In benzoin condensation

Acyloins (a-hydroxy ketones) are formed enzymatically by a mechanism similar to the classical benzoin condensation. The enzymes that can catalyze reactions of this type arc thiamine dependent. In this sense, the cofactor thiamine pyrophosphate may be regarded as a natural- equivalent of the cyanide catalyst needed for the umpolung step in benzoin condensations. Thus, a suitable carbonyl compound (a -synthon) reacts with thiamine pyrophosphate to form an enzyme-substrate complex that subsequently cleaves to the corresponding a-carbanion (d1-synthon). The latter adds to a carbonyl group resulting in an a-hydroxy ketone after elimination of thiamine pyrophosphate. Stereoselectivity of the addition step (i.e., addition to the Stand Re-face of the carbonyl group, respectively) is achieved by adjustment of a preferred active center conformation. A detailed discussion of the mechanisms involved in thiamine-dependent enzymes, as well as a comparison of the structural similarities, is found in references 1 -4. 

In benzoin condensations using benzaldehyde as starting material, the initial adduct, i.e. the C2a-hydroxybenzylthiazolium (HBT) compound or its alkoxide form, is readily tautomeiized to the enol, or enolate, that then condenses with a second benzaldehyde molecule. In a series of reports it was suggested that this is the result of carbene insertion behavior of the ylide " , rather than the result of nucleophilic addition. In aprotic media several mechanistic probes tended to disprove this thesis The need for a protic solvent to complete the condensation reaction (since compounds such as HBT are rather stable in DMSO ) prompted the suggestion of the intermediacy of the charged species... 

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. ... 

The new enantiopure thiazolium salts were tested in asymmetric Stetter reactions. As was the case in benzoin condensations catalyzed by chiral thiazolium salts and reported many years ago by Sheehan et al. [60,61] and Tagaki et al. [62], only moderate asymmetric inductions were observed. So far the best results are shown in scheme 22, a 30% chemical yield and an enantiomeric excess of 40% [63]. Nevertheless, the principle has been demonstrated, and we are confident to be able to improve the new procedure. 

N-Heterocychc carbenes (NHCs) derived from thiazolium salts (e.g., X) have been utihzed as catalysts in benzoin condensations, in additions of aldehydes to enones (Stetter reaction [17]) and recently in the reaction of acylsilanes with a, p-unsaturated carbonyl compounds (sila-SrEiTER reaction [18]), as exemplified in the following sequence of reactions ... 

The dramatic influence of a new tailor-made, task-specific, and stable ionic liquid, 3-[2-(l-butyl-lH-imidazol-3-ium-3-yl)ethyl]-4,5-dimethyl-l,3-thiazol-3-ium bromide (44, scheme-12), in benzoin condensations have been described by Mohanazadeh and Aghvami (Mohanazadeh Aghvami 2007). 

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