Thiazolium salts, base-catalyzed

In 1943, more than a century after the initial report, Ukai et al. showed that thia-zolium salts such as 7 and 8 catalyze the homodimerization of aldehydes in the presence of base [2], This discovery was paramount because, while cyanide ions are inherently achiral, thiazolium salts can be modified to act as a source of chirality to render the reaction enantioselective. 

Diketones are readily transformed to cyclic derivatives, such as cyclopentanones and furans. In this manner, the fragrance dihydrojasmone (3-methyl-2-pentyl-2-cyclopenten-l-one) is prepared by the base-catalyzed aldol condensation of 2,5-undecanedione. 2,5-Undecanedione is itself prepared from heptanal and methyl vinyl ketone in the presence of thiazolium salts (329). cis-jasmone can be similarly prepared (330,331). 

A further complicating feature in these reactions is the finding that HETh and its thiazolium and benzothiazolium analogs can, in the presence of a base such as Me3N or DBU, be tautomerized to the rather stable 2-benzoylthiazolines9,10. This reaction apparently requires a aprotic medium. Further, Chen showed55,57 that for a number of aromatic aldehydes, when the reaction is performed in methanol, the principal product is not HBT but rather the dimethoxyacetal of the precursor aldehyde. Thiazolium salts appear to catalyze conversion of some aromatic aldehydes to their acetals in reasonable yields. This appears to be a rare example of acetal formation under alkaline conditions. These various reactions of aldehydes and thiazolium salts, additional to the benzoin condensations, are outlined in Scheme 5. 

The diastereomerically pure thiazolium salt 509 which bears a 2-/i t7-butylphenyl substituent at the nitrogen atom was converted into a mixture of 510 and its atropisomer 510 (dr = 75 25) upon treatment with base (Scheme 128). The stereogenic center in the intermediate carbene favors one rotamer 510. Upon reaction with benzaldehyde, it accounts in a similar fashion for the formation of the major enol diastereoisomer 511 over 511, which, in turn, leads to the major enantiomer 512 rather than 512 observed in the benzoin condensation catalyzed by 509. The concept of axial chirality was proven to be viable for an efficient chirality transfer. Replacement of the isopropyl group at C-4 by the bulkier 2-phenyl-2-propyl substituent using 8-phenylmenthone is likely thought to increase the ee <2004EJ02025>. 

Studies on thiamine (vitamin Bi) catalyzed formation of acyloins from aliphatic aldehydes and on thiamine or thiamine diphosphate catalyzed decarboxylation of pyruvate have established the mechanism for the catalytic activity of 1,3-thiazolium salts in carbonyl condensation reactions. In the presence of bases, quaternary thiazolium salts are transformed into the ylide structure (2), the ylide being able to exert a cat ytic effect resembling that of the cyanide ion in the benzoin condensation (Scheme 2). Like cyanide, the zwitterion (2), formed by the reaction of thiazolium salts with base, is nucleophilic and reacts at the carbonyl group of aldehy s. The resultant intermediate can undergo base-catalyzed proton... 

Upon treating certain (but not all) aromatic aldehydes or glyoxals (a-keto aldehydes) with cyanide ion (CN ), benzoins (a-hydroxy-ketones or acyloins) are produced in a reaction called the benzoin condensation. The reverse process is called the retro-benzoin condensation, and it is frequently used for the preparation of ketones. The condensation involves the addition of one molecule of aldehyde to the C=0 group of another. One of the aldehydes serves as the donor and the other serves as the acceptor. Some aldehydes can only be donors (e.g. p-dimethylaminobenzaldehyde) or acceptors, so they are not able to self-condense, while other aldehydes (benzaldehyde) can perform both functions and are capable of self-condensation. Certain thiazolium salts can also catalyze the reaction in the presence of a mild base. This version of the benzoin condensation is more synthetically useful than the original procedure because it works with enolizable and non-enolizable aldehydes and asymmetric catalysts may be used. Aliphatic aldehydes can also be used and mixtures of aliphatic and aromatic aldehydes give mixed benzoins. Recently, it was also shown that thiazolium-ion based organic ionic liquids (Oils) promote the benzoin condensation in the presence of small amounts of triethylamine. The stereoselective synthesis of benzoins has been achieved using chiral thiazolium salts as catalysts. 

Castells, J., Lopez-Calahorra, F., Domingo, L. Postulation of bis(thiazolin-2-ylidene)s as the catalytic species in the benzoin condensation catalyzed by a thiazolium salt plus base. J. Org. Chem. 1988, 53,4433-4436. 

The thiazolo[2,3-6]oxazole (104) has also been prepared by a base-catalyzed type A cyclization <85CC454>. In this case, the cyclization of thiazolium salt (102) is believed to occur by intramolecular nucleophilic attack of a hydrate dianion intermediate (103) on the positively charged ring. However, other workers have cast doubt on the structure of the product from this reaction claiming, on the basis of x-ray analysis, that it exists as (105) in the solid phase <85CC1113>. 

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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