Additionally, another model compound 35 with improved water solubility was synthesized (Scheme 4). Its irradiation in methanol under different wavelengths gave mainly alkene 36. However, irradiation in acetonitrile-water mixtures already gave >30% of the needed insertion products 38, 39. Importantly, during experiments with aliphatic trifluoromethyl diazirines, the trifluoromethyl group was stable, and we did not observe its cleavage. In a short summary, experiments with model compounds 30, 35 revealed full compatibility of aliphatic trifluoromethyl diazirines with photoaffinity studies. Under non-optimized conditions, >40% of the O-H insertion products were achieved under irradiation at 350 nm. During the irradiation, the trifluoromethyl group was stable. At the same time, under identical conditions, the difluoromethyl diazirine motif was chemically labile due to extensive C-F bond solvolysis.