Computational ligand design in enantio- and diastereoselective ynamide [5+2] cycloisomerization
| Autor: | Straker, RN, Peng, Q, Mekareeya, A, Paton, RS, Anderson, EA |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | Nature Communications, Vol 7, Iss 1, Pp 1-9 (2016) Nature Communications |
| Popis: | Transition metals can catalyse the stereoselective synthesis of cyclic organic molecules in a highly atom-efficient process called cycloisomerization. Many diastereoselective (substrate stereocontrol), and enantioselective (catalyst stereocontrol) cycloisomerizations have been developed. However, asymmetric cycloisomerizations where a chiral catalyst specifies the stereochemical outcome of the cyclization of a single enantiomer substrate—regardless of its inherent preference—are unknown. Here we show how a combined theoretical and experimental approach enables the design of a highly reactive rhodium catalyst for the stereoselective cycloisomerization of ynamide-vinylcyclopropanes to [5.3.0]-azabicycles. We first establish highly diastereoselective cycloisomerizations using an achiral catalyst, and then explore phosphoramidite-complexed rhodium catalysts in the enantioselective variant, where theoretical investigations uncover an unexpected reaction pathway in which the electronic structure of the phosphoramidite dramatically influences reaction rate and enantioselectivity. A marked enhancement of both is observed using the optimal theory-designed ligand, which enables double stereodifferentiating cycloisomerizations in both matched and mismatched catalyst–substrate settings. Using a chiral catalyst to override the innate stereochemical outcome of a diastereoselective process is a challenging task. Here, the authors use theory and experiment to develop a cycloisomerization where the enantioselectivity is driven by the electronic nature of the ligand regardless of the reaction's inherent diastereoselectivity. |
| Databáze: | OpenAIRE |
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