Benzoin condensation enantioselective dimerization

The thiazolium and, particularly, triazolium catalysts discussed above have been developed to the extent that they perform remarkably well in the asymmetric benzoin condensation of aromatic aldehydes. Triazolium catalysts are also very effective in the (non-stereoselective) condensation of aliphatic aldehydes [250]. It seems, however, that no catalyst is yet available that enables condensation of aliphatic aldehydes with synthetically useful enantioselectivity. The best ee yet obtained are in the range 20-25%, e.g. in the dimerization of the straight-chain C2-C7 aldehydes [251]. 

Milller and co-workers recently developed an enantioselective benzoin dimerization using purified enzymes from Pseudomonas. The thiamine diphosphate (ThDP) dependent enzymes benzaldehyde lyase (BAL) and benzoylformate decarboxylase (BED) were found to catalyze the reversible benzoin condensation of aromatic aldehydes. The reaction is driven in the forward direction by the poor solubility of the benzoin products in aqueous media. A wide variety of aromatic aldehydes are accepted by BAL, and products of the (/ )-configuration are produced in excellent yield and enantiomeric purity. The (S)-enantiomer of benzoin is also available in high enantiomeric purity from a BAL-catalyzed kinetic resolution of rac-benzoin. In the presence of excess acetaldehyde, BAL selectively converts (i )-benzoin into (/ )-2-hydroxy-l-phenylpropanone, while the (iS)-benzoin enantiomer is not a substrate for the enzyme. At 49% conversion, (5)-benzoin is resolved to > 99% ee. BED can produce (i )-benzoin from benzaldehyde in comparable yield and enantiomeric purity with respect to BAL, but the substrate scope appears more limited. ... 

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