Melting point b 540 apparatus

The majority of the chemicals used in this work were commercially available from Merck or Aldrich. The starting compounds 1a–l were prepared by Ullmann coupling of 2-fluorobenzaldehyde and substituted phenols. Compounds 2a–l were synthesized by Grignard reaction of 1a–l and aryl(or alkyl)magnesium bromides. Then 3a–l were prepared by oxidation of 2a–l using PCC. The final alkene compounds 4a–l were obtained by Wittig reaction using Me(Ph)₃PBr, t-BuOK, and NaH. All substrates were purified by crystallization or column chromatography and were characterized by IR and GC–MS. All novel pruducts were characterized by IR, ¹H NMR, ¹³C NMR, elemental analysis and GC–MS. The reactions were monitored by TLC using silica gel plates and the products were purified by flash column chromatography on silica gel (Merck; 230–400 mesh), eluting with hexane/ethyl acetate (v/v 9:1). NMR spectra were recorded at 500 MHz for ¹H and 125 MHz for ¹³C using Me₄Si as the internal standard in CDCl₃. GC–MS were recorded on a Shimadzu/ QP2010 Plus spectrometer. IR spectra were recorded on a Mattson 1000 spectrometer. Melting points were determined with a Büchi Melting Point B-540 apparatus.

All the reagents were used without further purification unless otherwise specified. Solvents were dried and redistilled prior to use according to the standard method. Analytical thin layer chromatography (TLC) was performed using silica gel HF₂₅₄. Preparative column chromatography was performed with silica gel H. Melting points were determined on a Büchi melting point B-540 apparatus. ¹H- and ¹³C-NMR spectra were recorded on a Bruker ARX 600 MHz or 400 MHz spectrometer using DMSO-d₆ or C₅D₅N as solvents and TMS (tetramethylsilane) as the internal standard. High-resolution mass spectra (HR-MS) were obtained on a Bruker micrOTOF_Q spectrometer.

All reagents were purchased from different commercial sources and used directly without further purification. Reactions were monitored by thin-layer chromatography (TLC) on silica gel 60 F254 (0.25 mm). ¹H NMR and ¹³C NMR were recorded at 400 and 100 MHz, respectively, with Varian AS400 spectrometer and 600, 151, 100, 75 MHz, respectively, with Brucker spectrometer, using TMS as an internal standard with CDCl_3, DMSO-d₆, D₂O, and MeOD-d₄. The coupling constant (J values) and chemical shifts (δ_ppm) were reported in Hertz (Hz) and parts per million (ppm) respectively. Multiplicities are reported as follows: s (singlet), d (doublet), t (triplet), q (quartet), m (multiplet), and br (broadened). High-resolution mass spectra (HRMS) were recorded at Agilent Q-TOF mass spectrometer with a Z-spray source using built-in software for analysis of the recorded data. Melting point data were recorded at Buchi Melting Point B-540 apparatus. All the experimental procedures and protocols were followed in accordance with the institutional guidelines and regulations.

Chemicals, reagents, and solvents used for the preparation of compounds were purchased from Sigma-Aldrich (St. Louis, MO, USA). The reactions were monitored by thin-layer chromatography plates coated with silica gel (Sigma-Aldrich, St. Louis, MO, USA). TLC plates were visualized by UV irradiation (254 nm) or by iodine fumes. One-dimensional and two-dimensional ¹H and ¹³C NMR spectra (Figures S1–S12) were recorded on a Bruker Avance III HD 400 MHz/54 mm Ascend spectrometer (Bruker Optics Inc., Billerica, MA, USA). Chemical shifts are given in ppm downfield from tetramethylsilane (TMS) as an internal standard and coupling constants (J) in Hz. Splitting patterns are labeled as s (singlet), quin (quintet), or m (multiplet). For compounds 6, 7, 13, and 14, hydrogen and carbon atoms of the second quinuclidine ring are marked with prime. Alkyl hydrogen and carbon atoms are marked with a double prime (Figure 6). Melting points were determined on a Melting Point B-540 apparatus (Büchi, Essen, Germany) and are uncorrected. HRMS analyses were carried out on Q Exactive™ Plus Hybrid Quadrupole-Orbitrap™ Mass Spectrometer. Synthesis of compounds 1–5 [22 (link)] and 10–12 [21 (link),30 (link)] was published previously (Figure 6).

All commercial reagents and solvents were purchased and used without additional purification. The progression of the reaction was detected using thin layer chromatography (TLC), it was performed on silica gel 60 F254 plates (Jiangyou, Yantai). Column chromatography was run on silica gel (200–300 mesh) from Qingdao Ocean Chemicals (Qingdao, Shandong, China). The melting points of all compounds were determined with a Büchi Melting Point B-540 apparatus (Büchi Labortechnik, Flawil, Switzerland) and were uncorrected. The mass spectra (MS) were determined in the electrospray ionization (ESI) mode on an Agilent 1200 LC-MS (Agilent, Palo Alto, CA, USA). Nuclear magnetic resonance (¹H-NMR and ¹³C-NMR) spectra were recorded on a Bruker 500 MHz NMR spectrometer using tetramethylsilane (TMS) as an internal standard. The chemical shifts were reported in parts per million (ppm) and the coupling constants (J) were reported in Hertz (Hz). Peak multiplicities were expressed as follows: s, singlet; d, doublet; t, triplet; q, quartet; dd, doublet of doublets; dt, doublet of triplets; td, triplet of doublets; ddd, doublet of doublet of doublets; m, multiplet; and br, broad.