Thiazoles carbenes from

Lappert developed the thermolysis of an electron-rich olefin in the presence of a transition metal complex as another way to synthesise these compounds [4], When, in 1975, Clarke and Taube published their findings on carbon coordinated purine transition metal complexes [5], transition metal NHC complexes with functionalised NHC made their debut in biochemistry. The chemistry of carbenes from natural products became firmly established following the discovery that the catalytic activity of thiamine (vitamin Bl) is based on the intermediate formation of a carbene derived from thiazole [6-9] (see Figure 1.2). 

The most common ligands are those derived from imidazole and benzimidazol (Scheme 54), followed by the (benz)thiazols. The free Wanzlick-Arduengo carbenes can be isolated and employed for the synthesis of the complexes, but often it is more convenient to prepare the carbenes in situ from the dimers or the corresponding onium salts, or to use carbene-transfer reactions.256-259... 

Apart from imidazol-2-ylidenes (IV), eight other types of carbenes are included in this category imidazolidin-2-yhdenes (III), tetrahydropyrimid-2-yhdene (V)," ° benzimidazol-2-ylidene (VI)," l,2,4-triazol-5-ylidene (VII)," l,3-thiazol-2-yli-denes (VIII), as well as acyclic diamino- aminooxy- and aminothio-carbenes (XI) (Fig. 8.5). 

Scheme 61, yielded thiazole 200 as the major product, along with minor amounts of carbinol 201 [152]. On the other hand, treatment of the imine formed from 199 and p-methoxyphenylamine with catalytic tetrabutylammonium cyanide, produced suc-cinimide derivative 202. In both cases, the process is initiated by nucleophilic attack to the carbaldehyde C=0 (or azomethine s C=N) group, which is followed up by an anionic rearrangement. A variation of the above process using as catalysts /V-heterocyclic carbenes (NHC) derived from base treatment of azolium, imidazo-lium, or triazolium salts, has also been developed to access gem-disubstituted succinimides [153, 154]. Unfortunately, an attempt of kinetic resolution of racemic 4-formyl (3-lactams by using chiral NHC resulted in moderate selectivities only [154]. 

Given that thiazole is the active centre in vitamin Bl, thiamine has been the centre of intense research of its organocatalytic potential for decades it might be surprising that only very few examples of transition metal NHC complexes are known that use thiazol-2-ylidene or its benzo-annulated analogue benzothiazol-2-ylidene. As we have seen above, one major reason is the instability of the free carbene leading to dimerisation instead. Another major contribution is the apparent inability of thiazol-2-ylidene to coordinate to silver(I) [39] making carbene transfer from silver salts to other transition metals impossible. 

Raubenheimer et al. have developed a third route for transition metal NHC complexes with thiazol-2-ylidene, benzothiazol-2-yUdene and even isothiazol-5-ylidene ligands [45 9]. This method uses a thiazolyl transfer from lithium to a transition metal with subsequent protonation [47,49-54] or alkylation [41,45,46,48,51-56] of the nitrogen atom to generate the transition metal NHC complex. In this way, carbene complexes of copper(I)... 

The 1,3-dimethylimidazolium ylide, generated using sodium hydride, allows the introduction of electrophiles to C-2." Isolable, crystalline carbenes have been derived from 1,3-bis(adamantanyl)imidazolium chloride, " and from 1,3,4,5-tetra-phenylimidazolium chloride. A stable thiazol-2-ylidene carried methyl groups at positions 4 and 5 and a 2,6-di-/-propylphenyl substitutent on nitrogen. 

Breslow (1958JA3719) discussed carbene intermediates on decarboxylation of thiazole-2-carboxybc acid 32 (1948HCA924) which indeed forms thiazol-2-ylidene 33 photochemically starting from the rotamer 32, not 32, via a complex of the NHC 33 and carbon dioxide (Scheme 9) (1997AG1709). 

The general strategy for carrying out these MCRs starts with the generation of the NHC, which involves the deprotonation of the corresponding azolium salt by an appropriate base. Next, this carbene reacts with several electrophiles to produce reactive zwitterionic intermediates (typically from reaction with carbonyl compound or activated alkynes), followed by different rearrangements, rendering the final product. In this section, only examples based on thiazol-2-ylidenes... 

The benzoin condensation has been examined computationally as a function of the structure of three carbene organocatalysts, that is, imidazol-2-, triazol-3-, and thiazol-2-ylidenes. DFT studies have featured three aldehydes and the historical mechanism of Breslow appeared to be consistent with the calculated reaction energy profiles whatever the aldehydexarbene combination was. It is noteworthy that the Breslow intermediate (118) arising from thiazol-2-ylidene proved to be much more stable than (119)/(120)... 

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