Supporting Information

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1 Supporting Information Wiley-VC Weinheim, Germany

2 Chirally Aminated 2-aphthols rganocatalytic Synthesis of on-biaryl Atropisomers by Asymmetric Friedel-Crafts Amination Sebastian Brandes, Marco Bella,* Anne Kjærsgaard and Karl Anker Jørgensen* Danish ational Research Foundation: Center for Catalysis, Department of Chemistry Aarhus University, DK-8 Aarhus C, Denmark General Methods. The 1 MR and 13 C MR spectra were recorded at 4 Mz and 1 Mz, respectively. The chemical shifts are reported in ppm downfield to CCl 3 (δ = 7.26), CDCl 2 (δ = 5.32) or CD 2 C (δ = 1.94) for 1 MR, (δ = 77.), (δ = 53.5) or for 13 C MR relative to the central CDCl 3, CD 2 Cl 2 or CD 3 C (δ = 1.2) resonance, respectively. nly the spectra of compound 7e were recorded in CD 3 C. nly the spectra of compound 9a were recorded in CD 2 Cl 2. Most of the MR spectra show rotamers and therefore doubling of the signal set or line broadening. Therefore all 1 and 13 C spectra are attached to this file. Flash chromatography (FC) was carried out using Merck silica gel 6 (23-4 mesh). ptical rotations were measured on a Perkin-Elmer 241 polarimeter. The enantiomeric excess (ee) of the products was determined by PLC using a Daicel Chiralpak AD or Chiralcel D column (wavelength = 272 nm) with i- Pr/hexane as the eluent.

3 Materials. Catalysts 8a, 8b were prepared according to literature procedures. 1 aphthols 5a and 5b, diazocarboxylates 6a and 6b, cinchonine, quinine, diazabicycloundecene (DBU), pentane, Et 2, EtAc, toluene, 1,2-dichloroethane (DCE), C 2 Cl 2, Pd/C, ammonium formiate, Me, CF 3 C 2 (TFA), 3,5-(dinitro)-phenylisocyanate, a 2 C 2 and 4-bromo-benzoylchloride were obtained from Aldrich and used as received. The unsymmetric azodicarboxylate 6c was prepared by coupling -Boc hydrazine with Cbz-chloride and oxidation of the resulting product with BS in pyridine. 2 General Procedure for the Amination Reaction. The naphthol 5 (.2 mmole) was placed in a 4 ml vial, then the catalyst (DBU for racemates or quinine, cinchonine, 8a, 8b) (.4 mmole,.2 eq.) was added and the solids suspended (toluene) or dissolved (DCE) in.4 ml (.5 M) or 4. ml (.5 M) of the solvent. The vial was closed with a screw lid and left at rt or put into a freezer at -2 C, where the suspension/solution was stirred for at least 3 min. After this period the diazocarboxylate 6 was added and the solution stirred over night. The product was purified by FC. 1 M. eidelberger, W. A. Jacobs, J. Am. Chem. Soc. 1919, 41, D. Mackay, D. D. McIntyre, Can. J. Chem. 1984, 62,

4 Characterization Data for the Amination Products. The analytical data for 7a was in accordance with the literature. 3 (2-ydroxy-1-naphthyl)-hydrazine-, -dicarboxylic acid tert-butyl ester, 7b. Solvent: DCE, eluent: C 2 Cl 2, yield 66%; 1 MR: δ (m, 1 ), (m, 2 ), (m, 2 ), (m, 3 ), 1.57/1.51/1.48/1.28 (s, 18 ); RMS C [M+a] : calc.: ; found: The ee was determined by PLC using Chiralpak AD column (hexane/ i-pr (9:1); flow rate 1. ml/min: τ minor = 5.2 min, τ m ajor = 6.7 min; [α] DCE, -15% ee). RT D = (c = 1.8 g/1 ml, (8-Amino-2-hydroxy-1-naphthyl)-hydrazine-, -dicarboxylic tert-butyl ester, 7c. acid 2 Solvent: DCE, eluent: pentane/et 2 = 75:25; MR: 1 δ 9.39 (s, 1 ), 7.7 (d, 1, J = 8.8 z), 7.66 (s, 1 ), 7.35 (d, 1, J = 7.8 z), 7.23 (d, 1, J = 8.4 z), 7.12 (t, 1, J = 7.4 z), 6.83 (d, 1, J = 7.3 z), 3.88 (s, 2 ), 1.48/1.39 (s, 18 ); RMS C [M+a] + : calc.: ; found: The ee was determined by PLC using Chiralcel D column (hexane/i-pr (8:2); flow rate 3 W. J. Kinart, C. M. Kinart, J. rganomet. Chem. 23, 665,

5 1. ml/min: τ major = 5.8 min, τ minor = 7.5 min; [α] RT D = (c = 2. g/1 ml, CDCl 3, +84% ee). -(8-Amino-2-hydroxy-1-naphthyl)-hydrazine--carboxylic acid tertbutyl ester- -carboxylic acid benzyl ester, 7d. 2 Solvent: DCE, eluent: pentane/et 2 = 75:25; 1 MR: δ 8.96 (s, 1 ), 7.96 (s, 1 ), 7.56 (d, 1, J = 8.9 z), (m, 6 ), 7.1 (d, 1, J = 8.9 z), 6,98 (t, 1, J = 7.6 z), 6.68 (d, 1, J = 7.1 z), (m, 2 ), 3.74 (bs, 2 ), 1.28 (s, 9 ); RMS C [M+a] + : calc.: ; found: The ee was determined by PLC using Chiralpak AD column ( hexane/i-pr (8:2); flow rate 1. ml/min: τ minor = 9.7 min, τ major =11.6 min; [α] RT D = -4.1 (c = 4.26 g/1 ml, CDCl 3, from sample with 84% ee). Afte r eluting with pentane/et 2 = 5:5 compound 7i could be isolated (21%), originating possibly from the other regioisomer. (9-ydroxy-2-oxo-2,3-dihydro-perimidin-1-yl)-carbamic acid tertbutyl ester, 7i. 1 MR: δ 8.34 (s, 1 ), 7.86 (s, 1 ), 7.71 (s, 1 ), (m, 1 ), 7.25 (d, 1, J = 8.9 z), 7.18 (d, 1, J = 8.3 z), 7.1 (dd, 1, J = 7.2, J = 8.3 z), 7. (d, 1, J = 8.8 z), 6.55 (d, 4

6 1, J = 7.2 z), 1.45 (s, 9 ); RMS C [M+a] + : calc.: ; found: (8-Methylamino-2-hydroxy-1-naphthyl)-hydrazine-, -dicarboxylic acid tert-butyl ester, 7e. Eluent: pentane/et 2 = 8:2; 1 MR (6 C): δ 9.16 ( bs, 1 ), 7.69 (d, 1, J = 8.9 z), 7.32 (s, 1 ), 7.29 (d, 1, J = 7.9 z), (m, 2 ), 6.81 (d, 1, J = 7.4 z), 4.35 (bs, 1 ), 2.95 (s, 3 ), 1.5/1.45 (s, 18 ); RMS C ] [M+a : calc.: ; found: The ee was determined by PLC using Chiralcel D column (hexane/i-pr (9:1); flow rate 1. ml/min: τ 7.9 min; [α] RT minor = 6.5 min, τ major = D = 71.2 (c = 1. g/1 ml, CDCl 3, from sample with 93% ee). -(8-Benzylamino-2-hydroxy-1-naphthyl)-hydrazine-, -dicarboxylic acid tert-butyl ester, 7f. 1 Eluent: pentane/et 2 = 75:25; MR (6 C): δ 9.19 (s, 1 ), 7.7 (d, 1, J = 8.9 z), (m, 4 ), (m, 2 ), (m, 3 ), 6.86 (d, 1, J = 7.5 z), 4.59 (bs, 1 ), 4.37 (dd, 2, J = 12.8 z), 1.5 (s, 9 ), 1.34 (s, 9 ); RMS C [M+a] + : calc.: ; found: The ee was determined by PLC using Chiralcel D column (hexane/i-pr 5

7 (85:15); flow rate 1. ml/min: τ minor = 7. min, τ major =7.8 min; [α] RT D = 58.6 (c =.5 g/1 ml, CDCl 3, from sample with 98% ee). -(8-(2,2,-Dimethyl-propyl-amino)-2-hydroxy-1-naphthyl)-hydrazine-, -dicarboxylic acid tert-butyl ester, 7g. Eluent: pentane/et 2 = 9:1; 1 MR: δ 9.28 (s, 1 ), 7.71 (d, 1, J = 8.9 z), 7.63/7.46 (s, 1 ), 7.29 (d, 1, J = 8. z), (m, 2 ), 6.81 (d, 1, J = 7.4 z), 4.43 (s, 1 ), (m, 1 ), 2.88 (d, 1, J = 1.7 z), 1.58 (s, 1 ), 1.47 (s, 9 ), 1.41 (s, 5 ), 1.14 (s, 9 ); RMS C [M+a] + : calc.: ; found: The ee was determined by PLC using Chiralcel D column (hexane/i-pr (98:2); flow rate 1. ml/min: τ ] RT minor = 6.3 min, τ major =7.6 min; [α D = 1. (c =.92 g/1 ml, CDCl 3, from sample with 95% ee). -(8-Amino-5,7-dibromo-2-hydroxy-1-naphthyl)-hydrazine-, - dicarboxylic acid tert-butyl ester, 7h. Br 2 Br Eluent: pentane/et 2 = 75:25; 1 MR: δ 9.66 (s, 1 ), 8.14 (d, 1, J = 9.3 z), 7.71 (s, 1 ), 7.38 (s, 1 ), 7.34 (d, 1, J = 9.3 z), 4.43 (s, 2 ), 1.48 (s, 18 ); RMS C Br 8 Br 3 5 [M+a] + : calc.: 57.38; found: The ee was determined by PLC 6

8 using Chiralcel D column (hexane/i-pr (9:1); flow rate 1. ml/min: τ minor = 3.6 min, τ major = 4.1 min; [α] RT D = 56. (c = 4.1 g/1 ml, CDCl, from sample with 99% ee). 3 Examination of the Catalyst under Standard Reaction Conditions. 258 mg of the naphthol 5b (1.6 mmole) were placed in a 4 ml vial, then 1 mg of the catalyst 8a (.32 mmole,.2 eq.) were added and the solids dissolved in 3.2 ml of DCE. The vial was closed with a screw lid and put into a freezer at -2 C. The solution was stirred for 45 min. After this period 369 mg of the azodicarboxylate 6b (1.6 mmole, 1. eq.) were added and the solution stirred at -2 C for 72 h. The product was purified by FC, 1.2 L pentane/et 2 = 75:25, then.3 L Et 2, then 1. L EtAc/Me/24% 3 = 95:5: mg of 7c were isolated (92%), as well as 78 mg of 8a (78% recovery). Also trace amounts of an aminated catalyst were isolated, which were analysed by RMS: C [M+] + : calc.: , found General Procedure for the Amination of the Cinchona Alkaloids 8a and 8b. 1. g (3.2 mmole) of the cinchona alkaloid was placed in a 25 ml round bottom flask. The solid was suspended in 1 ml of C 2 Cl 2 and afterwards.89 g (3.84 mmole, 1.2 eq.) of di-tert-butyl azodicarboxylate 6b were added. After 2 h the suspension turned into a dark orange solution. Then the solvent was evaporated and the raw product purified by FC. 7

9 Characterization Data for the Cinchona Alkaloid Derivatives. S-(+)-ydrocupreidine-5 -(hydrazine-, -dicarboxylic acid tertbutyl ester), 9a. Boc Boc Eluent: pentane/etac = 5:5, yield 72%; 1 MR: δ 1.75/1.6 (s, 1 ), 8.37 (d, 1, J = 4.6 z), 7.89/7.88 (d, 1, J = 9.2 z), 7.58/7.53 (d, 1, J = 4.5 z), 7.28/7.26 (d, 1, J = 9.2 z), 5.63/5.61 (bs, 1 ), 3.69/3.53 (bs, 1 ), (m, 1 ), (m, 1 ), (m, 1 (m, 1 ), ), (m, 1 ), / (m, 1 ), (m, 1 ), (m, 2 ), (m, 11 ), (m, 7 ),.98 (s, 3 ), / (m, 1 ),.82/.75 (t, 3, J = 7.3 z); RMS C [M+] + : calc.: ; found: ; [α] RT 29 4 D = (c = 1. g/1 ml, C 2 Cl 2 ). R-(+)-ydrocupreidine-5 -(hydrazine-, -dicarboxylic acid tertbutyl ester), 9b. Boc Boc Eluent: EtAc/Me/24% 3aq = 95:5:1, yield 21%; 1 MR: δ 8.4 (m, 1 ), 7.86 (d, 1, J = 9.1 z), 7.44 (d, 1, J = 3.8 z), 7.33 (d, 1, J = 9.1 z), 5.71/5.54 (s, 1 ), 3.27 (bs, 1 ), (m, 1 ), (m, 3 ), / (m, 1 ), 1.83/1.76 (bs, 1 ), (m, 2 ), (m, 6 ),

10 1.33 (m, 13 ), 1.24 (s, 6 ), (m, 3 ); RMS C [M+] + : calc.: ; found: ; [α] RT D = (c = 1.62 g/1 ml, CCl ). 3 S-(-)-ydrocupreine-5 -(hydrazine-, -dicarboxylic acid tertbutyl ester), 1a. Boc Boc Eluent: pentane/etac = 5:5, yield 24%; 1 MR: δ 12.12/11.89 (bs, 1 ), 1.99/1.76 (s, 1 ), 8.62/8.6 (d, 1, J = 4.6 z), 8.4/8.3 (d, 1, J = 9.2 z), 7.67/7.63 (d, 1, J = 4.6 z), 7.46/7.44 (d, 1, J = 9.2z), 6.61/6.35 (s, 1 ), 3.42 (m, 1 ), 3. (m, 1 ), 2.71 (m, 2 ), (m, 2 ), (m, 1 ), (m, 2 ), (m, 15 ), (m, 1 ), (m, 2 ), (m, 5 ), (m, 3 ); RMS C α] RT [M+] + : calc.: ; found: ; [ D = (c =.6 g/1 ml, CCl 3 ). R-(-)-ydrocupreine-5 -(hydrazine-, -dicarboxylic acid tertbutyl ester), 1b. Boc Boc Eluent: EtAc/Me/24% 3aq = 95:5:1, yield 56%; 1 MR: δ 8.59 (d, 1, J = 4.6 z), 7.95 (d, 1, J = 9.1 z), 7.48 (d, 1, J = 4.6 z), 7.38 (d, 1, J = 9.2 z), (m, 1 ), (m, 1 ), (m, 1 ), (m, 1 ), (m, 3 ), 9

11 (m, 1 ), (m, 2 ), (m, 2 ), 1.56 (s, 3 ), (m, 13 ), (m, 6 ), (m, 3 ).; RMS C c.: ; found: ; [α] RT [M+] + : cal D = ( c =.96 g/1 ml, CCl 3 ). Chemical Transformations of Compound 7d. -(8-Amino-2-hydroxy-naphthalen-1-yl)-hydrazinecarboxylic acid tert-butyl ester, 11. Compound 7d (1 mg) was dissolved in Me (1 ml) and added to a suspension of Pd/C (5 mg) (CTI: FLAMMABLE) in Me (1 ml). The flask was filled with 2 and a solution of 1 g ammonium formiate in Me (4 ml) was added via a syringe. After 2 h the solution was filtrated on celite and the solvent removed in vacuo. The resulting solid was dissolved in 2 and this solution was extracted 3 times with EtAc (1 ml). The combined organic layers were dried over a 2 S 4, and the crude material purified by FC (EtAc) to afford pure 11 as an oil (85%) MR: δ 9.48 (s, 1 ), 8.9 (s, 1 ), 7.54 (d, 1, J = 8.8 z), 7.36 (d, 1, J = 8.1 z), 7.19 (d, 1, J = 8.8 z), 7.11 (t, 1, J = 7.7 z), 6.8 (d, 1, J = 7.2 z), 3.9 (bs, 2 ), 1.57 (s, 9 ). '-(8-Amino-2-hydroxy-naphthalen-1-yl)-hydrazinecarboxylic acid benzyl ester, 12. TFA, 1 ml, (neat) was added to compound 7d (1 mg). The solution was stirred for 5 min and then the excess solvent was removed in vacuo. The resulting solid was dissolved in EtAc and extracted with saturated ac 3 solution. The organic layer was separated, 1

12 dried over a 2 S 4 and the solvent evaporated to afford compound 12 (95%). 2 1 MR: δ 7.51 (d, 1, J = 9.7 z), (m, 5 ), 7.19 (t, 1, J = 7.8 z), 6.9 (d, 1, J = 8.2 z), 6.82 (d, 1, J = 7.3 z), 6.44 (d, 1, J = 9.7 z), 5.34 (s, 2 ). 1-(3,5-Dinitro-phenyl)-3-(7-hydroxy-8-(hydrazine--carboxylic acid tert-butyl ester- -carboxylic acid benzyl ester)-naphthalen-1- yl)-urea, 13. Compound 7d (77 mg,.18 mmol, sample with 58% ee) was dissolved in anhydrous TF (1 ml) and 3,5-(dinitro)-phenylisocyanate (4 mg,.2 mmol, 1.5 eq) was added. The resulting suspension was stirred at rt for 3 h. The mixture was directly purified by FC (pentane/et 2 = 6:1 then 1:1) to afford 7 mg of pure 13 as a yellow solid (62%) MR: δ 8.74 (s, 2 ), 8.63 (s, 1 ), 8.5 (s, 1 ), 8.15 (bs, 1 ), 8. (bs, 1 ), (m, 1 ), (m, 1 ), (m, 7 ), (m, 1 ), (m, 2 ), 1.14 (s, 9). The ee was determined by PLC using Chiralpak AD column 11

13 (hexane/i-pr (8:2); flow rate 1. ml/min: τ major = 13.1 min, τ minor = 16. min; [α] RT D = -25. (c =.7 g/1 ml, C 2 Cl 2, +57% ee). -(8-(4 -Bromobenzamido)-2-hydroxy-1-naphthyl)-hydrazine-- carboxylic acid tert-butyl ester- -carboxylic acid benzyl ester, 14. The amine 7d (21 mg,.48 mmole) (sample with 84% ee) was put into a flame dried round bottom flask. a 2 C 3 (58 mg,.55 mmole), 2 ml of C 2 Cl 2 and then 4-bromo-benzoylchloride was added and the reaction mixture stirred overnight. After addition of saturated 4 Cl solution (15 ml) the aqueous phase was extracted with 2 x 1 ml C 2 Cl 2. The combined organic phases were dried over a 2 S 4, filtered and evaporated. The crude product was purified by column chromatography, 3 ml pentane/etac = 2:1, then 2 ml pentane/etac = 1:1, to yield 211 mg (73%) of a slightly yellow solid 14 with 83% ee. Br 1 MR: δ (bs, 1 ), 9.34 (s, 1 ), (m, 2 ), 7.83 (bs, 1 ), 7.7 (sb, 1 ), (m, 2 ), 7.33 (bs, 4 ), 7.19 (bs, 1 ), 6.84 (bs, 1 ), (m, 2 ),.93 (s, 9 ); RMS C Br 3 6 [M+a] + : calc.: ; found: The ee was determined by PLC using Chiralpak AD column (hexane/i-pr (8:2); flow rate 1. ml/min: τ minor = 12.8 min, τ major = 16.5 min; [α] RT D = -4.2 (c = 1.1 g/1 ml, C 3 C, +83% ee). 12

14 Kinetic Measurements. For the experimental determination of the rotational barrier of 7b half-lives of the enatiomerically enriched sample were determined via optical rotation. The half-lives were determined at 9 C, 28 C and 45 C. The determination of a half-life at C was unsuccessful due to precipitation of the product at this temperature. To prepare the enantiomerically enriched sample 232 mg 2-naphthol (1.61 mmole) (5a) were suspended in 3.2 ml of toluene and 96 mg of cinchonine were added (.33 mmole,.2 eq). The sample was put into a freezer at -2 C and after 3 min 368 mg Dt-BuAD ( 6b) (1.6 mmole, 1. eq) were added and the slurry stirred over night at -2 C. The reaction mixture was filtered through a silica plug and rinsed with Et 2. The solvents were evaporated and the crude product dissolved in DCE. The ee of the sample (PLC) was 15%. For 9 C and 28 C the sample was filled in an optical rotation cuvette and stored in a refrigerator at 9 C or in the polarimeter, respectively. For 45 C the sample was kept in an oil bath at 45 C and aliquots of the sample were withdrawn from the solution, immediately cooled to C and analysed. 13

15 Data at 282 K: Data at 32 K: Data at 318 K: t/min ln(α / α) t/min ln(α /α) t/min ln(α /α) k 282K racem = 4.7(.38)x1-5 s -1 k 32K racem = 4.35(.12)x1-4 s -1 k 318K racem = 2.7(.28)x1-3 s -1 G # rac = 84(4) kj mol -1 ln(a rac /s -1 ) = 25.7(1.6) 14

16 Calculations. All quantum chemical calculations are carried out in the at F/6-31G level of theory by using the Gaussian3 4 gas phase suite of programs. Frequency analysis has been performed for all fully optimized structures, and the number of imaginary frequencies is zero for all minima structures. The amount of energy required for the rotation along the C- axis is estimated as the difference in energy between the minimum energy structure of the product and the optimized optimized structure with the dihedral angel defined by C 2 -C 1 -- being exactly 18º. The stereochemistry of the starting structures for optimisation is chosen to be like the one found by X-ray diffraction analysis of compound 14. Absolute energies and cartesian coordinates of fully optimised geometries for the structure 7b and the partially optimised structures for this compound having the dihedral angle defined by C 2 -C 2 -- restricted to 18º while all other degrees of freedom were optimised in the gas phase at the F/6-31G level of theory are listed below. 4 M. J. Frisch, G. W. Trucks,. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, J. A. Jr. Montgomery, T. Vreven, K.. Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani,. Rega, G. A. Petersson,. akatsuji, M. ada, M. Ehara, K. Toyota, R. Fukuda, J. asegawa, M. Ishida, T. akajima, Y. onda,. Kitao,. akai, M. Klene, X. Li, J. E. Knox,. P. ratchian, J. B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann,. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. chterski, P. Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannenberg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain,. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B. Foresman, J. V. rtiz, Q. Cui, A. G. Baboul, S. Clifford, J. Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham, C. Y. Peng, A. anayakkara, M. Challacombe, P. M. W. Gill, B. Johnson, W. Chen, M. W. Wong, C. Gonzalez, J. A. Pople, J. A. Gaussian 3, Revision B.5; Gaussian, Inc.: Pittsburgh PA,

17 (2-ydroxy-1-naphthyl)-hydrazine-, -dicarboxylic acid tert-butyl ester, 7b Charge = Multiplicity = 1 Stoichiometry = C Eelec (gas phase) = artree C C C C C C C C C C C C C C C C C C C C

18 (2-ydroxy-1-naphthyl)-hydrazine-, -dicarboxylic acid tert-butyl ester, 7b. Dihedral angel = 18º Charge = Multiplicity = 1 Stoichiometry = C

19 Eelec(gas phase) = artree C C C C C C C C C C

20 C C C C C C C C C C

21 MR-Spectra and PLC traces. ppm (t1) b ppm (t1) b 2

22 7b, racemate, with DBU as a base: Individual Sample Report Reported by User: group (group) Project ame: Sebastian S A M P L E I F R M A T I SB54 - A - AD28 Sample ame: Acquired By: group Sample Type: Date Acquired: 5/31/25 Unknow n 11:34:43 AM Vial: Acq. Method Set: 1 9_1_1 Injection #: Date Processed: 1 5/31/25 12:17:25 PM Injection Volume: Processing Method: 1. ul LC PQ Run Time: Channel ame: 1. Wvln Ch4 PDA Sample Set ame: Proc. Chnl. Descr.: nm RT Area % Area eight Spectrum Index Plot nm 25. nm 25. nm Report Method: ThomasP Printed 1:48:4 AM 7/4/25 Page: 1 of 1 7b, with cinchonine as base: Individual Sample Report Reported by User: group (group) Project ame: marco S A M P L E I F R M A T I seb ad 28 Sample ame: Acquired By: group Sample Type: Date Acquired: 6/1/25 Unknow n 4:36:4 PM Vial: Acq. Method Set: 1 9_1_1 Injection #: Date Processed: 1 6/1/25 4:46:3 PM Injection Volume: Processing Method: 1. ul LC PQ Run Time: Channel ame: 111. Wvln Ch5 PDA Sample Set ame: Proc. Chnl. Descr.: nm RT Area % Area eight Report Method: Default Individual Report Printed 11:5:35 AM 7/4/25 Page: 1 of 1 21

23 ppm (t1) MR(4Mz)7.7(d,1,J=8.8z)7.35(d,1,J=7.8z)7.23(d,1,J=8.4z)7.12(t,1,J=7.4z)6.83(d,1,J=7.3z)7c2 ppm (t1) c2 22

24 7c, Table 1, entry 4 (DCE, RT,.5 M, 8a) Individual Sample Report Reported by User: group (group) Project ame: Sebastian S A M P L E I F R M A T I Sample ame: SB55 - D - D19 Acquired By: group Sample Type: Unknow n Date Acquired: 6/6/25 2:22:19 PM Vial: Injection #: Injection Volume: Run Time: 1 Acq. Method Set: 8_2_1 2 Date Processed: 6/6/25 3:26:1 PM 1. ul Processing Method: LC PQ 1. Channel ame: Wvln Ch4 Sample Set ame: Proc. Chnl. Descr.: PDA nm RT Area % Area eight Spectrum Index Plot nm 25. nm Report Method: ThomasP Printed 5:33:7 PM 7/4/25 Page: 1 of 1 7c, Table 1, entry 6 (DCE, RT,.5 M, 8b) Individual Sample Report Reported by User: group (group) Project ame: Sebastian S A M P L E I F R M A T I Sample ame: SB52 - C - D19 Acquired By: group Sample Type: Unknow n Date Acquired: 5/25/25 1:52:12 AM Vial: Injection #: Injection Volume: Run Time: 1 Acq. Method Set: 8_2_1 9 Date Processed: 5/25/25 12:13:43 PM 1. ul Processing Method: LC PQ 1. Channel ame: Wvln Ch4 Sample Set ame: Proc. Chnl. Descr.: PDA nm RT Area % Area eight Spectrum Index Plot nm 25. nm Report Method: ThomasP Printed 2:7:1 PM 7/4/25 Page: 1 of 1 23

25 7c, Table 1, entry 8 (DCE, -2 C,.5 M, 8a) Individual Sample Report Reported by User: group (group) Project ame: Sebastian S A M P L E I F R M A T I Sample ame: SB57 - A - D15 Acquired By: group Sample Type: Unknow n Date Acquired: 6/13/25 1:9:38 PM Vial: 1 Acq. Method Set: 8_2_1 Injection #: 3 Date Processed: 7/4/25 5:38:29 PM Injection Volume: 1. ul Processing Method: LC PQ Run Time: 1. Channel ame: Wvln Ch4 Sample Set ame: Proc. Chnl. Descr.: PDA nm RT Area % Area eight Spectrum Index Plot nm nm Report Method: ThomasP Printed 5:39:21 PM 7/4/25 Page: 1 of 1 24

26 ppm (t1) MR(4Mz)7.56(d,1,J=8.9z)7.1(d,1,J=9.z)6.98(t,1,J=7.6z)6.68(d,1,J=7.1z)7d2 ppm (t1) d2 25

27 7d, Table 1, entry 9 (DCE, -2 C,.5 M, 8a) Individual Sample Report Reported by User: Marco Bella (Marco) S A M P L E Project ame: Training29 I F R M A T I Sample ame: Kolonne Flow Injection Volume: Run Time: Solvent mb32 new cat on ad 32 Acquired By: Marco Date Acquired: 16 June 25 1:59:23 Acq. Method Set: 8_2_1 Date Processed: 16 June 25 11:2:36 1. ul Processing Method: Training_process_method 142. Channel ame: Wvln Ch RT Area % Area eight Report Method: Default Report Printed 11:13:58 4 July 25 Page: 21 of 2 Individual Sample Report Reported by User: Marco Bella (Marco) Project ame: Training29 Spectrum Index Plot nm nm Report Method: Def ault Report Printed 11:13:58 4 July 25 26

28 ppm (t1) MR(4Mz)7.69(d,1,J=8.9z)7.29(d,1,J=7.9z),6.81(d,1,J=7.4z)7e ppm (t1) e 27

29 7e, Table 2, entry 2 (DCE, -2 C,.5M, 9b) Individual Sample Report Reported by User: group (group) Project ame: Sebastian S A M P L E I F R M A T I Sample ame: SB82 - B - D19 Acquired By: group Sample Type: Unknow n Date Acquired: 8/17/25 12:42:5 PM Vial: 1 Acq. Method Set: 9_1_1 Injection #: 14 Date Processed: 8/17/25 3:14:49 PM Injection Volume: 1. ul Processing Method: LC PQ Run Time: 1. Channel ame: Wvln Ch4 Sample Set ame: Proc. Chnl. Descr.: PDA nm RT Area % Area eigh t Spectrum Index Plot nm 25. nm A U Report Method: ThomasP Printed 11:2:42 AM9/3/25 Page: 1 of 1 7e, Table 2, entry 2 (DCE, -2 C,.5 M, 1b) Reported by User: group (group) Project ame: Sebastian Individual Sample Report S A M P L E I F R M A T I Sample ame: SB82 - D - D19 Acquired By: group Sample Type: Unknow n Date Acquired: 9/27/25 2:35:12 PM Vial: 1 Acq. Method Set: 9_1_1 Injection #: 3 Date Processed: 9/27/25 3:3:9 PM Injection Volume: 1. ul Processing Method: LC PQ Run Time: 1. Channel ame: Wvln Ch4 Sample Set ame: Proc. Chnl. Descr.: PDA nm RT Area % Area eight Spectrum Index Plot nm 25. nm Report Method: ThomasP Printed 11:1:56 AM9/3/25 Page: 1 of 1 28

30 ppm (t1) MR(4Mz):9.19(s,1),7.7(d,1,J=8.9z),7.44(m,4),7.33(m,2),7.22(m,3),6.86(d,1,J=7.5z),4.59(s,1),4.37(q,2,J=12.8z),1.5(s,9),1.34(s,9).7f ppm (t1) f 29

31 7f, Table 2, entry 3 (DCE, -2 C,.5 M, 9b) Individual Sample Report Reported by User: group (group) Project ame: Sebastian S A M P L E I F R M A T I Sample ame: SB85 - C -1 - D19 Acquired By: group Sample Type: Unknow n Date Acquired: 8/24/25 11:21:21 AM Vial: 1 Acq. Method Set: 85_15_1 Injection #: 4 Date Processed: 8/24/25 12:9:36 PM Injection Volume: 1. ul Processing Method: LC PQ Run Time: 1. Channel ame: Wvln Ch1 Sample Set ame: Proc. Chnl. Descr.: PDA nm RT Area % Area eig ht Spectrum Index Plot nm 25. nm A U Report Method: ThomasP Printed 1:59:36 AM9/3/25 Page: 1 of 1 7f, Table 2, entry 3 (DCE, -2 C,.5 M, 1b) Reported by User: group (group) Project ame: Sebastian Individual Sample Report S A M P L E I F R M A T I Sample ame: SB85 - D - D19 Acquired By: group Sample Type: Unknow n Date Acquired: 9/27/25 3:25:17 PM Vial: 1 Acq. Method Set: 85_15_1 Injection #: 4 Date Processed: 9/27/25 3:59:32 PM Injection Volume: 1. ul Processing Method: LC PQ Run Time: 1. Channel ame: Wvln Ch4 Sample Set ame: Proc. Chnl. Descr.: PDA nm RT Area % Area eight Spectrum Index Plot nm 25. nm Report Method: ThomasP Printed 11::56 AM9/3/25 Page: 1 of 1 3

32 ppm (t1) MR(4Mz):9.28(s,1),7.71(d,1,J=8.9z),7.63/7.46(s,1),7.29(d,1,J=8.z), (m,2),6.81(d,1,J=7.4z),4.43(s,1), (m,1),2.88(d,1,J=1.7z),1.58(s,1),1.47(s,9),1.41(s,5),1.14(s,9).7g ppm (t1) g 31

33 7g, Table 2, entry 4 (DCE, -2 C,.5 M, 9b) Individual Sample Report Reported by User: group (group) Project ame: marco S A M P L E I F R M A T I Sample ame: Mb 84 b on od 15 Acquired By: group Sample Type: Unknow n Date Acquired: 9/29/25 2:36:9 PM Vial: 1 Acq. Method Set: 98_2_1 Injection #: 1 Date Processed: 9/29/25 2:46:34 PM Injection Volume: 1. ul Processing Method: LC PQ Run Time: 96. Channel ame: Wvln Ch6 Sample Set ame: Proc. Chnl. Descr.: PDA nm RT Area % Area eight Report Method: Default Individual Report Printed 11:5:39 AM 9/3/25 Page: 1 of 1 7g, Table 2, entry 4 (DCE, -2 C,.5 M, 1b) Reported by User: group (group) Project ame: marco Individual Sample Report S A M P L E I F R M A T I Sample ame: Mb 84 c on od 15 Acquired By: group Sample Type: Unknow n Date Acquired: 9/29/25 2:25:18 PM Vial: 1 Acq. Method Set: 98_2_1 Injection #: 9 Date Processed: 9/29/25 2:37:1 PM Injection Volume: 1. ul Processing Method: LC PQ Run Time: 96. Channel ame: Wvln Ch5 Sample Set ame: Proc. Chnl. Descr.: PDA nm RT Area % Area eight Report Method: Default Individual Report Printed 11:4:5 AM 9/3/25 Page: 1 of 1 32

34 ppm (t1) MR(4Mz):9.66(s,1),8.14(d,1,J=9.3z),7.71(s,1),7.38(s,1),7.34(d,1,J=9.3z),4.43(s,2),1.48(s,18).7h2 Br Br ppm (t1) h2 Br Br 33

35 7h, Table 2, entry 5 (DCE, -2 C,.5 M, 9b) Individual Sample Report Reported by User: Marco Bella (Marco) S A M P L E Project ame: Training29 I F R M A T I Sample ame: Kolonne Flow Injection Volume: Run Time: Solvent mb61 di-br high ee on J 19 Acquired By: Marco Date Acquired: 19 August 25 1:15:37 Acq. Method Set: 8_2_1 Date Processed: 19 August 25 1:27:58 1. ul Processing Method: Training_process_method 142. Channel ame: Wvln Ch RT Area % Area eight Report Method: Default Report Printed 11:16:32 3 September 25 Page: 21 of 2 Individual Sample Report Reported by User: Marco Bella (Marco) Project ame: Training29 Spectrum Index Plot nm nm Report Method: Def ault Report Printed 11:16:32 3 September 25 34

36 7h, Table 2, entry 5 (DCE, -2 C,.5 M, 1b) Individual Sample Report Reported by User: group (group) Project ame: marco S A M P L E I F R M A T I Sample ame: Mb 86 b on od 19 Acquired By: group Sample Type: Unknow n Date Acquired: 9/3/25 9:48:39 AM Vial: 1 Acq. Method Set: 9_1_1 Injection #: 3 Date Processed: 9/3/25 11:7:59 AM Injection Volume: 1. ul Processing Method: LC PQ Run Time: 96. Channel ame: Wvln Ch7 Sample Set ame: Proc. Chnl. Descr.: PDA 27.1 nm RT Area % Area eight Report Method: Default Individual Report Printed 11:8:32 AM 9/3/25 Page: 1 of 1 35

37 ppm (t1) MR(4Mz):7.25(d,1,J=8.9z),7.18(d,1,J=8.3z),7.(d,1,J=8.8z),7.1(dd,1,J=6.9z,J=8.7z),6.55(d,1,J=7.2z)7i ppm (t1) i 36

38 ppm (t1) MR(4Mz):1.75/1.6(s,1),8.37(d,1,J=4.6z),7.89/7.88(d,1,J=9.2z),7.58/7.53(d,1,J=4.5z),7.28/7.26(d,1,J=9.2z),5.63/5.61(bs,1),3.69/3.53(bs,1), (m,1), (m,1), (m,1), (m,1), (m,1), / (m,1), (m,1), (m,2), (m,11), (m,7),.98(s,3), / (m,1),.82/.75(t,3,J=7.3z).a9 Boc Boc ppm (t1) a Boc Boc 37

39 ppm (t1) MR(4Mz):8.4(m,1),7.86(d,1,J=9.1z),7.44(d,1,J=3.8z),7.33(d,1,J=9.1z),5.71/5.54(s,1),3.27(bs,1), (m,1), (m,3), / (m,1),1.83/1.76(bs,1), (m,2), (m,6), (m,13),1.24(s,6), (m,3).9b Boc Boc ppm (t1) b Boc Boc 38

40 ppm (t1) MR(4Mz):12.12/11.89(bs,1),1.99/1.76(s,1),8.62/8.6(d,1,J=4.6z),8.4/8.3(d,1,J=9.2z),7.67/7.63(d,1,J=4.6z),7.46/7.44(d,1,J=9.2z),6.61/6.35(s,1),3.42(m,1),3.(m,1),2.71(m,2), (m,2), (m,1), (m,2), (m,15), (m,1), (m,2), (m,5), (m,3).1a Boc Boc ppm (t1) a Boc Boc 39

41 ppm (t1) b1-MR(4Mz):8.59(d,1,J=4.6z),7.95(d,1,J=9.1z),7.48(d,1,J=4.6z),7.38(d,1,J=9.2z), (m,1), (m,1), (m,1), (m,1), (m,3), (m,1), (m,2), (m,2),1.56(s,3), (m,13), (m,6), (m,3). Boc Boc ppm (t1) b Boc Boc 4

42 ppm (t1) MR(4Mz):7.54(d,1,J=8.8z),7.36(d,1,J=8.1z),7.19(d,1,J=8.9z),7.11(t,1,J=7.7z),6.8(d,1,J=7.2z)112 2 ppm (t1)

43 ppm (t1) MR(4Mz):7.51(d,1,J=9.8z),7.19(t,1,J=7.8z),6.9(d,1,J=8.2z),6.82(d,1,J=7.3z),6.44(d,1,J=9.7z).122 ppm (t1)

44 ppm (t1) ppm (t1)

45 13, after column chromatography, starting from 7d (58% ee) Individual Sample Report Reported by User: group (group) Project ame: marco S A M P L E I F R M A T I MB dintitro on ad 32 Sample ame: Acquired By: group Sample Type: Date Acquired: 7/5/25 Unknow n 1:52:47 AM Vial: Acq. Method Set: 1 8_2_1 Injection #: Date Processed: 14 7/5/25 12:2:55 PM Injection Volume: Processing Method: 1. ul LC PQ Run Time: Channel ame: 96. Wvln Ch5 PDA Sample Set ame: Proc. Chnl. Descr.: nm RT Area % Area eight Report Method: Default Individual Report Printed 12:21:29 PM 7/5/25 Page: 1 of 1 44

46 ppm (t1) Br ppm (t1) Br 45

47 14, after colum chromatography, starting from 7d (84% ee) Individual Sample Report Reported by User: group (group) Project ame: marco S A M P L E I F R M A T I MB pbromo on ad 32 Sample ame: Acquired By: group Sample Type: Date Acquired: 7/5/25 Unknow n 11:13:39 AM Vial: Acq. Method Set: 1 8_2_1 Injection #: Date Processed: 15 7/5/25 12:2:17 PM Injection Volume: Processing Method: 1. ul LC PQ Run Time: Channel ame: 96. Wvln Ch5 PDA Sample Set ame: Proc. Chnl. Descr.: nm RT Area % Area eight Report Method: Default Individual Report Printed 12:22:4 PM 7/5/25 Page: 1 of 1 46