触媒的不斉［3＋2］環化付加反応：多置換ピロリジン化合物の新立体化学制御

Abstract

Highly functionalized complex molecules are key tools for promoting biochemical research and developing pharmaceuticals, because the network of chiralities, positions of heteroatoms, and direction of lone-pairs in the molecules are strictly linked to their biological activities. Catalytic asymmetric synthesis is the basis and core technology to supply these complex compounds in a stereoselective manner. Here, the catalytic asymmetric [3+2]-cycloaddition of iminoesters and nitroalkenes has been intensively investigated for giving chiral pyrrolidine structures which are observed abundantly in natural products and pharmaceuticals. Although the endo- or exo-selective [3+2]-cycloaddition has been widely examined using chiral Cu-catalysts, there is no report on the catalytic asymmetric synthesis of exo’-adduct. We accomplished the first catalytic asymmetric exo’-selective [3+2]-cycloaddition of azomethine imines and nitroalkenes using imidazoline-aminophenol (IAP)-Ni(OAc)2 complex to give the exo’-adduct in up to 99% ee. The first catalytic asymmetric exo’-selective [3+2]-cycloaddition of methyleneindolinones with iminoesters was also achieved by the IAP-Ni(OAc)2 complex for the construction of a novel diastereomer of biologically important spiro[pyrrolidin-3,3’-oxindole]. Moreover, a novel C2-symmetric bis(imidazolidine)pyridine ligand (PyBidine) was easily synthesized in a single condensation of 2,6-pyridyl aldehyde and optically active (S,S)-diphenylethylene diamine. The newly developed PyBidine-Cu(OTf)2 complex enabled the highly endo-selective [3+2]-cycloaddition of iminoesters with nitroalkenes.