Elimination reactions, comparison stereoselective

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. 

There exist two simple rationales to explain the observed direction of the dia-stereoselective bond activation in 7/Fe+, i.e., more pronounced loss of H2 from 7a/Fe+ in comparison to 7b/Fe+. At first, one can safely assume that the reaction proceeds via insertion of the docked Fe+ in a terminal C-H bond to form a six-membered ring. Depending on the relative stereochemistry at C(3) and C(4), the eliminations of H2 and HD, respectively, therefore involve quasi-axial or quasi-equatorial orientations of the methyl substituents in the intermediates eq- and ax-lOa of course, similar considerations apply to the associated transition structures (TSs). By analogy to conventional arguments of conformational analysis, an equatorial position of the methyl group is assumed to be preferred, thereby accounting for the experimentally observed H2/HD ratios. Thus, for the stereoisomer shown in Scheme 8, both the KIE and the equatorial position of the methyl substituent favor loss of H2, whereas the SE favors loss of HD from 7b/Fe+. However, for the latter this path is impeded by the operation of a kinetic isotope effect that slows down activation of a C-D bond. Secondly, one arrives at... 

Better stereoselectivity for the (all- )-geometry is attained under such heterogeneous conditions in comparison with the homogeneous reaction in methanol or pyridine. This is ascribed to i-yw-elimination in a concerted manner on the surface of the solid base (Fig. 1). 

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