cannot operate when catalysis is effected by a single acid or base present in an aprotic solvent, and there are many examples of this, including typical prototropic reactions such as the halogenation of acetone, the racemization and inversion of optically active ketones, and the mutarotation of nitrocamphor. Moreover, in the isomerization of mesityl oxide oxalic ester in chlorobenzene, which depends kinetically on the interconversion of two isomeric enols, the velocity in a solution containing both an amine and an acid is no greater than the sum of the velocities for the two catalysts separately, in contrast to the behaviour found by Swain for the mutarotation reaction. 

Protoporphyrin-IX, N-methyl-, 4, 396 Protoporphyrins, 4, 382 photooxygenation, 4, 402 Prototropic tautomerism polyheteroatom six-membered rings, 3, 1055 Prozapine properties, 7, 545 Pschorr reaction carbolines from, 4, 523 dibenzazepines from, 7, 533 dibenzothiophenes from, 4, 107 phenanthridines from, 2, 433 Pseudilin, pentabromo-synthesis, 1, 449 Pseudoazulene synthesis, 4, 526 Pseudobases in synthesis reviews, 1, 62 Pseudocyanines, 2, 331 Pseudothiohydantoin synthesis, 6, 296 Pseudouracil structure, 3, 68 Pseudoyangonin IR spectra, 3, 596 Pseudoyohimbine synthesis, 2, 271 Psicofuranine biological activity, 5, 603 as pharmaceutical, 1, 153, 160... 

Allyl p-tolyl sulphoxide 535 reacts with sodium methoxide in methanol by initial prototropic isomerization and subsequent addition of methanol to give 536 (equation 333). Protic solvents are photochemically incorporated by the open chain olefinic bond of trans methyl )S-styryl sulphoxide 537 in a Markovnikov regiospecificity (equation 334). Mercaptanes and thiophenols add to vinyl sulphoxides in a similar manner (compare also Reference 604 and Section IV.B.3) to give fi-alkylthio(arylthio)ethyl sulphoxides 538 (equation 335). Addition of deuteriated thio-phenol (PhSD) to optically active p-tolyl vinyl sulphoxide is accompanied by a low asymmetric a-induction not exceeding 10% (equation 336) . Addition of amines to vinyl sulphoxides proceeds in the same way giving )S-aminoethyl sulphoxides in good to quantitative yields depending on the substituents at the vinyl moiety When optically active p-tolyl vinyl sulphoxides are used in this reaction, diastereoisomeric mixtures are always formed and asymmetric induction at the p- and a-carbon atoms is 80 20 (R = H, R = Me) and 1.8 1 (R = Me, R = H), respectively (equation 337) ... 

Michael acceptors which carry a good leaving group at the a-carbon atom or whose electron-withdrawing group itself can serve as the leaving group may be cyclopropanated by active methylene compounds under basic conditions via a prototropic shift subsequent to the Michael addition as outlined in equation 139. Thus, the basicity of the carbanions involved must be balanced to allow the requisite prototropic shift otherwise, the reaction will be very slow or will not work. 

Although K258A mutant is considered to be a dead enzyme, it has shown a small residual transaminase activity. The stereochemical fidelity of the K258A mutant enzyme was examined by measuring the residual transamination reaction in which the labilization of the pro-S C-4 hydrogen of PMP was monitored.42 During the normal transamination reaction, it was observed that the a-proton of the substrate was trasferred to the pro-S C-4 positionof PMP and the same proton was removed from the pro-S C-4 position then transferred to the second substrate, a part of the 1,3-prototropic shift in the transamination... 

When, on the other hand, organocatalyst 133 (possessing a bulky 2,5-diaryl-pyrrole moiety) is applied, product 134 was selectively formed by a highly diastereo- and enantioselective 1,3-dipolar cycloaddition (11 examples, 56-90%, 60-91% ee). This reaction most likely involves activation of the nitroalkene by the thiourea, via the earlier mentioned doubly hydrogen-bonded interaction, followed by a concerted attack of the in situ formed azomethine ylide (this ylide is not activated by nor coordinated to the organocatalyst, because of the bulky, nonbasic pyrrole group, but is most likely formed via a 1,2-prototropic rearrangement [92]). 

Mikami reported that BINOL derived titanium complex efficiently catalyzed the aldol reaction of silyl enol ether with excellent control of both absolute and relative stereochemistry [106] (Scheme 14.37). The reaction was proposed to proceed via a prototropic ene reaction pathway that is different from that of Mukaiyama aldol condensation. A cyclic antiperiplanar transition-state model was proposed to explain the pref erential formation of the syn diastereomer from either (E)- or (Z)-silyl enol ethers [106]. Further modifications of the catalyst system include the use of perfluorophenols and other activating additives [107], or performing the reaction in supercritical fluids [108]. Furthermore, the nucleophile could be extended to enoxysilacyclobutane derivatives [109]. 

An accurate determination of the pK values of prototropic groups involved in enzyme-catalyzed reactions is possible using other assays (cf. J.R. Whitaker, 1972). However, identification of these groups solely on the basis of pK values is not possible since the pK value is often strongly influenced by surrounding groups. Pertinent to this claim is our recollection that the pH of acetic acid in water is 4.75, whereas in 80% acetone it is about 7. Therefore, the enzyme activity data as related to pH have to be considered only as preliminary data which must be supported and verified by supplementary investigations. 

This rate is the overall rate of the halogenation process, as well as of the racemization process (if one starts with an optically active ketone) or of the deuterium exchange reaction. The reaction is prototropic and the rate-determining step is the formation of enol. 

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