Formal [2σ + 2σ]-Cycloaddition of Aziridines with Bicyclo[1.1.0]butanes: Access to Enantiopure 2-Azabicyclo[3.1.1]heptane Derivatives
Saturated nitrogen heterocycles are among the most significant structural components in small-molecule pharmaceuticals. Herein, a protocol for the construction of enantiopure 2-azabicyclo[3.1.1]heptane derivatives by a stereospecific intermolecular formal cycloaddition of aziridines with bicyclo[1.1.0]butanes is described. The reaction is run by using B(C<sub>6</sub>F<sub>5</sub>)<sub>3</sub> as a catalytic additive to give access to a library of enantiopure 2-azabicyclo[3.1.1]heptane derivatives (37 examples) under mild and operationally simple conditions. Successful scale-up reactions, mechanistic experiments, density functional theory (DFT) calculations and synthetic applications are presented.
Authors
- Christian Mück‐Lichtenfeld (ORCID: https://orcid.org/0000-0002-9742-7400)
- Shubham Dutta (ORCID: https://orcid.org/0000-0002-8372-8296)
- Constantin G. Daniliuc (ORCID: https://orcid.org/0000-0002-6709-3673)
- Armido Studer (ORCID: https://orcid.org/0000-0002-1706-513X)
Institutions
- University of Münster (DE)
Publication Details
- Journal
- Journal of the American Chemical Society
- Published
- 2024-09-19
- DOI
- https://doi.org/10.1021/jacs.4c11296
- Citations
- 73
- Primary Topic
- Synthesis and Catalytic Reactions
- Type
- article
- Field-Weighted Citation Impact
- 18.25
Funders
- Westfälische Wilhelms-Universität Münster