Cation-Directed Enantioselective N-Functionalization of Pyrroles

Abstract

Supporting Information Reactions requiring moisture-sensitive reagents were carried out in oven dried glassware, under an atmosphere of nitrogen (balloon pressure). Dichloromethane, diethyl ether, toluene and methanol were purified by filtration through activated alumina columns employing the method of Grubbs et al. 1 Water was purified by an Elix ® UV-10 system. Reagents were used directly as supplied by major chemical suppliers, or following purification procedures described by Perrin and Armarego. 2 Petrol 40-60 refers to the fraction of petroleum ether which boils in the range 40-60 o C. Brine refers to a saturated aqueous solution of sodium chloride. Column chromatography was carried out using Merck Geduran ® Silicagel (40-63 m particle size). Analytical thin layer chromatography was carried out using pre-coated, aluminium backed plates (Merck Kieselgel 60 F254). Visualisation was achieved with ultraviolet irradiation (254 nm) and staining with vanillin. NMR spectroscopy was carried out using Bruker Avance spectrometers in the deuterated solvent stated, using the residual non-deuterated solvent signal as an internal reference. Chemical shifts are quoted in ppm, based on appearance rather than interpretation. Infrared spectra samples were prepared as a neat film and were recorded using a Bruker Tensor 27 FTIR spectrometer using an ATR module. Low resolution mass spectroscopy was carried out using ESI and was performed on a Micromass LCT Premier spectrometer. HRMS was carried out using Bruker MicroTOF and Micromass GCT spectrometers under ESI or FI conditions respectively. Analytical chiral HPLC was carried out using a Dionex Ultimate 3000 HPLC system comprising a Dionex LPG-3400A pump, WPS-3000SL autosampler and TCC-3000SD column compartment, and a Daicel Chiralpak column (0.46 cm x 25 cm), equipped with an appropriate guard column (0.4 cm x 1 cm). Melting points were determined using a Reichert melting point apparatus and are uncorrected. Optical rotations were recorded on a Perkin-Elmer 241 polarimeter. Concentrations are quoted in g/100 mL. S3 1.2 General Experimental Procedures General Procedure A: Imine Formation/Asymmetric Cyclization Imine Formation: A slurry of pyrroloaniline 1, the appropriate aldehyde and oven dried anhydrous magnesium sulfate in anhydrous toluene was stirred at room temperature for 16 hours and then filtered through a plug of Celite ® washing with anhydrous diethyl ether. The filtrate was concentrated under reduced pressure. Cyclization: The crude imine thus obtained was dissolved in toluene and N-benzylcinchoninium chloride was added. The resulting stirred suspension was cooled to the appropriate temperature and aqueous potassium hydroxide precooled to the appropriate temperature was added. The biphasic reaction mixture was rapidly stirred at the appropriate temperature for the appropriate time. After this time, water was added and the solution was allowed to warm to room temperature. The organic layer was separated and the aqueous layer was extracted three times with dichloromet...

Progress on the Synthesis and Applications of Aminals: Scaffolds for Molecular Diversity

“…Furthermore, we would be remiss not to mention other efficient methods that have been successfully developed for the synthesis of chiral aminals. These include Toste's fluorination-initiated asymmetric cyclization, 27 Smith's asymmetric phase-transfer catalysis, 28 and Zhou's Brønsted acid-catalyzed (R-TRIP) synthesis. 29 Each of these approaches contributes uniquely to the diverse toolkit available for the preparation of chiral aminals, highlighting the richness of methodologies in contemporary asymmetric synthesis.…”