Issue 58, 2023

Stereoselective synthesis of highly substituted 1-isomorphans (1-azabicyclo[3.3.1]nonanes)

Abstract

We describe the first enantioselective synthesis of highly functionalized 1-azabicyclo[3.3.1]nonanes (1-IM). The 1-IM scaffold is present in natural products and drugs and is an isomer of the morphan moiety. The proposed methodology is based on an organocatalytic Michael addition of N-protected piperidine ketoesters to nitroalkenes and an intramolecular nitro-Mannich reaction as key transformations. The 1-IMs feature 6 contiguous stereocenters, substituents at positions 2 and 4, and nitro, ester, and hydroxyl functional groups at positions 3, 5, and 6 respectively. The synthesis is straightforward, highly stereoselective (up to 98% ee, >99 : 1 d.r.), with overall yields of up to 83% and requires only two purification steps.

Graphical abstract: Stereoselective synthesis of highly substituted 1-isomorphans (1-azabicyclo[3.3.1]nonanes)

Supplementary files

Article information

Article type
Communication
Submitted
10 Feb 2023
Accepted
19 Jun 2023
First published
20 Jun 2023

Chem. Commun., 2023,59, 8965-8968

Stereoselective synthesis of highly substituted 1-isomorphans (1-azabicyclo[3.3.1]nonanes)

D. A. Cruz-Aguilar and M. Hernández-Rodríguez, Chem. Commun., 2023, 59, 8965 DOI: 10.1039/D3CC00621B

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