*3.3. Work-Up Procedures*

#### 3.3.1. Procedure for Filtration on a Silica-Pad (Method **A**, Table 8)

A portion (18 mL corresponding to 22.8 mmol) of the first reaction (addition rate = 45 min) carried out on 100 mmol of limiting aldehyde **2d** (see Section 3.2.3) was filtered on a silica-pad: 1.5 cm height, 9.6 cm diameter, gooch porosity = 4 (10–16 μm), mobile phase = EtOAc. In the last EtOAc portions (25 mL each), the presence of product was checked by TLC. The filtered reaction mixture (total volume = 242 mL) was concentrated under reduced pressure. The product conversion (87%) with respect to the limiting aldehyde and the diastereomeric ratio (84:16 = *anti*:/*syn*) were determined by 1H-NMR in CDCl3 on the obtained residue.

#### 3.3.2. Procedure for Aqueous Work-Up Employing NH4Cl (Method **B**, Table 8)

A portion (18 mL corresponding to 22.8 mmol) of the first reaction (addition rate = 45 min) carried out on 100 mmol of limiting aldehyde **2d** (see Section 3.2.3) was diluted with EtOAc (5 mL) and treated with an aqueous solution of NH4Cl (242 mg, 2 equivalents with respect to proline, in 20 mL of H2O). The two layers were separated and the aqueous phase was further extracted with EtOAc (2 x 20 mL, the complete product extraction was checked by TLC). The collected solution was dried with Na2SO4 (1.15 g), and then it was filtered and washed with EtOAc (3 x 9 mL, the complete product recovery was checked by TLC). The filtered reaction mixture (total volume = 90 mL) was concentrated under reduced

pressure. The product conversion (86%) with respect to the limiting aldehyde and the diastereomeric ratio (83:17 = *anti*/*syn*) were determined by 1H-NMR in CDCl3 on the obtained residue.

#### 3.3.3. Procedure for Dilution with EtOAc and Cooling (Method **C**, Table 8).

A portion (10 mL corresponding to 12.6 mmol) of the first reaction (addition rate = 45 min) carried out on 100 mmol of limiting aldehyde **2d** (see Section 3.2.3) was diluted with EtOAc (4 mL) and placed at −15 ◦C for 36 h. A white precipitate was formed, was filtered under vacuum, and washed with cold EtOAc (2 × 4 mL). Here, 86.2 mg of white solid was recovered. The obtained solution was placed at −15 ◦C for further 36 h. A second portion of white solid was filtered under vacuum and washed with cold EtOAc (2 × 3 mL). Here, 27.1 mg of white solid was recovered. The collected solution was dried with Na2SO4 (650 mg), and then it was filtered and washed with EtOAc (3 × 6 mL, the complete product recovery was checked by TLC). The filtered reaction mixture (total volume = 46 mL) was concentrated under reduced pressure. The product conversion (89%) with respect to the limiting aldehyde and the diastereomeric ratio (84:16 = *anti*/*syn*) were determined by 1H-NMR in CDCl3 on the obtained residue. Total recovered proline = 113.3 mg (78%). The nature of the white solid was confirmed by 1H-NMR spectroscopy (see Supplementary Materials) and optical rotation measurement ([ α]D 25 = −84; c = 0.135, water) in comparison with the commercial compound ([ α]D 25 = −86; c = 0.133, water).

#### 3.3.4. Procedure for Dilution with Et2O and Cooling (Method **D**, Table 8).

A portion (10 mL corresponding to 12.6 mmol) of the first reaction (addition rate = 45 min) carried out on 100 mmol of limiting aldehyde **2d** (see Section 3.2.3) was diluted with Et2O (4 mL) and placed at −15 ◦C for 36 h. A white precipitate was formed, it was filtered under vacuum and washed with cold Et2O (2 × 4 mL). Here, 109.4 mg of white solid was recovered. The obtained solution was placed at −15 ◦C for further 36 h. A second portion of white solid was filtered under vacuum and washed with cold Et2O (2 × 3 mL). Here, 15.4 mg of white solid was recovered. The collected solution was dried with Na2SO4 (650 mg), and then it was filtered and washed with Et2O (3 × 8 mL, the complete product recovery was checked by TLC). The filtered reaction mixture (total volume = 52 mL) was concentrated under reduced pressure. The product conversion (90%) with respect to the limiting aldehyde and the diastereomeric ratio (85:15 = *anti*/*syn*) were determined by 1H-NMR in CDCl3 on the obtained residue. Total recovered proline = 124.8 mg (86%). The nature of the white solid was confirmed by 1H-NMR spectroscopy (see Supplementary Materials) and optical rotation measurement ([ α]D 25 = −80; c = 0.131, water) in comparison with the commercial compound ([ α]D 25 = −86; c = 0.133, water).

#### 3.3.5. Procedure for Dilution with DCM and Cooling (Method **E**, Table 8)

A portion (10 mL corresponding to 12.6 mmol) of the first reaction (addition rate = 45 min) carried out on 100 mmol of limiting aldehyde **2d** (see Section 3.2.3) was diluted with DCM (5 mL) and placed at −15 ◦C for 36 h. Two liquid phases were formed. The mixture was directly dried with Na2SO4 (650 mg), and then it was filtered and washed with DCM (3 × 7 mL, the complete product recovery was checked by TLC). The filtered reaction mixture (total volume = 36 mL) was concentrated under reduced pressure. The product conversion (88%) with respect to the limiting aldehyde and the diastereomeric ratio (85:15 = *anti*/*syn*) were determined by 1H-NMR in CDCl3 on the obtained residue.

#### 3.3.6. Procedure for Dilution with n-Hexane and Cooling (Method **F**, Table 8)

A portion (10 mL corresponding to 12.6 mmol) of the first reaction (addition rate = 45 min) carried out on 100 mmol of limiting aldehyde **2d** (see Section 3.2.3) was diluted with *n*-hexane (5 mL) and placed at −15 ◦C for 36 h. Two liquid phases were formed. The mixture was directly dried with Na2SO4 (650 mg), and then it was filtered and washed with *n*-hexane (4 × 7 mL, the complete product recovery was checked by TLC). The filtered reaction mixture (total volume = 43 mL) was concentrated under reduced pressure. The product conversion (89%) with respect to the limiting aldehyde and the diastereomeric ratio (86:14 = *anti*:*syn*) were determined by 1H-NMR in CDCl3 on the obtained residue.
