title: Bispalladacycle-catalyzed Michael addition of in situ formed azlactones to enones.
abstract: The development and further evolution of the first catalytic asymmetric conjugate additions of azlactones as activated amino acid derivatives to enones is described. Whereas the first-generation approach started from isolated azlactones, in the second-generation approach the azlactones could be generated in situ starting from racemic N-benzoylated amino acids. The third evolution stage could make use of racemic unprotected α-amino acids to directly form highly enantioenriched and diastereomerically pure masked quaternary amino acid products bearing an additional tertiary stereocenter. The step-economic transformations were accomplished by cooperative activation by using a robust planar chiral bis-Pd catalyst, a Brønsted acid (HOAc or BzOH; Ac=acetyl, Bz=benzoyl), and a Brønsted base (NaOAc). In particular the second- and third-generation approaches provide a rapid and divergent access to biologically interesting unnatural quaternary amino acid derivatives from inexpensive bulk chemicals. In that way highly enantioenriched acyclic α-amino acids, α-alkyl proline, and α-alkyl pyroglutamic acid derivatives could be prepared in diastereomerically pure form. In addition, a unique way is presented to prepare diastereomerically pure bicyclic dipeptides in just two steps from unprotected tertiary α-amino acids.
authors.affiliation: Institut für Organische Chemie, Universität Stuttgart, Germany.
authors.forename: Manuel
authors.initials: M
authors.lastname: Weber
authors.forename: Sascha
authors.initials: S
authors.lastname: Jautze
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Frey
authors.forename: René
authors.initials: R
authors.lastname: Peters
mesh_terms: D000596:Amino Acids / Q000138:chemical synthesis* / Q000737:chemistry*; D002384:Catalysis; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry*; D011392:Proline / Q000138:chemical synthesis* / Q000737:chemistry*; D011761:Pyrrolidonecarboxylic Acid / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000596:Amino Acids; D010165:Palladium; D011392:Proline; D011761:Pyrrolidonecarboxylic Acid