1380547-38-5Relevant articles and documents
Bispalladacycle-catalyzed Michael addition of in situ formed azlactones to enones
Weber, Manuel,Jautze, Sascha,Frey, Wolfgang,Peters, René
, p. 14792 - 14804 (2013/01/15)
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 Br?nsted acid (HOAc or BzOH; Ac=acetyl, Bz=benzoyl), and a Br?nsted 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. Flourishing step economy: The evolution of the catalytic asymmetric addition of azlactones to enones is described. The first-generation approach started from isolated azlactones. In the second-generation approach azlactones could be generated in situ from racemic N-benzoylated amino acids. The third evolution stage could directly use racemic unprotected α-amino acids to form a large number of highly enantioenriched quaternary amino acids derivatives (see figure). Copyright
