4.3.2. (±)-(3R,4R)-3-(4-Nitrophenyl)-1-oxo-4-phenyl-2-propyl-1,2,3,4 tetrahydroisoquinoline-4-carboxylic Acid (**9b**)

Prepared according to the general procedure GP2 from **10b** and *N*-(4-nitrobenzylidene) propan-1-amine. Yield 62 mg, 74%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO*d*6) *δ* 13.46 (s, 1H), 8.12–8.05 (m, 3H), 8.03–7.98 (m, 1H), 7.72–7.66 (m, 1H), 7.60 (t, *J* = 7.5 Hz, 1H), 7.39 (d, *J* = 8.5 Hz, 2H), 7.29 (p, *J* = 6.6 Hz, 5H), 5.80 (s, 1H), 3.51 (ddd, *J* = 13.2, 8.9, 6.7 Hz, 1H), 2.97 (ddd, *J* = 13.6, 9.0, 5.0 Hz, 1H), 1.23 (dt, *J* = 8.1, 4.9 Hz, 1H), 1.15–0.99 (m, 1H), 0.47 (t, *J* = 7.3 Hz, 3H). 13C NMR (101 MHz, DMSO-*d*6) *δ* 171.7, 162.7, 147.6, 147.2, 142.3, 137.0, 132.4, 130.5, 130.3, 130.0, 128.7, 128.5, 128.3, 128.1, 127.8, 123.5, 66.3, 59.5, 48.3, 20.7, 11.4. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C25H23N2O5 <sup>+</sup> 431.1601; Found 431.1606.

4.3.3. (±)-(3R,4R)-2-Ethyl-7-methyl-1-oxo-4-phenyl-3-(p-tolyl)-1,2,3,4 tetrahydroisoquinoline-4-carboxylic Acid (**9c**)

Prepared according to the general procedure GP2 from **10d** and *N*-(4-methylbenzylidene) ethanamine. Yield 45 mg, 61%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO-*d*6) *δ* 13.06 (s, 1H), 8.05–7.99 (m, 1H), 7.83–7.80 (m, 1H), 7.47–7.41 (m, 1H), 7.35–7.26 (m, 4H), 7.25–7.19 (m, 1H), 7.02–6.92 (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 (126 MHz, DMSO-*d*6) *δ* 171.8, 162.4, 142.8, 137.6, 137.5, 136.1, 134.9, 132.6, 130.2, 130.1, 129.0, 129.0, 128.5, 128.4, 128.0, 127.5, 66.5, 58.8, 42.1, 21.2, 21.0, 13.1. HRMS (ESI/Q-TOF) *m*/*z*: [M + Na+] <sup>+</sup> Calcd for C26H25NO3Na+ 422.1727; Found 422.1718.

4.3.4. (±)-(3R,4R)-2-Ethyl-4-(4-methoxyphenyl)-1-oxo-3-(p-tolyl)-1,2,3,4 tetrahydroisoquinoline-4-carboxylic Acid (**9d**)

Prepared according to the general procedure GP2 from **10c** and *N*-(4-methylbenzylidene) ethanamine. Yield 41 mg, 57%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO-*d*6) *δ* 13.04 (s, 1H), 8.17–8.09 (m, 1H), 8.05–7.94 (m, 1H), 7.64–7.59 (m, 1H), 7.54–7.46 (m, 1H), 7.25–7.19 (m, 2H), 7.02–6.95 (m, 4H), 6.88–6.82 (m, 2H), 5.54 (s, 1H), 3.70 (s, 3H), 3.57 (dq, *J* = 13.9, 7.2 Hz, 1H), 3.17 (dq, *J* = 13.9, 7.2 Hz, 1H), 2.20 (s, 3H), 0.77 (t, *J* = 7.1 Hz, 3H). 13C NMR

(101 MHz, DMSO-*d*6) *δ* 172.0, 162.4, 158.6, 138.1, 137.6, 136.0, 134.4, 131.8, 130.4, 130.1, 129.3, 129.0, 128.9, 128.1, 128.0, 113.8, 66.5, 58.4, 55.5, 42.1, 21.0, 13.1. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C26H26NO4 <sup>+</sup> 416.1856; Found 416.1848.

4.3.5. (±)-(3R,4R)-7-Chloro-4-(4-chlorophenyl)-2-ethyl-1-oxo-3-(p-tolyl)-1,2,3,4 tetrahydroisoquinoline-4-carboxylic acid (**9e**)

Prepared according to the general procedure GP2 from **10f** and *N*-(4-methylbenzylidene) ethanamine. Yield 43 mg, 61%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO-*d*6) *δ* 13.48 (s, 1H), 8.26–8.13 (m, 1H), 8.01–7.93 (m, 1H), 7.79–7.55 (m, 1H), 7.52–7.27 (m, 4H), 7.10–6.85 (m, 4H), 5.65 (s, 1H), 3.58 (dq, *J* = 14.1, 7.1 Hz, 1H), 3.19 (dq, *J* = 14.1, 7.1 Hz, 1H), 2.21 (s, 3H), 0.78 (t, *J* = 7.1 Hz, 3H). 13C NMR (101 MHz, DMSO-*d*6) *δ* 171.0, 161.2, 141.0, 137.9, 136.4, 135.2, 133.4, 132.6, 132.6, 132.3, 131.9, 130.1, 129.2, 128.9, 128.5, 127.5, 66.3, 58.6, 42.3, 21.0, 13.0. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C25H22Cl2NO3 <sup>+</sup> 454.0971; Found 454.0965.

4.3.6. (±)-(3R,4R)-3-(4-(Benzyloxy)-3-methoxyphenyl)-4-(4-chlorophenyl)-1-oxo-2-(prop-2-yn-1-yl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylic Acid (**9f**)

Prepared according to the general procedure GP2 from 10b and N-(4-(benzyloxy)-3 methoxybenzylidene)prop-2-yn-1-amine. Yield 76 mg, 80%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ 13.37 (s, 1H), 8.29–8.18 (m, 1H), 8.08–7.96 (m, 1H), 7.74–7.65 (m, 1H), 7.58–7.26 (m, 10H), 6.92–6.82 (m, 1H), 6.67–6.61 (m, 1H), 6.59–6.50 (m, 1H), 5.75 (s, 1H), 4.98 (s, 2H), 4.65 (d, J = 17.4 Hz, 1H), 3.77 (d, J = 17.4 Hz, 1H), 3.51 (s, 3H). 13C NMR (126 MHz, DMSO-d6) δ 171.2, 162.3, 148.5, 148.3, 141.2, 137.9, 137.4, 136.7, 133.1, 132.7, 132.5, 130.2, 129.8, 129.3, 129.2, 128.9, 128.8, 128.6, 128.5, 128.4, 128.3, 128.3, 121.2, 113.1, 79.0, 76.1, 70.2, 58.4, 55.5. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C33H27ClNO5 <sup>+</sup> 552.1572; Found 552.1574.

4.3.7. (±)-(3R,4R)-2-Benzyl-4-(4-chlorophenyl)-3-(2-methoxyphenyl)-1-oxo-1,2,3,4 tetrahydroisoquinoline-4-carboxylic Acid (**9g**)

Prepared according to the general procedure GP2 from **10a** and *N*-(2-methoxybenzylidene)- 1-phenylmethanamine. Yield 62 mg, 61%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO-*d*6) *δ* 12.95 (s, 1H), 8.20–8.11 (m, 1H), 7.71–7.65 (m, 1H), 7.64–7.58 (m, 1H), 7.55 (d, *J* = 7.7 Hz, 1H), 7.27–7.19 (m, 2H), 7.13–7.07 (m, 2H), 7.05–7.00 (m, 3H), 6.83–6.60 (m, 6H), 5.79 (s, 1H), 5.19 (d, *J* = 14.6 Hz, 1H), 3.87 (s, 3H), 3.40 (d, *J* = 14.6 Hz, 1H). 13C NMR (101 MHz, DMSO-*d*6) *δ* 171.5, 162.9, 158.3, 142.0, 137.4, 136.7, 132.8, 132.2, 129.9, 129.7, 128.8, 128.5, 128.5, 128.3, 127.9, 127.4, 127.3, 126.8, 120.8, 111.5, 59.5, 59.2, 56.2, 48.4. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C30H25ClNO4 <sup>+</sup> 498.1467; Found 498.1471.

4.3.8. (±)-(3R,4R)-2-Allyl-4-(4-chlorophenyl)-3-(2,4-dimethoxyphenyl)-1-oxo-1,2,3,4 tetrahydroisoquinoline-4-carboxylic Acid (**9h**)

Prepared according to the general procedure GP2 from **10a** and *N*-(2,4-dimethoxybenz ylidene)prop-2-en-1-amine. Yield 53 mg, 64%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO-*d*6) *δ* 12.95 (s, 1H), 8.11–8.04 (m, 1H), 7.71–7.52 (m, 3H), 7.41–7.31 (m, 2H), 7.18–7.07 (m, 2H), 6.59–6.47 (m, 2H), 6.33–6.26 (m, 1H), 5.81 (s, 1H), 5.28–5.16 (m, 1H), 4.97 (d, *J* = 10.1 Hz, 1H), 4.88 (d, *J* = 17.1 Hz, 1H), 4.38 (dd, *J* = 15.8, 4.8 Hz, 1H), 3.82 (s, 3H), 3.69 (s, 3H), 3.21 (dd, *J* = 15.2, 7.6 Hz, 1H). 13C NMR (126 MHz, DMSO-*d*6) *δ* 171.6, 162.6, 160.7, 159.2, 142.1, 137.7, 133.0, 132.6, 132.3, 130.2, 130.0, 129.7, 128.6, 128.2, 128.1, 118.9, 118.7, 105.2, 98.7, 59.2, 59.0, 56.2, 55.6, 48.2. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C27H25ClNO5 <sup>+</sup> 478.1416; Found 478.1421.

4.3.9. (±)-(3R,4R)-4-(4-Chlorophenyl)-1-oxo-3-phenyl-2-(p-tolyl)-1,2,3,4 tetrahydroisoquinoline-4-carboxylic Acid (**9i**)

Prepared according to the general procedure GP2 from **10a** and *N*-benzylidene-4-methylaniline. Yield 62 mg, 77%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO-*d*6) *δ* 13.48 (s, 1H), 8.17–8.03 (m, 2H), 7.77–7.69 (m, 1H), 7.66–7.59 (m, 1H), 7.50–7.41

(m, 2H), 7.37–7.30 (m, 2H), 7.27–7.17 (m, 3H), 7.11–7.03 (m, 4H), 6.67–6.49 (m, 2H), 5.75 (s, 1H), 2.25 (s, 3H). 13C NMR (126 MHz, DMSO-*d*6) *δ* 171.1, 162.7, 141.3, 139.5, 138.2, 137.1, 136.8, 132.8, 132.8, 130.6, 130.3, 129.9, 129.1, 128.9, 128.7, 128.7, 126.5, 70.4, 59.7, 21.0. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C29H23ClNO3 <sup>+</sup> 468.1361; Found 468.1368.

4.3.10. (±)-(3R,4R)-4-(4-Chlorophenyl)-3-(4-methoxyphenyl)-1-oxo-2-(4-(trifluoromethyl) phenyl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylic Acid (**9j**)

Prepared according to the general procedure GP2 from **10a** and *N*-(4-methoxybenzylidene)- 4-(trifluoromethyl)aniline. Yield 71 mg, 75%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO-*d*6) *δ* 13.50 (s, 1H), 8.17–8.09 (m, 2H), 7.79–7.73 (m, 1H), 7.73–7.68 (m, 2H), 7.67–7.61 (m, 1H), 7.46–7.40 (m, 2H), 7.37–7.30 (m, 2H), 7.07–7.01 (m, 4H), 6.81–6.77 (m, 2H), 5.92 (s, 1H), 3.69 (s, 3H). 13C NMR (101 MHz, DMSO-*d*6) *δ* 170.9, 162.9, 159.5, 145.6, 141.1, 137.4, 133.1, 132.8, 130.4, 130.3, 130.1, 129.6, 128.9, 128.8, 128.7, 127.5 (q, *J* = 32.3 Hz), 127.2, 126.5 (q, *J* = 3.6 Hz), 124.4 (q, *<sup>J</sup>* = 271.9 Hz), 114.2, 69.0, 59.8, 55.5. 19F NMR (376 MHz, DMSO-*d*6) *<sup>δ</sup>* −60.9. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C30H22ClF3NO4 <sup>+</sup> 552.1184; Found 552.1184.

4.3.11. (±)-(3S,4R)-4-(4-Chlorophenyl)-1-oxo-3-(thiophen-2-yl)-2-(p-tolyl)-1,2,3,4 tetrahydroisoquinoline-4-carboxylic Acid (**9k**)

Prepared according to the general procedure GP2 from **10a** and 4-methyl-*N*-(thiophen-2-ylmethylene)aniline. Yield 55 mg, 67%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO-*d*6) *δ* 13.55 (s, 1H), 8.26–8.19 (m, 1H), 8.12–8.05 (m, 1H), 7.78–7.70 (m, 1H), 7.67–7.59 (m, 1H), 7.48–7.41 (m, 2H), 7.37–7.33 (m, 1H), 7.30–7.26 (m, 2H), 7.13–7.05 (m, 3H), 6.63–6.51 (m, 3H), 5.88 (s, 1H), 2.27 (s, 3H). 13C NMR (101 MHz, DMSO-*d*6) *δ* 171.2, 162.7, 140.8, 139.6, 139.4, 137.3, 136.7, 132.9, 132.8, 130.7, 130.1, 129.9, 129.8, 128.9, 128.8, 128.8, 128.0, 126.6, 126.3, 125.5, 66.2, 59.2, 21.0. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C27H21ClNO3S+ 474.0925; Found 474.0926.

4.3.12. (±)-(3R,4R)-4-(4-Chlorophenyl)-3-(4-fluorophenyl)-2-(4-methoxybenzyl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic Acid (**9l**)

Prepared according to the general procedure GP2 from **10a** and *N*-(4-fluorobenzylidene)- 1-(4-methoxyphenyl)methanamine. Yield 64 mg, 72%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO-*d*6) *δ* 13.38 (s, 1H), 8.16–8.09 (m, 1H), 8.02–7.95 (m, 1H), 7.72–7.64 (m, 1H), 7.62–7.57 (m, 1H), 7.16–6.99 (m, 6H), 6.96–6.87 (m, 4H), 6.77–6.65 (m, 2H), 5.38 (s, 1H), 5.04 (d, *J* = 14.3 Hz, 1H), 3.76 (s, 3H), 3.69 (d, *J* = 14.3 Hz, 1H). 13C NMR (101 MHz, DMSO-*d*6) *δ* 171.3, 162.5, 162.3 (d, *J* = 244.5 Hz), 159.1, 140.9, 136.7, 134.1 (d, *J* = 3.1 Hz), 132.6, 132.3, 131.2 (d, *J* = 8.2 Hz), 130.6, 130.3, 130.0, 129.6, 128.8, 128.6, 128.5, 128.2, 115.4 (d, *J* = 21.3 Hz), 114.0, 65.5, 58.8, 55.5, 48.2. 19F NMR (376 MHz, DMSO-*d*6) *<sup>δ</sup>* −114.0. HRMS (ESI/Q-TOF) *<sup>m</sup>*/*z*: [M + H+] + Calcd for C30H24ClFNO4 <sup>+</sup> 516.1372; Found 516.1373.

4.3.13. (±)-(3R,4R)-4-(4-Chlorophenyl)-1-oxo-2,3-di-p-tolyl-1,2,3,4 tetrahydroisoquinoline-4-carboxylic Acid (**9m**)

Prepared according to the general procedure GP2 from **10a** and 4-methyl-*N*-(4-methylb enzylidene)aniline. Yield 55 mg, 66%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO-*d*6) *δ* 13.44 (s, 1H), 8.12–8.06 (m, 2H), 7.76–7.68 (m, 1H), 7.66–7.57 (m, 1H), 7.49–7.38 (m, 2H), 7.35–7.29 (m, 2H), 7.12–7.07 (m, 2H), 7.04–6.89 (m, 2H), 6.65–6.58 (m, 2H), 5.72 (s, 1H), 2.25 (s, 3H), 2.22 (s, 3H). 13C NMR (101 MHz, DMSO-*d*6) *δ* 171.1, 162.7, 141.3, 139.6, 137.9, 137.2, 136.7, 135.2, 132.7, 132.7, 130.6, 130.3, 129.8, 129.3, 129.0, 128.8, 128.7, 126.4, 70.1, 59.7, 21.0, 21.0. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C30H25ClNO3 <sup>+</sup> 482.1517; Found 482.1518.

4.3.14. (±)-(3S,4R)-4-(4-Chlorophenyl)-2-(2-(cyclopentylthio)ethyl)-3-(furan-2-yl)-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylic Acid (**9n**)

Prepared according to the general procedure GP2 from **10a** and 2-(cyclopentylthio)-*N*- (furan-2-ylmethylene)ethanamine. Yield 56 mg, 66%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO-*d*6) *δ* 13.52 (s, 1H), 8.20–8.14 (m, 1H), 8.00–7.94 (m, 1H), 7.73–7.64 (m,

1H), 7.59–7.50 (m, 1H), 7.48–7.43 (m, 1H), 7.42–7.35 (m, 2H), 7.32–7.23 (m, 2H), 6.27 (dd, *J* = 3.3, 1.9 Hz, 1H), 5.87 (d, *J* = 3.3 Hz, 1H), 5.84 (s, 1H), 3.68 (td, *J* = 13.2, 11.2, 5.0 Hz, 1H), 3.37 (td, 1H), 3.10 (p, *J* = 7.1 Hz, 1H), 2.33 (td, *J* = 12.8, 11.1, 5.0 Hz, 1H), 2.03 (ddd, *J* = 12.8, 11.1, 5.0 Hz, 1H), 1.92 (dt, *J* = 13.9, 6.9 Hz, 2H), 1.70–1.57 (m, 2H), 1.60–1.48 (m, 2H), 1.32 (dt, *J* = 13.9, 6.9 Hz, 2H). 13C NMR (101 MHz, DMSO-*d*6) *δ* 171.4, 163.1, 152.4, 143.0, 140.3, 132.8, 132.3, 130.0, 130.0, 129.1, 128.6, 128.5, 128.5, 110.8, 109.0, 61.2, 57.8, 47.7, 43.4, 33.9, 28.2, 24.8, 24.7. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C27H27ClNO4S<sup>+</sup> 496.1344; Found 496.1344.
