Electrophilic Reactivities of Substituted Cyclopropanes

Cyclopropanes are small three-membered all-carbon rings. The making of cyclopropanes costs some extra energy because of the strain introduced by the compressed chemical bonds in these molecules. The energy stored in the three-membered ring is not lost, however, but can be used to promote reactions, in which the ring is opened. This is why synthetic chemists have been able to utilize cyclopropanes for many decades to produce a broad range of new products. However, the ability to predict if (and how fast) reactions of cyclopropanes take place has remained challenging and is not well explored to date. This project is going to investigate the physicochemical properties of cyclopropanes to enhance the fundamental understanding of their reactivity in ring-opening reactions. In an effort to enable informed planning of syntheses with cyclopropanes, this project will systematically study the factors that govern their polar reactivity. To achieve this, several cyclopropanes with additional functional groups will be prepared. The functional groups attached to the cyclopropanes are used to tune their reactivity, and the rates of cyclopropane reactions with reaction partners will be measured. To gain deeper insights into the individual steps in the molecular transformations, the experimentally observed rates will then be compared with modelled data from quantum-chemical computational methods. At the end of the first phase of the project (24 months at the LMU München), it is anticipated that the results can be used to predict straightforwardly whether cyclopropanes will react under certain conditions with a diverse set of reaction partners. The approach path of reaction partners to the cyclopropanes can be directed by interactions with catalyst molecules. Thus, the spatial structure of the products can be controlled. On the basis of the fundamental understanding of the cyclopropane reactivity, synthetic methods that use cyclopropanes in combination with catalysts will be developed to achieve sophisticated molecular architectures. The application of catalysts in cyclopropane reactions will be explored during the return phase of the project (12 months at the JKU Linz).

Cyclopropanes are small three-membered all-carbon rings. The making of cyclopropanes costs some extra energy because of the strain introduced by the compressed chemical bonds. The energy stored in the three-membered ring is not lost, however, but can be used to promote reactions, in which the ring is opened. This is why synthetic chemists have been able to utilize cyclopropanes for many decades to produce a broad range of new products. However, the ability to predict if (and how fast) reactions of cyclopropanes take place has remained challenging. This project aimed to investigate the physicochemical properties of cyclopropanes to enhance the understanding of their reactivity. A range of cyclopropanes with different functional groups, which are used to tune their reactivity, were prepared. Even though cyclopropanes have ring strain and thus a large driving force to form ring-opened products, it was found that they usually react more slowly than many other commonly used organic compounds because a lot of activation energy is required to initiate the reaction. For this reason, either catalysts or reaction partners with high reactivity need to be employed for reactions to proceed in reasonable time. Finding suitable reaction partners proved challenging, however two reliable classes of compounds were found and reaction rates could even be recorded via two different methods. Although trends were identified, cyclopropane ring-opening reactions are too complex for their reactivities to be directly incorporated into a scale alongside most other simple organic compounds. This is due to the nature of the ring-opening reaction itself and how the specific properties of the cyclopropane influence this process. Interestingly, the related cyclobutanes, which are strained all-carbon four-membered rings, do not undergo ring-opening reactions in the absence of a catalyst, regardless of which of the reaction partners were employed. During the search for suitable reaction partners for cyclopropanes, novel, highly reactive and colored compounds termed N-heterocyclic olefins were investigated. While reactions with cyclopropanes did not proceed in a straightforward way and were thus ineligible for kinetic investigations, these compounds could still be incorporated into reactivity scales. In fact, one newly studied derivative even turned out to be the most reactive electron-rich compound ever recorded in the comprehensive Mayr database, which chemists worldwide use to estimate reaction speeds.