Synthesis and optical resolution of 4,5-diaminohomoadamantane: a promising scaffold for chiral ligands and bioactive
Polina Anatolyevna Man'kova1, Vadim Andreevich Shiryaev1, Olga S Podlipnova1
1Department of Organic Chemistry Samara State Technical University, Molodogvardeyskaya st. 244, 443100 Samara, Russia.
Abstract:
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 LiAlH4. 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 (4R,5R)-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 CH2Cl2 in the SMD model on the base of conformational analysis. Catalytic systems based on (4R,5R)-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.
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