Organometallics
Article
2-Methylbenzoyl Fluoride (4).5b The general procedure was
applied using benzoyl fluoride (1; 62.7 mg, 0.5 mmol) and 2-
methylbenzoic anhydride (381.4 mg, 1.5 mmol). Column chromatog-
raphy (hexane/EtOAc 97/3, v/v) afforded 4 (48.2 mg, 69%) as a
Subsequently, we carried out an equimolar reaction between
1 and 2 (identical with entry 12 in Table 1), and the
concentrations of the starting materials and products were
monitored as a function of time by GC analysis.15 The
symmetrical acid anhydride (PhCO)2O (16), which originates
from two molecules of 1, was observed as the major side
product together with the formation of the desired acyl
fluoride 3. On the other hand, only trace amounts of the
unsymmetrical acid anhydride 17, which would be formed
through a simple acyl exchange between 1 and 2, were
detected during the reaction. These results indicate that further
acyl exchange occurs after the formation of 3 and that the
present reaction is the result of fast and complex equilibria
(Figure 2).
1
colorless oil: H NMR (500.2 MHz, CDCl3) δ 2.66 (s, 3 H, CH3),
7.32−7.35 (m, 2 H, ArH), 7.54−7.57 (m, 1 H, ArH), 8.00 (d, J = 7.0
Hz, 1 H, ArH); 13C NMR (125.8 MHz, CDCl3) δ 21.9, 123.5 (d, JC−F
= 55.4 Hz), 126.3, 132.2 (d, JC−F = 3.8 Hz), 132.5 (d, JC−F = 2.5 Hz),
134.6, 143.6 (d, JC−F = 7.5 Hz), 156.7 (d, JC−F = 344.7 Hz); 19F NMR
(470.6 MHz, CDCl3) δ 29.3; LRMS (EI) m/z (% relative intensity)
138 (M+, 100), 119 (11), 118 (44), 110 (11), 109 (32), 91 (61), 90
(35), 89 (13), 66 (10), 64 (13).
3-Methylbenzoyl Fluoride (5).5b The general procedure was
applied using benzoyl fluoride (1; 62.7 mg, 0.5 mmol) and 3-
methylbenzoic anhydride (381.8 mg, 1.5 mmol). Column chromatog-
raphy (hexane/EtOAc 97/3, v/v) afforded 5 (48.7 mg, 70%) as a
1
colorless oil: H NMR (500.2 MHz, CDCl3) δ 2.44 (s, 3 H, CH3),
CONCLUSIONS
7.41 (t, J = 8.0 Hz, 1 H, ArH), 7.51 (d, J = 8.0 Hz, 1 H, ArH), 7.85−
■
7.86 (m, 2 H, ArH); 13C NMR (125.8 MHz, CDCl3) δ 21.2, 124.8 (d,
We have developed a novel synthetic route to complex acyl
fluorides via the palladium-catalyzed acyl exchange between
acid anhydrides and benzoyl fluoride (1). This study
represents the first practical protocol to use commercially
available 1 as a fluorination reagent for the catalytic generation
of a variety of value-added acyl fluorides. The reversible acyl
C−F bond cleavage/formation by the palladium catalyst is the
key process in this transformation. This reversibility could
potentially be applied to several other catalytic fluorination
reactions using acyl fluorides as F− equivalents.
J
C−F = 60.4 Hz), 128.6 (d, JC−F = 3.8 Hz), 128.9, 131.9 (d, JC−F = 3.8
Hz), 136.1, 139.1, 157.6 (d, JC−F = 343.7 Hz); 19F NMR (470.6 MHz,
CDCl3) δ 18.4; LRMS (EI) m/z (% relative intensity) 138 (M+, 86),
137 (15), 110 (11), 109 (38), 91 (100), 83 (10), 65 (12), 63 (13).
4-Methylbenzoyl Fluoride (6).5b The general procedure was
applied using benzoyl fluoride (1; 63.6 mg, 0.5 mmol) and 4-
methylbenzoic anhydride (382.7 mg, 1.5 mmol). Column chromatog-
raphy (hexane/EtOAc 97/3, v/v) afforded 6 (40.6 mg, 57%) as a
1
colorless oil: H NMR (500.2 MHz, CDCl3) δ 2.46 (s, 3 H, CH3),
7.32 (d, J = 8.0 Hz, 2 H, ArH), 7.94 (d, J = 8.0 Hz, 2 H, ArH); 13C
NMR (125.8 MHz, CDCl3) δ 21.9, 122.1 (d, JC−F = 61.5 Hz), 129.8,
131.5 (d, JC−F = 3.8 Hz), 146.6, 157.5 (d, JC−F = 342.7 Hz); 19F NMR
(470.6 MHz, CDCl3) δ 17.5; LRMS (EI) m/z (% relative intensity)
138 (M+, 77), 119 (13), 110 (21), 109 (36), 91 (100), 89 (10), 83
(10), 66 (14), 64 (15).
EXPERIMENTAL SECTION
■
General Information. 1H, 13C, and 19F NMR spectra were
recorded on a 500 MHz spectrometer. Chemical shifts in the 1H and
13C NMR spectra are reported in ppm relative to residual solvent
4-Methoxybenzoyl Fluoride (7).5b The general procedure was
applied using benzoyl fluoride (1; 63.1 mg, 0.5 mmol) and 4-
methoxybenzoic anhydride (428.0 mg, 1.5 mmol). Column
chromatography (hexane) afforded 7 (82.9 mg, 80%) as a colorless
oil: 1H NMR (500.2 MHz, CDCl3) δ 3.90 (s, 3 H, OCH3), 6.98 (d, J
= 8.0 Hz, 2 H, ArH), 7.99 (d, J = 8.0 Hz, 2 H, ArH); 13C NMR (125.8
MHz, CDCl3) δ 55.6, 114.4, 116.8 (d, JC−F = 62.9 Hz), 133.7 (d, JC−F
= 3.8 Hz), 157.3 (d, JC−F = 339.7 Hz), 165.2; 19F NMR (470.6 MHz,
CDCl3) δ 16.1; LRMS (EI) m/z (% relative intensity) 154 (M+, 100),
135 (21), 126 (46), 111 (28), 96 (14), 83 (31), 75 (10), 63 (13), 57
(12).
peaks such as those of chloroform (1H, δ 7.26; 13C, δ 77.0) or the
internal reference tetramethylsilane (1H and 13C, δ 0.00). Chemical
shifts in the 19F NMR spectra are reported in ppm relative to the
external reference CF3C6H5 (δ −62.6). GC analyses were performed
using a DB-5 capillary column (30 m × 0.25 mm; film thickness 0.25
μm). Toluene was distilled from Na/benzophenone ketyl prior to use.
Benzoyl fluoride (1), Pd(dba)2, and DPPP were purchased from
common commercial suppliers and used as received. Acid anhydrides
were synthesized from the corresponding carboxylic acids using
thionyl chloride, pyridine, and DMF in DCM. Unless otherwise
noted, all reactions were performed under an atmosphere of N2.
General Procedure for the Palladium-Catalyzed Acyl-
Exchange Reactions. A carboxylic anhydride (1.5 mmol) was
placed in a screw-capped vial with a stir bar. Then, in a N2-filled
glovebox, Pd(dba)2 (14.4 mg, 0.025 mmol), DPPB (16.0 mg, 0.038
mmol), and toluene (0.5 mL) were added. The vial was then sealed
and removed from the glovebox, before benzoyl fluoride (1; 0.5
mmol) was added under ambient conditions. The mixture was then
stirred for 24 h at 80 °C. Thereafter, the mixture was analyzed by 19F
NMR spectroscopy using 1,3-(CF3)2C6H4 (δ −62.79) as the internal
standard. The crude reaction mixture was evaporated to dryness
under reduced pressure, and the residue thus obtained was purified by
column chromatography on silica gel to afford the corresponding acyl
fluoride.
4-(Methylthio)benzoyl Fluoride (8).5c The general procedure was
applied using benzoyl fluoride (1; 62.3 mg, 0.5 mmol) and 4-
(methylthio)benzoic anhydride (477.7 mg, 1.5 mmol). Column
chromatography (hexane/EtOAc 97/3, v/v) afforded 8 (46.3 mg,
1
54%) as a yellow solid: mp 37.6−40.2 °C; H NMR (500.2 MHz,
CDCl3) δ 2.54 (s, 3 H, SCH3), 7.30 (d, J = 8.5 Hz, 2 H, ArH), 7.91
(d, J = 8.5 Hz, 2 H, ArH); 13C NMR (125.8 MHz, CDCl3) δ 14.5,
120.3 (d, JC−F = 61.6 Hz), 125.0, 131.5 (d, JC−F = 5.0 Hz), 149.4,
157.3 (d, JC−F = 342.2 Hz); 19F NMR (470.6 MHz, CDCl3) δ 16.7;
LRMS (EI) m/z (% relative intensity) 170 (M+, 100), 142 (53), 127
(22), 109 (14), 83 (11).
4-Phenylbenzoyl Fluoride (11).5c The general procedure was
applied using benzoyl fluoride (1; 64.6 mg, 0.5 mmol) and 4-
phenylbenzoic anhydride (567.9 mg, 1.5 mmol), except that the
reaction was performed at 120 °C. Column chromatography (hexane)
afforded 11 (54.4 mg, 52%) as a colorless solid: mp 89.0−91.0 °C; 1H
NMR (500.2 MHz, CDCl3) δ 7.44 (t, J = 6.5 Hz, 1 H, ArH), 7.50 (t, J
= 6.5 Hz, 2 H, ArH), 7.64 (d, J = 6.5 Hz, 2 H, ArH), 7.74 (d, J = 8.5
Hz, 2 H, ArH), 8.12 (d, J = 8.5 Hz, 2 H, ArH); 13C NMR (125.8
MHz, CDCl3) δ 123.4 (d, JC−F = 60.4 Hz), 127.4, 127.7, 128.8, 129.1,
3,5-Dimethylbenzoyl Fluoride (3).5b The general procedure was
applied using benzoyl fluoride (1; 62.7 mg, 0.5 mmol) and 3,5-
dimethylbenzoic anhydride (422.6 mg, 1.5 mmol). Column
chromatography (hexane) afforded 3 (50.3 mg, 65%) as a colorless
oil: 1H NMR (500.2 MHz, CDCl3) δ 2.38 (s, 6 H, CH3), 7.32 (s, 1 H,
ArH), 7.65 (s, 2 H, ArH); 13C NMR (125.8 MHz, CDCl3) δ 21.0,
124.7 (d, JC−F = 59.1 Hz), 129.1 (d, JC−F = 2.5 Hz), 137.0, 138.9,
157.7 (d, JC−F = 344.7 Hz); 19F NMR (470.6 MHz, CDCl3) δ 18.5;
LRMS (EI) m/z (% relative intensity) 152 (M+, 92), 137 (45), 132
(10), 109 (28), 105 (12), 104 (13), 103 (14), 77 (19), 51 (11).
132.0 (d, JC−F = 3.8 Hz), 139.2, 148.1, 157.4 (d, JC−F = 342.2 Hz); 19
F
NMR (470.6 MHz, CDCl3) δ 18.3; LRMS (EI) m/z (% relative
intensity) 201 (14), 200 (M+, 100), 172 (42), 171 (16), 152 (20), 86
(10), 85 (11), 76 (17).
D
Organometallics XXXX, XXX, XXX−XXX