Trifluoromethylation of Aryl Iodides
FULL PAPER
into their benzotrifluoride derivates in DMSO at 608C. The
reaction is applicable to both electron-deficient and -rich
arenes, as well as heteroarenes, and tolerates a broad range
of functional groups. In all cases, the yields are comparable
or in excess of those achieved with Ruppertꢀs reagent. The
latter is a low-boiling liquid, whereas the new trifluorome-
thylation reagents have advantageous properties that simpli-
fy their use, being nonvolatile, air-stable salts. Moreover,
analysis calcd (%) for C10
3 3
H21BF KO (296): C 34.90, H 6.15; found: C
3
4.81, H 6.28.
Potassium (trifluoromethyl)tris(tetrahydrofurfuryl alcohol)borate (3d):
An oven-dried 100 mL crimp-top vial was charged with potassium fluo-
ride (2.37 g, 40.9 mmol), then evacuated and refilled with nitrogen three
times. Anhydrous THF (60 mL), tris(tetrahydrofurfuryl alcohol) borate
(13.9 g, 43.9 mmol), and (trifluoromethyl)trimethylsilane (Ruppertꢀs re-
agent; 6.83 g, 48.0 mmol, 7.6 mL) were added and the suspension was
stirred until a colorless solution was obtained (approx. 24–48 h). The mix-
ture was concentrated to dryness, anhydrous pentane (100 mL) was
added and the resulting colorless solid was filtered, washed with anhy-
they are able to transfer the CF groups under mild and neu-
3
tral conditions with liberation of trimethyl borate without
the need for basic additives.
drous pentane (2ꢄ50 mL) and dried in vacuo to yield 3d as a colorless
1
solid (7.47 g, 43%). M.p. 142–1448C; H NMR (400 MHz, D
2
O): d=3.96
(
m, 3H; CH
CH ), 1.80–1.98 (m, 9H; CH
101 MHz, D O): d=79.5, 68.0, 63.6, 26.8, 25.2 ppm; F NMR (376 MHz,
2
), 3.69–3.81 (m, 6H; CH
2
), 3.56 (m, 3H; CH
2
), 3.46 (m, 3H;
2
); C NMR
The properties of the CF3 borate salts depend on the
alkoxy substituents, and it is thus likely that by varying
these side chains, even more effective trifluoromethylating
reagents can be developed in the near future. The new re-
agents may also open up new opportunities for other tri-
fluoromethylation reactions including Buchwaldꢀs recently
discovered Pd-catalyzed trifluoromethylation of aryl chlor-
ides.
1
3
2
2
), 1.50–1.61 ppm (m, 3H; CH
1
9
(
D
(
2
11
2
O): d=À74.87 ppm (q); B NMR (128 MHz, D
2
O): d=À1.16 ppm
À1
m); IR (KBr): n˜ =2881 (m), 1653 (w), 1559 (w), 1080 (s), 898 cm (m);
elemental analysis calcd (%) for C16
found: C 45.86, H 6.58.
3 6
H27BF KO (422): C 45.51, H 6.44;
N-Methyl-4-iodoacetanilide (4v): A modified literature procedure was
[
30]
followed.
A 100 mL round-bottomed Schlenk flask with a rubber
septum was charged with sodium hydride suspension in mineral oil
(
(
60%, 480 mg, 12 mmol), which was washed with anhydrous pentane
20 mL), and evacuated and refilled with nitrogen three times. A solution
of 4-iodoacetanilide (2.61 g, 10.0 mmol) in anhydrous THF (50 mL) was
added and the mixture was stirred for 15 min. Methyl iodide (1.70 g,
Experimental Section
1
2.0 mmol, 747 mL) was added at 58C and stirring was continued for 1 h
at RT. The reaction mixture was diluted with CHCl (50 mL) and washed
with 1n HCl (100 mL). The washing was re-extracted with CHCl (2ꢄ
0 mL) and the combined organic layers were washed with brine
50 mL), dried over MgSO , filtered, and concentrated to yield 4v as a
colorless solid (2.81 g, 83%). M.p. 144–1468C; H NMR (400 MHz,
CDCl ): d=7.70 (m, 2H; CH), 6.92 (m, 2H; CH), 3.20 (s, 3H; CH ),
): d=170.0 (CO),
); MS (Ion trap, EI):
General: All reactions were performed under a nitrogen atmosphere in
oven-dried glassware using Teflon-coated stirrer bars. Solvents were puri-
fied by standard procedures and deoxygenated by passing argon through
the liquid for 30 min prior to use. Unless otherwise noted, all other mate-
rials were obtained from commercial suppliers and used without further
3
3
2
(
4
1
À3
purification. Potassium fluoride was dried in vacuo (<3ꢄ10 mbar) at
3
3
2
008C overnight and stored under nitrogen. All reactions were moni-
13
1
1
.83 ppm (s, 3H; CH
3
); C NMR (101 MHz, CDCl
), 22.3 ppm (CH
3
tored by GC analysis using n-tetradecane as an internal standard. Re-
sponse factors of the products with regard to n-tetradecane were ob-
tained experimentally by analyzing known quantities of the substances.
Column chromatography was performed by using a Combi Flash Com-
panion-Chromatography-System (Isco-Systems) and RediSep packed col-
umns (12 g). Gas chromatographic analyses were performed with a HP-5
capillary column (Phenyl Methyl Siloxane; 30 m ꢄ 320ꢄ0.25 and a time
program: 2 min at 608C followed by 308Cmin ramp to 3008C and then
3
3 6 2
CDCl , [D ]DMSO, or D O as solvent, with H, C, F, and B resonan-
ces at 600/400, 151/101, 128, and 376 MHz, respectively. Mass spectrome-
try was performed with a GC-MS Varian Saturn 2100 T instrument; the
ionization was achieved by EI AGC. CHN elemental analysis was per-
formed with a Hanau Elemental Analyzer vario Micro cube. Infrared
spectra were recorded with a Perkin–Elmer Fourier transform spectrome-
ter; liquids were analyzed as a thin film between NaCl plates and solids
as KBr pellets. Frequencies are reported in wavenumbers (cm ). Syn-
thetic procedures and characterization data for known compounds are
given in the Supporting Information.
44.1, 138.7, 128.9, 92.6, 36.9 (CH
3
3
+
m/z (%): 275 (36) [M] , 233 (100), 105 (18), 77 (21), 63 (17), 56 (68); IR
(
5
KBr): n˜ =2927 (w), 1644 (s, C=O), 1482 (s) 1379 (m), 1006 (m), 823 (m),
À1
52 cm (m); elemental analysis calcd (%) for C
9
H
10INO (275): C 39.30,
H 3.66, N 5.09; found: C 39.53, H 3.66, N 5.07.
p-(1,3-Dioxolan-2-yl)iodobenzene (4x): A modified procedure was fol-
[
31]
À1
lowed.
A 100 mL round-bottomed flask was fitted with a dropping
funnel filled with 3 ꢃ molecular sieves and a condenser. The reaction
vessel was charged with 4-iodobenzaldehyde (1.56 g, 6.45 mmol), p-tolue-
nesulfonic acid (207 mg, 1.20 mmol), ethylene glycol (16.7 g, 269 mol,
min at this temperature. NMR spectra were recorded at 258C by using
1
13
19
11
1
3
5 mL), and CHCl (50 mL). The mixture was heated to reflux for 16 h,
then cooled to RT, and washed with water (50 mL) and saturated aque-
ous sodium bicarbonate (50 mL). The combined washings were re-ex-
tracted with CHCl
washed with brine (100 mL), dried over MgSO
ed to yield 4x as a colorless solid (1.74 g, 98%). M.p. 48–508C; H NMR
3
(2ꢄ20 mL), and the combined organic layers were
4
, filtered, and concentrat-
1
À1
3
3
(
400 MHz, CDCl
3
): d=7.73 (d, J ACHTUTGNRENNUG( H,H)=8.3 Hz, 2H; CH), 7.23 (d, J-
AHCTUNGTREG(NNNU H,H)=8.3 Hz, 2H; CH), 5.76 (s, 1H; CH), 3.99–4.14 ppm (m, 4H,
1
3
CH
(
(
2
); C NMR (101 MHz, CDCl
3
): d=137.6, 137.3, 128.2, 103.0, 95.0
+
Potassium (trifluoromethyl)tris(2-methoxyethyl)borate (3c): An oven-
dried 100 mL crimp-top vial was charged with potassium fluoride (2.63 g,
CH), 65.2 ppm (CH ); MS (Ion trap, EI): m/z (%): 275 (100) [M] , 231
29), 204 (22), 105 (43), 91 (15), 73 (41), 51 (16); IR (KBr): n˜ =2874 (w),
589 (w), 1420 (m), 1076 (s), 1005 (s), 817 cm (s); elemental analysis
2
4
5.2 mmol), then evacuated and refilled with nitrogen three times. Anhy-
drous THF (60 mL), tris(2-methoxyethyl) borate (11.8 g, 49.5 mmol), and
trifluoromethyl)trimethylsilane (Ruppertꢀs reagent; 7.68 g, 54.0 mmol,
.6 mL) were added and the suspension was stirred until a colorless solu-
À1
1
9 9 2
calcd (%) for C H IO (276): C 39.16, H 3.29; found: C 39.23, H 3.40.
(
8
General procedure for Cu-catalyzed trifluoromethylations: An oven-
dried crimp-top vial equipped with a septum cap and a stirrer bar was
charged with copper(I) iodide (152 mg, 0.80 mmol), 1,10-phenanthroline
(144 mg, 0.80 mmol), and 3a (2.54 g, 12.0 mmol). The reaction vessel was
closed, then evacuated and refilled with nitrogen three times. Anhydrous
deoxygenated DMSO (8.0 mL) and aryl iodide (4.00 mmol) were added
by using a syringe. Solid aryl iodides were weighed directly in the reac-
tion vessel. The resulting orange–brown suspension was stirred for 16 h
at 608C. After cooling to ambient temperature, the orange solution was
tion was obtained (approx. 24–48 h). The mixture was concentrated to
dryness, anhydrous pentane (100 mL) was added and the resulting color-
less solid was filtered, washed with anhydrous pentane (2ꢄ50 mL) and
dried in vacuo to yield 3c as a colorless solid (10.5 g, 67%). M.p. 106–
1
1
088C; H NMR (400 MHz, D
2
O): d=3.62–3.71 (m, 6H; CH
2
), 3.48–3.56
); C NMR (101 MHz, D O): d=
O): d=
O): d=À1.12 ppm (m); IR
KBr): n˜ =2895 (m), 1559 (w), 1090 (s), 872 (m), 682 cm (s); elemental
1
3
(
m, 6H; CH
2
), 3.33 ppm (s, 9H; CH
3
2
1
9
7
3.1 (CH
2
), 60.1 (CH ), 58.0 ppm (CH ); F NMR (376 MHz, D
2
3
2
1
1
À74.73 ppm (m); B NMR (128 MHz, D
2
À1
(
2
diluted with Et O (20 mL) and washed with 1n HCl (50 mL). Acidic
Chem. Eur. J. 2011, 17, 2689 – 2697
ꢂ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2695