Palladium-catalyzed synthesis of mono- and diphosphorylated 1,10-phenanthrolines

Article abstract of DOI:10.1055/s-0032-1317517

A general protocol for the coupling of mono- and dihalo-1,10- phenanthrolines with diethyl phosphite is reported. This reaction proceeds smoothly in the presence of a Pd(OAc)₂/dppf catalytic system and triethylamine as a base. Georg Thieme Verlag KG · Stuttgart · New York.

Full text of DOI:10.1055/s-0032-1317517

PAPER
▌3805
paper
Palladium-Catalyzed Synthesis of Mono- and Diphosphorylated
1,10-Phenanthrolines
Phosphorylated 1,10-Phenanthrolines
Alexandre Mitrofanov,a,b Alla Bessmertnykh Lemeune,a Christine Stern,a Roger Guilard,*a Nataliya Gulyukina,b,c
Irina Beletskaya*b,c
a
Institut de Chimie Moléculaire de l’Université de Bourgogne (ICMUB) - UMR 6302 CNRS, 9 Av. Alain Savary, 21000 Dijon, France
Phone +33(3)80396117; E-mail: Roger.Guilard@u-bourgogne.fr
b
Department of Chemistry, Moscow State University, Leninskie Gory, GSP-1, 119991 Moscow, Russian Federation
c
Frumkin Institute of Physical Chemistry and Electrochemistry, Russian Academy of Sciences, Leninsky Pr. 31, 119991 Moscow,
Russian Federation
Fax +7(495)9393618; E-mail: beletska@org.chem.msu.ru
Received: 27.09.2012; Accepted after revision: 10.10.2012
um-catalyzed reaction of the corresponding bromides
Abstract: A general protocol for the coupling of mono- and dihalo-
with dialkyl phosphites may be difficult taking into ac-
1,10-phenanthrolines with diethyl phosphite is reported. This reac-
count the analogous reactions of 2,2′-bipyridine deriva-
tion proceeds smoothly in the presence of a Pd(OAc)2/dppf catalytic
system and triethylamine as a base.
tives.20,30 Indeed, 1,10-phenanthrolines and 2,2′-
bipyridines would compete with tertiary phosphines to co-
Key words: catalysis, cross-coupling, palladium, heterocycles,
ordinate the palladium center, rending the catalytic reac-
tion impractical. Here, we report a convenient protocol for
the palladium-catalyzed synthesis of diethoxyphosphoryl-
substituted 1,10-phenanthrolines from the corresponding
halides which are readily accessible by literature methods.
phosphorylation
The palladium-catalyzed reaction of aromatic or vinylic
halides with dialkyl phosphites, disclosed by Hirao and
co-workers in the 1980s, is widely used for the synthesis
of vinyl-, aryl- and heteroarylphosphonates.1–6 This reac-
tion is now recognized as a convenient method for the in-
troduction of a dialkoxyphosphoryl substituent in
versatile ligands for metal ions,7,8 organic building blocks
in materials chemistry,9–12 and biologically relevant com-
pounds such as peptide mimetics,13 porphyrins14 and nu-
cleosides.15–17 Prompted by rapidly expanding
applications, this reaction has been carefully studied. Nu-
merous practical protocols have been developed, and the
choice of the best experimental conditions for new sub-
strates is challenging. Indeed, the product yield depends
on the palladium source, ligand and base nature, the reac-
tion solvent and the temperature.13,15,18–21 In some cases,
application of metal salts of diethyl phosphite,3,22 potassi-
um acetate additives,23 biphasic systems24 or microwave
irradiation16,17 is needed for efficient coupling.
The reaction of 5-bromo-1,10-phenanthroline (1) with di-
ethyl phosphite was selected as the model reaction (Table
1).
Table 1 Palladium-Catalyzed Coupling of Bromide 1 with Diethyl
Phosphitea
Br
N
P(O)(OEt)2
Pd(OAc)2
ligand
+ HP(O)(OEt)2
Et3N
N
N
N
1
2
Entry
Pd(OAc)2
(mol%)
Ligand
(mol%)
Time
(h)
Yieldb,c
(%)
1
2
3
4
5
25
50
10
5
Ph3P (75)
Ph3P (150)
Ph3P (1000)
dppf (10)
dppf (20)
20
20
20
20
8
–
12
46d
80
79
In the context of our work on organic–inorganic hybrid
materials, we have faced the need for diethoxyphospho-
ryl-substituted 1,10-phenanthrolines. Indeed, the elabora-
tion of new materials using the corresponding
phosphonates as molecular precursors25–29 is of particular
interest for the development of new materials possessing
useful photophysical and catalytic properties. Surprising-
ly, dialkoxyphosphoryl-substituted 1,10-phenanthrolines
have not been previously described in the literature. Fur-
thermore, the introduction of a dialkoxyphosphoryl group
on the 1,10-phenanthroline backbone using the palladi-
10
a Reaction conditions: bromide 1 (1 equiv), HP(O)(OEt)2 (1.2 equiv),
Et3N (1.2 equiv), toluene, reflux under N2.
b Isolated yield.
c The reactions were monitored by 1H NMR spectroscopy. A complete
conversion of 1 was observed for entries 2–5. For entry 1, the ratio 2/1
was 1:4.
d Ammonium salt 3 (23%) was isolated as major byproduct.
Under Hirao’s conditions2 or using the Pd(OAc)2/Ph3P
catalytic system and triethylamine as a base in toluene at
reflux, the product yield was low and an increase in the
catalyst loading was inefficient in optimizing the yield
SYNTHESIS 2012, 44, 3805–3810
Advanced online publication: 05.11.2012
DOI: 10.1055/s-0032-1317517; Art ID: SS-2012-Z0765-OP
© Georg Thieme Verlag Stuttgart · New York
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

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A. Mitrofanov et al.
PAPER
(Table 1, entries 1 and 2). In accordance with the literature were needed for a complete conversion of the starting ha-
data on the reaction of bromo-2,2′-bipyridines with dieth- lides. The target diethyl phosphonate 9 was isolated in
yl phosphite,30 an increase in the ligand amount to 10 good 71% yield (Table 2, entry 4). The reaction of bro-
equivalents [ratio Ph3P/Pd(OAc)2 = 100:1] allowed the mide 5 was more complicated. The chemoselectivity and
target product to be obtained in 46% yield (Table 1, entry the product yield were significantly lower than those of
3). Under these conditions, a complete conversion of the halides 4 and 6 (Table 2, entry 2). The product yield was
bromide 1 was observed; however, more than three prod- increased when dioxane was used as a solvent (Table 2,
ucts were detected in the reaction mixture by 1H and 31
P
entry 3); however, even under these experimental condi-
NMR spectroscopy, the mono salt 3 being the major by- tions, the chemoselectivity of the reaction was quite low
product (Scheme 1). Compound 3, resulting from dealkyl- and only half of the starting bromide 5 reacted with dieth-
ation of the desired phosphonate 2 by triethylamine or yl phosphite to give the desired product.
triphenylphosphine, was isolated in 23% yield by column
Interestingly, reaction of the isomeric symmetric dihalo-
1,10-phenanthrolines 10–12 with diethyl phosphite under
these conditions is more rapid than the corresponding
monosubstituted halides 4–6 (Table 3). It appears that
both steps of the reaction proceed smoothly, the first being
accelerated by a higher concentration of diethyl phosphite
and the second by a higher reactivity of the monophos-
phorylated intermediate compounds. Indeed, intermediate
chromatography.31,32 It is worth noting that the amount of
the dealkylation product increased in the presence of a
large excess of triphenylphosphine. Such a result should
be due to the reaction of triphenylphosphine with diethyl
phosphonate 2 under these conditions, because of its high-
er nucleophilicity;33 however, the ethyl phosphonate 3
was obtained predominantly as the triethylammonium
salt, resulting from ion exchange with triethylammonium
monophosphonate derivatives were never observed in the
bromide formed during the catalytic reaction.
reaction mixtures (1H and 31P NMR monitoring). A priori,
an electron-withdrawing substituent on the 1,10-phenan-
P(O)(OEt)O– [R3XEt]+
P(O)(OEt)2
throline moiety enhances the rate of the coupling reac-
tion.34,35 Moreover, the reactivity of the different isomers
in the series of mono- and disubstituted halides is different
(bromide 4 is more reactive than dibromide 10, but chlo-
ride 6 reacts more slowly than dichloride 12), and 4,7-di-
bromo-1,10-phenanthroline (11) is more reactive than
bromide 5 and provides a better yield of the product.
R3X
N
N
N
N
2
3
R3X = Ph3P, Et3N
Scheme 1
Taking into account recent data on the positive effect of
potassium acetate additives on the cross-coupling of aryl
halides with diethyl phosphite in tetrahydrofuran,23 such
conditions were tested for the halo-1,10-phenanthrolines.
The reactions of the 3-bromo, 5-bromo and 4,7-dibromo
derivatives with diethyl phosphite were carried out using
10/20 mol% of Pd(OAc)2/dppf and triethylamine in tetra-
hydrofuran, with and without potassium acetate additives.
All studied cross-coupling reactions proceeded slowly in
refluxing tetrahydrofuran compared to the corresponding
coupling in toluene at reflux. For example, potassium ace-
tate did accelerate the reaction of 3-bromo-1,10-phenan-
throline (4) with diethyl phosphite in tetrahydrofuran;
however, the reaction was still slow and the reaction yield
was worse than that in toluene.
Considering the competition of phenanthroline 1 and tri-
phenylphosphine to coordinate the palladium center and
the difficulties related to the product purification from an
excess of triphenylphosphine, for further optimization we
employed bidentate ligands, which coordinate much
stronger to the palladium ion. 1,1′-Bis(diphenylphosphi-
no)ferrocene (dppf) is known to be efficient for the cata-
lytic phosphorylation of various aryl halides.15,32 Even
under these conditions, a quite high loading of the catalyt-
ic system Pd(OAc)2/dppf was needed to obtain the full
conversion of bromide 1. If 5/10 mol% of Pd(OAc)2/dppf
was used, the reaction was completed only in 20 hours and
the target product 2 was isolated in 80% yield (Table 1,
entry 4). When 10/20 mol% of Pd(OAc)2/dppf was em-
ployed, a full conversion and a similar yield of the isolated
product was obtained after 8 hours (Table 1, entry 5).
In conclusion, a general and structurally tolerant synthetic
procedure for the synthesis of diethyl phosphonate deriv-
atives of 1,10-phenanthroline was developed.
A
Then, these optimized conditions were used for the func-
tionalization of isomeric halo-1,10-phenanthrolines 4–6,
namely 3-bromo-, 4-bromo- and 2-chloro-1,10-phenan-
throline (Table 2).
Pd(OAc)2/dppf catalytic system is efficient for the cou-
pling of mono- and dihalo-1,10-phenanthrolines with di-
ethyl phosphite in the presence of triethylamine in toluene
at reflux. Currently, we are studying the coordination
properties of these ligands.
3-Bromo-1,10-phenanthroline (4) was the most reactive
compound and its full conversion was observed after 5
hours, even if the catalyst loading was quite low [5/10
mol% of Pd(OAc)2/dppf]; diethyl phosphonate 7 was iso-
lated in 81% yield (Table 2, entry 1). Less reactive bro-
mide 5 and chloride 6 were reacted with diethyl phosphite
employing 10/20 mol% of Pd(OAc)2/dppf and 20 hours
All chemicals except the halo-1,10-phenanthrolines were of com-
mercial quality (Aldrich, Acros) and used from freshly opened con-
tainers. 5-Bromo-1,10-phenanthroline (1),36 3-bromo-1,10-
phenanthroline (4),37 4-bromo-1,10-phenanthroline (5),38 2-chloro-
1,10-phenanthroline (6),39 3,8-dibromo-1,10-phenanthroline (10),37
Synthesis 2012, 44, 3805–3810
© Georg Thieme Verlag Stuttgart · New York

PAPER
Phosphorylated 1,10-Phenanthrolines
3807
Table 2 Palladium-Catalyzed Coupling of Halides 4–6 with Diethyl Phosphitea
Pd(OAc)2
Hal
dppf
Et3N
P(O)(OEt)2
+
HP(O)(OEt)2
N
N
N
N
4–6
7–9
Hal = Br (4, 5), Cl (6)
Entry
1
Halide
[Pd]/dppf (mol%)
5/10
Time (h)
Product
Yieldb,c (%)
P(O)(OEt)2
4
5
81
N
N
7
P(O)(OEt)2
2
5
5
10/20
10/20
20d
12
30
52
3e
N
N
8
4
6
10/20
20
71
N
N
(EtO)2(O)P
P(O)(OEt)2
9
a Reaction conditions: halide (1 equiv), HP(O)(OEt)2 (1.2 equiv), Et3N (1.2 equiv), Pd(OAc)2/dppf, toluene, reflux under N2.
b Isolated yield.
c A full conversion of the starting halide was observed, except for entry 2.
d The ratio 8/5 in the reaction mixture was 3:2, according to 1H NMR spectroscopy.
e Dioxane was used as the solvent.
Table 3 Palladium-Catalyzed Coupling of Dihalides 10–12 with Diethyl Phosphitea
Hal
Hal
HP(O)(OEt)2
(EtO)2(O)P
P(O)(OEt)2
Pd(OAc)2, dppf
Et3N
N
N
10–12
N
N
13–15
Hal = Br (10, 11), Cl (12)
Entry
1
Dihalide
Time (h)
Product
Yieldb,c (%)
P(O)(OEt)2
(EtO)2(O)P
10
11
5
70
N
N
13
P(O)(OEt)2
(EtO)2(O)P
2
3
20
71
80
N
N
N
N
14
12
3
P(O)(OEt)2
(EtO)2(O)P
15
a Reaction conditions: dihalide (1 equiv), HP(O)(OEt)2 (2.4 equiv), Et3N (2.4 equiv), Pd(OAc)2/dppf (10/20 mol%), toluene, reflux under N2.
b Isolated yield.
c Conversion of the starting dihalides was complete.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3805–3810

3808
A. Mitrofanov et al.
PAPER
4,7-dibromo-1,10-phenanthroline (11)40 and 2,9-dichloro-1,10-
phenanthroline (12)39 were prepared according to literature meth-
ods. Toluene was dried by distillation over sodium under N2. Pre-
parative column chromatography was performed with SDS silica
gel 60 ACC (Chromagel, particle size 70–200 μm). Analytical TLC
was carried out using silica gel 60 F254 plates (Merck). IR spectra
were recorded on a Bruker IFS 66v spectrophotometer. NMR spec-
tra were recorded with Bruker Avance 300 and 600 instruments; the
chemical shifts (δ) are reported in ppm and the coupling constants
are expressed in Hz. Mass spectra were obtained by ESI on an Or-
bitrap spectrometer. The measurements were undertaken at the
‘Pôle Chimie Moléculaire’, a technological platform for chemical
analysis and molecular synthesis (http://www.wpcm.fr) which re-
lies on the Institute of Molecular Chemistry of the University of
Burgundy and Welience®, a Burgundy University private subsid-
iary.
1H NMR (300 MHz, CDCl3): δ = 1.04 (t, 3JHH = 7.1 Hz, 3 H, CH3),
3
3
1.26 (t, JHH = 7.3 Hz, 9 H, CH3), 3.01 (q, JHH = 7.3 Hz, 6 H,
3
3
NCH2), 3.76 (m, 2 H, OCH2), 7.56 (dd, JHH = 8.1 Hz, JHH = 4.4
Hz, 2 H, H-3,8), 8.23 (dd, 3JHH = 8.1 Hz, 4JHH = 1.5 Hz, 1 H, H-7),
3
8.53 (d, JHP = 15.4 Hz, 1 H, H-6), 9.09 (m, 1 H, H-9), 9.14 (dd,
3JHH = 4.4 Hz, 4JHH = 1.5 Hz, 1 H, H-2), 9.29 (d, 3JHH = 8.1 Hz, 1 H,
H-4).
31P NMR (121 MHz, CDCl3): δ = 9.25.
Diethyl 1,10-Phenanthrolin-3-ylphosphonate (7)
Prepared from 3-bromo-1,10-phenanthroline (4; 518 mg, 2 mmol),
Pd(OAc)2 (22.4 mg, 0.1 mmol), dppf (111 mg, 0.2 mmol),
HP(O)(OEt)2 (308 μL, 2.4 mmol) and Et3N (320 μL, 2.4 mmol) in
toluene. The reaction mixture was chromatographed (CH2Cl2–
MeOH, 97.5:2.5) to give phosphonate 7 as a yellow oil; yield: 512
mg (81%).
IR (KBr): 2980, 1618, 1502, 1423, 1237, 1050, 1012, 970 cm–1.
Diethyl 1,10-Phenanthrolin-5-ylphosphonates; General Proce-
dure
1H NMR (300 MHz, CDCl3): δ = 1.35 (t, 3JHH = 7.1 Hz, 6 H), 4.20
(m, 4 H), 7.68 (dd, 3JHH = 8.1 Hz, 3JHH = 4.3 Hz, 1 H, H-8), 7.84 (d,
3JHH = 8.9 Hz, 1 H, H-6), 7.87 (d, 3JHH = 8.9 Hz, 1 H, H-5), 8.27 (dd,
A 25-mL round-bottom flask equipped with a reflux condenser and
a magnetic stirrer bar was charged with the bromo-1,10-phenan-
throline, Pd(OAc)2 and the ligand. The reaction vessel was evacuat-
ed and purged with N2 three times. Subsequently, solvent,
HP(O)(OEt)2 and Et3N were added via syringe. The reaction mix-
ture was stirred at reflux until complete conversion of the bromide,
according to 1H NMR spectroscopy. The reaction mixture was
cooled and then concentrated under reduced pressure. The residue
was taken up in CH2Cl2 (5–10 mL) and the product was isolated by
column chromatography on silica gel.
3
3JHH = 8.1 Hz, 4JHH = 1.7 Hz, 1 H, H-7), 8.76 (dd, JHP = 14.6
3
Hz, 4JHH = 2.0 Hz, 1 H, H-4), 9.21 (dd, JHH = 4.3 Hz, 4JHH = 1.7
Hz, 1 H, H-9), 9.41 (dd, 3JHP = 4.8 Hz, 4JHH = 2.0 Hz, 1 H, H-2).
13C NMR (75 MHz, CDCl3): δ = 16.55 (d, J = 6.1 Hz, 2 C, CH3),
63.93 (d, J = 5.5 Hz, 2 C, CH2), 124.09 (C-8), 124.23 (d, J = 188.2
Hz, C-3), 126.62 (C-5), 127.55 (d, J = 13.0 Hz, C-4a), 127.85 (C-
6), 129.90 (C-6a), 136.30 (C-7), 141.38 (d, J = 8.9 Hz, C-4), 145.94
(C-10a), 148.13 (C-10b), 150.98 (C-9), 151.21 (d, J = 12.1 Hz, C-
2).
Diethyl 1,10-Phenanthrolin-5-ylphosphonate (2)
31P NMR (121 MHz, CDCl3): δ = 15.68.
HRMS: m/z [M + Na]+ calcd for C16H17O3N2NaP: 339.0869; found:
Method A (Table 1, Entry 5)
Prepared from 5-bromo-1,10-phenanthroline (1; 518 mg, 2 mmol),
Pd(OAc)2 (44.9 mg, 0.2 mmol), dppf (222 mg, 0.4 mmol),
HP(O)(OEt)2 (308 μL, 2.4 mmol) and Et3N (320 μL, 2.4 mmol) in
toluene. Diethyl phosphonate 2 was obtained by chromatography
(CH2Cl2–MeOH, 98:2) as a yellow oil; yield: 499 mg (79%).
339.0882.
Diethyl 1,10-Phenanthrolin-4-ylphosphonate (8)
Prepared from 4-bromo-1,10-phenanthroline (5; 518 mg, 2 mmol),
Pd(OAc)2 (44.9 mg, 0.2 mmol), dppf (222 mg, 0.4 mmol),
HP(O)(OEt)2 (308 μL, 2.4 mmol) and Et3N (320 μL, 2.4 mmol) in
dioxane. The reaction mixture was chromatographed (CH2Cl2–
MeOH, 98:2) to give phosphonate 8 as a yellow oil; yield: 330 mg
(52%).
IR (KBr): 2987, 1506, 1447, 1415, 1387, 1251, 1018, 971, 802
cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.28 (t, 3JHH = 7.1 Hz, 6 H), 4.11
(m, 2 H), 4.21 (m, 2 H), 7.69 (dd, 3JHH = 8.3 Hz, 3JHH = 4.4 Hz, 2 H,
H-3,8), 8.33 (dd, 3JHH = 8.1 Hz, 4JHH = 1.7 Hz, 1 H, H-7), 8.63 (d,
3JHP = 17.5 Hz, 1 H, H-6), 8.88 (dd, 3JHH = 8.4 Hz, 4JHH = 1.7 Hz, 1
H, H-4), 9.21 (dd, 3JHH = 4.4 Hz, 4JHH = 1.7 Hz, 1 H, H-9), 9.27 (dd,
3JHH = 4.4 Hz, 4JHH = 1.7 Hz, 1 H, H-2).
13C NMR (75 MHz, CDCl3): δ = 16.49 (d, J = 6.3 Hz, 2 C, CH3),
62.78 (d, J = 5.3 Hz, 2 C, CH2), 123.46 (C-8), 123.83 (C-3), 126.68
(d, J = 122.6 Hz, C-5), 126.85 (d, J = 18.4 Hz, C-4a), 127.36 (C-
6a), 135.42 (d, J = 3.3 Hz, C-4), 136.88 (d, J = 8.8 Hz, C-6), 137.31
(C-7), 146.40 (d, J = 12.0 Hz, C-10b), 148.00 (d, J = 2.7 Hz, C-
10a), 150.71 (C-9), 152.68 (C-2).
IR (film): 2934, 1647, 1499, 1419, 1370, 1250, 1224, 1153, 1125,
1096, 1050, 1017, 973 cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.29 (t, 3JHH = 7.1 Hz, 6 H, CH3),
3
4.13 (m, 2 H, CH2), 4.22 (m, 2 H, CH2), 7.62 (dd, JHH = 8.1 Hz,
3JHH = 4.3 Hz, 1 H, H-8), 7.87 (d, 3JHH = 9.1 Hz, 1 H, H-6), 8.14 (dd,
3
3
3JHP = 15.4 Hz, JHH = 4.3 Hz, 1 H, H-3), 8.23 (dd, JHH = 8.1 Hz,
4JHH = 1.7 Hz, 1 H, H-7), 8.49 (d, 3JHH = 9.1 Hz, 1 H, H-5), 9.17 (dd,
4
4
3JHH = 4.3 Hz, JHH = 1.7 Hz, 1 H, H-9), 9.26 (dd, JHP = 4.6 Hz,
3JHH = 4.5 Hz, 1 H, H-2).
13C NMR (75 MHz, CDCl3): δ = 16.48 (d, J = 6.1 Hz, 2 C, CH3),
63.14 (d, J = 5.5 Hz, 2 C, CH2), 123.71 (C-8), 124.95 (d, J = 4.5 Hz,
C-5), 127.84 (d, J = 7.1 Hz, C-3), 127.99 (d, J = 9.1 Hz, C-4a),
128.05 (C-6), 128.53 (C-6a), 134.72 (d, J = 180.4 Hz, C-4), 136.07
(C-7), 146.24 (C-10a), 146.82 (d, J = 11.0 Hz, C-10b), 149.57 (d,
J = 13.3 Hz, C-2), 150.82 (C-9).
31P NMR (121 MHz, CDCl3): δ = 16.65.
HRMS: m/z [M + Na]+ calcd for C16H17O3N2NaP: 339.0869; found:
339.0878.
Method B (Table 1, Entry 3)
Prepared from 5-bromo-1,10-phenanthroline (1; 130 mg, 0.5
mmol), Pd(OAc)2 (11.2 mg, 0.05 mmol), Ph3P (1.31 g, 5 mmol),
HP(O)(OEt)2 (77 μL, 0.6 mmol) and Et3N (80 μL, 0.6 mmol) in tol-
uene. The reaction mixture was chromatographed (CH2Cl2–MeOH,
98:2) to give the diethyl phosphonate 2 which was isolated as a yel-
low oil; yield: 73 mg (46%).
31P NMR (121 MHz, CDCl3): δ = 14.92.
HRMS: m/z [M + Na]+ calcd for C16H17O3N2NaP: 339.0869; found:
339.0877.
Diethyl 1,10-Phenanthrolin-2-ylphosphonate (9)
Prepared from 2-chloro-1,10-phenanthroline (6; 108 mg, 0.5
mmol), Pd(OAc)2 (11.2 mg, 0.05 mmol), dppf (55.4 mg, 0.1 mmol),
HP(O)(OEt)2 (77 μL, 0.6 mmol) and Et3N (80 μL, 0.6 mmol) in tol-
uene. Purification by column chromatography (CH2Cl2–MeOH,
96:4) gave phosphonate 9 as a yellow oil; yield: 112 mg (71%).
Elution with 25% NH3–MeOH–CH2Cl2 (1:4:20) gave triethylam-
monium ethyl 1,10-phenanthrolin-5-ylphosphonate (3) as a yellow
oil; yield: 45 mg (23%); purity >85% [impurity signals in the 1H and
31P NMR spectra are tentatively assigned to the tetraethylammoni-
um salt (5%) and ethyltriphenylphosphonium salt (10%)].
Synthesis 2012, 44, 3805–3810
© Georg Thieme Verlag Stuttgart · New York

PAPER
Phosphorylated 1,10-Phenanthrolines
3809
1H NMR (300 MHz, CDCl3): δ = 1.39 (t, 3JHH = 7.1 Hz, 6 H, CH3),
4.37 (m, 4 H, CH2), 7.62 (dd, 3JHH = 8.1 Hz, 3JHH = 4.3 Hz, 1 H, H-
8), 7.77 (d, 3JHH = 8.8 Hz, 1 H, H-6), 7.83 (d, 3JHH = 8.8 Hz, 1 H, H-
toluene. Purification by column chromatography (CH2Cl2–MeOH,
96:4) gave diphosphonate 15 as a yellow oil; yield: 181 mg (80%).
1H NMR (300 MHz, CDCl3): δ = 1.39 (t, 3JHH = 7.1 Hz, 12 H, CH3),
3
4
5), 8.21 (dd, JHH = 8.1 Hz, JHH = 1.7 Hz, 1 H, H-7), 8.24 (dd,
3
4.41 (m, 8 H, CH2), 7.84 (s, 2 H, H-5,6), 8.22 (dd, JHH = 8.1 Hz,
3
3
3JHH = 8.1 Hz, JHP = 5.0 Hz, 1 H, H-3), 8.31 (dd, JHH = 8.1
Hz, 4JHH = 5.6 Hz, 1 H, H-4), 9.19 (dd, 3JHH = 4.3 Hz, 4JHH = 1.7 Hz,
1 H, H-9).
3JHP = 4.9 Hz, 2 H, H-3,8), 8.31 (dd, 3JHH = 8.1 Hz, 4JHP = 5.6 Hz, 2
H, H-4,7).
13C NMR (75 MHz, CDCl3): δ = 16.62 (d, J = 6.3 Hz, 4 C, CH3),
63.89 (d, J = 6.5 Hz, 4 C, CH2), 126.42 (d, J = 27.0 Hz, 2 C, C-3,8),
128.29 (2 C, C-5,6), 129.82 (d, J = 3.8 Hz, 2 C, C-4a,6a), 136.14 (d,
J = 12.0 Hz, 2 C, C-4,7), 146.25 (dd, J = 24.9, 1.2 Hz, 2 C, C-
10a,10b), 153.38 (d, J = 226.8 Hz, 2 C, C-2,9).
31P NMR (121 MHz, CDCl3): δ = 9.25.
HRMS: m/z [M + Na]+ calcd for C20H26O6N2NaP2: 475.1158;
13C NMR (75 MHz, CDCl3): δ = 16.61 (d, J = 6.1 Hz, 2 C, CH3),
63.53 (d, J = 6.2 Hz, 2 C, CH2), 123.62 (C-8), 126.13 (d, J = 26.7
Hz, C-3), 126.39 (d, J = 1.7 Hz, C-5), 128.78 (C6), 129.21 (C-6a),
129.68 (d, J = 3.7 Hz, C-4a), 136.19 (d, J = 11.8 Hz, C-4), 136.36
(C-7), 146.15 (C-10a), 146.38 (d, J = 24.6 Hz, C-10b), 150.82 (C-
9), 152.67 (d, J = 227.8 Hz, C-2).
31P NMR (121 MHz, CDCl3): δ = 10.58.
HRMS: m/z [M + Na]+ calcd for C16H17O3N2NaP: 339.0869; found:
found: 475.1158.
339.0867.
Acknowledgment
Tetraethyl 1,10-Phenanthroline-3,8-diyldiphosphonate (13)
Prepared from 3,8-dibromo-1,10-phenanthroline (10; 338 mg, 1
mmol), Pd(OAc)2 (22.4 mg, 0.1 mmol), dppf (111 mg, 0.2 mmol),
HP(O)(OEt)2 (308 μL, 2.4 mmol) and Et3N (320 μL, 2.4 mmol) in
toluene. Purification by column chromatography (CH2Cl2–MeOH,
98:2) gave diphosphonate 13 as a yellow oil; yield: 317 mg (70%).
This work was supported by the CNRS and the Russian Foundation
for Basic Research (grant 12-03-93114-NTzNIL_a), and was car-
ried out in the frame of the International Associated French–Russian
Laboratory of Macrocyclic Systems and Related Materials
(LAMREM) of CNRS.
IR (film): 2984, 1480, 1435, 1423, 1392, 1371, 1249, 1201, 1166,
1143, 1119, 1100, 1051, 1029, 969 cm–1.
1H NMR (300 MHz, CDCl3): δ = 1.28 (t, 3JHH = 7.1 Hz, 12 H, CH3),
4.14 (m, 8 H, CH2), 7.86 (s, 2 H, H-5,6), 8.71 (dd, 3JHP = 14.6 Hz,
4JHH = 1.9 Hz, 2 H, H-4,7), 9.40 (dd, 3JHP = 4.8 Hz, 4JHH = 1.9 Hz, 2
H, H-2,9).
13C NMR (75 MHz, CDCl3): δ = 16.48 (d, J = 6.3 Hz, 4 C, CH3),
62.89 (d, J = 5.5 Hz, 4 C, CH2), 125.14 (d, J = 188.3 Hz, 2 C, C-
3,8), 127.60 (2 C, C-5,6), 128.42 (d, J = 13.0 Hz, 2 C, C-4a,6a),
141.29 (d, J = 8.9 Hz, 2 C, C-4,7), 147.37 (2 C, C-10a,10b), 151.42
(d, J = 12.1 Hz, 2 C, C-2,9).
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnoIufproi
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