Unusual reversal of regioselectivity in antibody-mediated aldol additions with unsymmetrical methyl ketones

A catalytic regio- and enantioselective aldol reaction of various unsymmetrical methyl ketones with para-nitrobenzaldehyde has been developed using aldolase antibodies as the catalysts. It has been found that the sense and level of regioselectivity for the reactions catalysed by antibody 38C2 and 33F12 are highly dependent on the structure of both the donor and the acceptor but in contrast, antibodies 84G3 and 93F3 catalyse the exclusive formation of the linear regioisomer independent of the structure of the reactants examined. The level of enantiocontrol is very high for most reactions. Both linear aldol enantiomers could be accessed through aldol or retro-aldol reactions using the same antibody. Theoretical studies on regioisomeric α- and β-heteroatom substituted enamines derived from unsymmetrical ketones suggest that most of the linear aldol products formed in the presence of antibodies 84G3 and 93F3 must be formed from intermediate enamines which are not the thermodynamically most favourable. © 2003 Elsevier Ltd. All rights reserved

Asymmetric synthesis of aldol products derived from unsymmetrical ketones: assignment of the absolute configuration of antibody aldol products

Compounds 1-7 are the products formed by aldol condensation of p-nitrobenzaldehyde with a series of unsymmetrical ketones, the reaction occurring at the less substituted carbon. The asymmetric synthesis of 1-7 using the Evans's asymmetric aldol methodology is described in detail. These syntheses were completed to allow us to assign the absolute configuration of products 1-3, obtained in a single step in the presence of the aldolase I antibody 84G3. © 2002 Elsevier Science Ltd. All rights reserved