Thiazolylidene carbene

Stetter expanded Umpolung reactivity to include the addition of acyl anion equivalents to a,P-unsaturated acceptors to afford 1,4-dicarbonyls Eq. 5a [57-60]. Utilizing cyanide or thiazolylidene carbenes as catalysts, Stetter showed that a variety of aromatic and aliphatic aldehydes act as competent nucleophilic coupling partners with a wide range of a,p-unsaturated ketones, esters, and nitriles [61]. The ability to bring two different electrophilic partners... 

The proposed catalytic cycle for this reaction begins with the initial attack of the in situ generated thiazolylidene carbene on the epoxyaldehyde followed by intramolecular proton transfer (Scheme 28, XXXII-XXXIII). Isomerization occurs to open the epoxide forming XXXIV which undergoes a second proton transfer forming XXXV. Diastereoselective protonation provides activated carboxylate intermediate XXXVI. Nucleophilic attack of the activated carboxylate regenerates the catalyst and provides the desired P-hydroxy ester. 

The first example of an aldehyde-imine cross-benzoin reaction catalyzed by thiazolylidene carbenes was reported by Murry, Frantz, and co-workers, using arylsulfonylamides as imine precursors. Later, Miller and co-workers disclosed an asymmetric variant of this work by implementing their peptide-derived thiazolium salt as a precatalyst to deliver aryl aldehyde... 

This review will focus on the use of chiral nucleophilic A-heterocyclic carbenes, commonly termed NHCs, as catalysts in organic transformations. Although other examples are known, by far the most common NHCs are thiazolylidene, imida-zolinylidene, imidazolylidene and triazolylidene, I-IV. Rather than simply presenting a laundry list of results, the focus of the current review will be to summarize and place in context the key advances made, with particular attention paid to recent and conceptual breakthroughs. These aspects, by definition, will include a heavy emphasis on mechanism. In a number of instances, the asymmetric version of the reaction has yet to be reported in those cases, we include the state-of-the-art in order to further illustrate the broad utility and reactivity of nucleophilic carbenes. 

Breslow and co-workers elucidated the currently accepted mechanism of the benzoin reaction in 1958 using thiamin 8. The mechanism is closely related to Lapworth s mechanism for cyanide anion catalyzed benzoin reaction (Scheme 2) [28, 29], The carbene, formed in situ by deprotonation of the corresponding thiazolium salt, undergoes nucleophilic addition to the aldehyde. A subsequent proton transfer generates a nucleophilic acyl anion equivalent known as the Breslow intermediate IX. Subsequent attack of the acyl anion equivalent into another molecule of aldehyde generates a new carbon - carbon bond XI. A proton transfer forms tetrahedral intermediate XII, allowing for collapse to produce the a-hydroxy ketone accompanied by liberation of the active catalyst. As with the cyanide catalyzed benzoin reaction, the thiazolylidene catalyzed benzoin reaction is reversible [30]. 

In a similar study, the catalytic activity of the classical carbene complex 31 and its abnormal thiazolylidene analogues 32 and 33, obtained by oxidative addition, were tested in the Suzuki coupling of activated aryl bromides (Figure 5.9). At 70 °C, the catalytic activity decreased in the order 31 >32 >33. The abnormal thiazolylidene complexes were thus less active than their normal counterpart. It is worth noting that the steric impact of the ligand in the normal carbene... 

Figure 5.18 Examples of transient thiazolylidene radical 159, and carbene-supported stable radicals 160-168.

---