The chemistry of polyfluorinated azides

In 2017, we reported a breakthrough in azide chemistry. CF3N3 and longer carbon chain analogues were prepared from silanes or other carbanion precursors, which opened a door to study properties and reactivity of these compounds. They are no longer regarded as chemical curiosities. Furthermore, they were shown to be stable and not explosive (Angewandte Chemie International Edition  56: 346, 2017). Subsequently, other fluorinated azides such as HCF2N3 (European Journal of Organic Chemistry 5087, 2018), BrCF2N3, BrCF2CF2N3 (Journal of Organic Chemistry  85: 11482, 2020), RCF2CF2N3 (Organic and Biomolecular Chemistry  15: 4962, 2017) and FCH2N3 (Organic Chemistry Frontiers  7: 10, 2020), PhSO2CF2CF2N3 (Journal of Organic Chemistry  88: 6939, 2023), and HCF2CF2N3 (Journal of Organic Chemistry  88: 14969, 2023) were prepared. They readily underwent copper(I)-catalyzed azide-alkyne cycyloadditions (CuAAC) and enamine-mediated azide-ketone cycloadditions (ChemistrySelect  3: 7045, 208) to form novel N-perfluoroalkyl triazoles. Preparation and reactivity of fluorinated azides was recently reviewed (Chemistry – A European Journal 773, 2020, Aldrichimica Acta  55: 37, 2022).

In the presence of superacids, azidotrifluoromethane protonates on nitrogen one to trifluoromethylamino diazonium cations (CF3NHN2)+ (Angewandte Chemie International Eddition  59: 12520, 2020) (collaboration with the University of Southern California).

Heating N-(per)fluoroalkyl triazoles in the presence of rhodium catalyst allows to enter rhodium carbene chemistry for the synthesis of novel N-(per)fluoroalkyl pyrroles, imidazoles, azepines, oxazoles, thiazoles and other heterocycles (Chemical Communications  54: 3258, 2018, Journal of Organic Chemistry  83: 15195, 2018, Organic Chemistry Frontiers  6: 3776, 2019), Beilstein Journal of Organic Chemistry  17: 504, 2021). 4-Cyclohexenyl-substituted N-(per)fluoroalkyl 1,2,3-triazoles undergo transannulation to provide N-(per)fluoroalkyl indoles after oxidation (Organic & Biomolecular Chemistry  21: 7924, 2023).

A new reactive mode was discovered in N-(per)fluoroalkyl triazoles. In the presence of superacids, such as triflic acid or fluorosulfonic acid, the triazoles ring open and vinyl triflates enamides are formed via a vinyl cation (Chemistry – A European Journal  25: 7640, 2019).

This reactive mode was extended to Lewis acids – in the presence of boron trifluoride β-enamido fluorides are formed (Organic Letters 23: 4224, 2021) and with aluminium halides highly functionalized haloalkenyl imidoyl halides are produced (Advanced Synthesis & Catalysis 363: 3528, 2021). Utilization of the vinyl cation intermediates for intramolecular C-C bond formation was also demonstrated (Journal of Organic Chemistry  88: 1155, 2023).

Microwave heating of N-(per)fluoroalkyl-1,2,3-triazoles led to denitrogenation and rearrangement to provide stable ketenimines, which underwent addition of nucleophiles or [2 + 2] cycloadditions (Organic Chemistry Frontiers  10: 3201, 2023).