Stereoselective synthesis of [2.2]triphenylenophanes via intramolecular double [2 + 2 + 2] cycloadditions

Planar chiral [2.2]cyclophanes with two aromatic rings in close proximity have attracted much attention for their applications as chiral materials and catalysts because of their stable chirality and transannular interactions. Although numerous [2.2]cyclophanes have been synthesized to date, only a few polycyclic aromatic hydrocarbon (PAH)-based ones have been reported, and the simultaneous control of two planar chiralities of the two aromatic rings facing each other has not been achieved. Here we report the enantio- and/or diastereoselective synthesis of planar chiral PAH-based [2.2]cyclophanes ([2.2]triphenylenophanes) via the high-yielding base-mediated intermolecular macrocyclization and Rh- or Ni-catalyzed intramolecular double [2 + 2 + 2] cycloadditions. DFT calculations have revealed that the second [2 + 2 + 2] cycloaddition kinetically determines the diastereoselectivity. Single crystal X-ray diffraction analyses have confirmed that the facing triphenylene or [5]helicene skeletons strongly repel each other, resulting in curved structures with bulged centers.

To a solution of the crude S5 in THF (50 mL) was added tetrabutylammonium fluoride (TBAF, 15.0 mL, 15.0 mmol, 1.0 mol/L in THF) at 0 °C. After being stirred at room temperature for 30 min, the reaction mixture was diluted with water, and extracted with CH 2 Cl 2 (100 mL x 3). The organic layer was washed with brine, dried with Na 2 SO 4 , filtered, and concentrated. The residue was purified by silica gel column chromatography (n-hexane) to give 6e (
To a solution of the crude S9 in THF (10 mL) was added TBAF (1.0 mL, 1.0 mmol, 1.0 mol/L in THF) at 0 °C. After being stirred at room temperature for 30 min, the reaction mixture was diluted with water and extracted with CH 2 Cl 2 (20 mL x 3). The organic layer was washed with brine, dried with Na 2 SO 4 , filtered, and concentrated. The residue was purified by silica gel PTLC (eluent: nhexane/EtOAc = 2:1) to give 9a (0.106 g, 0.201 mmol, 40% yield).
To a solution of the crude S10 in THF (10 mL) was added TBAF (1.0 mL, 1.0 mmol, 1.0 mol/L in THF) at 0 °C. After being stirred at room temperature for 30 min, the reaction mixture was diluted with water, and extracted with CH 2 Cl 2 (20 mL x 3). The organic layer was washed with brine, dried with Na 2 SO 4 , filtered, and concentrated. The residue was purified by silica gel PTLC (eluent: n-hexane/EtOAc = 2:1) to give 9b (0.0719 g, 0.192 mmol, 38% yield).
To a solution of the crude S11 in THF (10 mL) was added TBAF (0.5 mL, 0.5 mmol, 1.0 mol/L in THF) at 0 °C. After being stirred at room temperature for 30 min, the reaction mixture was diluted with water, and extracted with CH 2 Cl 2 (20 mL x 3). The organic layer was washed with brine, dried with Na 2 SO 4 , filtered, and concentrated. The residue was purified by silica gel PTLC (eluent: n-hexane/EtOAc = 1:1) to give 9c (0.0493 g, 0.0820 mmol, 41% yield).
To a solution of the crude S13 in THF (10 mL) was added TBAF (1.0 mL, 1.0 mmol, 1.0 mol/L in THF) at 0 °C. After being stirred at room temperature for 30 min, the reaction mixture was diluted with water, and extracted with CH 2 Cl 2 (20 mL x 3). The organic layer was washed with brine, dried with Na 2 SO 4 , filtered, and concentrated. The residue was purified by silica gel PTLC (eluent: n-hexane/EtOAc = 2:1) to give 9e (0.179 g, 0.341 mmol, 68% yield).

Hexayne 2b
To a Schlenk tube was added a solution of 1b (60.6 mg, 0.154 mmol) and K 2 CO 3 (106 mg, 0.770 mmol) in DMF (6 mL) at room temperature. The mixture was stirred at 40 °C for 18 h. The reaction mixture was diluted with water and extracted with CH 2 Cl 2 (100 mL x 3). The organic layer was washed with brine, dried with Na 2 SO 4 , filtered, and concentrated. The residue was purified by silica gel PTLC (eluent: n-hexane/EtOAc = 2:1) to give 2b (25.2 mg, 0.0403 mmol, 52% yield). The melting point was determined using a sample, re-extracted from PTLC with ethyl acetate, concentrated, and solidified.

Hexayne 2c
To a Schlenk tube was added a solution of 1c (83.6 mg, 0.135 mmol) and K 2 CO 3 (93.3 mg, 0.675 mmol) in DMF (5 mL) at room temperature. The mixture was stirred at 40 °C for 18 h. The reaction mixture was diluted with water and extracted with CH 2 Cl 2 (100 mL x 3). The organic layer was washed with brine, dried with Na 2 SO 4 , filtered, and concentrated. The residue was purified by silica gel PTLC (eluent: n-hexane/EtOAc = 3:2) to give 2c (41.0 mg, 0.0381 mmol, 56% yield). The melting point was determined using a sample, re-extracted from PTLC with ethyl acetate, concentrated, and solidified.

Hexayne 2d
To a Schlenk tube was added a solution of 1d (93.1 mg, 0.153 mmol) and K 2 CO 3 (106 mg, 0.765 mmol) in DMF (6 mL) at room temperature. The mixture was stirred at 40 °C for 18 h. The reaction mixture was diluted with water and extracted with CH 2 Cl 2 (100 mL x 3). The organic layer was washed with brine, dried with Na 2 SO 4 , filtered, and concentrated. The residue was purified by silica gel PTLC (eluent: n-hexane/EtOAc = 3:2) to give 2d (46.3 mg, 0.0438 mmol, 57% yield). The melting point was determined using a sample, re-extracted from PTLC with ethyl acetate, concentrated, and solidified.

Crystal Data
Single crystals of (±)-3a and (±)-3e suitable for X-ray crystallographic analyses were obtained by recrystallization from CH 2 Cl 2 /hexane solutions at room temperature.

Theoretical Calculations
All calculations were carried out using the Gaussian 16 program. [10] The hybrid density functional method based on B3LYP [11,12] with 6-31g(d) basis set or M06 [13] with a 6-31g(d) basis set (LANL2DZ basis set for Rh) was used for geometry optimizations.
Harmonic vibrational analysis at the same level as optimization was performed to confirm the number of imaginary frequencies for all stationary points (0 for minima and 1 for TSs). The intrinsic reaction coordinate (IRC) method was used to track minimum energy paths from transition structures to the corresponding local minima.
Excitation wavelengths, oscillator strengths, and rotatory strengths were obtained at the density functional level using the time-dependent perturbation theory (TD-DFT) approach. The half-width of the simulated ECD spectrum of (Rp,Rp)-3b and (Rp,Rp)-3e are 0.12 eV and 0.15 eV, respectively.