Step 2. The Castagnoli–Cushman reaction

#### *For products* **9a**–**9u**:

The resulting crude anhydride from the previous step was dissolved in MeCN (0.3 mL, dry) in a screw-cap vial, then imine (1.05 equiv.) dissolved in MeCN (0.2 mL, dry) was

added with stirring. The reaction mixture was kept at 80 ◦C overnight in a metal heating block. Then, the solvent was evaporated. Next, the crude product was treated with diethyl ether (1 mL), after which pentane (3 mL) was added and the solid was thoroughly ground. After cooling to −20 ◦C for 20 min, the liquid was decanted. The resulting solid was dried in vacuo to give pure title compound.

Dr values were calculated from integrals of methine protons (1H NMR spectra) from lactam ring.

4.3.1. (±)-(3R,4R)-2-Ethyl-1-oxo-4-phenyl-3-(p-tolyl)-1,2,3,4-tetrahydroisoquinoline-4 carboxylic Acid (**9a**)

Prepared according to the general procedure GP2 from **10b** and *N*-(4-methylbenzylidene) ethanamine. Yield 52 mg, 72%. Colorless amorphous solid. 1H NMR (400 MHz, DMSO-*d*6) *δ* 13.14 (s, 1H), 8.19–8.10 (m, 1H), 8.05–7.98 (m, 1H), 7.64 (s, 1H), 7.59–7.47 (m, 1H), 7.36–7.26 (m, 4H), 7.26–7.21 (m, 1H), 6.98 (s, 4H), 5.59 (s, 1H), 3.58 (dq, *J* = 14.0, 7.1 Hz, 1H), 3.20 (dq, *J* = 14.0, 7.1 Hz, 1H), 2.21 (s, 3H), 0.76 (t, *J* = 7.0 Hz, 3H). 13C NMR (101 MHz, DMSO-*d*6) *δ* 171.7, 162.3, 142.6, 137.8, 137.7, 136.0, 131.9, 130.4, 130.1, 129.0, 129.0, 128.5, 128.2, 128.0, 128.0, 127.6, 66.4, 59.0, 42.1, 21.0, 13.1. HRMS (ESI/Q-TOF) *m*/*z*: [M + H+] <sup>+</sup> Calcd for C25H24NO3 <sup>+</sup> 386.1751; Found 386.1744.

Crystal Data for C28.571429H26.285714N1.142857O3.428571 (*M* = 440.51 g/mol): orthorhombic, space group Pbca (no. 61), *a* = 15.8652(2) Å, *b* = 14.6469(2) Å, *c* = 16.7176(2) Å, *V* = 3884.77(9) Å3, *Z* = 7, *T* = 100.15 K, μ(CuKα) = 0.689 mm−1, *Dcalc* = 1.318 g/cm3, 41,022 reflections measured (9.774◦ ≤ 2Θ ≤ 152.44◦), 4053 unique (*R*int = 0.0439, Rsigma = 0.0168) which were used in all calculations. The final *R*<sup>1</sup> was 0.0408 (I > 2σ(I)) and *wR*<sup>2</sup> was 0.1105 (all data). Please see ESI (p.S2-5) for details.
