Vicinal diamines based on a rigid polycyclic framework such as homoadamantane remain underexplored. We anticipated that the unique steric and lipophilic properties of chiral trans -4,5-diaminohomoadamantane could provide the necessary stereoinduction in metal-catalyzed asymmetric reactions. In addition, such structures may serve as a novel scaffold for bioactive compounds. Herein, we report a synthetic approach to this previously inaccessible chiral scaffold. 4,5-Diaminohomoadamantane was prepared as a mixture of cis - and trans -isomers by reduction of the corresponding vicinal azidoxime with LiAlH 4 . In contrast, the trans -isomer was selectively obtained via ring-opening of an N -Tf-protected aziridine. The racemic trans -4,5-diaminohomoadamantane was resolved with dibenzoyl-ʟ-tartaric acid. The absolute (4 R ,5 R )-configuration was proposed on the basis of TDDFT calculations of the specific optical rotation using the CAM-B3LYP functional and the 6-311G++(2d,2p) basis set with solvation by CH 2 Cl 2 in the SMD model on the base of conformational analysis. Catalytic systems based on (4 R ,5 R )-4,5-diaminohomoadamantane derivatives exhibited low to moderate asymmetric induction in Henry and Michael reactions. These results suggest that further molecular design of homoadamantane-based chiral N , N -ligands is promising.
Man’kova et al. (Wed,) studied this question.
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