Facile Preparation of 1,2-Dihydroisoquinolines from N-Benzylsulfonamides and Bromoacetylenes

Abstract

General. 1 H and 13 C NMR spectra were taken on an Agilent 400-MR spectrometer at 400 and 100 MHz. CDCl 3 was used as the solvent unless otherwise noted. Chemical shifts are reported in parts per million shift (δ value) from Me 4 Si (δ 0 ppm for 1 H) or based on the middle peak of the solvent (CDCl 3) (δ 77.00 ppm for 13 C) as an internal standard. Signal patterns are indicated as br, broad; s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet. Coupling constants (J) are given in Hertz. When yields were determined by 1 H NMR spectroscopy, a known amount of trichloroethylene was added as an internal standard. Infrared (IR) spectra were recorded on a JASCO A-100 spectrometer and are reported in wave numbers (cm-1). High resolution mass spectra (HRMS) were obtained on a Bruker micrOTOF by the positive electrospray ionization (ESI) method calibrated with sodium formate or on a JEOL JMS-700 by the fast atom bombardment (FAB) method (matrix: m-nitrobenzyl alcohol (NBA)) calibrated with perfluoropolyether or by the electron ionization (EI) method calibrated with perfluorokerosene at the Suzukake-dai Material Analysis Center, Technical Department, Tokyo Institute of Technology. Column chromatography was performed with silica gel [Wakogel® R-200, size 100-200 mesh (75-150 μm), Cat. No. 233-00077, Wako Pure Chemical Industries, Ltd. (Japan)]. Dry solvents (THF, CH 2 Cl 2 , and DMF) were purchased from Kanto Chemicals Co. (Japan). K 3 PO 4 was purchased from Koso Chemical Co. (Japan). Chemicals were purified or dried in a standard manner, if necessary. 1-Chloro-1-octyne (1). Starting haloacetylene for 8.

Synthesis of 1,2-Dihydroisoquinolines by a Modified Pomeranz–Fritsch Cyclization

“…Modifications have been reported, including Perchonock’s use of excess aluminum trichloride (AlCl 3 , >4 equiv) at room temperature, and Miranda’s use of trifluoroacetic acid as a solvent at 50 °C. However, in spite of these adjustments, Pomeranz–Fritsch reactions remain capricious, and 1,2- DHIQs are more commonly prepared by partial dearomatization of IQs , or transition metal-mediated annulation reactions . Each comes with its own set of limitations, including the need for a previously constructed IQ core, the potential for over-reduction to the THIQ , or a carbonyl at C1 that leads to isoquinolinones …”