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

Mikhail A Kalinin; Aleksei V Medved'ko; Mikhail E Minyaev; Sergey Z Vatsadze

doi:10.1021/acs.joc.3c00514

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

J Org Chem. 2023 Jun 2;88(11):7272-7280. doi: 10.1021/acs.joc.3c00514. Epub 2023 May 23.

Authors

Mikhail A Kalinin¹, Aleksei V Medved'ko¹, Mikhail E Minyaev¹, Sergey Z Vatsadze¹

Affiliation

¹ N.D. Zelinsky Institute of Organic Chemistry, 119991 Moscow, Russia.

PMID: 37219844
DOI: 10.1021/acs.joc.3c00514

Abstract

A new approach to the preparation of N,N'-unsymmetrically substituted 9-aminobispidines through aminal bridge removal reaction has been developed, the principal feature of which is the ability to selectively functionalize all three nitrogen atoms. The intermediates of 1,3-diazaadamantane's aminal bridge removal reaction are characterized, and the mechanism of 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-trisubstituted bispidines containing acetyl, Boc, and benzyl groups at nitrogen atoms, which can be independently removed (orthogonal protective groups).