Ferric(III) Chloride Catalyzed Halogenation Reaction of Alcohols and Carboxylic Acids using - Dichlorodiphenylmethane

Supporting Information Ferric(III) Chloride Catalyzed Halogenation Reaction of Alcohols and Carboxylic Acids using - Dichlorodiphenylmethane Chang-Hee Lee,, Soo-Min Lee,, Byul-Hana Min, Dong-Su Kim, Chul-Ho Jun* Department of Chemistry, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Republic of Korea *E-mail: junch@yonsei.ac.kr Table of Contents 1. General.. S2 2. Materials S2 3. Experimental S2 4. Compounds characterization data S4 5. 1 H and 13 C NMR spectra S10 6. Mechanistic investigation of bromination of alcohol S45 7. Chiral GC data of the chlorination reaction product S46 8. References S46 S1

1. General Flash column chromatography was performed using 230-400 mesh silica gel and was monitored by using analytical thin-layer chromatography (TLC) on silica gel plates using UV light as a visualizing agent, p-anisaldehyde and KMnO 4 solution as the staining solutions, and heat as developing agent. Gas chromatographic analyses were performed using an Agilent 7890A instrument with FID detector and an Agilent HP-5 capillary column. Mass chromatography analyses were performed using a HP- 5MS column. Chiral gas chromatographic analyses were performed using a Donam Instruments INC. DS 6200 instrument with an FID detector and an RtRbDEXcst column. 1 H NMR (400 MHz) and 13 C NMR (100 MHz) data was collected with reported chemical shifts being relative to residual deuteriated solvent peaks (for 1 H NMR spectra deuteriated solvent peaks for CDCl 3 (for 1 H, δ = 7.26), DMSO (for 1 H, δ = 2.50). Chemical shifts are reported in ppm and multiplicities as s = singlet, d = doublet, t = triplet, q = quartet, quint = quintet, m = multiplet. 13 C NMR spectra peaks are referenced to CDCl 3 (for 13 C, δ = 77.26), DMSO (for 13 C, δ 39.5) as internal standard. 2. Materials Commercially available, reagent grade chemicals 1a-q, 2b-d, 3b-f, 5a-b, 10a-j were used as received unless otherwise stated. Ferric chloride (3a) and α,α-dichlorodiphenylmethane 1 (2a) were purchased from Sigma Aldrich and Alfa Aesar. 3. Experimental - Example procedure for preparation of (1-chloroethyl)benzene (4a) (Table 1) To a 1 ml pressure vial were added 1-phenylethanol (1a, 24.1 μl, 0.2 mmol), dichlorodiphenylmethane (2a, 46.2 μl, 0.24 mmol), ferric trichloride (3a, 0.097 mg, 0.006 mmol) and chloroform (0.1 ml). The mixture was stirred at room temperature for 1 h, diluted with chloroform, and filtered through a silica column. The yield of (1-chloroethyl)benzene (4a, 99%) was determined by using GC-MS analysis with hexadecane as the internal standard. - Example procedure for preparation of (bromomethyl)benzene (4m) and S2

(iodomethyl)benzene (4n) (Table 3) To a 1 ml pressure vial were added benzyl alcohol (1b, 24.1 μl, 0.2 mmol), dichlorodiphenylmethane (2a, 46.2 μl, 0.24 mmol), ferric trichloride (3a, 0.097 mg, 0.006 mmol), Lithium halide (LiBr (5a), LiI (5b), 0.8 mmol) and chloroform (0.1 ml). The mixture was stirred at room temperature for 1 h, diluted with chloroform, and filtered through a silica column. The yields of (bromomethyl)benzene (4m, 98%) and (iodomethyl)benzene (4n, 97%) were determined by using GC-MS analysis with hexadecane as the internal standard. - Example procedure for preparation of N-benzylbenzamide (13a) (Table 5) To a 1 ml pressure vial were added benzoic acid (10a, 244.2 mg, 2.0 mmol), dichlorodiphenylmethane (2a, 462.0 μl, 2.4 mmol), ferric trichloride (3a, 16.2 mg, 0.1 mmol) and chloroform (1.0 ml). The mixture was stirred at room temperature for 1 h, and a mixture of triethylamine (558.0 μl, 4.0 mmol) and benzyl amine (14a, 328.0 μl, 3.0 mmol) were then added. The mixture was diluted with dichloromethane, dried over anhydrous MgSO 4 and filtered through Celite. The concentrated filtrate was subjected to column chromatography on silica gel using 10% EtOAc in hexane to give N-benzylbenzamide (13a, 388.7 mg, 92%) as a white solid. S3

4. Compounds characterization data (1-chloroethyl)benzene (4a) [CAS No. 672-65-1]; Obtained as a colorless liquid (99% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 7.45-7.30 (m, 5H), 5.12 (q, J = 6.8 Hz, 1H) 1.87 (dd, J = 6.8 Hz, J = 0.8 Hz,3H); 13 C NMR (100 MHz, CDCl 3 ) δ 143.0, 128.9, 128.5, 126.7, 59.0, 26.7. (chloromethyl)benzene (4b) [CAS No. 100-44-7]; Obtained as a colorless liquid (99% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 7.43-7.32 (m, 5H), 4.61 (s, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 137.7, 129.0, 128.8, 128.6, 46.5. 1-(chloromethyl)-4-methylbenzene (4c) [CAS No. 104-82-5]; Obtained as a colorless liquid (99% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 7.44 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 7.9 Hz, 2H), 4.72 (s, 2H), 2.52 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 138.2, 135.1, 129.9, 129.1, 46.8, 21.7. 1-(chloromethyl)-4-(trifluoromethyl)benzene (4d) [CAS No. 939-99-1]; Obtained as a colorless liquid (90% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 7.63 (d, J = 8.1 Hz, 2H), 7.52 (d, J = 8.1 Hz, 2H), 4.62 (s, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 141.2, 130.5 (q, J = 31.9 Hz), 129.4, 126.3 (q, J = 3.8 Hz), 124.5 (q, J = 270.3 Hz), 45.6. 1-chloro-4-(chloromethyl)benzene (4e) [CAS No. 104-83-6]; Obtained as a colorless liquid (93% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 7.33 (d, J = 1.6 Hz, 4H), 4.55 (s, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 136.1, 134.5, 130.1, 129.1, 45.5. 2-chloromethylfuran (4g) [CAS No. 617-88-9]; Obtained as a colorless liquid (65% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 7.43-7.42 (m, 1H), 6.38-6.35. (m, 2H), 4.60 (s, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 150.2, 143.7, 111.0, 110.0, 37.8. S4

2-(chloromethyl)thiophene (4h) [CAS No. 765-50-4]; Obtained as a colorless liquid (53% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 7.34 (dd, J 1 = 1.5 Hz, J 2 = 6.8 Hz, 1H), 7.12 (d, J = 4.5 Hz, 1H), 7.00 (dd, J 1 = 4.7 Hz, J 2 = 6.8 Hz, 1H), 4.84 (s, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 140.0, 127.6, 126.8 (2C), 40.3. (2-chloroethyl)benzene (4i) [CAS No. 622-24-2]; Obtained as a colorless liquid (92% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 7.42-7.28 (m, 5H), 3.78 (t, J = 7.4 Hz, 2H), 3.14 (t, J = 7.48 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 138.3, 129.0, 128.9, 128.7, 127.0, 45.1, 39.3. (2-chloropropyl)benzene (4j) [CAS No. 10304-81-1]; Obtained as a colorless liquid (78% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 7.34-7.21 (m, 5H), 4.27-4.19 (m, 1H), 3.04 (spilitted AB quartet, J = 13.8 Hz, J = 7.0 Hz, 2H), 1.52 (d, J = 6.5 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 138.2, 129.6, 128.6, 127.0, 58.8, 46.9, 24.9. (2-chloro-2-methylpropyl)benzene (4k) [CAS No. 1754-74-1]; Obtained as a colorless liquid (94% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 7.35-7.26 (m, 5H), 3.09 (s, 2H), 1.59 (s, 6H); 13 C NMR (100 MHz, CDCl 3 ) δ 137.2, 131.0, 128.2, 127.1, 70.3, 52.0, 32.4. 1-chlorooctane (4l) [CAS No. 111-85-3]; Obtained as a colorless liquid (86% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 3.54 (t, J = 6.8 Hz, 2H), 1.80-1.73 (m, 2H), 1.45-1.38 (m, 2H), 1.32-1.28 (m, 8H), 0.88 (t, J = 6.8 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 45.4, 32.9, 32.0, 29.4, 29.1, 27.1, 22.9, 14.3. 5-Chloro-2-pentanone (4m) [CAS No. 5891-21-4]; Obtained as a colorless liquid (69% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 3.59-3.54 (m, 2H), 2.61 (t, J = 18.8 Hz, 2H), 2.16 (s, 3H), 2.01 (t, J = 17.6 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 207.8, 44.6, 40.4, 30.3, 26.5. S5

4-(chloromethyl)cyclohex-1-ene (4n) [CAS No. 2555-08-0]; Obtained as a colorless liquid (71% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 5.71-5.62 (m, 2H), 3.47 (d, J = 8.4 Hz, 2H), 2.24-2.16 (m, 1H), 2.11-2.06 (m, 2H), 2.00-1.92 (m, 1H), 1.91-1.76 (m, 2H), 1.41-1.30 (m, 1H); 13 C NMR (100 MHz, CDCl 3 ) δ 127.2, 125.6, 50.4, 36.4, 29.5, 26.5, 24.8. (bromomethyl)benzene (4o) [CAS No. 100-39-0]; Obtained as a colorless liquid (98% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 7.45-7.43 (m, 2H), 7.41-7.34 (m, 3H), 4.53 (s, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 138.0, 129.2, 129.0, 128.5, 33.8. (iodomethyl)benzene (4p) [CAS No. 620-05-3]; Obtained as a colorless liquid (97% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 7.43-7.42 (m, 2H), 7.40-7.26 (m, 3H), 4.49 (s, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 139.4, 129.0, 128.9, 128.0, 6.0. 1-bromooctane (4q) [CAS No. 111-83-1]; Obtained as a colorless liquid (85% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 3.37 (t, J = 18.4 Hz, 2H), 1.90-1.80 (m, 2H), 1.44-1.40 (m, 2H), 1.29-1.28 (m, 8H), 0.86 (t, J = 18.0 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 34.2, 33.1, 32.0, 29.3, 29.0, 28.4, 22.9, 14.3. 1-iodooctane (4r) [CAS No. 629-27-6]; Obtained as a colorless liquid (79% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 3.15 (t, J = 18.8 Hz, 2H), 1.86-1.77 (m, 2H), 1.40-1.27 (m, 10H), 0.86 (t, J = 17.6 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 33.8, 32.0, 30.7, 29.3, 28.7, 22.8, 14.3, 7.5. 2-chlorooctane (rac-4s) [CAS No. 628-61-5]; Obtained as a colorless liquid (27.8 mg, 94%); 1 H NMR (400 MHz, CDCl 3 ) δ 4.07-4.00 (m, 1H), 1.74-1.67 (m, 2H), 1.50 (d, J = 6.5 Hz, 3H), 1.48-1.37 (m, 2H), 1.31-1.29 (m, 6H), 0.89 (t, J = 6.7 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 59.2, 40.6, 32.0, 29.0, 26.9, 25.6, 22.8, 14.3. 4-(chloromethyl)benzoic acid (4t) [CAS No. 1642-81-5]; Obtained as a white solid (299.2 mg, 88%); 1 H NMR (400 MHz, DMSO) δ 13.0 (s, 1H), 7.95 (d, J = S6

8.2 Hz, 2H), 7.54 (d, J = 8.2 Hz, 2H), 4.81 (s, 2H); 13 C NMR (100 MHz, DMSO) δ 167.0, 142.4, 130.7, 129.7, 128.9, 45.3. Benzoyl chloride (11a) [CAS No. 98-88-4]; Obtained as a colorless liquid (95% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 8.14-8.11 (m, 2H), 7.71-7.67 (m, 1H), 7.54-7.50 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 168.7, 135.6, 133.4, 131.7, 129.2. 4-methylbenzoyl chloride (11b) [CAS No. 874-60-2]; Obtained as a colorless liquid (92% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 7.99-7.96 (m, 2H), 7.30-7.27 (m, 2H), 2.44 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 168.2, 147.0, 131.7, 130.6, 129.8, 22,0. 4-fluorobenzoyl chloride (11c) [CAS No. 403-43-0]; Obtained as a colorless liquid (78% in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 8.17-8.12 (m, 2H), 7.26-7.16 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 168.6, 166.7 (d, J = 520 Hz), 134.5 (d, J = 40 Hz), 129.7 (d, J = 40 Hz), 116.5 (d, J = 80 Hz). 4-(trifluoromethyl)benzoyl chloride (11d) [CAS No. 329-15-7]; Obtained as a colorless liquid (57 % in GC yield with hexadecane as the internal standard); 1 H NMR (400 MHz, CDCl 3 ) δ 8.25-8.23 (m, 2H), 7.80-7.78 (m, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 167.9, 136.8, 136.5, 136.4, 131.8, 126.3 (q, J = 14 Hz), 124.8, 122.0. N-benzylbenzamide (13a) [CAS No. 1485-70-1]; Obtained as a white solid (388.4 mg, 92%); 1 H NMR (400 MHz, CDCl 3 ) δ 7.80-7.78 (m, 2H), 7.52-7.26 (m, 8H), 6.47 (s, 1H), 4.65 (d, J = 5.7 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 167.6, 138.4, 134.6, 131.8, 129.0, 128.8, 128.2, 127.9, 127.2, 44.4. N-benzyl-4-methylbenzamide (13b) [CAS No. 5436-83-9]; Obtained as a white solid (360.2 mg, 80%); 1 H NMR (400 MHz, CDCl 3 ) δ 7.70 (d, J = 8.0 Hz, 2H), 7.34-7.27 (m, 5H), 7.72 (d, J = 7.8 Hz, 2H), 6.62 (s, 1H), 4.60 (d, J = 5.5 Hz, 2H), 2.39 (s, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 167.5, 142.1, 138.6, 131.7, 129.4, 128.9, S7

128.0, 127.7, 127.2, 44.2, 21.6. N-benzyl-4-fluorobenzamide (13c) [CAS No. 725-38-2]; Obtained as a white solid (330.0 mg, 72%); 1 H NMR (400 MHz, CDCl 3 ) δ 8.13-8.10 (m, 1H), 7.83-7.78 (m, 2H), 7.38-7.34 (m, 4H), 7.32-7.29 (m, 1H), 7.27-7.08 (m, 2H), 6.45 (s, 1H), 4.63 (d, J = 5.6 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 166.6, 138.2, 129.6, 129.5, 129.1, 128.2, 127.9, 116.0, 115.8, 44.5. N-benzyl-4-(trifluoromethyl)benzamide (13d) [CAS No. 365274-70-0]; Obtained as a white solid (295.8 mg, 53%); 1 H NMR (400 MHz, CDCl 3 ) δ 7.89 (d, J = 8.1 Hz, 2H), 7.68 (d, J = 8.2 Hz, 2H), 7.39-7.30 (m, 5H), 6.52 (s, 1H), 4.65 (d, J = 5.6 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 166.7, 138.3, 138.2, 133.8 (q, J = 32.4 Hz), 129.4, 128.4, 128.3, 128.0, 126.1 (q, J = 3.4 Hz), 124.2 (q, J = 271.0 Hz), 44.8 N-benzyl-4-cyanobenzamide (13e) [CAS No. 17922-99-5]; Obtained as a white solid (264.4 mg, 56%); 1 H NMR (400 MHz, CDCl 3 ) δ 7.88 (d, J = 1.7 Hz, 2H), 7.86 (d, J = 1.8 Hz, 2H), 7.71-7.30 (m, 5H), 6.62 (s, 1H), 4.63 (d, J = 5.6 Hz, 2); 13 C NMR (100 MHz, CDCl 3 ) δ 165.8, 138.4, 137.8, 132.6, 128.9, 128.5, 128.2, 127.9, 118.2, 115.2, 44.5. N-benzyl-2-naphthamide (13f) [CAS No. 149358-58-7]; Obtained as a white solid (433.5 mg, 83%); 1 H NMR (400 MHz, CDCl 3 ) δ 8.31 (s, 1H), 7.86-7.84 (m, 4H), 7.58-7.50 (m, 2H) 7.42-7.30 (m, 5H), 6.63 (s, 1H), 4.71 (d, J = 5.6 Hz, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 167.7, 138.4, 135.0, 132.8, 131.8, 129.1, 129.0, 128.7, 128.2, 128.0, 127.9, 127.7, 127.0, 123.8, 44.5. N-benzylcyclohexanecarboxamide (13g) [CAS No. 35665-26-0]; Obtained as a white solid (373.5 mg, 86%); 1 H NMR (400 MHz, CDCl 3 ) δ 7.35-7.25 (m, 5H), 5.73 (s, 1H), 4.43 (d, J = 5.7 Hz, 2H), 2.17-2.07 (m, 1H), 1.91 (d, J = 1.8 Hz, 2H), 1.88-1.77 (m, 2H), 1.68-1.66 (m, 1H), 1.51-1.42 (m, 2H), 1.29-1.22 (m, 3H) ; 13 C NMR (100 MHz, CDCl 3 ) δ 176.4, 139.1, 129.3, 128.3, 128.0, 46.1, 44.0, 30.3, 26.3. N-benzyloctanamide (13h) [CAS No. 70659-87-9]; Obtained as a white solid S8

(265.8 mg, 57%); 1 H NMR (400 MHz, CDCl 3 ) δ 7.36-7.27 (m, 5H), 5.71 (s, 1H), 4.44 (d, J = 5.7 Hz, 2H), 2.21 (t, J = 7.4 Hz, 2H), 1.65 (quint, J = 14.8 Hz, J = 7.0 Hz, 2H), 1.31-1.26 (m, 8H), 0.89-0.86 (m, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 173.5, 139.0, 1283, 1284, 128.1, 44.1, 37.4, 32.2, 29.8, 29.6, 26.3, 23.1, 14.6. N-benzyl-2-methylheptanamide (13i) [CAS No. 113248-86-5]; Obtained as a white solid (346.3 mg, 79%); 1 H NMR (400 MHz, CDCl 3 ) δ 7.35-7.27 (m, 5H), 5.73 (s, 1H), 4.45 (dd, J = 5.6 Hz, J = 1.4 Hz, 2H), 2.23-2.15 (m, 1H), 1.72-1.63 (m, 1H), 1.44-1.35 (m, 1H), 1.34-1.24 (m, 4H), 1.16(d, J = 6.8 Hz, 3H), 0.88 (t, J = 6.7 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 176.4, 138.5, 128.6, 127.7, 127.4, 43.4, 41.6, 34.0, 29.6, 22.6, 17.8, 13.9. N-benzylpivalamide (13j) [CAS No. 26209-45-0]; Obtained as a white solid (259.9 mg, 68%); 1 H NMR (400 MHz, CDCl 3 ) δ 7.35-7.24 (m, 5H), 5.94 (s, 1H), 4.43 (d, J = 5.6 Hz, 2H), 1.22 (s, 9H); 13 C NMR (100 MHz, CDCl 3 ) δ 178.5, 138.9, 128.9, 127.8, 127.6, 43.8, 38.9, 27.8. N-cyclohexylbenzamide (13k) [CAS No. 1759-68-8]; Obtained as a white solid (349.4 mg, 86%); 1 H NMR (400 MHz, CDCl 3 ) δ 7.76 (d, J = 1.1 Hz, 2H), 7.75-7.40 (m, 3H), 5.99 (s, 1H), 4.02-3.94 (m, 1H), 2.05-2.01 (m, 2H), 1.78-1.73 (m, 2H), 1.68-1.63 (m, 1H), 1.48-1.37 (m, 2H), 1.39-1.19 (m, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 166.8, 135.3, 131.4, 128.7, 127.1, 48.9, 33.4, 25.8, 25.1. Heptyl benzoate (13l) [CAS No. 7155-12-6]; Obtained as a colorless liquid (352.2 mg, 80%); 1 H NMR (400 MHz, CDCl 3 ) δ 8.06-8.04 (m, 2H), 7.55 (tt, J = 7.4 Hz, J = 1.9 Hz, 1H), 7.44 (t, J = 7.8 Hz, 2H), 4.32 (t, J = 6.7 Hz, 2H), 1.80-1.73 (m, 2H), 1.48-1.30 (m, 8H), 0.89 (t, J = 6.8 Hz, 3H); 13 C NMR (100 MHz, CDCl 3 ) δ 166.9, 133.0, 130.7, 129.8, 128.5, 65.4, 32.0, 29.2, 29.0, 26.2, 22.8, 14.3. S9

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6. Mechanistic investigation of bromination of alcohol - Preparation of a,a-dibromodiphenylmethane (Scheme 1) To a 1 ml pressure vial were added dichlorodiphenylmethane (2a, 38.5 μl, 0.2 mmol), ferric trichloride (3a, 0.097 mg, 0.006 mmol), lithium bromide (5a, 69.5 mg, 0.8 mmol) and CDCl 3 (0.1 ml). The mixture was stirred at room temperature for 2 h. After 2 h, the mixture was filtered through a silica column. - Preparation of (bromomethyl)benzene (4o) (Scheme 1) To a 1 ml pressure vial were added dichlorodiphenylmethane (2a, 46.2 μl, 0.24 mmol), ferric trichloride (3a, 0.097 mg, 0.006 mmol), lithium bromide (5a, 69.5 mg, 0.8 mmol) and chloroform (0.1 ml). The mixture was stirred at room temperature for 2 h and benzyl alcohol (1b, 24.1 μl, 0.2 mmol) was then added. The mixture was diluted with dichloromethane, dried over anhydrous MgSO 4 S45

and filtered through a silica column. The yields of (bromomethyl)benzene (4o, 98%) was determined by using GC-MS analysis with hexadecane as the internal standard. 1 H NMR (400 MHz, CDCl 3 ) δ 7.45-7.43 (m, 2H), 7.41-7.34 (m, 3H), 4.53 (s, 2H); 13 C NMR (100 MHz, CDCl 3 ) δ 138.0, 129.2, 129.0, 128.5, 33.8. 7. Chiral GC data of the chlorination reaction product (Scheme 2) entry reaction scheme ee (%) GC data (retention time) 1 2 2 99 3 99 4 0 8. Reference (1) (a) Newman, M. S.; Sujeeth, P. K. J. Org. Chem. 1978, 43, 4367. (b) Spaggiari, A.; Vaccari, D.; Davoli, P.; Torre, G.; Prati, F. J. Org. Chem. 2007, 72, 2216. S46