Synthesis of N,N′-Unsymmetrical 9-Amino-5,7-dimethyl-bispidines

A new approach to the preparation of N,N '-unsymmetrically substituted 9-aminobispidinesthrough aminal bridge removal reaction has been developed, the principalfeature of which is the ability to selectively functionalize all threenitrogen atoms. The intermediates of 1,3-diazaadamantane'saminal bridge removal reaction are characterized, and the mechanismof this reaction is proposed based on the analysis of their structures.Representatives of the previously unknown saturated heterocyclic 1,5,9-triazatricyclo-[5.3.1.0(3,8)]-undecane system were obtained and structurally characterized.Thus, it was possible for the first time to obtain 3,7,9-trisubstitutedbispidines containing acetyl, Boc, and benzyl groups at nitrogen atoms,which can be independently removed (orthogonal protective groups).

Automated summary

A new method for synthesizing N,N'-unsymmetrically substituted 9-aminobispidines has been developed using aminal bridge removal reaction, which allows selective functionalization of all three nitrogen atoms. The reaction intermediates and mechanism of the 1,3-diazaadamantane's aminal bridge removal reaction have been characterized and proposed. Novel saturated heterocyclic 1,5,9-triazatricyclo-[5.3.1.0(3,8)]-undecanes have been synthesized and structurally characterized. This study also successfully obtained 3,7,9-trisubstituted bispidines with acetyl, Boc, and benzyl groups at nitrogen atoms, which can be independently removed (orthogonal protective groups) for the first time.