Ylides thiazolium

With thiazolium ylides. Thiazolium-N-dicyanomethylide (103) combines with acyclic olefins (dimethylfumarate, maleate, and trana-1,2-dibenzoylethylene) to form only the corresponding [3+2] cycloadducts (104 R1=H R2=R3=COOMe R1 = R3=COOMe,R2=H R1=H,R2sR3rCOPh,... 

By protodetritiation of the thiazolium salt (152) and of 2 tritiothiamine (153) Kemp and O Brien (432) measured a kinetic isotope effect, of 2.7 for (152). They evaluated the rate of protonation of the corresponding yiides and found that the enzyme-mediated reaction of thiamine with pyruvate is at least 10 times faster than the maximum rate possible with 152. The scale of this rate ratio establishes the presence within the enzyme of a higher concentration of thiamine ylide than can be realized in water. Thus a major role of the enzyme might be to change the relative thermodynamic stabilities of thiamine and its ylide (432). 

However, depending on the nature of the initial heterocycle, rearrangements are possible. Alkylation of thiazole to form the thiazolium salt (390) and generation of the ylide (391) with triethylamine in the presence of DMAD gave not (392) but the isomeric product (393) by the rearrangement indicated (76JOC187). Rearrangements of these types are described in Chapters 4.07 and 4.19. 

Although the catalysis of the dimerization of aldehydes to acyloins by thiazolium ion has been known for some tlrae, the development of procedures using anhydrous solvents which give satisfactory yields of acyloins on a preparative scale was first realized in the submitters laboratories. The mechanism proposed by Breslow - for the thiazolium ion-catalyzed reactions is similar to the Lapworth mechanism for the benzoin condensation with a thiazolium ylide replacing the cyanide ion. Similar mechanisms are involved... 

The reaction can also be catalyzed by certain thiazolium ylides, in which case it also works with aliphatic substrates. For this modified procedure the following mechanism has been formulated ... 

Thiamin, structure of, 530, 1045 thiazolium ring in, 530 Thiamin diphosphate, p/Ca of, 1151 reaction with pyruvate, 1151-1153 structure of. 1151 ylide from. 1151 Thiazole, basicity of. 948 thio-, thioester name ending, 787 Thioacetal, synthesis of, 743 Thioanisole, electrostatic potential map of. 777... 

A study of the mechanism of the reaction of 2-silylthiazole (65) with formaldehyde has concluded that the reaction occurs via the initial fast formation of an N-(silyloxymethyl)thiazolium-2-ylide (66) followed by a rate determining second addition of formaldehyde to give (67). This is followed by a fast 1,6-silyl migration and loss of a molecule of formaldehyde to give the final product (68) <96JOC1922>. 

It is well known that the use of a synthetic equivalent of azomethine ylide, the thiazolium ylide, a known synthon for the simple azomethine dipole, undergoes cycloadditions with higher regioselectivity than the parent ylide <1994JOC4304, 1994JOC2773>. In order to control the enantioselectivity of the reaction, an Evans oxazolidionone was incorporated into the acrylate dipolarophile as in Scheme 71. The cycloaddition was carried out by reaction of 4 equiv of the acrylate with the thiazolium salt to afford the diastereomeric tricyclic adduct 27 (Scheme 71) <2002BMC3509>. 

Imidazolium, thiazolium and pyridinium ylides 198 also react with the acylmethylenecyclopropenes 208-210 to give the analogous heterocyclic cage compounds 212 (Table 20). 

The proton in the thiazolium ring is relatively acidic (pATa about 18) and can be removed by even weak bases to generate the carbanion or ylid (see Box 11.8). An ylid (also ylide) is a species with positive and negative charges on adjacent atoms this ylid is an ammonium ylid with extra stabilization from the sulfur atom. 

The 1 2 adduct 184 has a side chain similar to that of a product obtained from the reaction of dihydroimidazo[2,l-b]thiazolium ylides and DMAD (92JOC2347). 

Reaction with acetylenic dipolarophiles represents an efficient method for the preparation of 2,5-dihydrothiophenes. These products can be either isolated or directly converted to thiophene derivatives by dehydration procedures. The most frequently used dipolarophile is dimethyl acetylenedicarboxylate (DMAD), which easily combines with thiocarbonyl ylides generated by the extrusion of nitrogen from 2,5-dihydro-1,3,4-thiadiazoles (8,25,28,36,41,92,94,152). Other methods involve the desilylation (31,53,129) protocol as well as the reaction with 1,3-dithiolium-4-olates and l,3-thiazolium-4-olates (153-158). Cycloaddition of (S)-methylides formed by the N2-extrusion or desilylation method leads to stable 2,5-dihydrothiophenes of type 98 and 99. In contrast, bicyclic cycloadducts of type 100 usually decompose to give thiophene (101) or pyridine derivatives (102) (Scheme 5.37). 

The thiazolium salt 3-benzyl-5-(2-hydroxyethyl)-4-methyl-l,3-thiazolium chloride is an excellent catalyst for the addition of unsaturated aliphatic aldehydes to vinylketones (79CB84). The presence of a base such as sodium acetate or triethylamine is required, for the thiazolium salt must first be transformed into the ylide structure (615), which then exerts a catalytic effect resembling that of cyanide ion in the benzoin condensation (Scheme 137). Yields of 1,4-diketones (616) produced in this process were generally good. The use of thiazolium salts for other related reactions has been reviewed (76AG(E)639). 

The mechanism of the thiazolium ion-catalyzed conjugate addition reactions5 1s considered to be analogous to the Lapworth mechanism for the cyanide-catalyzed benzoin condensation, the thiazolium ylide playing the role of cyanide. The resulting intermediate carbanion is presumed to be the actual Michael donor. After conjugate addition to the activated olefin, the thiazolium ylide is eliminated to form the product and regenerate the catalyst. 

In the thiazolium cation the proton in the 2-position is acidic and its removal gives rise to the ylide/carbene 227. This nucleophilic carbene 227 can add, e.g., to an aldehyde to produce the cationic primary addition product 228. The latter, again via C-deprotonation, affords the enamine-like structure 229. Nucleophilic addition of 229 to either an aldehyde or a Michael-acceptor affords compound(s) 230. The catalytic cycle is completed by deprotonation and elimination of the carbene 227. Strictly speaking, the thiazolium salts (and the 1,2,4-triazolium salts discussed below) are thus not the actual catalysts but pre-catalysts that provide the catalytically active nucleophilic carbenes under the reaction conditions used. This mechanism of action of thiamine was first formulated by Breslow [234] and applies to the benzoin and Stetter-reactions catalyzed by thiazolium salts [235-237] and to those... 

The thiazolium salts may be converted into ylides by deprotonation. These ylides are comparable to the cyanide adducts in their ability to catalyze the Stetter Reaction effectively. 

The 13C NMR spectrum of the condensation product of thiazolium AT-ylide (194) with DMAD provided definitive evidence in support of the pyrrolo[2,l-c][l,4]thiazine (196) structure. Particularly important is the absence of an absorption that could be assigned to the tertiary C-5 in (195), this absorption being anticipated at 565.5 (76JOC187). 

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