Efficient Bis(oxazolidine)pyridine Ligands Utilized for the Asymmetric [3+2] Cycloaddition

Bis(oxazolidine)pyridine (=PyBodine) ligands are tridentate ligands developed by Arai et al. PyBodine ligands 1 and 2 are easily prepared from optically active hydroxyamines derived from the related amino acids allowing the design of various chiral asymmetrical fields by replacing optically active hydroxyamines. The reactivity and enantioselectivity of various PyBodine ligands are evaluated by using a high-throughput screening system for analyzing the asymmetric induction with circular dichroism as a detector. As a result, in the presence of copper(II) acetate, the ligands 1 and 2 derived from L-alanine and L-proline respectively, show high reactivities for the catalytic asymmetric [3+2] cycloaddition of azomethine imines with propiolates. In this reaction, when using 1 as a ligand, (R)-adducts of N,N-bicyclic pyrazolidinone derivatives are given with excellent enantioselectively. Whereas, (S)-adducts are enantioselectively formed by using the ligand 2. Thus, the ligands 1 and 2 can be complementarily used for the enantioselective synthesis of R/S-isomers.