Thiazolium ylide

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 ... 

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>. 

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). 

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. 

Hachisu Y, Bode JW, Suzuki K (2003) Catalytic intramolecular crossed aldehyde-ketone benzoin reactions a novel synthesis of functionalized prean-thraquinones. J Am Chem Soc 125 8432-8433 Hachisu Y, Bode JW, Suzuki K (2004) Thiazolium ylide-catalyzed intramolecular aldehyde-ketone benzoin-forming reactions substrate scope. Adv Synth Catal 346 1097-1100... 

Ho, T. L., Liu, S. H. Stetter condensation catalyzed by a polymer-bound thiazolium ylide. Synth. Commun. 1983, 13,1125-1127. 

Nucleophilic carbenoids (also called ylides by some authors) react with heterocumulenes, such as isocyanates and isothiocyanates, to yield hy-dantoins, 2-thiohydantoins, and 2,4-dithiohydantoins via dipolar intermediates. Thus dimethoxycarbene adds to aryl isocyanates and isothiocyanates to form 5,5-dimethoxyhydantoins and dithiohydantoins.107 Thiazolium ylides (61) (resulting from thiazolium salts and NEt3 in DMF) give dipolar 1 1 adducts (62) or l 2-cycloadducts (63) with isocyanates or isothiocyanates.108-110 Other substrates are imidazolidine111 or 2-imidazoline derivatives.112... 

The role of a thiazolium ylide in the enzyme-catalysed decarboxylation of pyruvate... 

As with all reactive intermediates it is important that they are not too stabilised to prevent facile further reaction. The thiazolium ylide is a potent carbon nucleophile but also a good leaving group. This is reminiscent of cyanide ion in the benzoin condensation and, in fact, the chemical logic of that reaction mechanism is similar to the thiamine-catalysed decarboxylations of a-keto acids (Scheme 2). 

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,... 

Various azole ylides react with alkynes or alkenes with subsequent ring opening and recyclization. Thus pyrazolium ylide (348) gives compound (349) (Equation (188)) <93JCS(P1)883>, imidazolium ylide (350) gives (351) (Equation (189)) <91H(32)2217>, and thiazolium ylide (352) gives (353) (Equation (190)) <76JOC187>. 

The thiazolium ylide (172) obtained from the 5-hydroxyethyl-4-methylthiazole derivative reacts with a suitable alkene CH2CHR to afford ultimately (15a) (Table 2) <81TL2727>. If the alkene CH2CHR is replaced by a,)S-unsaturated esters or nitriles a fused thiazoline (173) can be isolated. Surprisingly (173) cyclizes to give (15b) (Table 2) when it is purified by chromatography over silica gel. 

The same thiazolium ylide (172) was utilized for the synthesis of other compounds (15) (Table 2) through 1,3-dipolar cycloaddition reactions exploiting assorted dipolarophiles (e.g., MeCOCHCHMe, MeCOCHCHPh, CH2CHC02Et) followed by silica gel-assisted cyclization <85T3537>. Other thiazolium ylides (172b) were also used for the preparation of this type of heterocycle. 

A -Alkylated thiazolium and benzothiazolium salts also experience base-promoted deprotonation at the 2-position to form ylides. Such compounds, often referred to as TV-heterocyclic carbene (NHC), are nucleophilic catalysts in benzoin condensation. In 1943, Ugai and co-workers reported that thiazolium salts catalyze self-condensation of benzaldehyde to generate benzoin via an umpoulong process. Breslow at Columbia University in 1958 proposed thiazolium ylide as the actual catalyst for this transformation. In this mechanism, the catalytically active species was represented as a thiazolium zwitterion, the resonance structure of an NHC, and the reaction was postulated to ensue via the enaminol or the Breslow intermediate. ... 

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