Divergent Synthesis of γ‐Amino Acid and γ‐Lactam Derivatives frommeso‐Glutaric Anhydrides
| Autor: | Simon N. Smith, Ryan Craig, Stephen J. Connon |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
chemistry.chemical_classification
Lactams 010405 organic chemistry Organic Chemistry General Chemistry 010402 general chemistry 01 natural sciences Isocyanate Combinatorial chemistry Catalysis Anhydrides 0104 chemical sciences Amino acid Acyl azide chemistry.chemical_compound chemistry Nucleophile Lactam Amines Amino Acids Ammonium azide Divergent synthesis Curtius rearrangement Isocyanates |
| Zdroj: | Chemistry – A European Journal. 26:13378-13382 |
| ISSN: | 1521-3765 0947-6539 |
| DOI: | 10.1002/chem.202003280 |
| Popis: | The first divergent synthesis of both γ-amino acid and γ-lactam derivatives from meso-glutaric anhydrides is described. The organocatalytic desymmetrisation with TMSN3 relies on controlled generation of a nucleophilic ammonium azide species mediated by a polystyrene-bound base to promote efficient silylazidation. After Curtius rearrangement of the acyl azide intermediate to access the corresponding isocyanate, hydrolysis/alcoholysis provided uniformly high yields of γ-amino acids and their N-protected counterparts. The same intermediates were shown to undergo an unprecedented decarboxylation-cyclisation cascade in situ to provide synthetically useful yields of γ-lactam derivatives without using any further activating agents. Mechanistic insights invoke the intermediacy of an unconventional γ-N-carboxyanhydride (γ-NCA) in the latter process. Among the examples prepared using this transformation are 8 APIs/molecules of considerable medicinal interest. |
| Databáze: | OpenAIRE |
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