Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

Readily synthesized biphenyl-2-carbaldehyde O-acetyl oximes were exposed to UV radiation affording phenanthridines. The scope and limitations of this novel reaction were explored. For example, exposure of 2',3'-dimethoxy-[1,1'-biphenyl]-2-carbaldehyde O-acetyl oxime to UV radiation afforded 4-methoxyphenanthridine in 54% yield. This methodology was applied to the synthesis of trisphaeridine to afford the product in four linear steps in an overall yield of 6.5% from 1-bromo-2,4,5-trimethoxybenzene.


General experimental procedures:
Solvents utilized for chromatography (ethyl acetate and n-hexane) were distilled prior to use by means of conventional distillation processes. The solvents employed in reactions were first dried over the suitable drying agent, followed by distillation under an inert atmosphere (argon or nitrogen gas). Acetonitrile and dichloromethane were distilled over calcium hydride, whereas tetrahydrofuran was distilled over sodium with benzophenone as an indicator. Toluene was distilled over sodium. All the required chemicals or reagents were obtained from FLUKA, SIGMA ALDRICH or MERCK and were used without further purification.
Normal chromatography was performed with silica gel 60 (Macherey-Nagel, particle size 0.063-0.200 mm) adsorbent, with both isocratic and gradient eluent systems being employed. Thin layer chromatography (TLC) of the compounds was executed on Macherey-Nagel Alugram Silica G/UV254 plates pre-coated with 0.25 mm silica gel 60. The TLC plates were viewed under UV light (254 nm and 366 nm).
Nuclear magnetic resonance (NMR) spectra were recorded on either a Bruker AVANCE 300 MHz or Bruker AVANCE 400 MHz, Bruker AVANCE III 500 MHz spectrometer. All chemical shift values are reported in parts per million referenced against tetramethylsilane which is given an assignment of zero parts per million. Coupling constants (J-values) are given in Hertz (Hz).
The infrared spectra were recorded on a Bruker Tensor 27 standard system spectrometer. Measurements were made by loading the sample directly onto a diamond cell. The measurements are reported on the wavenumber scale (cm −1 ).
Melting points were determined on a Reichert hot-stage microscope, and remain uncorrected. All crystalline compounds were recrystallized in the appropriate solvents prior to melting point determination. Microwave reactions were conducted in a CEM Discover microwave.
High resolution mass spectra were obtained with a Waters-LCT-Premier mass spectrometer. The sample was dissolved in methanol to a concentration of 2 ng/μL and introduced by direct infusion. The ionization mode was electrospray positive with a capillary voltage of 2500 V and a desolvation temperature of 250 °C using nitrogen gas at 250 L/h.