Complete stereocontrol in organocatalytic additions of β-ketosulfoxides to conjugated aldehydes

Abstract

The use of β-ketosulfoxides as nucleophiles in reactions with α,β-unsaturated aldehydes catalyzed by proline derivatives allows complete control of configuration at the two chiral centers that are created during 1,4-addition reactions. The sulfinyl group can be used to create additional chiral centers in the resulting compounds and then removed while preserving the chirality of the carbon joined to the sulfur. The catalyst and the sulfinyl group are mainly responsible for the configurational control of the carbon atoms acting as electrophile and nucleophile, respectively, which allows the preparation of the four possible diastereoisomers in optically pure form. Theoretical calculations of the possible chiral nucleophilic species bearing diastereotopic faces allow us to postulate, for the first time, that enolates, instead of enols, are the active reagents in these reactions.