Rarely does fluorine appear in organic molecules that are produced spontaneously. For the creation of pharmaceuticals or agrochemicals, this chemical ingredient is necessary. The creation of novel fluorine-containing molecular fragments depends heavily on synthetic chemistry.
Simple, modular synthesis strategies are extremely valuable. A team led by Prof. Ryan Gilmour at the Organic Chemistry Institute at the University of Münster has now developed a cascade reaction that enabled multiple fluorination reactions to occur through the sequential generation of reactive intermediates.
The group has demonstrated that a type of “molecular origami” to build a novel class of di- and trifluorinated compounds in a single operation using affordable organic catalysts and basic starting ingredients may control the substrate. The study is published in the journal Nature Communications.
Complex fluorinated compounds may require numerous purification stages throughout their step-by-step production. This has repercussions for trash production, expenses, and time management.
The strategy has parallels with the art of origami, where you fold complex figures from a simple piece of paper. This principle can be transferred to our chemical method.Dr. Louise Ruyet
Dr. Joel Häfliger and Dr. Louise Ruyet from Ryan Gilmour’s research group discovered that by fine-tuning the reaction conditions, multiple sequential reactions are possible in a one-pot fashion. In this way, they generated three new classes of complex fluorinated products from simple cyclobutanol derivatives.
“The strategy has parallels with the art of origami, where you fold complex figures from a simple piece of paper,” Louise Ruyet illustrates. “This principle can be transferred to our chemical method.”
The multiple folding steps represents successive reactions. “Starting with our piece of paper the cyclobutanol-derivative an intermediate compound is produced. This compound can be processed into different products depending on the reaction conditions,” says Joel Häfliger, the lead author of the paper.
The utilization of an acidic medium to activate the substrate and create an intermediate that could be caught by a catalytic cycle was crucial to the strategy’s success. As an example of an application, the researchers created a fluorinated version of the drug nafenopin, which is used for hypolipidaemia, a startlingly low lipid content in the blood.