Enantioselective synthesis of DIANANE, a novel C2-symmetric chiral diamine for asymmetric catalysis

DIANANE (endo,endo-2,5-diaminonorbornane) is a novel chiral C-2-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 greater than or equal to99%) 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.