Molecules 2018, 23, 3292
6 of 8
◦
at 60 C for 24 h. The crude product was purified by column chromatography on silica gel
1
(
hexane/EtOAc = 3/1) to give product 2d (51.1 mg, 36% yield) as a colorless oil. H-NMR (CDCl ,):
.95 (2H, d, J = 7.6), 7.54 (2H, d, J = 7.6), 4.23–4.10 (4H, m), 3.83 (3H, s), 1.30 (6H, t, J = 6.8); F-NMR
3
19
7
(
CDCl ): 54.6 (d, J = 115.8 Hz, 2F).
3
Diethyl difluoro(naphthalen-1-yl)methylphosphonate (3e). Following a general procedure, CuI
95.2 mg, 0.50 mmol), CsF (91.1 mg, 0.60 mmol), 1-iodonaphthalene (1e, 127.0 mg, 0.50 mmol),
(
[
(trimethylsilyl)difluoromethyl]phosphonate (
2
, 156.2 mg, 0.60 mmol) were used in THF (1.0 mL)
◦
at 60 C for 24 h. The crude product was purified by column chromatography on silica gel
1
(hexane/EtOAc = 3/1) to give product 2e (77.1 mg, 49% yield) as a colorless oil. H-NMR (CDCl ):
3
8
4
.44 (1H, d, J = 8.4), 7.97 (1H, d, J = 8.4), 7.88 (1H, d, J = 8.4), 7.81 (1H, d, J = 7.2), 7.60–7.48 (3H, m),
.24–4.00 (4H, m), 1.27 (6H, t, J = 7.2); 19F-NMR (CDCl ): 53.2 (d, J = 112.8 Hz, 2F).
3
Diethyl difluoro(pyridin-2-yl)methylphosphonate (3f). Following a general procedure, CuI
(95.2 mg, 0.50 mmol), CsF (91.1 mg, 0.60 mmol), 2-iodopyridine (1f, 102.5 mg, 0.50 mmol),
[
(trimethylsilyl)difluoromethyl]phosphonate (
2
, 157.6 mg, 0.61 mmol) were used in THF (1.0 mL)
◦
at 60 C for 24 h. The crude product was purified by column chromatography on silica gel
1
(
hexane/EtOAc = 2/1) to give product 2e (67.0 mg, 51% yield) as a pale yellow oil. H-NMR (CDCl ):
3
8
(
.72 (1H, d, J = 4.4), 7.85 (1H, t, J = 8.0), 7.71 (1H, d, J = 8.0), 7.44–7.41 (1H, m), 4.24–4.37 (4H, m), 1.36
6H, t, J = 7.0); 19F-NMR (CDCl ): 51.1 (d, J = 109.8 Hz, 2F).
3
Diethyl difluoro(quinolin-2-yl)methylphosphonate (3g).
To a mixture of CuI (9.5 mg,
127.5 mg, 0.50 mmol),
2, 151.0 mg, 0.58 mmol), and THF (1.0 mL) was
0
.05 mmol), CsF (91.1 mg, 0.60 mmol), 2-iodoquinoline (1g
,
[(trimethylsilyl)difluoromethyl]-phosphonate (
added [(trimethylsilyl)-difluoromethyl]phosphonate (
The reaction mixture was stirred at 60 C in an atmosphere of nitrogen for 24 h and quenched
with water. The aqueous layer was extracted with ethyl acetate. Then, the combined organic phase
2
, 156.2 mg, 0.60 mmol) at room temperature.
◦
was washed with water, dried over anhydrous Na SO . The crude product was purified by column
2
4
chromatography on silica gel (hexane/EtOAc = 2/1) to give 3g (110.0 mg, 69% yield) as a pale yellow oil.
1
H-NMR (CDCl ,): 8.32 (1H, d, J = 8.4), 8.19 (1H, d, J = 8.4), 7.89 (1H, d, J = 8.0), 7.81–7.77 (1H, m), 7.64
3
19
(
(
1H, t, J = 8.0), 4.39–4.32 (4H, m), 1.38 (6H, t, J = 7.2); F-NMR (CDCl ): 51.1 (d, J = 103.8 Hz, 2F).
3
Diethyl (3,4-dichlorophenyl)difluoromethylphosphonate (3h). Following a general procedure, CuI
91.4 mg, 0.48 mmol), CsF (89.3 mg, 0.59 mmol), 3,4-dichloro-1-iodobenzene (1h, 131.7 mg, 0.48 mmol),
[
(trimethylsilyl)difluoromethyl]phosphonate (
2
, 153.1 mg, 0.58 mmol) were used in THF (1.0 mL)
◦
at 60 C for 24 h. The crude product was purified by column chromatography on silica gel
1
(hexane/EtOAc = 3/1) to give product 3h (71.2 mg, 44% yield) as a pale yellow oil. H-NMR (CDCl ):
3
19
7
.70 (1H, s), 7.55 (1H, d, J = 8.3), 7.47 (1H, d, J = 8.3), 4.33–4.14 (4H, m), 1.35 (6H, t, J = 7.0); F-NMR
(
CDCl ): 52.8 (2F, d, J = 113.4 Hz).
3
Diethyl (4-bromophenyl)difluoromethylphosphonate (3i). Following a general procedure, CuI
95.2 mg, 0.50 mmol), CsF (91.1 mg, 0.60 mmol), 4-bromo-1-iodobenzene (1i, 142.0 mg, 0.50 mmol),
(
[
(trimethylsilyl)difluoromethyl]phosphonate (
2
, 156.2 mg, 0.60 mmol) were used in THF (1.0 mL)
◦
at 60 C for 24 h. The crude product was purified by column chromatography on silica gel
1
(hexane/EtOAc = 3/1) to give product 3i (100.0 mg, 58% yield) as a pale yellow oil. H-NMR (CDCl ):
3
7
.60 (2H, d, J = 8.4), 7.49 (2H, d, J = 8.4), 4.10–4.30 (4H, m), 1.33 (6H, t, J = 7.1); 19F-NMR (CDCl ): 52.8
3
(2F, d, J = 113.4 Hz).
4
. Conclusions
In summary, we have developed a convenient route to aryl(difluoromethyl)phosphonates
from aryl iodides. Using a simple combination of the coupling partners (iodoarenes and
Me Si-CF PO(OEt) ), the cross-coupling proceeded smoothly under mild reaction conditions.
3
2
2
The present transformations employing CuI are synthetically useful. In some cases, a small amount