phenylpyridine (1.69 g, 10 mmol) and NBS (2.14 g, 12 mmol)
in 50 mL of carbon tetrachloride, 0.024 g of benzoyl peroxide
was added. The mixture was refluxed for 3 h and then cooled
overnight. The succinimide precipitate was filtered off and the
filtrate was rotary evaporated to dryness. The residue was
purified by column chromatography on silica gel eluting with
hexane and ethyl acetate to give 5-(bromomethyl)-2-phenylpyri-
dine (1.32 g, 53% yield). To a mixture of 5-(bromomethyl)-2-
phenylpyridine (1.17 g, 4.70 mmol), cis,cis-1,3,5-cyclohexane-
triol dihydrate (0.24 g, 1.43 mmol) and 60% sodium
hydride (1.7 g, 42.5 mmol) under argon, DMF (10 mL)
was added using a syringe through a rubber septum. The
mixture was stirred at room temperature for 24 h and then
poured into ice water. The organic phase was separated by
extracting three times with dichloromethane. The solvents were
removed in vacuo and the residue was purified by column
chromatography on silica gel eluting with hexane and ethyl
acetate to afford the desired tripodal ligand 1a as a pale yellow
solid (0.67 g, 74% yield).
septum. The mixture was stirred at room temperature for 24 h
and then poured into ice water. The organic phase was separated
by extracting three times with dichloromethane. The solvents
were removed in vacuo and the residue was purified by column
chromatography on silica gel eluting with hexane and ethyl
acetate to afford the desired tripodal ligand 1b as a pale yellow
solid (0.25 g, 61% yield).
1b: IR (KBr) 3042, 2954, 2869, 1600, 1568, 1513, 1479,
1
1354, 1229, 1082 cm−1; H NMR (400 MHz, CD2Cl2) δ 8.61
(dd, 3H, J = 2.2, 0.7 Hz), 8.05–8.00 (m, 6H), 7.76 (dd, 3H, J =
8.2, 2.2 Hz), 7.71 (dd, 3H, J = 8.2, 0.7 Hz), 7.19–7.13 (m, 6H),
4.62 (s, 6H), 3.41 (tt, 3H, J = 11.4, 4.1 Hz), 2.54 (dt, 3H, J =
11.4, 4.1 Hz), 1.37 (dt, 3H, J = 11.4, 11.4 Hz); 13C NMR
1
(100 MHz, CD2Cl2) 163.9 (d, JF–C = 248.1 Hz), 155.9, 149.3,
3
136.6, 135.8, 133.0, 129.0 (d, JF–C = 8.4 Hz), 120.0, 115.9 (d,
2JF–C = 22.1 Hz), 73.3, 68.0, 38.6 ppm; HRMS (FAB) m/z calcd
for C42H36N3O3F3 (M+ + H), 688.2787; found, 688.2780.
1a: IR (KBr) 3034, 2940, 2860, 1600, 1563, 1475, 1446,
Synthesis of tripodal ligand 1c
1
1350, 1076 cm−1; H NMR (400 MHz, CD2Cl2) δ 8.63 (s, 3H),
8.03–8.00 (m, 6H), 7.76–7.75 (m, 6H), 7.49–7.45 (m, 6H),
7.43–7.39 (m, 3H), 4.63 (s, 6H), 3.42 (tt, 3H, J = 11.4, 4.0 Hz),
2.55 (dt, 3H, J = 11.4, 4.0 Hz), 1.38 (dt, 3H, J = 11.4, 11.4 Hz);
13C NMR (100 MHz, CD2Cl2) 156.9, 149.3, 139.5, 136.5,
133.0, 129.3, 129.0, 127.1, 120.3, 73.3, 68.0, 38.6 ppm; HRMS
(FAB) m/z calcd for C42H39N3O3 (M+ + H), 634.3070; found,
634.3058.
Hydrogen chloride was bubbled into a suspension of cis,cis-
1,3,5-cyclohexanetricarboxylic acid (1.0 g, 4.6 mmol) in 20 mL
of dry 1-propanol for 2 h. The suspension was heated under
reflux for 1 h and then cooled to room temperature. Volatiles
were removed under reduced pressure and the residue was
treated with ice water. The oily product was extracted with ether.
After being dried over anhydrous MgSO4, followed by filtration,
the filtrate was concentrated to remove volatiles, affording tripro-
pyl cis,cis-1,3,5-cyclohexanetricarboxylate quantitatively. A sol-
ution of tripropyl cis,cis-1,3,5-cyclohexanetricarboxylate (1.5 g,
4.5 mmol) in dry THF (20 mL) was added dropwise to a suspen-
sion of LiAlH4 (1.0 g) in dry THF (10 mL). The mixture was
refluxed for 24 h and cooled to 0 °C, the salts were decomposed
with water and ethanol. After filtration followed by rotary evap-
oration, cis,cis-1,3,5-cyclohexanetrimethanol was obtained
(0.7 g, 89% yield). Triphenylphosphine (1.9 g, 7.2 mmol) and
cis,cis-1,3,5-cyclohexanetrimethanol (0.4 g, 2.3 mmol) were dis-
solved in dry DMF(10 mL). Bromine (1.9 g, 11.9 mmol) was
added dropwise to the stirred mixture below room temperature.
The reaction was stirred at ambient conditions for 24 h. Removal
of the DMF under reduced pressure gave an orange-red oil. The
purification by column chromatography led to isolation of
cis,cis-1,3,5-tris(bromomethyl)cyclohexane in 55% yield (0.46 g).
To a solution of 2-phenyl-5-lithiomethylpyridine in THF (3 mL),
which was generated from 2-phenyl-5-methylpyridine (0.51 g,
3.0 mmol), cis,cis-1,3,5-tris(bromomethyl)cyclohexane (0.36 g,
1.0 mmol) was added dropwise in THF (2 mL) at 0 °C. The
reaction was warmed to room temperature and stirred for 24 h.
Then, the mixture was poured into ice water and the product was
extracted with ether three times. The residue was purified by
column chromatography on silica gel eluting with hexane and
ethyl acetate to afford the desired tripodal ligand 1c as a pale
yellow solid (0.23 g, 25% yield).
Synthesis of tripodal ligand 1b
A 200 mL two-necked bottle with a magnetic stirrer was charged
with 2-chloro-5-methylpyridine (2.7 mL, 25 mmol), 4-fluoro-
phenyl boronic acid (4.2 g, 30 mmol) and Pd(PPh3)4 (0.86 g,
3 mol%) under argon. To the mixture, toluene (75 mL), ethanol
(10 mL) and potassium carbonate (2.0 M in water, 28 mL) were
added successively and the whole mixture was refluxed for 48 h.
Then, it was cooled to room temperature. The aqueous layer was
separated and extracted three times with dichloromethane. The
combined organic layer was dried over anhydrous Na2SO4,
filtered and evaporated to give a red oil which solidified upon
standing. The crude product was purified by column chromato-
graphy on silica gel eluting with hexane and ethyl acetate to give
2-(4-fluorophenyl)-5-methylpyridine. Repeated precipitation at
−78 °C provided pure 2-(4-fluorophenyl)-5-methylpyridine
(2.48 g, 53%). To a 100 mL round bottle with a magnetic stirrer
were added 2-(4-fluorophenyl)-5-methylpyridine (1.0 g,
5.3 mmol), NBS (1.14 g, 6.4 mmol), benzoyl peroxide (13 mg,
0.05 mmol) and carbon tetrachloride (20 mL). The mixture was
heated to reflux for 5 h, then it was cooled and the resulting
solid was filtered off. The filtrate was evaporated to give a pale
yellow solid, which was purified by column chromatography on
silica gel eluting with hexane and ethyl acetate to give 5-(bromo-
methyl)-2-(4-fluorophenyl)pyridine (0.91 g, 65%). To a mixture
of 5-(bromomethyl)-2-(4-fluorophenyl)pyridine (0.53 g,
2.0 mmol), cis,cis-1,3,5-cyclohexanetriol dihydrate (0.1 g,
0.6 mmol) and 60% sodium hydride (0.8 g, 20 mmol) under
argon, DMF (2 mL) was added using a syringe through a rubber
1c: IR (KBr) 3029, 2914, 2848, 1596, 1561, 1473, 1446,
1390, 1019 cm−1; 1H NMR (400 MHz, CD2Cl2) δ 8.52 (dd, 3H,
J = 2.4, 0.7 Hz), 8.01–7.98 (m, 6H), 7.68 (dd, 3H, J = 8.2,
0.7 Hz), 7.58 (dd, 3H, J = 8.2, 2.4 Hz), 7.47–7.43 (m, 6H),
7.40–7.36 (m, 3H), 2.72–2.68 (m, 6H), 1.91 (d, 3H, J = 12.1 Hz),
This journal is © The Royal Society of Chemistry 2012
Dalton Trans., 2012, 41, 9519–9525 | 9523