Synlett 2007(14): 2227-2231  
DOI: 10.1055/s-2007-985565
LETTER
© Georg Thieme Verlag Stuttgart · New York

Facile Preparation of 2-Iodophenyl Trifluoromethanesulfonates: Superior Aryne Precursors

Ashok Ganta, Timothy S. Snowden*
Department of Chemistry, The University of Alabama, Box 870336, Tuscaloosa, AL 35487-0336, USA
Fax: +1(205)3489104; e-Mail: snowden@bama.ua.edu;
Further Information

Publication History

Received 18 December 2006
Publication Date:
13 August 2007 (online)

Abstract

A comparative study of 3-methoxyaryne precursors ­revealed 2-iodo-3-methoxyphenyl triflate as the most effective in nonpolar solvent. Use of Hoppe’s N-isopropyl carbamate allows for the systematic preparation of a variety of 2-iodophenyl triflates via a ­directed ortho-lithiation-iodination-decarbamation sequence. These steps are possible without isolation of the intermediate ­iodophenyl carbamates.

    References and Notes

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15

General Procedure for the Preparation of 2-Iodophenols 11-20
To a solution of the carbamate (2.5 mmol) dissolved in dry Et2O (25 mL) under argon was added TMEDA (1.1 equiv, 2.75 mmol) at 0 °C. Then TMSOTf (1.1 equiv, 2.75 mmol) was slowly added to the solution and the reaction mixture was allowed to warm to r.t. over a period of 30 min. After cooling the solution to -78 °C, TMEDA (2.0 equiv, 5.0 mmol) was added followed by the dropwise addition of n-BuLi or t-BuLi (2.0-2.5 equiv, 5.0-6.2 mmol). The reaction mixture was stirred for 1 h and was then treated with I2 (1.0 equiv, 2.5 mmol) dissolved in THF (3 mL). After reacting for 2 h, EtOH (0.25 mL) was added and the solvent was removed by rotary evaporation. The resultant residue was dissolved in EtOH (25 mL) and treated with 5 mL of aq 2 N NaOH (4 equiv, 10 mmol). The reaction proceeded for 2 h, after which the pH was adjusted to 6-8 with 2 N HCl. The aqueous layer was extracted with Et2O (3 × 25 mL) and the combined organic layers were washed with a 1 M solution of Na2S2O3 (25 mL), then dried and filtered. Upon concen-tration, the resulting residue was purified using flash chromatography (hexane-EtOAc, 95:5 to 9:1) affording the desired 2-iodophenol.

16

General Procedure for the Preparation of 2-Iodophenyl Triflates 21-30
To a -78 °C solution of 2-iodophenol (1.0 mmol) in CH2Cl2 (3 mL) was added anhydrous i-Pr2NEt (1.25 mmol) and Tf2O (1.25 mmol). After 10 min, the cooling bath was removed and the reaction mixture was allowed to warm to r.t. The reaction was quenched with H2O (5 mL) after 1-2 h, and the aqueous phase was extracted with Et2O (3 × 5 mL). The combined organic layers were dried and concentrated. The crude material was then purified by flash chromatog-raphy (100% hexane to hexane-EtOAc, 98:2) or recrystal-lized from hexane to afford the desired 2-iodophenyl triflate.

17

Compound 2: white solid, mp 54-55 °C. IR (neat): 3441 (m), 1734 (s), 1507 (m), 908 (m), 732 (m) cm-1. 1H NMR (500 MHz, CDCl3): δ = 7.16 (t, J = 8.2 Hz, 1 H), 6.66 (dt, J = 5.0, 2.0 Hz, 2 H), 6.62 (t, J = 2.0 Hz, 1 H), 4.79 (d, J = 0.7 Hz, 1 H), 3.82 (dt, J = 13.2, 6.4 Hz, 1 H), 3.72 (s, 3 H), 1.16 (d, J = 6.5 Hz, 6 H). 13C NMR (125 MHz, CDCl3): δ = 160.3, 153.5, 152.0, 129.5, 113.8, 111.1, 107.5, 55.3, 43.4, 22.8. HRMS (EI): m/z [M]+ calcd for C11H15NO3: 209.1052; found: 209.1056.

18

Compound 3: white solid, mp 105-106 °C. IR (neat): 3343 (m), 1739 (s), 1608 (m), 739 (m) cm-1. 1H NMR (500 MHz, CDCl3): δ = 6.96 (d, J = 8.0 Hz, 1 H), 6.75 (s, 1 H), 6.71 (d, J = 8.0 Hz, 1 H), 4.97 (d, J = 4.0 Hz, 1 H,), 3.86 (td, J = 6.7, 13.1 Hz, 1 H), 3.81 (s, 3 H), 2.32 (s, 3 H), 1.20 (d, J = 6.5 Hz, 6 H). 13C NMR (125 MHz, CDCl3): δ = 153.5, 151.1, 137.6, 136.0, 122.7, 120.9, 113.1, 55.7, 43.3, 22.7, 21.2. HRMS (EI): m/z [M]+ calcd for C12H17NO3: 223.1208; found: 223.1210.

19

Compound 5: white solid, mp 151-152 °C. IR (neat): 3391 (m), 1738 (s), 1502 (s), 847 (w), 746 (s) cm-1. 1H NMR (500 MHz, CDCl3): δ = 7.55 (d, J = 7.5 Hz, 4 H), 7.42 (t, J = 7.4 Hz, 2 H), 7.33 (t, J = 7.1 Hz, 1 H), 7.20 (d, J = 8.0 Hz, 2 H), 4.89 (d, J = 4.9 Hz, 1 H), 3.91 (dd, J = 12.8, 6.3 Hz, 1 H), 1.24 (d, J = 6.3 Hz, 6 H). 13C NMR (125 MHz, CDCl3): δ = 153.6, 150.4, 140.5, 138.3, 128.7, 127.9, 127.1, 127.0, 121.8, 43.4, 22.8. HRMS (EI): m/z [M]+ calcd for C16H17NO2: 255.1259; found: 255.1259.

21

Compound 7: white solid, mp 123-124 °C. IR (neat): 3326 (br), 1739 (s), 1495 (s), 845 (s), 746 (s) cm-1. 1H NMR (500 MHz, CDCl3): δ = 7.04 (td, J = 8.6, 16.7 Hz, 4 H), 4.98 (s, 1 H), 3.87 (dd, J = 6.5, 13.1 Hz, 1 H), 1.20 (d, J = 6.4 Hz, 6 H). 13C NMR (125 MHz, CDCl3): δ = 159.7 [d, J(CF) = 243.2 Hz], 153.6, 146.8 [d, J(CF) = 2.6 Hz], 122.9 [d, J(CF) = 8.4 Hz], 115.6 [d, J(CF) = 23.4 Hz], 43.4, 22.7. HRMS (EI): m/z [M]+ calcd for C10H12FNO2: 197.0852; found: 197.0853.

22

Compound 8: white solid, mp 85-86 °C. IR (neat): 3433 (m), 1601 (s), 1508 (m), 748 (s) cm-1. 1H NMR (500 MHz, CDCl3): δ = 7.29 (dd, J = 8.3, 15.3 Hz, 1 H), 6.91 (ddd, J = 6.0, 8.1, 6.6 Hz, 3 H), 4.84 (d, J = 0.9 Hz, 1 H), 3.89 (qd, J = 6.6, 13.4 Hz, 1 H), 1.24 (d, J = 6.6 Hz, 6 H). 13C NMR (125 MHz, CDCl3): δ = 162.7 [d, J(CF) = 246.6 Hz], 153.0, 151.9 [d, J(CF) = 11.0 Hz], 129.8 [d, J(CF) = 9.4 Hz], 117.2 [d, J(CF) = 2.0 Hz], 112.0 [d, J(CF) = 21.1 Hz], 109.5 [d, J(CF) = 24.3 Hz], 43.4, 22.7. HRMS (EI): m/z [M]+ calcd for C10H12FNO2: 197.0852; found: 197.0850.

23

Compound 9: white solid, mp 119-120 °C. IR (neat): 3316 (br), 1739 (s), 1535 (s), 814 (m), 700 (s) cm-1. 1H NMR (500 MHz, CDCl3): δ = 7.36 (m, 3 H), 7.25 (d, J = 7.0 Hz, 1 H), 4.93 (d, J = 3.9 Hz, 1 H), 3.81 (qd, J = 13.5, 6.6 Hz, 1 H), 1.15 (d, J = 6.6 Hz, 6 H). 13C NMR (125 MHz, CDCl3): δ = 153.0, 151.1, 131.6 [q, J(CF) = 32.8 Hz], 129.6, 125.1, 125.1, 123.6 [q, J(CF) = 272.3 Hz], 121.7 [d, J(CF) = 3.7 Hz], 118.7 [dd, J(CF) = 3.6 Hz, J = 7.4 Hz], 43.5, 22.6. HRMS (EI): m/z [M]+ calcd for C11H12F3NO2: 247.0820; found: 247.0824.

24

Compound 10: white solid, mp 88-89 °C. IR (neat): 3339 (br), 1743 (s), 1490 (s), 804 (m), 743 (s) cm-1. 1H NMR (500 MHz, CDCl3): δ = 7.46 (m, 2 H), 7.41 (s, 1 H), 7.36 (d, J = 7.3 Hz, 1 H), 4.89 (d, J = 4.6 Hz, 1 H), 3.90 (qd, J = 6.7, 13.4 Hz, 1 H), 1.25 (d, J = 6.5 Hz, 6 H). 13C NMR (125 MHz, CDCl3): δ = 153.05, 151.1, 131.6 [q, J(CF) = 32.7 Hz], 129.6, 125.1, 123.6 [q, J(CF) = 272.3 Hz], 121.79 [d, J(CF) = 3.6 Hz], 118.7 [dd, J(CF) = 7.3, 3.5 Hz], 43.5, 22.6. HRMS (EI): m/z [M]+ calcd for C11H12F3NO2: 247.0820; found: 247.0822.

26

Compound is commercially available.

31

Compound 21: recrystallization from hexane, white solid, mp 79-80 °C. IR (neat): 3053 (m), 2987 (w), 1600 (m), 1573 (w), 1456 (m), 1423 (m), 1326 (m), 1265 (s), 1245 (m), 1218 (s), 1160 (m), 1139 (m), 1083 (m), 1059 (m), 1020 (w), 968 (m), 895 (m), 826 (m), 810 (m), 740 (s) cm-1. 1H NMR (500 MHz, CDCl3): δ = 6.54 (d, J = 2.45 Hz, 1 H), 6.42 (d, J = 2.47 Hz, 1 H), 3.88 (s, 3 H), 3.82 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 161.8, 160.4, 151.4, 118.6 [q, J(CF) = 318.5 Hz], 99.8, 98.1, 71.4, 56.8, 55.8. HRMS (EI): m/z [M]+ calcd for C9H8F3IO5S: 411.9089; found: 411.9106.

32

Compound 23: viscous liquid. IR (neat): 2946 (w), 1590 (s), 1504 (s), 1461 (s), 1421 (m), 1301 (m), 1211 (m), 1133 (m), 1041 (m), 946 (m), 873 (m), 836 (m), 798 (m), 769 (m) cm-1. 1H NMR (360 MHz, CDCl3): δ = 7.23 (dd, J = 0.6, 1.8 Hz, 1 H), 6.77 (d, J = 1.3 Hz, 1 H), 3.84 (s, 3 H), 2.30 (s, 3 H). 13C NMR (125 MHz, CDCl3): δ = 151.1, 140.7, 138.1, 131.6, 122.5, 118.7 [q, J(CF) = 321.0 Hz], 89.5, 56.1, 20.9. HRMS (EI): m/z [M]+ calcd for C9H8F3IO4S: 395.9140; found: 395.9142.

34

Compound 25: recrystallization from hexane, white needles, mp 41-42 °C. IR (neat): 2925 (w), 1583 (s), 1469 (s), 1425 (s), 1375 (m), 1247 (m), 1213 (s), 1172 (m), 1137 (m), 1031 (m), 885 (m), 833 (m), 798 (m), 761 (m) cm-1. 1H NMR (500 MHz, CDCl3): δ = 8.10 (d, J = 2.2 Hz, 1 H), 7.60 (dd, J = 2.2, 8.6 Hz, 1 H), 7.53 (td, J = 1.8, 3.3 Hz, 1 H), 7.46 (td, J = 1.6, 15.0 Hz, 2 H), 7.46 (d, J = 1.6, 4.8 Hz, 1 H), 7.42 (td, J = 1.9, 4.8 Hz, 1 H), 7.38 (d, J = 8.6 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 149.5, 143.0, 139.1, 137.9, 129.1, 128.6, 128.5, 127.2, 122.0, 118.7 [q, J(CF) = 321.0 Hz], 89.4. HRMS (EI): m/z [M]+ calcd for C13H8F3IO3S: 427.9191; found: 427.9190.

35

Compound 26: liquid. IR (neat): 2960 (w), 1569 (s), 1461 (s), 1428 (s), 1371 (m), 1214 (m), 1174 (m), 1137 (m), 1101 (m), 1031 (m), 883 (m), 821 (m), 790 (m), 763 (m) cm-1. 1H NMR (500 MHz, CDCl3): δ = 7.90 (d, J = 2.5 Hz, 1 H), 7.40 (dd, J = 2.5, 8.8 Hz, 1 H), 7.25 (d, J = 8.9 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 148.9, 140.0, 134.6, 130.1, 122.6, 118.6 [q, J(CF) = 320.7 Hz], 89.6. HRMS (EI): m/z [M]+ calcd for C7H3ClF3IO3S: 385.8488; found: 385.8497.

36

Compound 27: liquid. IR (neat): 2985 (w), 1588 (s), 1474 (s), 1428 (s), 1250 (m), 1226 (m), 1139 (m), 1029 (m), 907 (m), 856 (m), 817 (m), 734 (m) cm-1. 1H NMR (500 MHz, CDCl3): δ = 7.61 (dd, J = 3.0, 7.3 Hz, 1 H), 7.29 (dd, J = 4.6, 9.1 Hz, 1 H), 7.14 (ddd, J = 3.0, 7.3, 9.1 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 160.8 [d, J(CF) = 254.0 Hz], 146.5 [d, J(CF) = 3.4 Hz], 127.5 [d, J(CF) = 25.6 Hz], 122.9 [d, J(CF) = 9.2 Hz], 118.7 [q, J(CF) = 320.6 Hz], 116.9 [d, J(CF) = 23.7 Hz], 89.4 [d, J(CF) = 8.8 Hz]. HRMS (EI): m/z [M]+ calcd for C7H3F4IO3S: 369.8772; found: 369.8778.

37

Compound 28: viscous liquid. IR (neat): 3154 (w), 1577 (m), 1457 (s), 1428 (s), 1281 (w), 1248 (m), 1220 (s), 1139 (s), 1096 (w), 1035 (w), 975 (s), 906 (s), 835 (m), 787 (m), 725 (s) cm-1. 1H NMR (500 MHz, CDCl3): δ = 7.43 (dt, J = 8.4, 6.1 Hz, 1 H), 7.16 (d, J = 8.4 Hz, 1 H), 7.11 (ddd, J = 8.3, 7.2, 1.2 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 163.0 [d, J(CF) = 252.6 Hz], 151.0 [d, J(CF) = 4.5 Hz], 130.7 [d, J(CF) = 9.0 Hz], 118.7 [q, J(CF) = 320.7 Hz], 117.7 [d, J(CF) = 2.8 Hz], 115.3 [d, J(CF) = 24.2 Hz], 79.2 [d, J(CF) = 29.5 Hz]. HRMS (EI): m/z [M]+ calcd for C7H3F4IO3S: 369.8784; found: 369.8783.

38

Compound 29: recrystallization from hexane, white needles, mp 37-38 °C. IR (neat): 3154 (w), 1606 (s), 1479 (s), 1430 (s), 1398 (m), 1323 (m), 1246 (m), 1221 (m), 1140 (m), 1181 (m), 1080 (m), 1023 (m), 906 (m), 829 (m), 808 (m), 735 (m) cm-1. 1H NMR (500 MHz, CDCl3): δ = 8.08 (d, J = 8.3 Hz, 1 H), 7.54 (d, J = 1.3 Hz, 1 H), 7.38 (dd, J = 8.3, 1.7 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 150.3, 141.6, 132.9 [q, J(CF) = 34.2 Hz], 126.1 [q, J(CF) = 3.5 Hz], 122.7 [q, J(CF) = 272.9 Hz], 119.1 [q, J(CF) = 3.6 Hz], 118.7 [q, J(CF) = 320.8 Hz], 94.1 [d, J(CF) = 0.9 Hz]. HRMS (EI): m/z [M - Tf]+ calcd for C7H3F3IO: 286.9181; found: 286.9175.

39

Compound 30: recrystallization from hexane, white needles, mp 39-40 °C. IR (neat): 2985 (w), 1430 (s), 1399 (m), 1323 (m), 1265 (m), 1246 (m), 1221 (m), 1180 (m), 1139 (m), 1080 (m), 1023 (m), 906 (m), 808 (m), 729 (m) cm-1. 1H NMR (500 MHz, CDCl3): δ = 8.08 (dd, J = 8.3, 0.5, Hz, 1 H), 7.54 (d, J = 1.4 Hz, 1 H), 7.38 (dd, J = 8.3, 1.3 Hz, 1 H). 13C NMR (125 MHz, CDCl3): δ = 150.3, 141.6, 132.8 [q, J(CF) = 34.2 Hz], 126.1 [q, J(CF) = 3.5 Hz], 122.7 [q, J(CF) = 272.7 Hz], 119.1 [q, J(CF) = 3.3 Hz], 118.6 [q, J(CF) = 320.7 Hz], 94.1. HRMS (EI): m/z [M - Tf]+ calcd for C7H3F3IO: 286.9181; found: 286.9192.