Our laboratory is currently interested in the development of new sustainable methodology for oxidative amination and oxygenation of hydrocarbons. To this end, we have developed reactions based on defined molecular iodine(III) reagents and photochemical iodine-catalysed C-H functionalisation.
Our research centres on the selective construction of carbon-nitrogen bonds. While traditionally reliant on transition metal catalysed transformations (for an overview: J. Org. Chem. 2013, 78, 2168), we have recently shifted our focus towards iodine-promoted reactions. Initial efforts have served to identify new hypervalent iodine(III) derivatives with unprecedented I-N bonds (key publication: Angew. Chem. Int. Ed. 2013, 52, 1324). This chemistry comprised the development of a highly enantioselective diamination of styrenes (Angew. Chem. Int. Ed. 2011, 50, 9478).
More recent efforts have been devoted to the development of new catalytic reactivity concepts within defined halide redox manifolds. Studies in the field have provided entirely new enantioselective transformations as well as conceptually novel amination reactions of alkenes and alkanes.
1) Enantioselective catalysis with defined hypervalent aryliodine derivatives.
The main objective is to achieve the combination of benign oxidants such as peracids with chiral aryliodine(I) reagents in order to arrive at chiral catalysts using the iodine(I/III) redox manifold. We have recently identified a supramolecular hydrogen-bonding scenario as a guiding principle for catalyst design. Its feasibility was demonstrated by the development of pioneering intermolecular asymmetric vicinal difunctionalisation of alkenes under hypervalent iodine catalysis. Examples include the enantioselective diacetoxylation (Angew. Chem. Int. Ed. 2016, 55, 413) and enantioselective diamination of styrenes (J. Am. Chem. Soc. 2017, 139, 4354).
2) Carbon-nitrogen bond formation using halide catalysts.
The observation that simple Br(-I/I) catalysis is capable of promoting intramolecular vicinal diamination of alkenes (Chem. Sci. 2012, 3, 2375) has triggered interest in the corresponding Csp3-amination reactions for pyrrolidine synthesis. We have identified suitable catalysis conditions in order to arrive at a pioneering iodine(I/III)-catalysed Hofmann-Löffler reaction (Angew. Chem. Int. Ed. 2015, 54, 8287). Light-initiation appears to stand out as a powerful concept in this distinctive type of halide catalysis. The unique mechanistic scenario relies on two intertwined catalytic cycles. This C-H amination chemistry has been extended to the combination of iodine(-I/I) catalysis with photoredox catalysis (Angew. Chem. Int. Ed. 2017, 56, 8004).
3) Application in synthesis of small biomolecules
Halide redox catalysis offers unique synthetic strategies for preparation of C-N bonds. We exploit this key technology for the construction of small molecular entities of biological, pharmaceutical or medicinal interest. Recent studies include a de novo synthesis of indoles (Angew. Chem. Int. Ed. 2014, 53, 7349) and of tryptamide-based alkaloids (J. Org. Chem. 2016, 81, 6496).