Annulation cascade of arylnitriles with alkynes to stable delocalized PAH carbocations via intramolecular rhodium migration

An annulation cascade of arylnitriles with alkynes is disclosed to provide stable delocalized carbocations with the ability to specifically target lysosomes.


I. General remarks
NMR spectra were recorded on a Varian Inova 400 spectrometer. The 1 H NMR (400 MHz) chemical shifts were recorded relative to CDCl 3 or CD 3 CN as the internal reference (CDCl 3 : δ H = 7.26 ppm; CD 3 CN: δ H = 1.94 ppm). The 13 C NMR (100 MHz) chemical shifts were given using CDCl 3 or CD 3 CN as the internal standard (CDCl 3 : δ C = 77.16 ppm; CD 3 CN: δ C = 118.26 ppm). High-resolution mass spectra (HRMS) were obtained with a Shimadzu LCMS-IT-TOF (ESI) or a Waters-Q-TOF-Premier

III. General procedure for the synthesis of delocalized carbocation
A Schlenk tube with a magnetic stir bar was charged with AgSbF 6 (6.9 mg, 20 µmol),

Control experiments
A Schlenk tube with a magnetic stir bar was charged with AgSbF 6 (6.9 mg, 20 µmol), The resulting mixture was stirred at room temperature for 10 min and then at 120 o C for 12 h. The mixture was diluted with 10 mL of dichloromethane when it cooled down. The mixture was evaporated under reduced pressure and the residue was absorbed into small amounts of silica gel. Purification was performed by column chromatography on silica gel to provide compound 1i (27.7 mg, 86% yield recovered).
The proposed amide was not detected.

Intermolecular competition experiment
A Schlenk tube with a magnetic stir bar was charged with AgSbF 6 (6.9 mg, 20 µmol),

Spectra of MAIDL-TOF-MS
General procedure for the preparation of the sample: A Schlenk tube with a magnetic stir bar was charged with AgSbF 6 (6.9 mg, 20 µmol), NaSbF 6 (38.9 mg,    streptomycin (100 mg/mL) was supplemented at 37 o C in a 5% CO 2 containing humidified atmosphere.

Cytotoxicity assay
The cytotoxicity experiments of 3da and 3ia were investigated by CellTiler

Computational Methods
The DFT calculations were carried out with the GAUSSIAN 09 series of programs.
Density functional theory B3LYP 1 with a standard 6-31+G(d) basis set was used for geometry optimizations. Harmonic frequency calculations were performed for stationary point to confirm them as a local minima.