1. Skeletal Editing Approach to Bridge-Functionalized Bicyclo[1.1.1]pentanes from Azabicyclo[2.1.1]hexanes
- Author
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Wright, Brandon A, Matviitsuk, Anastassia, Black, Michael J, García-Reynaga, Pablo, Hanna, Luke E, Herrmann, Aaron T, Ameriks, Michael K, Sarpong, Richmond, and Lebold, Terry P
- Subjects
Organic Chemistry ,Chemical Sciences ,General Chemistry ,Chemical sciences ,Engineering - Abstract
Azabicyclo[2.1.1]hexanes (aza-BCHs) and bicyclo[1.1.1]pentanes (BCPs) have emerged as attractive classes of sp3-rich cores for replacing flat, aromatic groups with metabolically resistant, three-dimensional frameworks in drug scaffolds. Strategies to directly convert, or "scaffold hop", between these bioisosteric subclasses through single-atom skeletal editing would enable efficient interpolation within this valuable chemical space. Herein, we describe a strategy to "scaffold hop" between aza-BCH and BCP cores through a nitrogen-deleting skeletal edit. Photochemical [2+2] cycloadditions, used to prepare multifunctionalized aza-BCH frameworks, are coupled with a subsequent deamination step to afford bridge-functionalized BCPs, for which few synthetic solutions currently exist. The modular sequence provides access to various privileged bridged bicycles of pharmaceutical relevance.
- Published
- 2023