Thiazol-4-ylidene

Despite the numerous reports concerning NHC-Ru olefin metathesis initiators, a complex incorporating a carbene that has only one exocyclic substituent adjacent to the carbenic centre was not reported until 2008. Studies by Grubbs and co-workers led to the development of ruthenium-based catalysts bearing such carbene ligands, in this case incorporating thiazole-2-ylidenes [63] (Fig. 3.19). 

Two major routes give access to (thiazol-2-ylidene)gold(i) complexes with 1 1 stoichiometry. The corresponding thiazolium salts react with base in the presence of gold(i) precursors to give the products in high yield. Alternatively, the corresponding carbeniate complexes can be A-protonated or A-alkylated to afford compounds of this series (Scheme 65).257,266... 

It is noteworthy that both types of reactions can also be applied to prepare (carbene)gold(m) compounds A-alkyl-thiazolium salts react with HAuG14 or NaAuCl4, followed by the addition of base, to give (thiazol-2-ylidene)gold(m)... 

One Au-C bond in bis(thiazol-2-ylidene)gold cations is cleaved in the reaction with elemental iodine to give the corresponding (carbene)AuI complex and a 2-iodo-thiazolium salt, while chlorine and bromine oxidize the gold center to the gold(m) state.267... 

Isopropylidene (l,3-thiazol-2-ylidene)malonates (473) were prepared in 52-60% yields in the reactions of (2-methylthio)thiazolium salts (472) and Meldrum s acid (421) at ambient temperature for 5-10 hr (77KGS341). 

A similar reaction was carried out with 3a-iodo-5a-androstan-2/3-yl isothiocyanate and di-(7er/-butyl) malonate to give (andost-2-eno[2,3-[Pg.132]

Di-terf-butyl 2-thiazolylidenemalonates (1637) were treated with trifluo-roacetic acid in methylene chloride at ambient temperature for 30-40 min to afford equilibrium mixtures of (thiazol-2-ylidene)acetates (1638) and (thiazolin-2-yl)acetates (1639) in 82-100% yields (85AJC745). 

However, besides the work by Wanzlick, several examples of aminocarbene dimerizations have been reported." Noteworthy is the isolation of both the thiazol-2-ylidene (Villa) and of its dimer VIIIa 2" and the spectroscopic characterization by Alder and Blake of the bis(A-piperidinyl)carbene (IXb) and of the tetrakis(A-piperidinyl)ethene ( IXb 2) (Scheme 8.12). 

Enders D, Muller-Huwen A (2004) Asymmetric synthesis of 2-amino-1,3-diols and D-erythro-sphinganine. Eur J Org Chem 2004 1732 Enders D, Niemeier O (2004) Thiazol-2-ylidene catalysis in intramolecular crossed aldehyde-ketone benzoin reactions. Synlett 2004 2111-2114... 

Other heterocyclic ylids have been generated in the gas-phase by collisional reduction of stable ylid cation-radicals using synthetic strategies similar to that described for 35+, e.g., imidazol-2-ylidene [149], thiazol-2-ylidene [150], pyrazine ylids [151], pyrimidine ylids [152], and pyridinium methylids [153]. 

Thiazol-2-ylidenes are less well studied than their imidazole and triazol analogues. Only one isolated and structurally characterised example is known in the literature, the 3-(2,6-diis opropylphenyl)thiazol-2-ylidene synthesised by Arduengo et al. in 1997 [2] (see Figure 6.8). The parent compound, 2,3-dihydrothiazol-2-ylidene, was generated in an argon matrix at 10 K from thiazol-2-carboxylic acid as the starting material [33] (see Figure 6.9). 

Figure 6,10 Acid catalysed monomer-dimer equilibrium of 3-(2,6-diisopropylphenyl) thiazol-2-ylidene.

Note Thiazol-2-ylidenes, although stable at ambient temperatures, readily dimerise reversibly to the respective electron-rich olefin. 

How close the stability of the monomeric 3-(2,6-diisopropylphenyl)thiazol-2-ylidene actually is at its dimerisation limit was demonstrated by Arduengo et al. in an attempt to synthesise the less bulky 3-(mesityl)thiazol-2-ylidene. When the monomer was generated at low temperatures using Bu OK as the base, it dimerised at temperatures above 0°C in solution, whereas synthesis at ambient temperature using KH [same reaction conditions as for 3-(2,6-diisopropylphenyl)thiazol-2-ylidene] resulted in the dimer exclusively [2]. With a methyl group on the nitrogen atom, the intermediate carbene monomer could no longer be unequivocally detected even at low temperatures. 

Note The tendency to dimerise and form electron-rich olefins follows the sequence isothiazol-3-ylidene > thiazol-2-ylidene > imidazol-2-ylidene. 

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. 

Instead, only two reaction pathways are used to generate transition metal NHC complexes with thiazol-2-ylidene orbenzothiazol-2-ylidene (i) thermal cleavage of an electron-rich olefin in the presence of a suitable transition metal (see Figure 6.12) [40,41] and (ii) deprotonation of a thiazolium or benzothiazolium salt in the presence of a transition metal (see Figure 6.13) [40,42-44]. 

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)... 

Whereas copper(I) thiazol-2-ylidene complexes are monocarbene and linear complexes that can form weak dimers in the solid state, the analogons gold(I) complexes could be synthesised as linear mono- or bis-carbene complexes. Since the metal requires a monoanionic ligand to balance its one positive charge, monocarbene complexes are normally neutral whereas the corresponding bis-carbene complexes are ionic. Partial protonation... 

Figure 6.14 Synthesis of copper(l) thiazol-2-ylidene complexes.

Note This reaction can serve as an alternative to the thermolysis of electron-rich olefins, in this case the dimers of thiazol-2-ylidene and benzothiazoT2-ylidene, developed by... 

Utilisation of transition metal benzothiazol-2-yMene and especially thiazol-2-ylidene complexes in homogenous catalysis reactions are very rare [42-44], Calo et al. reported the use of bis-(3-methyl-benzothiazol-2-ylidene) palladium diiodide in the Heck reaction of aryl bromides and iodides with a catalyst loading of down to KU mol% and near quantitative yields [42,44],... 

The reaction mechanism is similar to the one employed by Raubenheimer el al. for their chromium(O) thiazol-2-ylidene complex [48], In the case of the ruthenium imidazol-2-ylidene complexes, 4,5-dimethylimidazole stabilised the carbene complex compared with unsubstituted imidazole. Likewise, the carbonyl ligand in trans position was necessary to isolate and crystallise the complex. This can be expected, when an excellent o-donor (NHC) is trans to an excellent tr-acceptor (CO). 

Imidazol l,3-DimethyI-5-[2-(3-methyl-tetrahydro-l,3-thiazol-2-yliden)-ethyliden]-4-oxo-2-thiono-tetrahydro- V/ld, 288... 

Much time and effort has been spent in recent years seeking long-lived carbenes.92 This flurry of activity has met limited success. Persistent triplet carbenes,93 such as triplet bis(10-phenylanthracen-9-yl)carbene (11) (t /2 — 19 min, D/hc — 0.105 cm-1) (Fig. 7),92a 93a b 94 constitute one area of promising research. Ylide-like singlet carbenes, such as Breslow thiazol-2-ylidenes (12),95 Arduengo imidazolin-2-ylidenes (13),92f 96,97 Bertrand phosphinocarbenes (14),920,98 and Wanzlick imidazolidin-2-ylidenes (15),97,99 comprise another (Fig. 8).100 However, supramolecular inclusion of more typical carbenes within suitable hosts may offer distinct advantages. 

Orsini M, Chiarotto I, Sotgiu G, Inesi A (2010) Polarity reversal induced by electrochemically generated thiazol-2-ylidenes the Stetter reaction. Electrochim Acta 55 3511—3517... 

Imidazol-2-ylidines and imidazolin-2-ylidenes are the most commonly employed phosphine surrogates in Ru-based metathesis catalysts but a variety of other related carbenes have also been explored. Catalysts 25-29 containing A -aryl-thiazol-2-ylidenes with varying steric bulk of the aryl substituent have been prepared (Figure 9) [29]. 

The thiazolium-mediated three-component reaction of thiazolium salts 201, aryl aldehydes and dimethyl acetylenedicarboxylate provides a facile synthesis of 2-amino-2-arylfurans 202 <05OL1343>. The reaction pathway may involve the sequential nucleophilic addition of thiazol-2-ylidene 203 with the aldehyde and DMAD to form the spirocyclic intermediate 204 through the simultaneous formation of two C-C bonds and a C-O bond Selective ring opening of the spirocyclic intermediate 204 followed by hydrolysis leads to 3-aminofuran 202 via 205. 

Ethyl-2-[3-(3-ethyI-2,3-dihydro-1,3-thiazol-2-yliden)-l-triazeno]-1,3-thiazolium-tetra-fluoroborat1043 79% Schmp. 196 201°... 

Ethyl-2-[3-(3-ethyl-2,3-dihydro-l, 3-thiazol-2-yliden)-I-propenyl]-l, 3-thiazolium-iodid1503 51% Schmp. 223-224°... 

---