Antibody Catalysis of a Disfavored Chemical Transformation

Abstract

Organic reactions are often limited by stereoelectronic constrains that appear along the reaction coordinate. An antibody has been generated that overcomes these constraints and catalyzes a highly disfavored chemical transformation. The antibody facilitates the difficult 6-endo-tet ring closure of an epoxy-alcohol to form a tetrahydropyran. The catalyzed process is in formal violation of what has become known as Baldwin's rules for ring-closure reactions. In addition to controlling the regiochemistry of the disfavored cyclization reaction, these catalytic antibodies resolve enantiomeric substrates to afford a stereochemically pure product. The principles demonstrated in this study may be applicable to other disfavored chemical processes.