Total synthesis of ascididemin via anionic cascade ring closure
Starting materials and reagents were obtained from commercial suppliers and used without further purifications. Syringes which were used to transfer anhydrous solvents or reagents were purged with nitrogen prior to use. Other solvents were analytical or HPLC grade and were used as received. n-BuLi was titrated following the procedure described by Burchat and co-workers. 1 Yields refer to isolated compounds estimated to be > 95 % pure as determined by 1 H NMR (25 °C). Thinlayer chromatography
... r chromatography (TLC) was carried out on silica gel 60 F 254 plates from Merck (Germany). Visualization was accomplished by UV lamp (254 nm). Column chromatography was performed on chromatography grade silica 60Å particle size 35-70 micron from Fisher Scientific using the solvent system as stated; where otherwise noted activated neutral alumina (approx. 150 mesh) from Aldrich was used instead. Microwave-assisted synthesis was carried out in a Biotage Initiator apparatus operating in single mode; the microwave cavity producing controlled irradiation at 2.45 GHz (Biotage AB, Uppsala, Sweden). The reactions were run in sealed vessels. These experiments were performed by employing magnetic stirring and a fixed hold time using variable power to reach (during 1-2 min) and then maintain the desired temperature in the vessel for the programmed time period. The temperature was monitored by an IR sensor focused on a point on the reactor vial glass. The IR sensor was calibrated to internal solution reaction temperature by the manufacturer. 1 H NMR and 13 C NMR spectra were recorded on Varian 300 Mercury instrument, using CDCl 3 as deuterated solvent and with the residual solvent as the internal reference; where otherwise noted a mixture CDCl 3 /CD 3 OD (4:1) was used instead. For all NMR experiences the CDCl 3 signal was used as the internal lock. Coupling constants (J values) are given in Hertz (Hz). Multiplicities of 1 H NMR signals are reported as follows: s, singlet; d, doublet; dd, doublet of doublets; ddd, doublet of 1 Burchat, A. F.; Chong, J. M.; Nielsen, N.