A R T I C L E S
Friedle et al.
3.44 (s, 2H), 1.27-1.22 (t, J ) 7.2 Hz, 3H). LRMS (ESI): calcd
for C16H18BrN3O2Na [M + Na]+, 386; found, 386.
In the present article we report the synthesis of the syn
N-donor ligand H2BPG2DEV (Chart 2) and three of its deriva-
tives containing oxo-bridged diiron(III) cores. Two tripodal
N,N′-bis(2-pyridylmethyl)-3-aminoacetate (BPG-) centers bridged
by diethynylveratrole converge to incorporate diiron units and
provide carboxylate groups that more accurately represent the
aspartate and glutamate residues of non-heme diiron enzymes
than earlier constructs. We describe how this dinucleating ligand
stabilizes the oxo-bridged diiron(III) cores and considerably
influences the chemical and physical properties of a peroxodi-
iron(III) intermediate generated by addition of hydrogen peroxide.
Et2BPG2DEV ·2HCl (5 ·2HCl, Diethyl 2,2′-(5,5′-(4,5-Dimethoxy-
1,2-phenylene)bis(ethyne-2,1-diyl)bis(pyridine-5,2-diyl))bis(meth-
ylene)bis((pyridin-2-ylmethyl)azanediyl)diacetate Hydrochloride).
4,5-Diethynylveratrole (0.474 g, 2.55 mmol), 4 (1.82 g, 5.03 mmol),
[Pd(PPh3)4] (0.250 g, 0.216 mmol), Et3N (3.6 mL, 26 mmol), and
THF (24 mL) were combined in a sealed tube under an inert
atmosphere and stirred for 2.5 d at 60 °C. After the reaction mixture
was cooled to room temperature, it was combined with EtOAc (50
mL), washed three times with a solution of Na2CO3 (aq), dried
over Na2SO4, filtered, and evaporated to dryness. The crude material
was purified by column chromatography (alumina; EtOAc/hexanes,
1
Experimental Section
1:1-1:0) to give 5 as a thick yellow oil. H NMR spectroscopy
confirmed complete conversion to the desired product, but a
phosphine oxide impurity was observed. To purify the material,
the hydrochloride salt of the amine, 5·2HCl, was synthesized. The
oil was dissolved in ca. 100 mL of EtOAc, and ca. 4 mL of a
solution of HCl in Et2O (2 M) was added dropwise with stirring
until no further precipitation occurred. The yellow solid was filtered
off and dried in vacuum. Yield: 1.20 g (57%). 1H NMR (300 MHz,
CD3OD): δ ) 8.92 (m, 2H), 8.89 (m, 2H), 8.54 (dt, J ) 1.5, 7.8
Hz, 2H), 8.37 (dd, J ) 2.1, 9.0 Hz, 2H), 8.07 (d, J ) 7.8 Hz, 2H),
8.00-7.96 (m, 2H), 7.90 (d, J ) 8.4 Hz, 2H), 7.25 (s, 2H), 4.58
(s, 4H), 4.56 (s, 4H), 4.18 (q, J ) 7.2 Hz, 4H), 3.92 (s, 6H), 3.74
(s, 4H), 1.25 (t, J ) 7.2 Hz, 6H). 13C NMR (125 MHz, CD3OD):
δ ) 171.27, 154.21, 153.90, 151.40, 147.44, 146.96, 145.77, 142.35,
127.61, 127.31, 126.77, 122.78, 117.88, 115.47, 94.90, 86.30, 61.68,
56.97, 56.48, 56.24, 54.90, 13.87. HRMS (ESI): calcd for [M +
H]+, 753.3397; found, 753.3397. IR (KBr, cm-1): 2979 (m), 2914
(m), 2611 (m), 2214 (m, νC≡C), 1731 (s), 1614 (m), 1593 (m), 1511
(s), 1464 (m), 1371 (m), 1251 (s), 1215 (s), 1155 (m), 1086 (m),
1024 (m), 987 (m), 858 (w), 772 (w). Mp: 103-105 °C.
Materials and Methods. Reagents were purchased from com-
mercial sources and used as received. Acetonitrile (CH3CN),
dichloromethane (CH2Cl2), and tetrahydrofuran (THF) were satu-
rated with nitrogen and purified by passing though activated alumina
columns under argon. Triethylamine (Et3N) was distilled from CaH2.
The compounds (5-bromopyridin-2-yl)methanol (2b),32 [(pyridin-
2-ylmethyl)amino]acetic acid ethyl ester (3),33 4,5-diethynylvera-
trole (DEV),31 and (Et4N)2[Fe2(µ-O)Cl6]34,35 were prepared using
methods described in the literature. The compound 2,6-diisoprop-
oxybenzoic acid (HO2CAriPrO) was synthesized by using a modified
literature procedure.36
Caution! The perchlorate salts used in this study are potentially
explosiVe and should be handled with care!
NMR spectra were recorded on a Varian 300 spectrometer in
the Massachusetts Institute of Technology Department of Chemistry
Instrument Facility (MIT DCIF). All spectra were recorded at
ambient probe temperature, 293 K. IR spectra were taken on a
Thermo Nicolet Avatar 360 spectrometer with OMNIC software.
Mass spectra were recorded in electrospray ionization mode. ESI-
MS data were obtained with an Agilent 1100 series LC/MSD mass
spectrometer. UV-vis experiments were performed on a Cary 50
spectrophotometer.
H2BPG2DEV (5a, 2,2′-(5,5′-(4,5-Dimethoxy-1,2-phenylene)bis-
(ethyne-2,1-diyl)bis(pyridine-5,2-diyl))bis(methylene)bis((pyridin-
2-ylmethyl)azanediyl)diacetic Acid. An aqueous solution of 5·2HCl
(0.55 g, 0.67 mmol) and KOH (1.4 g, 25 mmol) were combined to
yield a total volume of 100 mL. The resulting suspension was heated
to 60 °C under a nitrogen atmosphere for ca. 4 h. After cooling to
room temperature, the reaction mixture was acidified with dilute
HCl to pH 5, and the product was extracted with CH2Cl2. The
organic phase was dried over Na2SO4, filtered, and reduced to
[(5-Bromopyridin-2-ylmethyl)pyridin-2-ylmethylamino]acetic Acid
Ethyl Ester (4). A solution of (5-bromopyridin-2-yl)methanol (2b)
(4.69 g, 24.9 mmol) and Et3N (4.53 mL, 32.4 mmol) in THF (95
mL) was cooled to 0 °C and treated dropwise with methanesulfonyl
chloride (MsCl; 2.32 mL, 29.9 mmol). The mixture was warmed
to room temperature, stirred for 2 h, and then combined with
aqueous NH4Cl (200 mL). The aqueous phase was extracted with
CH2Cl2 (3 × 200 mL), and the organic layers were dried (Na2SO4),
filtered, and concentrated to afford a solid (6.78 g, quant) that was
used without further purification. This purple solid, K2CO3 (4.12
mg, 29.9 mmol), and [(pyridin-2-ylmethyl)amino]acetic acid ethyl
ester (3) (5.80 g, 29.9 mmol) were stirred overnight in CH3CN
(100 mL). During this period the color changed from purple-red to
orange. The reaction mixture was combined with CH2Cl2 (300 mL),
and the organics were washed with aqueous Na2CO3 (3 × 100 mL).
The organic layer was dried (Na2SO4), filtered, and evaporated to
dryness. The crude product was purified by column chromatography
(alumina; EtOAc/hexanes, 1:3) to give 4 as a yellow oil, which
was identical to the compound synthesized previously as judged
by 1H NMR spectroscopy and ESI-MS.28 Yield: 7.92 g (87%). 1H
NMR (300 MHz, CDCl3): δ ) 8.56-8.50 (m, 2H), 7.67-7.61 (dt,
J ) 1.8, 7.5 Hz, 1H), 7.29 (d, J ) 8.1 Hz, 1H), 7.17-7.12 (m,
2H), 4.19-4.11 (q, J ) 7.2 Hz, 2H), 3.96 (s, 2H), 3.94 (s, 2H),
1
dryness to yield a yellow-brown solid. Yield: 0.42 g (91%). H
NMR (300 MHz, CDCl3): δ ) 13.11 (s, 2H), 8.68 (m, 2H), 8.58
(m, 2H), 7.73 (m, 4H), 7.35 (m, 4H), 7.24 (m, 2H), 7.03 (s, 2H),
4.13 (s, 4H), 4.07 (s, 4H), 3.94 (s, 6H), 3.57 (s, 4H). 13C NMR
(125 MHz, DMSO-d6): δ ) 173.44, 160.29, 160.05, 151.76, 150.64,
149.93, 139.86, 137.83, 123.93, 123.65, 123.40, 118.94, 118.40,
115.49, 92.16, 90.19, 60.32, 60.22, 57.00, 55.46. HRMS (ESI):
calcd for [M + H]+, 697.2770; found, 697.2770. IR (KBr, cm-1):
3054 (w), 3002 (w), 2912 (w), 2832 (w), 2206 (w, νC≡C), 1714
(m), 1637 (w), 1593 (m), 1551 (w), 1511 (s), 1437 (m), 1401 (m),
1359 (m), 1248 (s), 1215 (s), 1149 (m), 1119 (m), 1085 (m), 1024
(m), 993 (m), 858 (w), 761 (m), 722 (m), 695 (m), 649 (w), 621
(w), 541 (m). Mp: 60-62 °C.
[Fe2(µ-O)(H2O)2(BPG2DEV)](ClO4)2 (6). To a solution (2 mL;
CH3CN/H2O, 10:1) of Fe(ClO4)3 ·9H2O (77 mg, 150 µmol) was
added a suspension of 5a (50 mg, 72 µmol) in the same solvent
mixture (2 mL). The color instantly changed to deep red, and the
resulting solution was stirred for ca. 5 min. After filtration, the
solution was subjected to vapor diffusion of Et2O to yield crystalline
red plates that were analyzed by X-ray crystallography. The yield
of crystalline material was highly dependent on the H2O content
of the solution. Yield: 60 mg (78%). X-ray diffraction quality
crystals were grown from vapor diffusion of Et2O into a solution
of 6 in CH3OH and H2O. LRMS (ESI): calcd for [M - H]+, 857.1;
found, 875.2. IR (KBr, cm-1): 3430 (m), 3073(w), 2921 (w), 2854
(w), 2210 (w, νC≡C), 1608 (s), 1590 (s), 1550 (m), 1512 (s), 1492
(m), 1462 (w), 1446 (m), 1402 (w), 1367 (m), 1348 (m), 1301 (w),
(32) Wang, X.; Rabbat, P.; O’Shea, P.; Tillyer, R.; Grabowski, E. J. J.;
Reider, P. J. Tetrahedron Lett. 2000, 41, 4335–4338.
(33) Policar, C.; Lambert, F.; Cesario, M.; Morgenstern-Badarau, I. Eur.
J. Inorg. Chem. 1999, 2201–2207.
(34) Armstrong, W. H.; Lippard, S. J. Inorg. Chem. 1985, 24, 981–982.
(35) Dunbar, K. R.; Longridge, J. J.; Rawson, J. M.; Sun, J.-S.; Hagen,
K. S.; Do, B. Inorg. Synth. 2002, 33, 103–107.
(36) Gumanov, L. L.; Shteinman, A. A.; Nordlander, E.; Koldobskii, G. I.
Russ. J. Org. Chem. 2002, 38, 606–608.
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14510 J. AM. CHEM. SOC. VOL. 131, NO. 40, 2009