Benzoin catalytic cycle

In contrast to Nair, Bode and co-workers propose that cross-benzoin adduct LVII is formed which then undergoes an oxy-Cope rearrangement to form LVIII (Scheme 38). Tautomerization and indamolecular aldol reaction occurs following the catalytic cycle proposed by Nair. 

In the thiazolium cation the proton in the 2-position is acidic and its removal gives rise to the ylide/carbene 227. This nucleophilic carbene 227 can add, e.g., to an aldehyde to produce the cationic primary addition product 228. The latter, again via C-deprotonation, affords the enamine-like structure 229. Nucleophilic addition of 229 to either an aldehyde or a Michael-acceptor affords compound(s) 230. The catalytic cycle is completed by deprotonation and elimination of the carbene 227. Strictly speaking, the thiazolium salts (and the 1,2,4-triazolium salts discussed below) are thus not the actual catalysts but pre-catalysts that provide the catalytically active nucleophilic carbenes under the reaction conditions used. This mechanism of action of thiamine was first formulated by Breslow [234] and applies to the benzoin and Stetter-reactions catalyzed by thiazolium salts [235-237] and to those... 

It should, however, be pointed out that - where applicable - product composition can be significantly different. For example, whereas thiazolium catalysts afford exclusively dihydroxyacetone with formaldehyde as substrate, the triazolium systems afford glycolic aldehyde (plus glyceraldehyde and C4 and C5 sugars as secondary products) [246], Catalyst-dependent differences in the relative rates of the partial reactions within the catalytic cycle (Scheme 6.105) most probably account for this phenomenon. A subsequent study by Enders et al. on chiral triazolium salts identified the derivative 233 as a first catalyst for the asymmetric benzoin condensation that affords substantial enantiomeric excesses (up to 86%) with satisfactory chemical yields (Table 6.3) [247]. 

Scheme 9.1 The catalytic cycle of the benzoin condensation, as proposed by Breslow.

Scheme 19. Catalytic cycle of the benzoin condensation as proposed by Bres-low...

The benzoin condensation is the coupling of two aldehydes to afford ot-hydro>ycarbonyl compounds. In 1958, Breslow proposed the mechanism of the thiazolium-catalysed benzoin condensation reaction. It is believed that tetrahedral intermediate I is formed by nucleophilic attack of the in situ generated carbene A to the aldehyde. After proton transfer, intermediate II, now called the Breslow intermediate, is generated and reacts with an aldehyde to afford a new tetrahedral intermediate III. Elimination of the carbene catalyst affords the benzoin product and completes the catalytic cycle (Scheme 20.1). 

Two related modifications have been developed to provide cross-benzoin products not accessible under classical benzoin condensation conditions. In the first approach, one aldehyde partner is converted to a cyanohydrin derivative which serves as the stoichiometric equivalent of intermediate 3a on the catalytic cycle of the cyanide-catalyzed benzoin condensation. A number of cyanohydrin derivatives can be used, with the most popular being the O-silyl cyanohydrin 14, first reported by Hiinig and Wehner. In a subsequent step, the cyanohydrin derivative is treated with stoichiometric base followed by the second aldehyde to give the silylated cross-benzoin product 16 in high yield. 

Mo02(Cys-OMe)2, Mo02(S2CNEt2) and other complexes are reported" to catalyze the air oxidation of benzoin to benzil. The complex MoO2(Cys-0R)2 (R = Me, Et, Pr1 and CH2Ph) catalyzes the 02 oxidation128,184 of PPh3 in DMF by a mechanistically involved process in which excess H20 prevents the catalytic redox cycle.184,185... 

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