Enantioselective Synthesis of DIANANE, a Novel C2-Symmetric Chiral Diamine for Asymmetric Catalysis

Abstract

DIANANE (endo,endo-2,5-diaminonorbornane) is a novel chiral C₂-symmetric diamine, based on the rigid bicyclo[2.2.1]heptane scaffold. Schiff-base ligands derived from DIANANE have already found use in asymmetric catalysis, e.g., in the highly enantioselective Nozaki−Hiyama−Kishi reaction. We herein describe a practical synthesis of enantiomerically pure DIANANE, starting from norbornadiene in four steps: (i) Pd-MOP catalyzed Hayashi-hydrosilylation/Tamao−Fleming oxidation, (ii) oxidation to norbornane-2,5-dione, (iii) endo-selective reductive amination with benzylamine, and (iv) hydrogenolytic debenzylation. None of the steps involves chromatographic purification. For the Tamao−Fleming oxidation, the use of hydrogen peroxide in the form of its urea clathrate instead of aqueous solution proved beneficial. By the above sequence, enantiomerically pure (ee ≥99%) DIANANE was obtained from norbornadiene in 40−50% overall yield. The relative and absolute configuration of DIANANE was confirmed by X-ray crystallography of the DIANANE bis-tosylamide, and of its bis-camphorsulfonamide. Furthermore, the synthesis and X-ray crystal structure of the Schiff-base ligand derived from DIANANE and 3,5-di-tert-butyl salicylic aldehyde are reported.