Stereochemistry iminium activation

The iminium salts of 3,3,5-trimethylcyclohex-2-en-l-one were reduced with 1,4-dihydronicotinamide sugar pyranosides to give the corresponding optically active saturated ketone in enantiomeric excess ranging over 3-31%. The product stereochemistry changed sensitively with structural variations in the sugar residues. ... 

Working with dehydroquinase isolated from E. coli 83-2, Butler et al. [119] demonstrated that the reaction was catalyzed via iminium ion formation, in a manner analogous with the model system shown in Scheme 19. They demonstrated that the enzyme was inhibited in the presence of both substrate and sodium borohydride. The inhibited enzyme did not regain activity upon dialysis. The enzymatic SYN elimination is contrasted with the non-enzymatic, base-catalyzed, trans-eUmination found in aqueous solution, in which the pro-S proton is stereo-selectively removed (Scheme 20). The stereochemistry of proton abstraction in the non-enzymatic case arises from the pro-S proton being in an axial position such that... 

Although this review concerns those reactions catalyzed by iminium ion formation, it is important to note that there are enzymatic reactions that could logically be catalyzed by iminium ion formation but which are not. Yeast aldolase, for example, is the best known case [26] (see Ch. 6). This enzyme is metal ion dependent, does not demonstrate the loss activity in the presence of both substrate and borohydride, and is sensitive to inhibition by EDTA. The reaction catalyzed by this enzyme is identical to that catalyzed by the imine-forming enzyme, and even has evolved to exhibit the same retention stereochemistry. Another example is A -3-oxosteroid reductase which is responsible for the NADPH-dependent reduction of the enone double bond to the corresponding dihydrosteroid [124]. Even though iminium ion formation would increase the reactivity of this substrate toward the -hydride addition, a demonstrated lack of the required oxygen exchange proves that this does not occur. 

Sequential Iminium-Enamine Catalysis. Directed Electrostatic Activation. A comparison of the standard catalytic cycles for enamine activation (Scheme 2.1) and for iminium ion activation (Scheme 2.12) show that iminium catalysis proceeds, after the addition of the nucleophile, via an ( )-enamine. In the presence of a suitable electrophile, this enamine gives rise to an iminium ion that after hydrolysis can give rise to an a,p-diftmctionalyzed carbonyl (Scheme 2.13) [85]. Scheme 2.13 also shows that when using a chiral 2-substituted pyrrohdine or an imidazolidinone as the catalyst, the sequential apphcation of the steric model for Michael addition to iminium ions (Figure 2.15) and of the steric model for electrophilic attack to enamines (Figure 2.IB) predicts the absolute stereochemistry of the major isomer obtained in the reaction. 

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