We propose the development of new redox active catalysis for the selective oxidative amination of various hydrocarbon compounds such as alkanes and alkenes. The envisioned transformations include C-H amination and diamination reactions. They constitute a further development of our recent expertise on halide mediated amination reactions. Our project aims for the realisation of a conceptually novel synthetic methodology with a potential to become a disruptive innovation in the area of C-N bond construction, which is of major importance to the fields of medicinal, pharmaceutical and biological chemistry. Modern societies require sustainable reaction performances
in order to meet with the demands of environmentally and economically benign production. Halides represent cheap, abundant, readily available and non-toxic elements that should be of major interest in academic development and industrial application. We have pioneered the use of iodine as homogeneous oxidation catalyst within practical applications that are not accessible through the common approach of transition metal methodology. This halide chemistry is now receiving more and more attention and with the contents of present project we intend to stay at the forefront of its development. To foster the use of our proposed methodology, we will centre our investigation on the
realisation of two work packages as the major tasks. One package is the development of chiral, non-racemic high oxidation state iodine(III) catalysts. The design of such iodine(I/III) manifolds will require gaining precise knowledge over the exact thre-dimensional working mode of carefully designed catalysts. They need to exercise high stereochemical control in the oxidative enantioselective structural refinement of bulk alkene components transforming them into chiral 1,2-difunctionalised building blocks for fine chemical synthesis. We will carry out the
required stereochemical optimisation of the chiral catalyst structures through the modular use of individual components. The thematic context of the second package is the development of molecular catalysts based on iodine and bromine that are derived from simple halide precursor molecules. These compounds display an inherent redox activity that should permit the realisation of currently unavailable synthetic transformations. The most important aspect lies with the development of protocols for an unprecedented intermolecular amination of hydrocarbon bonds. By addressing this elusive synthetic transformation, we will enable entirely new amination chemistry with an immediate application in chemical and biological sciences. In order to demonstrate the matureness of homogeneous halide redox manifolds, they will be employed in unprecedented syntheses of cycloamines using uncommon carbon-nitrogen bond formation.
Specifically, these applications will comprise alkaloid natural product synthesis and the exploration of new chemical space through latestage C-H amination of highly decorated molecules. Common to both of the two work packages is the exploration of suitable reoxidation conditons. Environmental aspects demand that the development of new technology embraces the concept of sustainability. To this end, we will develop conditions for an accurate compatibility of our methodology with green economically viable terminal oxidants such as common hydrogen peroxide and related peracids.
HalOx
Ministerio de Ciencia e Innovación