Synthesis of BCP Benzylamines From 2-Azaallyl Anions and [1.1.1]Propellane
| Autor: | Russell A. Shelp, Patrick J. Walsh |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Bicyclic molecule
010405 organic chemistry Isostere Bioactive molecules General Medicine General Chemistry Pentanes 010402 general chemistry 01 natural sciences Combinatorial chemistry Catalysis 0104 chemical sciences chemistry.chemical_compound Propellane Benzylamine chemistry Amine gas treating Bioisostere |
| Zdroj: | Angewandte Chemie (International ed. in English). 57(48) |
| ISSN: | 1521-3773 |
| Popis: | For bioactive molecules, bicyclo[1.1.1]pentanes (BCPs) are an emerging isostere of rigid spacer groups that have shown potential to improve drug-like qualities. As BCPs become an increasingly popular motif for evaluation in drug candidates, organic chemists must meet the demand to reliably incorporate them into new targets. To provide access to BCP analogues of diaryl methanamines, a ubiquitous scaffold in medicinal chemistry, we report the synthesis of BCP benzylamines through reactivity of [1.1.1]propellane with 2-azaallyl anions, which are generated in situ from N-benzyl ketimines. The reaction proceeds rapidly at room temperature and tolerates a broad substrate scope, providing straightforward access to 23 new BCP benzylamine derivatives. Initial experiments support the intermediacy of a BCP anion. Additionally, the reaction can be promoted by substoichiometric loadings of base, highlighting an unusual reactivity of both 2-azaallyls and [1.1.1]propellane. |
| Databáze: | OpenAIRE |
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