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DOI: 10.1055/s-0029-1219184
Iron-Catalyzed Direct Arylation of Aryl Pyridines and Imines Using Oxygen as an Oxidant
Publication History
Publication Date:
08 January 2010 (online)
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Abstract
An iron-catalyzed ortho C-H bond arylation reaction of an aryl pyridine or imine with an arylzinc reagent, which previously required the use of a rather expensive organodichloride as an oxidant, can now be achieved under oxygen atmosphere. By slowly introducing oxygen into the reaction, oxidative cross-coupling of the two reactants took place smoothly to give a biaryl product in moderate to good yield.
Key words
iron - C-H bond activation - cross-coupling - biaryls
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References and Notes
Present address: N. Yoshikai, Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore.
10The reaction needs 1 equiv of the zinc reagent for removal of the ortho hydrogen atom, 1 equiv for arylation, and small amount for generation of the active catalyst.9a
12The yields of biphenyl and phenol were typically in the range of 50-150% and 120-180%, respectively (based on the substrate).
16
A Typical Procedure
for Arylation of 2-Arylpyridine
An oven-dried Schlenk
tube was charged with ZnCl2˙TMEDA (505 mg, 2.0
mmol), 2,2′-bipyridine (9.3 mg, 60 µmol), and
2-arylpyridine (0.40 mmol) and cooled in an ice bath, followed by
addition of a THF solution of PhMgBr (1.0 M, 4.0 mL, 4.0 mmol).
After stirring for 1 h, a THF solution of FeCl3 (0.10
M, 0.60 mL, 60 µmol) was added to the mixture. Then oxygen
gas (10 mL, 0.45 mmol) was allowed to diffuse into the reaction
by attaching a gastight syringe fitted with a 20G needle (38 mm).
The reaction mixture was stirred for 36 h with gradual warming to
r.t., while every 12 h the gastight syringe was filled with fresh
O2 gas. The reaction was quenched by the addition of sat.
aq solution of Rochelle salt and extracted with EtOAc (3 × 5
mL). The organic solution was dried over Na2SO4 and concentrated
under reduced pressure. The crude product was purified by silica
gel chromatography to afford the arylation product.
A Typical Procedure for Arylation of Aryl Imine
The
reaction was carried out by the same procedure as above except for
the use of 4,4′-di-tert-butyl-2,2′-bipyridine
(16.1 mg, 60 µmol) instead of 2,2′-bipyridine.
The reaction was quenched by the addition of 3 M HCl aq (5 mL),
and the resulting mixture was stirred for 3 h at r.t. Further workup and
purification was carried out in a similar manner as above to obtain
the biaryl ketone product.
2-(4,5-Dimethoxybiphenyl-2-yl)pyridine
(2f)
Mp 97.4-98.2 ˚C. IR (powder):
3062, 3035, 3008, 2964, 2933, 2838, 1688, 1598, 1580, 1520, 1478,
1453, 1441, 1385, 1351, 1320, 1273, 1260, 1243, 1179, 1113, 1081, 1038,
1011, 973, 924, 888, 818, 791, 770, 743, 702 cm-¹. ¹H NMR
(500 MHz, CDCl3): δ = 8.54 (d, J = 5.8 Hz,
1 H), 7.24-7.21 (m, 2 H), 7.15-7.12 (m, 3 H),
7.09-7.07 (m, 2 H), 6.98-6.95 (m, 1 H), 6.82 (s,
1 H), 6.71 (d, J = 8.0
Hz, 1 H), 3.89 (s, 3 H), 3.85 (s, 3 H). ¹³C
NMR (125 MHz, CDCl3): δ = 158.7, 149.2,
148.8, 148.3, 141.2, 135.0, 133.3, 131.8, 129.7 (2 C), 128.0 (2
C), 126.5, 125.5, 120.9, 113.3, 113.1, 55.9, 55.8. HRMS (APCI): m/z calcd for C19H18NO2
+ [M + H]+:
292.13375; found: 292.13331.
2-(5,6-Dimethoxybiphenyl-2-yl)pyridine
(2g)
Mp 102.0-103.2 ˚C. IR (powder):
3058, 3000, 2962, 2931, 2834, 1582, 1563, 1519, 1485, 1428, 1407,
1279, 1256, 1219, 1162, 1117, 1108, 1009, 797, 776, 747, 718, 700,
685 cm-¹. ¹H NMR
(500 MHz, CDCl3): δ = 8.56 (d, J = 5.2 Hz, 1
H), 7.46 (d, J = 8.6
Hz, 1 H), 7.30-7.21 (m, 4 H), 7.18-7.16 (m, 2
H), 7.05 (d, J = 8.6
Hz, 1 H), 7.02-6.95 (m, 1 H), 6.69 (d, J = 8.0
Hz, 1 H), 3.95 (s, 3 H), 3.50 (s, 3 H). ¹³C NMR
(125 MHz, CDCl3): δ = 158.6, 153.1,
149.1, 146.4, 136.5, 135.3, 134,9, 133.6, 130.8 (2 C), 127.6 (2
C), 126.7, 126.0, 125.2, 120.8, 111,6, 60.4, 55.9. HRMS (APCI):
m/z calcd for C19H18NO2
+ [M + H]+:
292.13375; found: 292.13395.
1-(4′-Fluorobiphenyl-2-yl)ethanone
(2l)
IR (neat): 3062, 3043, 3025, 3002, 2971, 1684,
1607, 1598, 1513, 1474, 1443, 1355, 1287, 1268, 1221, 1160, 1117, 1096,
1077, 1042, 1017, 1007, 955, 837, 820, 802, 750, 720, 671 cm-¹. ¹H
NMR (500 MHz, CDCl3): δ = 7.56-7.54
(m, 1 H), 7.52-7.49 (m, 1 H), 7.43-7.40 (m, 1
H), 7.36-7.34 (m, 1 H), 7.32-7.29 (m, 2 H), 7.14-7.09
(m, 2 H), 2.05 (s, 3 H). ¹³C NMR (125
MHz, CDCl3): δ = 204.4, 162.6 (d, ¹
J
C-F = 246.8 Hz),
140.7, 139.3, 136.7 (d, 4
J
C-F = 3.6
Hz), 130.7, 130.4 (d, ³
J
C-F = 8.4
Hz, 2 C), 130.3, 127.9, 127.5, 115.6 (d, ²
J
C-F = 21.5
Hz, 2 C), 30.3. HRMS (APCI): m/z calcd
for C14H12FO+ [M + H]+:
215.0872; found: 215.0875.