Multicomponent Pyrazole Synthesis from Alkynes, Nitriles, and Titanium Imido Complexes via Oxidatively Induced N–N Bond Coupling
| Autor: | Alexander C. Wotal, Rachel J. Dunscomb, Benjamin R. Reiner, Robin P. Harkins, Ian A. Tonks, Adam J. Pearce |
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| Rok vydání: | 2020 |
| Předmět: |
Metalation
Hydrazine Disproportionation Pyrazole 010402 general chemistry Ring (chemistry) 01 natural sciences Biochemistry Article Catalysis chemistry.chemical_compound Colloid and Surface Chemistry Coordination Complexes Nitriles Titanium General Chemistry Combinatorial chemistry 0104 chemical sciences Models Chemical chemistry Cyclization Alkynes Reagent Pyrazoles Oxidative coupling of methane Oxidation-Reduction Stoichiometry |
| Zdroj: | J Am Chem Soc |
| ISSN: | 1520-5126 0002-7863 |
| Popis: | Pyrazoles are an important class of heterocycles found in a wide range of bioactive compounds and pharmaceuticals. Pyrazole synthesis often requires hydrazine or related reagents where an intact N-N bond is conservatively installed into a pyrazole precursor fragment. Herein, we report the multicomponent oxidative coupling of alkynes, nitriles, and Ti imido complexes for the synthesis of multisubstituted pyrazoles. This modular method avoids potentially hazardous reagents like hydrazine, instead forming the N-N bond in the final step via oxidation-induced coupling on Ti. The mechanism of this transformation has been studied in-depth through stoichiometric reactions of the key diazatitanacyclohexadiene intermediate, which can be accessed via multicomponent coupling of Ti imidos with nitriles and alkynes, ring opening of 2-imino-2H-azirines, or direct metalation of 4-azadiene-1-amine derivatives. The critical transformation in this reaction is the 2-electron oxidation-induced N-N coupling on Ti. This is a rare example of formal N-N coupling on a metal center, which likely occurs through an electrocyclic mechanism analogous to a Nazarov cyclization. Conveniently, these 2-electron-oxidized diazatitanacyclohexadiene intermediates can be accessed via disproportionation of the 1-electron-oxidized species, which allows utilization of weak oxidants such as TEMPO. |
| Databáze: | OpenAIRE |
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