Catalytic Enantioselective Hetero-[6+4] and -[6+2] Cycloadditions for the Construction of Condensed Polycyclic Pyrroles, Imidazoles, and Pyrazoles
| Autor: | Andreu Vidal-Albalat, Kendall N. Houk, Giulio Bertuzzi, Maxime Giardinetti, Karl Anker Jørgensen, Adam Simon, Mathias Kirk Thøgersen |
|---|---|
| Přispěvatelé: | Bertuzzi G., Thogersen M.K., Giardinetti M., Vidal-Albalat A., Simon A., Houk K.N., Jorgensen K.A. |
| Rok vydání: | 2019 |
| Předmět: |
Diene
Stereoisomerism Pyrrole 010402 general chemistry 01 natural sciences Biochemistry Catalysis Catalysi chemistry.chemical_compound Colloid and Surface Chemistry Pyrroles Imidazole Density Functional Theory Pyrrolizidine Alkaloids Cycloaddition Reaction Imidazoles Enantioselective synthesis Iminium General Chemistry Combinatorial chemistry Asymmetric induction Cycloaddition 0104 chemical sciences Pyrrolizidine Alkaloid Models Chemical chemistry Pyrazole Pyrazoles Stereoselectivity Heterocyclic Compounds 3-Ring |
| Zdroj: | Bertuzzi, G, Thøgersen, M K, Giardinetti, M, Vidal-Albalat, A, Simon, A, Houk, K N & Jørgensen, K A 2019, ' Catalytic Enantioselective Hetero-[6+4] and-[6+2] Cycloadditions for the Construction of Condensed Polycyclic Pyrroles, Imidazoles, and Pyrazoles ', Journal of the American Chemical Society, vol. 141, no. 7, pp. 3288-3297 . https://doi.org/10.1021/jacs.8b13659 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.8b13659 |
| Popis: | The development of the first chemo-, regio-, and stereoselective hetero-[6+4] and -[6+2] cycloadditions of heteroaromatic compounds via amino aza- and diazafulvenes is presented. Pyrroles, imidazoles, and pyrazoles substituted with a formyl group react with an aminocatalyst to generate an electron-rich hetero-6π-component that reacts in a chemo-, regio-, and stereoselective manner with electron-deficient dienes and olefins. For the hetero-[6+4] cycloaddition of the pyrrole system with dienes, a wide variation of both reaction partners is possible, providing attractive pyrrolo-azepine products in high yields and excellent enantioselectivities (99% ee). The hetero-[6+4] cycloaddition reaction concept is extended to include imidazoles and pyrazoles, giving imidazolo- and pyrazolo-azepines. The same activation concept is successfully employed to include hetero-[6+2] cycloadditions of the pyrrole system with nitroolefins, giving important pyrrolizidine-alkaloid scaffolds. Experimental NMR and mechanistic studies allowed for the identification of two different types of intermediates in the reaction. The first intermediate is the result of a rapid formation of an iminium ion, which generates a hetero-6π aminofulvene intermediate as a mixture of two isomers. Density functional theory calculations were used to determine the mechanism and sources of asymmetric induction in the hetero-[6+4] and -[6+2] cycloadditions. After formation of the reactive hetero-6π-components, a stepwise addition occurs with the diene or olefin, leading to a zwitterionic intermediate that undergoes cyclization to afford the cycloadduct, followed by eliminative catalyst release. The stereoselectivity is controlled by the second step, and computations elaborate on the various substrate and catalyst effects that alter the experimentally observed enantioselectivities. The computational studies provided a basis for improving the enantioselectivity of the hetero-[6+2] cycloaddition. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|