Ring-opening functionalizations of unstrained cyclic amines enabled by difluorocarbene transfer
Youyoung Kim1,2, Joon Heo1,2, Dongwook Kim1,2
1Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
Nature Communications
|September 22, 2020
Summary
This study introduces a new method for selectively opening and functionalizing cyclic amines using difluorocarbene. This approach creates diverse molecular structures, useful for modifying natural products and pharmaceuticals.
Area of Science:
- Organic Chemistry
- Synthetic Chemistry
- Medicinal Chemistry
Background:
- Chemical synthesis often relies on modifying molecular structures to achieve desired properties.
- Unstrained cyclic amines are common building blocks, but their direct modification is challenging.
- Accessing novel chemical space is crucial for drug discovery and materials science.
Purpose of the Study:
- To develop an efficient and practical method for the selective ring-opening functionalization of unstrained cyclic amines.
- To demonstrate the versatility of this strategy for creating diverse acyclic and cyclic scaffolds.
- To showcase the applicability of this deconstructive approach in modifying complex molecules like natural products and pharmaceutical analogs.
Main Methods:
- Employing difluorocarbene for the selective ring-opening of unstrained cyclic amines.
- Utilizing the resulting acyclic intermediates for further diversification.
- Applying the developed strategy to modify existing natural products and pharmaceutical compounds.
Main Results:
- A highly efficient and practical strategy for cyclic amine functionalization was established.
- A wide array of multifaceted acyclic architectures were synthesized.
- These intermediates were successfully converted into diverse, homologative cyclic scaffolds.
- The method proved effective in modifying natural products and pharmaceutical analogues, demonstrating its practical utility.
Conclusions:
- The reported deconstructive strategy provides an efficient platform for accessing unique chemical space through cyclic amine modification.
- This method offers a versatile route to complex acyclic and cyclic molecules.
- The successful application to natural products and pharmaceuticals highlights the potential impact on drug discovery and development.
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