Photoactivation of (p‐Methoxyphenyl)(trifluoromethyl)diazirine in the Presence of Phenolic Reaction Partners

Abstract

Shine light on your chemistry! Irradiating 3-(4-methoxyphenyl)-3-(trifluoromethyl)-3H-diazirine in the presence of equimolar solutions of phenol and tyrosine derivatives leads to Friedel-Crafts alkylations (see scheme), which suggests a strategy for the development of "cleaner" diazirines for chemical biology.

Synthesis, Stability, and Photoreactivity of Diazirinyl‐SubstitutedN‐Heterocycles Based on Indole, Benzimidazole, and Imidazole

“…The solution was condensed in a cooling trap at -78°C, warmed to room temperature overnight, and subjected to column chromatography after evaporation of EtOH. Another possibility could be the formation of an azine with a 19 F NMR chemical shift expected at around -67 ppm, [20] and we indeed observed a signal in the crude mixture. Decay of diazirine 24 in EtOH appears to follow first order kinetics at room temperature (see the Supporting Information).…”

“…Only phototryptophans carrying a trifluoromethyldiazirinyl moiety at the benzene portion of the indole side-chain have been reported recently. [20] DFT calculations predict that all of carbenes resulting from nitrogen loss prefer a singlet ground state. In the case of N-unsubstituted 2-diazirinylindole, even the synthesis of precursor diaziridine 4a proved difficult, and provided mainly hydrazone 5 instead.…”

“…[19] In contrast to its indole analog, N-methylbenzimidazolebased diazirine 14 proved to be stable up to 88°C, according to DSC measurements. [20] We identified five major products (Scheme 3), besides traces of unidentified signals in the 19 F NMR spectrum. Photoreaction of N-methylbenzimidazole-based diazirine 14 in EtOH (350 nm, Rayonet) was slow and ethoxy adduct 15 formed as the only product (46 % after 2 h, Scheme 3).…”

Enantioselective Synthesis and Photoreactivity of a Diazirinyl-substituted (R)-β-Phenylalanine

“…The 19 Chromatography led to the disappearance of the 19 F NMR signal at δ F = −57 ppm, which was probably caused by the diazo isomer of 9 [36]. However, we were not able to separate the remaining mixture by normal-phase column chromatography or reversedphase HPLC.…”

Water Compatible Photoarylation of Amino Acids and Peptides

“…[7] Benzophenones, phenylazides, and diazirines [8] react with limited chemoselectivity. [9] It can be stated that there is still room for improvement, ideally involving new chemistry. Recently, we reported that irradiation of N-(p-fluorobenzyl)-2-azidobenzimidazole in AcOH/CH 2 Cl 2 afforded the 2-amino-6-acetoxybenzimidazole in high yield and perfect regioselectivity.…”