4.3.15. (±)-(3R,4R)-4-(4-Chlorophenyl)-2-ethyl-1-oxo-3-(p-tolyl)-1,2,3,4 tetrahydroisoquinoline-4-carboxylic acid (**9o**)

Prepared according to the general procedure GP2 from **10a** and *N*-(4-methylbenzylidene) ethanamine. Yield 34 mg, 47%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO-*d*6) *δ* 13.06 (s, 1H), 8.09–7.97 (m, 1H), 7.86–7.79 (m, 1H), 7.49–7.42 (m, 1H), 7.34–7.26 (m, 4H), 7.25–7.19 (m, 1H), 7.04–6.92 (m, 4H), 5.55 (s, 1H), 3.57 (dq, *J* = 14.0, 7.1 Hz, 1H), 3.18 (dq, *J* = 14.0, 7.1 Hz, 1H), 2.42 (s, 3H), 2.21 (s, 3H), 0.74 (t, *J* = 7.1 Hz, 3H). 13C NMR (101 MHz, DMSO-*d*6) *δ* 171.3, 162.3, 141.5, 137.8, 137.3, 135.7, 132.4, 132.1, 130.4, 130.2, 130.1, 129.1, 128.9, 128.5, 128.4, 128.1, 66.4, 58.9, 42.0, 21.0, 13.1. HRMS (ESI/Q-TOF) *m*/*z*: [M + Na+] <sup>+</sup> Calcd for C25H22ClNO3Na+ 442.1180; Found 442.1175.

4.3.16. (±)-(3S,4R)-4-(4-Chlorophenyl)-1-oxo-2-propyl-3-(pyridin-2-yl)-1,2,3,4 tetrahydroisoquinoline-4-carboxylic Acid (**9p**)

Prepared according to the general procedure GP2 from **10a** and *N*-(pyridin-3-ylmethylene) propan-1-amine. Yield 34 mg, 47%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO*d*6) *δ* 13.50 (s, 1H), 8.50–8.37 (m, 2H), 8.13–8.02 (m, 1H), 8.02–7.93 (m, 1H), 7.72–7.65 (m, 1H), 7.64–7.58 (m, 1H), 7.43–7.37 (m, 2H), 7.35–7.26 (m, 3H), 7.24–7.18 (m, 1H), 5.68 (s, 1H), 3.55–3.45 (m, 1H), 3.04–2.93 (m, 1H), 1.32–1.21 (m, 1H), 1.15–1.03 (m, 1H), 0.49 (t, *J* = 7.3 Hz, 3H). 13C NMR (101 MHz, DMSO-*d*6) *δ* 171.4, 162.6, 150.5, 149.6, 141.1, 136.5, 135.9, 134.7, 132.7, 132.5, 130.4, 130.1, 130.1, 128.9, 128.5, 128.4, 123.6, 64.7, 59.1, 48.2, 20.8, 11.3. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C24H22ClN2O3 <sup>+</sup> 421.1313; Found 421.1315.

4.3.17. (±)-(3S,4R)-3-(2-Chlorophenyl)-4-(4-fluorophenyl)-1-oxo-2-propyl-1,2,3,4 tetrahydroisoquinoline-4-carboxylic Acid (**9q**)

Prepared according to the general procedure GP2 from **10e** and *N*-(2-chlorobenzylidene) propan-2-amine. Yield 45 mg, 56% (*dr* = 3/1). Colorless amorphous solid. Major isomer: 1H NMR (400 MHz, DMSO-*d*6) *δ* 13.34 (s, 1H), 8.17–8.10 (m, 1H), 7.75–7.69 (m, 1H), 7.68–7.60 (m, 2H), 7.51–7.45 (m, 1H), 7.30–7.24 (m, 1H), 7.22–7.07 (m, 5H), 6.80–6.73 (m, 1H), 5.90 (s, 1H), 3.71–3.58 (m, 1H), 2.62–2.54 (m, 1H), 1.28–1.13 (m, 1H), 1.09–0.96 (m, 1H), 0.38 (t, *J* = 7.5 Hz, 3H). 13C NMR (126 MHz, DMSO-*d*6) *δ* 171.3, 161.9, 161.2 (d, *J* = 244.8 Hz), 158.7, 138.0 (d, *J* = 2.9 Hz), 136.2, 131.6, 131.1, 131.1, 130.4 (d, *J* = 8.2 Hz), 130.1, 130.0, 128.1, 127.7, 114.6 (d, *J* = 21.5 Hz), 113.3, 64.1, 59.2, 55.0, 19.9, 19.6. 19F NMR (376 MHz, DMSO-*d*6) *δ* -115.5. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C25H22ClFNO3 <sup>+</sup> 438.1267; Found 438.1271. Minor isomer, partial data: 1H NMR (400 MHz, DMSO) δ 7.44 (d, *J* = 7.9 Hz, 1H), 7.40–7.33 (m, 2H), 7.04 (t, *J* = 7.3 Hz, 2H), 6.63 (dd, *J* = 7.9, 1.6 Hz, 1H), 6.32 (t, *J* = 7.8 Hz, 1H), 5.98 (d, *J* = 1.9 Hz, 1H). 19F NMR (376 MHz, DMSO) <sup>δ</sup> −108.77.

4.3.18. (±)-(3R,4R)-4-(4-Fluorophenyl)-2-isopropyl-3-(4-methoxyphenyl)-1-oxo-1,2,3,4 tetrahydroisoquinoline-4-carboxylic Acid (**9r**)

Prepared according to the general procedure GP2 from **10e** and *N*-(4-methoxybenzylidene) propan-2-amine. Yield 41 mg, 52% (*dr* = 4/1). Colorless amorphous solid. Major isomer: 1H NMR (400 MHz, DMSO-*d*6) *δ* 13.21 (s, 1H), 8.12–8.04 (m, 1H), 7.98–7.88 (m, 1H), 7.66–7.59 (m, 1H), 7.61–7.51 (m, 1H), 7.38–7.30 (m, 2H), 7.18–7.07 (m, 2H), 7.06–7.00 (m, 2H), 6.77–6.66 (m, 2H), 5.51 (s, 1H), 4.27 (hept, *J* = 6.7 Hz, 1H), 3.67 (s, 3H), 0.83 (dd, *J* = 20.2, 6.7 Hz, 6H). 13C NMR (126 MHz, DMSO-*d*6) *δ* 171.7, 162.3, 161.6 (d, *J* = 244.8 Hz), 159.1, 138.4 (d, *J* = 2.9 Hz), 136.6, 132.0, 131.5, 131.5, 130.8 (d, *J* = 8.2 Hz), 130.5, 130.4, 128.5, 128.1, 115.0 (d, *J* = 21.5 Hz), 113.7, 64.5, 59.6, 55.4, 48.8, 20.3, 20.0. 19F NMR (376 MHz, DMSO-*d*6) *<sup>δ</sup>* −115.1. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C26H25FNO4 <sup>+</sup> 434.1762; Found 434.1768. Minor isomer, partial data: 1H NMR (400 MHz, DMSO-*d*6) <sup>δ</sup> 7.23 (dd, *<sup>J</sup>* = 12.4, 8.1 Hz, 1H), 6.95–6.81 (m, 2H), 5.35 (s, 1H). 19F NMR (376 MHz, DMSO-*d*6) <sup>δ</sup> <sup>−</sup>108.81.

4.3.19. (±)-(3R,4R)-2-Butyl-4-(4-fluorophenyl)-3-(4-methoxyphenyl)-1-oxo-1,2,3,4 tetrahydroisoquinoline-4-carboxylic Acid (**9s**)

Prepared according to the general procedure GP2 from **10e** and *N*-(4-methoxybenzylidene) butan-1-amine. Yield 61 mg, 75% (*dr* = 4/1). Colorless amorphous solid. Major isomer: 1H NMR (400 MHz, DMSO-*d*6) *δ* 13.20 (s, 1H), 8.13–7.98 (m, 2H), 7.69–7.62 (m, 1H), 7.59–7.53 (m, 1H), 7.39–7.28 (m, 2H), 7.17–7.08 (m, 2H), 7.07–6.97 (m, 2H), 6.78–6.71 (m, 2H), 5.49 (s, 1H), 3.68 (s, 3H), 3.65–3.52 (m, 1H), 3.04–2.89 (m, 1H), 1.32–1.18 (m, 1H), 1.16–1.05 (m, 1H), 0.96–0.85 (m, 1H), 0.85–0.73 (m, 1H), 0.67 (t, *J* = 7.2 Hz, 3H). 13C NMR (126 MHz, DMSO-*d*6) *δ* 171.6, 162.6, 160.6, 159.3, 138.6 (d, *J* = 3.1 Hz), 137.3, 132.1, 130.4 (d, *J* = 5.9 Hz), 130.4, 130.3, 128.5, 128.1, 115.1 (d, *<sup>J</sup>* = 21.2 Hz), 113.8, 66.7, 58.9, 55.4, 46.0, 29.5, 19.8, 14.1. 19F NMR (376 MHz, DMSO-*d*6) *<sup>δ</sup>* −115.7. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C27H27FNO4 <sup>+</sup> 448.1919; Found 448.1924. Minor isomer, partial data: 1H NMR (400 MHz, DMSO-*d*6) δ 7.72 (dd, *J* = 8.1, 2.9 Hz, 2H), 7.25–7.18 (m, 1H), 7.06 (d, *J* = 8.2 Hz, 1H), 6.88 (d, *J* = 8.4 Hz, 2H), 5.31 (s, 1H), 3.24–3.12 (m, 1H). 19F NMR (376 MHz, DMSO-*d*6) δ −108.66.

4.3.20. (±)-(3R,4R)-4-(4-Fluorophenyl)-3-(2-methoxyphenyl)-1-oxo-2-(p-tolyl)-1,2,3,4 tetrahydroisoquinoline-4-carboxylic Acid (**9t**)

Prepared according to the general procedure GP2 from **10e** and 2-methoxy-*N*-(4-methylb enzylidene)aniline. Yield 52 mg, 71% (dr = 3/1). Colorless amorphous solid. 1H NMR (400 MHz, DMSO-*d*6) *δ* 12.98 (s, 1H), 8.22–8.11 (m, 1H), 7.77–7.67 (m, 1H), 7.66–7.58 (m, 1H), 7.48–7.41 (m, 1H), 7.25–7.18 (m, 3H), 7.16–7.09 (m, 2H), 7.05–6.98 (m, 2H), 6.96–6.88 (m, 2H), 6.84–6.65 (m, 1H), 6.49–6.37 (m, 2H), 6.09 (s, 1H), 3.68 (s, 3H), 2.21 (s, 3H). 13C NMR (101 MHz, DMSO-*d*6) *δ* 171.6, 162.9, 161.6 (d, *J* = 244.7 Hz), 158.0, 140.0, 139.6 (d, *J* = 2.6 Hz), 137.8, 136.8, 133.0, 130.7 (d, *J* = 8.3 Hz), 130.3, 130.0, 129.8, 129.6, 128.8, 128.4, 127.7, 127.0, 126.3, 120.7, 115.1 (d, *<sup>J</sup>* = 21.2 Hz), 111.3, 65.2, 60.5, 55.9, 21.0. 19F NMR (376 MHz, DMSO-*d*6) *<sup>δ</sup>* −115.5. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C30H25FNO4 <sup>+</sup> 482.1762; Found 482.1763. Minor isomer, partial data: 1H NMR (400 MHz, DMSO-*d*6) δ 7.37–7.26 (m, 2H), 6.36 (d, *J* = 8.0 Hz, 2H), 6.27 (d, *<sup>J</sup>* = 2.8 Hz, 1H), 3.64 (s, 3H). 19F NMR (376 MHz, DMSO-*d*6) <sup>δ</sup> −108.30.

4.3.21. (±)-(3R,4R)-2-Ethyl-4-(4-fluorophenyl)-1-oxo-3-(p-tolyl)-1,2,3,4 tetrahydroisoquinoline-4-carboxylic acid (**9u**)

Prepared according to the general procedure GP2 from **10e** and *N*-(4-methylbenzylidene) ethanamine. Yield 50 mg, 68%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO-*d*6) *δ* 13.25 (s, 1H), 8.17–8.06 (m, 1H), 8.07–8.00 (m, 1H), 7.69–7.59 (m, 1H), 7.58–7.48 (m, 1H), 7.40–7.30 (m, 2H), 7.17–7.06 (m, 2H), 6.98 (s, 4H), 5.58 (s, 1H), 3.59 (dq, *J* = 13.9, 7.0 Hz, 1H), 3.15 (dq, *J* = 14.0, 6.8 Hz, 1H), 2.21 (s, 3H), 0.76 (t, *J* = 7.1 Hz, 3H). 13C NMR (101 MHz, DMSO-*d*6) *δ* 171.6, 162.3, 161.5 (d, *J* = 244.5 Hz), 138.8 (d, *J* = 3.4 Hz), 137.7, 135.8, 132.0, 130.4, 130.3, 130.2, 130.2, 129.0, 128.9, 128.3, 128.0, 115.2 (d, *J* = 21.2 Hz), 66.7, 58.7, 42.0, 21.0, 13.1. 19F NMR (376 MHz, DMSO-*d*6) *<sup>δ</sup>* −115.7. HRMS (ESI/Q-TOF) *<sup>m</sup>*/*z*: [M + Na+] <sup>+</sup> Calcd for C25H22FNO3Na+ 426.1476; Found 426.1469.
