Stereodivergent Carbon–Carbon Bond Formation between Iminium and Enolate Intermediates by Synergistic Organocatalysis

We report here a stereodivergent
method for the Michael addition
of aryl acetic acid esters to α,β-unsaturated aldehydes
catalyzed by a combination of a chiral pyrrolidine and a chiral Lewis
base. This reaction proceeds through a synergistic catalytic cycle
which consists of one cycle leading to a chiral iminium electrophile
and a second cycle generating a nucleophilic chiral enolate for the
construction of a carbon–carbon bond. By varying the combinations
of catalyst enantiomers, all four stereoisomers of the products with
two vicinal stereocenters are accessible with high enantio- and diastereoselectivity.
The products of the Michael addition, 1,5-aldehyde esters, can be
readily transformed into a variety of other valuable enantioenriched
structures, including those bearing three contiguous stereocenters
in an acyclic system, thus providing an efficient route to an array
of structural and stereochemical diversity.