M. Villien et al. / Tetrahedron 63 (2007) 11299–11306
11303
oligonucleotides using 50% aqueous acetonitrile as eluent. 1H
and 13C NMR spectra were recorded on Bruker Spectrospin
spectrometer.
was stirred in a CH2Cl2/TFA solution (10 mL, 50:50, v/v) at
room temperature for 2 h. The solvent was then removed un-
der vacuum and the product 5a was obtained in quantitative
1
yield and was used without further purification. H NMR
4.2. Syntheses of ligands
(300 MHz, DMSO-d6): d 4.08 (s, 2H, CH2NH), 7.85 (dd,
J¼8.0 Hz, J¼4.0 Hz, 1H, H–Ar), 7.91 (dd, J¼8.0 Hz,
J¼4.0 Hz, 1H, H–Ar), 8.23 (s, 1H, H–Ar), 8.34 (br s, 2H,
NH2), 8.60 (dd, J¼8.0 Hz, J¼1.5 Hz, 1H, H–Ar), 8.75 (dd,
J¼8.0 Hz, J¼1.5 Hz, 1H, H–Ar), 9.09 (dd, J¼4.0 Hz,
J¼1.5 Hz, 1H, H–Ar), 9.17 (dd, J¼4.0 Hz, J¼1.5 Hz, 1H,
H–Ar), 10.80 (br s, 1H, NH). 13C NMR (75 MHz, DMSO-
d6) d 41.0 (CH2), 119.8 (CH), 123.5 (CH), 124.2 (CH),
124.6 (Cq), 128.2 (Cq), 131.3 (Cq), 132.7 (CH), 137.8
(CH), 141.7 (Cq), 144.0 (Cq), 148.7 (CH), 150.0 (CH),
166.4 (Cq). MS (EI) m/z 252 (M)+.
The 5-amino-1,10-phenanthroline 3a has been prepared
from commercially available 5-nitro-1,10-phenanthroline
by reduction with Pd/C/N2H4.21 The preparation of
9-amino-1,4,5,8-tetraazaphenanthrene 3b has been reported
previously.22 The N-hydroxy succinimide activated ester 6
was prepared from N-Boc-O-(carboxymethyl)-hydroxyl-
amine by using standard protocol.
4.2.1. 5-(N-(tert-Butoxycarbonyl)glycinamido)-1,10-phe-
nanthroline (4a). A solution of commercial N-(tert-butoxy-
carbonyl)glycine (2.7 g, 15 mmol) and DCC (1.6 g,
7.8 mmol) in acetonitrile (30 mL) was stirred at room tem-
perature for 1 h and filtered to remove the DCU precipitate.
The so-formed anhydride was used without further purifica-
tion and added to a solution of 5-amino-1,10-phenanthroline
3a (304 mg, 1.55 mmol) in acetonitrile (30 mL). The solution
was stirred at room temperature for 20 h under argon and the
solvent was removed under reduced pressure. The ligand 4a
(445 mg, 81%) was obtained as a paleyellow powderafter pu-
rification by silica gel column chromatography using 2–6%
4.2.4. 9-(Glycinamido)-1,4,5,8-tetraazaphenanthrene
(5b). The derivative 5b was obtained from protected deriva-
tive 4b (164 mg, 0.46 mmol) by using the same protocol as
discussed for 5a and was obtained in quantitative yield and
used without further purification. 1H NMR (300 MHz,
DMSO-d6): d 4.19 (s, 2H, CH2NH), 8.30 (br s, 2H, NH2),
9.11 (m, 3H, H–Ar), 9.24 (d, J¼2.0 Hz, 1H, H–Ar), 9.34
(d, J¼2.0 Hz, 1H, H–Ar), 11.11 (br s, 1H, NH). 13C NMR
(75 MHz, DMSO-d6): d 41.7 (CH2), 116.5 (CH), 135.2
(Cq), 136.1 (Cq), 137.2 (Cq), 140.2 (Cq) 144.2 (CH+Cq),
145.0 (CH), 146.3 (CH), 147.2 (CH), 168.9 (Cq). MS (EI)
m/z 254 (M)+.
1
MeOH in CH2Cl2 as eluent. H NMR (300 MHz, DMSO-
d6): d 1.43 (s, 9H, t-Bu), 3.94 (d, J¼5.5 Hz, 2H, CH2NH),
7.26 (t, J¼5.5 Hz, NH), 7.74 (dd, J¼8.0 Hz, J¼4.0 Hz, 1H,
H–Ar), 7.80 (dd, J¼8.0 Hz, J¼4.0 Hz, 1H, H–Ar), 8.14 (s,
1H, H–Ar), 8.46 (dd, J¼8.0 Hz, J¼1.5 Hz, 1H, H–Ar), 8.64
(dd, J¼8.0 Hz, J¼1.5 Hz, 1H, H–Ar), 9.04 (dd, J¼4.0 Hz,
J¼1.5 Hz, 1H, H–Ar), 9.12 (dd, J¼4.0 Hz, J¼1.5 Hz, 1H,
H–Ar), 10.28 (s, 1H, NH). 13C NMR (75 MHz, DMSO-d6):
d 28.1 (CH3), 43.8 (CH2), 78.1 (Cq), 120.1 (CH), 122.7
(CH), 123.5 (CH), 124.7 (Cq), 128.0 (Cq), 131.7 (Cq),
131.8 (CH), 135.7 (CH), 143.7 (Cq), 145.7 (Cq), 149.3
(CH), 149.8 (CH), 156.0 (Cq), 169.6 (Cq). Anal. Calcd for
C19H20N4O3$1H2O: C, 61.61; H, 5.80; N, 14.79. Found: C,
62.06; H, 5.80; N, 14.79. HRMS (ESI) m/z 353.1603
(M+H+ C19H21N4O3 requires 353.1608).
4.2.5. Protected phenanthroline ligand (7a). To a suspen-
sion of the deprotected phenanthroline derivative 5a
(73 mg, 0.29 mmol) in anhydrous DMF (15 mL), the acti-
vated ester of N-Boc-O-(carboxymethyl)-hydroxylamine 6
(112 mg, 0.39 mmol) and DIEA (0.167 mL, 0.94 mmol)
were added. The mixture was stirred at room temperature
for 1 h under argon. The solvent was then removed under re-
duced pressure and the product was purified by silica gel
column chromatography (eluent 5–8% MeOH in CH2Cl2).
The protected ligand 7a (68 mg, 55%) was obtained as
1
a white solid. H NMR (300 MHz, DMSO-d6): d 1.40 (s,
9H, t-Bu), 4.18 (d, J¼5.5 Hz, 2H, CH2NH), 4.30 (s, 2H,
CH2–O), 7.75 (dd, J¼8.0 Hz, J¼4.0 Hz, 1H, H–Ar), 7.82
(dd, J¼8.0 Hz, J¼4.0 Hz, 1H, H–Ar), 8.14 (s, 1H, H–Ar),
8.43 (t, J¼5.5 Hz, 1H, NH), 8.46 (dd, J¼8.0 Hz,
J¼1.5 Hz, 1H, H–Ar), 8.62 (dd, J¼8.0 Hz, J¼1.5 Hz, 1H,
H–Ar), 9.05 (dd, J¼4.0 Hz, J¼1.5 Hz, 1H, H–Ar), 9.13
(dd, J¼4.0 Hz, J¼1.5 Hz, 1H, H–Ar), 10.22 (br s, 1H,
NH), 10.31 (br s, 1H, O–NH). 13C NMR (75 MHz,
DMSO-d6): d 27.9 (CH3), 42.3 (CH2), 74.7 (CH2), 80.5
(Cq), 120.5 (CH), 122.8 (CH), 123.5 (CH), 124.7 (Cq),
127.9 (Cq), 131.4 (Cq), 131.7 (CH), 135.8 (CH), 143.9
(Cq), 145.8 (Cq), 149.4 (CH), 149.8 (CH), 156.6 (Cq),
168.6 (Cq). Anal. Calcd for C21H23N5O5$0.5 H2O: C,
58.06; H, 5.57; N, 16.12. Found: C, 58.10; H, 5.98; N,
16.08. HRMS (ESI) m/z 426.1764 (M+H+ C21H24N5O5 re-
quires 426.1772).
4.2.2. 9-(N-(tert-Butoxycarbonyl)glycinamido)-1,4,5,8-
tetraazaphenanthrene (4b). The ligand 4b was prepared
from 9-amino-1,4,5,8-tetraazaphenanthrene 3b (150 mg,
0.76 mmol) by using the same protocol as mentioned above
for 4a. Purification by silica gel column chromatography (el-
uent 0–2% MeOH in CH2Cl2) gave the ligand 4b (164 mg,
1
61%) as pale yellow powder. H NMR (300 MHz, DMSO-
d6): d 1.46 (s, 9H, t-Bu), 3.97 (d, J¼6.0 Hz, 2H, CH2NH),
7.61 (t, J¼6.0 Hz, 1H, NH), 9.07 (m, 2H, H–Ar), 9.10 (d,
J¼2.0 Hz, 1H, H–Ar), 9.20 (d, J¼2.0 Hz, 1H, H–Ar), 9.33
(d, J¼2.0 Hz, 1H, H–Ar), 10.53 (s, 1H, NH). 13C NMR
(75 MHz, DMSO-d6): d 28.1 (CH3), 44.9 (CH2), 78.70
(Cq), 114.9 (CH), 134.9 (Cq), 135.7 (Cq), 137.0 (Cq),
140.2 (Cq), 143.8 (CH), 144.4 (Cq), 145.0 (CH), 146.4
(CH), 147.1 (CH), 156.0 (Cq), 169.7 (Cq). Anal. Calcd for
C17H18N6O3: C, 57.62; H, 5.12; N, 23.72. Found: C,
57.78; H, 5.26; N, 23.30. HRMS (ESI) m/z 377.1327
(M+Na+ C17H18N6O3Na requires 377.1333).
4.2.6. Protected tetraazaphenanthrene ligand (7b). The
protected ligand 7b was obtained in 76% yield (149 mg,
0.35 mmol) from tetraazaphenanthrene derivative 5b
(117 mg, 0.46 mmol) after purification by silica gel column
chromatography (eluent 0–5% MeOH in CH2Cl2) using the
4.2.3. 5-(Glycinamido)-1,10-phenanthroline (5a). The
protected phenanthroline derivative 4a (102 mg, 0.29 mmol)
1
same protocol as above. H NMR (300 MHz, DMSO-d6):