3.6.4. *N*-Benzyl-1-((1*R*,2*S*,4*R*)-2-{3-[3,5-bis(trifluoromethyl)phenyl]thioureido}-7,7 dimethylbicyclo[2.2.1]heptan-1-yl)-*N*,*N*-dimethylmethanaminium 2,2,2-Trifluoroacetate (**IV**)

Following *GP4*. Prepared from compound **7a** (0.39 mmol, 200 mg) and 3,5-bis (trifluoromethyl)phenyl isothiocyanate (0.70 mmol, 128 μL), CH2Cl2 (4 mL), 25 ◦C, 16 h. Isolation by column chromatography (Silica gel 60, EtOAc/MeOH = 4:1). Yield: 250 mg (0.37 mmol, 95%) of colorless solid, mp = 153–155 ◦C. [α] r.t.D = +2.1 (0.11, MeOH). EI-HRMS: *m*/*z* = 558.2363 (M)+; C28H34F6N3S+ requires: *m*/*z* = 558.2372 (M)+; νmax 3275, 3247, 3047, 2961, 2890, 1682, 1542, 1473, 1385, 1278, 1177, 1132, 966, 887, 848, 801, 719, 702, 680 cm−1. 1H-NMR (500 MHz, CDCl3): δ 0.97 (s, 3H), 1.05 (s, 3H), 1.10 (dd, *J* = 13.4, 3.7, 1H), 1.51 (ddd, *J* = 13.4, 9.2, 4.7, 1H), 1.73 (t, *J* = 4.6, 1H), 1.78–1.89 (m, 1H), 1.95–2.12 (m, 1H), 2.59–2.67 (m, 1H), 2.68–2.76 (m, 1H), 3.03 (s, 3H), 3.04 (s, 3H), 3.47 (d, *J* = 13.7, 1H), 3.72 (d, *J* = 13.7, 1H), 4.55 (d, *J* = 12.6, 1H), 4.71 (d, *J* = 12.6, 1H), 5.22 (tt, *J* = 10.2, 3.0, 1H), 7.34–7.40 (m, 4H), 7.43–7.48 (m, 1H), 7.53 (s, 1H), 8.29 (s, 2H), 8.91 (d, *J* = 9.8, 1H), 11.09 (s, 1H). 13C-NMR (126 MHz, CDCl3): δ 19.81, 20.25, 28.05, 28.57, 38.68, 43.75, 50.78, 51.03, 51.76, 54.43, 56.70, 69.58, 73.03, 117.02 (q, *J* = 294.4), 117.24–117.53 (m), 122.72 (d, *J* = 3.4), 123.39 (q, *J* = 272.7), 126.96, 129.47, 131.24, 131.48 (q, *J* = 33.4), 133.03, 141.44, 161.62 (q, *J* = 34.1), 181.96.

3.6.5. *N*-Benzyl-1-((1*R*,2*S*,4*R*)-2-{3-[3,5-bis(trifluoromethyl)phenyl]thioureido}-7,7 dimethylbicyclo[2.2.1]heptan-1-yl)-*N*,*N*-dimethylmethanaminium Iodide (**V**)

Following *GP5*. Prepared from catalyst **IV** (0.17 mmol, 116 mg), dissolved in ethyl acetate (3 mL) and filtered through a pad of NaI. Volatile components were evaporated in vacuo. Yield: 109 mg (0.16 mmol, 92%) of white solid, mp = decomposition above 350 ◦C. [α] r.t.D = +69.2 (0.013, MeOH). EI-HRMS: *m*/*z* = 558.2368 (M)+; C28H34F6N3S+ requires: *m*/*z* = 558.2372 (M)+; νmax 3247, 2960, 2928, 2857, 2175, 2163, 2135, 2034, 1996, 1954, 1722, 1595, 1534, 1473, 1385, 1277, 1177, 1135, 965, 887, 730, 701, 680 cm−1. 1H-NMR (500 MHz, DMSO-*d*6): δ 0.98 (s, 3H), 1.02 (dd, *J* = 13.0, 3.7, 1H), 1.05 (s, 3H), 1.43–1.52 (m, 1H), 1.72 (t, *J* = 4.4, 1H), 1.90–2.06 (m, 2H), 2.16–2.24 (m, 1H), 2.45–2.49 (m, 1H), 2.95 (s, 3H), 2.99 (s, 3H), 3.60 (d, *J* = 14.1, 1H), 3.71 (d, *J* = 14.0, 1H), 4.52–4.63 (m, 2H), 5.04–5.12 (m, 1H), 7.43–7.59 (m, 5H), 7.81 (s, 1H), 8.28 (s, 2H), 8.38 (d, *J* = 9.8, 1H), 10.32 (s, 1H). 13C-NMR (126 MHz, DMSO-*d6*): δ 19.25, 20.04, 26.97, 28.11, 38.10, 42.97, 49.08, 50.46, 51.23, 53.88, 56.13, 67.81, 70.46, 116.76–117.00 (m), 122.27–122.44 (m), 123.17 (q, *J* = 272.8), 128.03, 128.86, 130.17 (q, *J* = 32.8), 130.38, 133.06, 141.46, 181.00.

3.6.6. *N*-Benzyl-1-[(1*R*,2*S*,4*R*)-7,7-dimethyl-2-(3-phenylthioureido)bicyclo[2.2.1]heptan-1 yl]-*N*,*N*-dimethylmethanaminium 2,2,2-Trifluoroacetate (**VI**)

Following *GP4*. Prepared from compound **7a** (0.39 mmol, 200 mg) and phenyl isothiocyanate (0.70 mmol, 84 μL), CH2Cl2 (4 mL), 25 ◦C, 16 h. Isolation by evaporation followed by column chromatography (Silica gel 60, EtOAc/MeOH = 4:1). Yield: 119 mg (0.22 mmol, 56 %) of colorless solid, mp = 180–183 ◦C. [α] r.t.D = +6.7 (0.06, MeOH). EI-HRMS: *m*/*z* = 422.2618 (M)+; C26H36N3S+ requires: *m*/*z* = 422.2624 (M)+; νmax 3244, 2959, 2884, 1683, 1540, 1507, 1489, 1473, 1457, 1362, 1317, 1202, 1148, 1056, 1033, 851, 801, 727 cm−1. 1H-NMR (500 MHz, CDCl3): δ 0.96 (s, 3H); 1.04 (s, 3H); 1.08 (dd, *J* = 13.3, 3.7, 1H); 1.45–1.53 (m, 1H); 1.67–1.79 (m, 2H); 1.96–2.06 (m, 1H); 2.57–2.65 (m, 1H); 2.67–2.76 (m, 1H); 2.98 (s, 3H); 3.03 (s, 3H); 3.41 (d, *J* = 13.6, 1H); 3.73 (d, *J* = 13.8, 1H); 4.54 (d, *J* = 12.5, 1H); 4.79 (d, *J* = 12.4, 1H), 5.24–5.31 (m, 1H), 7.04–7.10 (m, 1H); 7.22–7.29 (m, 2H); 7.33–7.47 (m, 5H); 7.60–7.68 (m, 2H); 8.64 (d, *J* = 9.9, 1H); 10.45 (s, 1H). 13C-NMR (126 MHz, CDCl3): δ 19.95, 20.50, 28.53, 28.65, 38.67, 43.85, 51.11, 51.22, 51.72, 54.34, 56.50, 69.08, 72.83, 123.82, 124.84, 127.30, 128.46, 129.38, 130.98, 133.35, 139.65, 182.21 (two signals missing).

3.6.7. *N*-Benzyl-1-[(1*R*,2*S*,4*R*)-7,7-dimethyl-2-(3-phenylureido)bicyclo[2.2.1]heptan-1-yl]- *N*,*N*-dimethylmethanaminium 2,2,2-Trifluoroacetate (**VII**)

Following *GP4*. Prepared from compound **7a** (0.39 mmol, 200 mg) and phenyl isocyanate (0.69 mmol, 76 μL), CH2Cl2 (4 mL), 25 ◦C, 16 h. Isolation by evaporation followed by column chromatography (Silica gel 60, EtOAc/MeOH = 5:1). Yield: 57 mg (0.11 mmol, 28%) of colorless solid, mp = 120.0–123.8 ◦C. [α] r.t.D = +5 (0.08, MeOH). EI-HRMS: *m*/*z* = 406.2850 (M)+; C26H36N3O+ requires: *m*/*z* = 406.2853 (M)+; νmax 3261, 2960, 2886, 2150, 1683, 1598, 1550, 1489, 1457, 1313, 1202, 1139, 846, 801, 727, 702 cm<sup>−</sup>1. 1H-NMR (500 MHz, CDCl3): δ 0.95 (s, 3H), 1.00 (s, 3H), 1.12 (dd, *J* = 13.3, 3.6, 1H), 1.44–1.53 (m, 1H), 1.55–1.68 (m, 2H), 2.03–2.11 (m, 1H), 2.47–2.55 (m, 1H), 2.60–2.67 (m, 1H), 3.04 (s, 3H), 3.08 (s, 3H), 3.36 (d, *J* = 13.7, 1H), 3.88 (d, *J* = 13.7, 1H), 4.52–4.59 (m, 1H), 4.73 (d, *J* = 12.4, 1H), 4.97 (d, *J* = 12.3, 1H), 6.91–6.98 (m, 1H), 7.18–7.24 (m, 2H), 7.25–7.30 (m, 3H), 7.35–7.40 (m, 1H), 7.42–7.47 (m, 2H), 7.51–7.57 (m, 2H), 9.31 (s, 1H). 13C-NMR (126 MHz, CDCl3): δ 19.71, 20.51, 28.46, 28.68, 39.90, 44.00, 50.46, 51.29, 51.76, 52.02, 54.06, 68.41, 72.90, 117.34 (d, *J* = 295.3), 118.79, 122.19, 127.49, 128.82, 129.24, 130.75, 133.32, 139.93, 156.51, 161.52 (q, *J* = 33.5).

3.6.8. *N*-Benzyl-1-[(1*R*,2*S*,4*R*)-7,7-dimethyl-2-(3-phenylureido)bicyclo[2.2.1]heptan-1-yl]- *N*,*N*-dimethylmethanaminium Iodide (**VIII**)

Following *GP5*. Prepared from catalyst **VII** (0.26 mmol, 139 mg), dissolved in ethyl acetate (5 mL), and filtered through a pad of NaI. All volatile components were evaporated in vacuo. Yield: 111 mg (0.21 mmol, 80%) of colorless solid, mp = 153–155 ◦C. [α] r.t.D = +78 (0.073, MeOH). EI-HRMS: *m*/*z* = 406.2850 (M)+; C26H36N3O+ requires: *m*/*z* = 406.2853 (M)+; νmax 3277, 2967, 2881, 1678, 1597, 1543, 1487, 1442, 1377, 1311, 1217, 1158, 1128, 1030, 949, 852, 816, 753, 729, 694 cm−1. 1H-NMR (500 MHz, CDCl3): δ 1.01 (s, 6H), 1.14 (dd, *J* = 13.3; 3.6, 1H), 1.46–1.60 (m, 2H), 1.62 (t, *J* = 4.5, 1H), 2.23–2.31 (m, 1H), 2.48–2.56 (m, 1H), 2.67–2.76 (m, 1H), 3.08 (s, 3H), 3.11 (s, 3H), 3.34 (d, *J* = 13.7, 1H), 4.07 (d, *J* = 13.6, 1H), 4.54–4.65 (m, 1H), 4.80 (d, *J* = 12.3, 1H), 5.05 (d, *J* = 12.3, 1H), 6.75 (d, *J* = 10.8, 1H), 6.94–7.00 (m, 1H), 7.19–7.25 (m, 2H), 7.31 (t, *J* = 7.6, 2H), 7.38–7.43 (m, 1H), 7.48–7.53 (m, 2H), 7.56–7.62 (m, 2H), 8.93 (s, 1H). 13C-NMR (126 MHz, CDCl3): δ 19.88, 20.81, 28.41, 29.13, 39.96, 44.02, 50.51, 51.57, 51.95, 52.34, 54.45, 68.01, 72.56, 118.82, 122.49, 127.33, 128.83, 129.29, 130.86, 133.38, 139.60, 156.34.

3.6.9. *N*-Benzyl-1-{(1*R*,2*S*,4*R*)-2-[(2-{[3,5-bis(trifluoromethyl)phenyl]amino}- 3,4-dioxocyclobut-1-en-1-yl)amino]-7,7-dimethylbicyclo[2.2.1]heptan-1-yl}-*N*,*N*dimethylmethanaminium 2,2,2-Trifluoroacetate (**IX**)

Following *GP4*. Prepared from compound **7a** (0.19 mmol, 100 mg) and 3-((3,5 bis(trifluoromethyl)phenyl)amino)-4-ethoxycyclobut-3-ene-1,2-dione (0.30 mmol, 106.4 mg), CH2Cl2 (2 mL), 25 ◦C, 16 h. Isolation by evaporation followed by column chromatography (Silica gel 60, EtOAc/MeOH = 4:1). Yield: 106 mg (0.15 mmol, 75%) of colorless solid, mp = 148.9–150.1 ◦C. [α] r.t.D = +65 (0.006, MeOH). EI-HRMS: *m*/*z* = 594.2545 (M)+; C31H34F6N3O2 requires: *m*/*z* = 594.2550 (M)+; νmax 3420, 3153, 3034, 2967, 2888, 1791, 1686, 1603, 1551, 1475, 1427, 1377, 1276, 1176, 1127, 948, 931, 880, 848, 831, 730, 701, 684, 666 cm<sup>−</sup>1. 1H-NMR (500 MHz, CDCl3): δ 1.02 (s, 3H), 1.17 (s, 3H), 1.35 (dd, *J* = 13.2, 3.6, 1H), 1.60–1.66 (m, 1H), 1.77 (t, *J* = 4.5, 1H), 1.89 (br t, *J* = 13.3, 1H), 1.93–2.05 (m, 1H), 2.52–2.62 (m, 1H), 3.01 (s, 1H), 3.14 (s, 3H), 3.16 (s, 3H), 3.42 (d, *J* = 13.8, 1H), 4.33 (d, *J* = 13.9, 1H), 4.63 (d, *J* = 12.5, 1H), 4.76 (d, *J* = 12.5, 1H), 5.27 (t, *J* = 9.9, 1H), 7.41 (t, *J* = 7.4, 2H), 7.45–7.50 (m, 2H), 7.55–7.66 (m, 2H), 8.21 (s, 2H), 9.13 (d, *J* = 9.2, 1H), 11.34 (s, 1H). 13C-NMR (126 MHz, CDCl3): δ 19.80, 20.66, 26.61, 28.93, 41.29, 44.05, 50.80, 51.47, 52.79, 55.04, 58.56, 70.65, 73.17, 116.24, 119.01, 123.33 (q, *J* = 272.9), 126.85, 129.59, 131.38, 132.65 (q, *J* = 33.4), 133.40, 140.74, 165.81, 169.02, 181.07, 185.00 (two carbons missing).
