Synthesis of PPAR Agonist via Asymmetric Hydrogenation of a Cinnamic Acid Derivative and Stereospecific Displacement of (S)-2-Chloropropionic Acid

The synthesis of the peroxime proliferator activated receptor (PPAR) α,γ-agonist (1) was accomplished with high enantio- and diastereoselectivity by employing an asymmetric hydrogenation strategy, of an α-alkoxy cinnamic acid derivative, to set the C-2 chiral center. A diastereospecific SN2 displacement under mild basic conditions established the C-10 stereochemistry without any detectable racemization of the two epimerizable chiral centers.