Synthesis of phosphane oxide bridged bis- and triscatechol derivatives

Article abstract of DOI:10.1055/s-2006-950185

Linear biscatechols and triangular triscatechols possessing spacers containing phosphane oxide were synthesized. For this, the central phosphorus was introduced by the reaction of active organometallic intermediates with either dichlorophenylphosphane or

Full text of DOI:10.1055/s-2006-950185

PAPER
3037
Synthesis of Phosphane Oxide Bridged Bis- and Triscatechol Derivatives
S
ynthesis of Phosphan
a
Oxide Br
i
r
dged Bi
k
u
techol
D
eriv
s
a
tive
s
Albrecht,*a Yun Songa,b
a
b
Received 17 May 2006; revised 18 June 2006
In our previous work, a series of bis- and triscatechol
ligands 1 and 2 (Figure 1) with central carbon or nitrogen
atoms have been synthesized. Systematic investigations
of the binding behavior of these ligands with various met-
Abstract: Linear biscatechols and triangular triscatechols possess-
ing spacers containing phosphane oxide were synthesized. For this,
the central phosphorus was introduced by the reaction of active or-
ganometallic intermediates with either dichlorophenylphosphane or
phosphorus trichloride/phosphoryl chloride. In the final steps, the al ions as well as the structural analysis of the resulting
methyl ethers at the veratrol units were cleaved by boron tribromide
complexes indicated that the structures of the supramolec-
to afford the free phosphane oxide catechol derivatives, which in
ular aggregates mainly depend on the geometry of the
metal-directed self-assembly processes would lead to helical or tet-
ligands.7 To further understand the influence of slight al-
rahedral supramolecular aggregates.
terations of the central atoms on the structure of the aggre-
gates and to elucidate the general assembly mechanisms,
we now introduce phosphane oxide as the central unit in-
Key words: phosphane oxide, amides, catechol, ligands, Suzuki
coupling
stead of carbon or nitrogen, and prepared a series of linear
and triangular bis- and triscatechol ligands. This work is
The metal-directed self-assembly process of linear or tri-
expected to open up a new approach for the design of
angular catechol ligands can lead to helicate-type dinucle-
helicate-type complexes and molecular containers with
ar complexes1 or to supramolecular tetrahedra.2 The
internal cavity of the resulting aggregates allows them to
act as ‘molecular containers’ with certain reactive func-
tionalities.3 As a fascinating kind of ‘reactors’, molecular
containers can stabilize reactive intermediates,4 promote
chemical reactions,5 and enhance selectivities of intra- or
intermolecular reactions6 through accommodation of
guest molecules. Therefore, the design of functionalized
ligands which can assemble to functional molecular con-
tainers is currently one of the most challenging topics in
supramolecular chemistry.
functionalities introduced in the ‘wall’ of the containers.8
Linear Dicatechols
In earlier studies, we showed that linear biscatechol 1
(Figure 1), with a methylene unit providing the central
carbon atom, can assemble with titanium(IV) ions in the
presence of sodium or lithium cations to form triple-
stranded meso-helicates.7a
In the present work, we substituted the methylene unit of
1 by a phosphoryl group, to obtain the linear biscatechol 3
(Scheme 1). Ligand 3 was prepared from veratrole (4),
which was ortho-metalated with butyllithium (Scheme 1).
Transmetalation to form the copper(I) species 5 was fol-
lowed by coupling with dichlorophenylphosphane; subse-
quent oxidation with 30% hydrogen peroxide afforded
phosphane oxide 6. Deprotection with boron tribromide
led to the free ligand 3.
OH
OH
HO
HO
H
H
C
N
HO
2
OH
1
1. n-BuLi,
TMEDA
2. CuI
N
OMe
OMe
1. PhPCl2
2. H2O2
CuLi
2
2
N
N
OH
12%
MeO
OMe
OH
4
OH
5
OH
OMe
OMe
OH
Figure 1 Structures of bis- and triscatechol ligands 1 and 2 with
central carbon or nitrogen atoms
BBr3
92%
OMe
OH
OH
O
O
MeO
P
HO
P
6
3
SYNTHESIS 2006, No. 18, pp 3037–3042
Advanced online publication: 15.08.2006
DOI: 10.1055/s-2006-950185; Art ID: Z09806SS
x
x.
x
x
.
2
0
0
6
Scheme 1 Preparation of linear biscatechol 3 with a phosphoryl
group as the central unit
© Georg Thieme Verlag Stuttgart · New York

3038
M. Albrecht, Y. Song
PAPER
To separate the two catechol units by a longer spacer, we here, analogue 14, in which the central triangular unit is
prepared compound 7 from 4-bromoaniline (8) by a six- substituted by a phosphoryl group, was prepared
step reaction sequence (Scheme 2). The amine group of 4- (Scheme 3). Triscatechol 14 was prepared by procedures
bromoaniline (8) was first protected by the addition of similar to those employed in the synthesis of ligand 7. In
hexane-2,5-dione.9 The organometallic species formed by the first step, either phosphorus trichloride (followed by
the reaction of protected aniline 9 with magnesium or bu- oxidation with hydrogen peroxide) or phosphoryl chloride
tyllithium subsequently reacted with dichlorophenylphos- could be coupled with three equivalents of the organolith-
phane, and oxidation by 30% hydrogen peroxide ium reagent obtained from protected aniline 9. The reac-
followed. For this reaction step, we found that butyllithi- tion afforded phosphane oxide 15, which was deprotected
um in dry diethyl ether gives more of the active with hydroxylamine hydrochloride to yield triaminophen-
organometallic intermediate of 9 than magnesium in tetra- yl phosphane oxide 16, for which we had developed a re-
hydrofuran can, to give phosphane oxide 10 in 76% yield liable synthetic procedure.12 This building block could be
instead of 14%. After cleavage of the protected pyrrole also of interest as a ligand for catalysis or for materials sci-
groups of 10 with hydroxylamine hydrochloride, the di- ence. Three equivalents of 2,3-dimethoxybenzoyl chlo-
amino derivative 11 was acylated by addition of 2,3- ride (12) were coupled with phosphane oxide 16 in the
dimethoxybenzoyl chloride (12). Finally, removal of the presence of O-benzotriazol-1-yl-N,N,N¢,N¢-tetramethyl-
methoxy groups of derivative 13 by boron tribromide uronium hexafluorophosphate (HBTU) to yield 17, whose
gave ligand 7 in 95% yield (Scheme 2).
deprotection gave ligand 14.
Triangular Triscatechols
1. n-BuLi
2. PCl3
3. H2O2
N
Triangular catechol amides similar to imine 2 were pre-
N
pared by us10 and by Raymond.11 In the study presented
HONH3Cl,
Et3N, H2O
30%
1. n-BuLi
2. POCl3
1. Mg, THF
2. PhPCl2
43%
O
O
36%
3. H2O2
P
9
N
Br
14%
O
toluene
N
N
NH2
15
1. n-BuLi
91%
2. PhPCl2
3. H2O2
Br
9
76%
OMe
8
O
MeO
Br
MeO
NH2
H
N
OMe
HN
COCl
NH2
OMe
N
O
P
12
O
HONH3Cl,
Et3N, H2O
OMe
BBr3
90%
12, HBTU
O
O
63%
42%
P
60%
P
O
P
O
NH
H2N
NH2
17
H2N
16
N
MeO
11
10
MeO
OMe
OH
OH
OMe
O
O
HO
HO
OH
H
OH
HN
P
HN
N
HN
O
BBr3
95%
O
P
O
O
14
O
O
P
O
N
H
O
NH
N
H
OMe
HO
13
OH
7
OMe
OH
HO
Scheme 2 Preparation of linear biscatechol 7 with a phosphoryl
group in the center and with long spacers between the catechol units
Scheme 3 Synthesis of triscatechol amide 14 via phosphane oxide
16 as a key intermediate
Synthesis 2006, No. 18, 3037–3042 © Thieme Stuttgart · New York

PAPER
Synthesis of Phosphane Oxide Bridged Bis- and Triscatechol Derivatives
3039
1H, 31P, and 13C NMR spectra were recorded on a Varian Inova 400
spectrometer. FT-IR spectra were recorded on a Bruker IFS spec-
trometer (KBr or neat). Mass spectra (EI, 70 eV; FAB) were mea-
sured on a Finnigan MAT 95 or 212 mass spectrometer. Elemental
analyses were obtained with a Heraeus CHNO-Rapid analyzer.
Melting points were determined on a Büchi B-540 apparatus and are
uncorrected. For organometallic reactions, the reaction flasks were
flame-dried and the reactions were performed under an atmosphere
of dry N2.
Scheme 4 illustrates the synthetic route to an alternative
triscatechol 18, in which a purely carbon skeleton con-
nects the ligand units to the phosphoryl center. 1,4-Dibro-
mobenzene 19 was metalated with butyllithium and then
reacted with phosphoryl chloride or phosphorus trichlo-
ride/hydrogen peroxide. The thus obtained tris(4-bro-
mophenyl)phosphane oxide (20) was coupled with (2,3-
dimethoxyphenyl)boronic acid (21) in a Suzuki cross-
coupling reaction13 to afford hexamethoxy derivative 22.
Removal of the methoxy protecting groups of precursor
22 by boron tribromide smoothly gave triscatechol ligand
18.
Bis(2,3-dimethoxyphenyl)(phenyl)phosphane Oxide (6)
A 1.6 M soln of n-BuLi in hexane (5.6 mL, 8.96 mmol) was added
to 1,2-dimethoxybenzene (4; 1.2 g, 8.7 mmol) and TMEDA (1.2
mL, 7.95 mmol) in dry Et2O (20 mL). After being stirred for 3 h at
r.t., the mixture was added dropwise to a rapidly stirring slurry of
CuI (835.0 mg, 4.4 mmol) in anhyd THF (25 mL) at –78 °C. The
resulting mixture was stirred at –78 °C for 15 min. PhPCl2 (780.0
mg, 4.4 mmol) and a few drops of HMPA were added. The mixture
was allowed to warm to r.t. and was washed with sat. aq NH4Cl. Af-
ter the aqueous phase had been extracted with Et2O (3 × 30 mL), the
combined organic layer was concentrated (to 30 mL), and 30%
H2O2 (3.0 mL) was added. After the mixture had refluxed for 4 h,
the solvent was removed and the residue was dissolved in EtOAc
(30 mL). A 10% soln of NaOH (10 mL) was added and the mixture
was stirred for an additional 20 min. The organic layer was washed
with sat. aq NaCl (15 mL). The aqueous layer was extracted with
EtOAc (2 × 20 mL). The combined organic phase was dried
(MgSO4), the solvent was removed, and the crude product was pu-
rified by column chromatography (silica gel, EtOAc, Rf = 0.38);
this gave 6 as an off-white solid.
HO
OH
B
OMe
OMe
Br
1. n-BuLi
2. POCl3
Br
19%
21
1. n-BuLi
2. PCl3
3. H2O2
O
Suzuki, 65%
Br
P
Br
19
57%
Br
20
OMe
OMe
Yield: 207 mg (12%); mp 137–138 °C.
BBr3, CH2Cl2
95%
IR (KBr): 3060, 2988, 2938, 2839, 2348, 2076, 1973, 1909, 1734,
1674, 1577, 1465, 1270, 1195, 1079, 1041, 990, 865, 790, 747, 699,
663, 589, 514, 480 cm–1.
O
P
OMe
31P NMR (162 MHz, CDCl3): d = 25.2 (s).
OMe
1H NMR (400 MHz, CDCl3): d = 7.90 (m, 2 H), 7.45 (m, 3 H), 7.18
(m, 2 H), 7.10 (m, 4 H), 3.85 (s, 6 H), 3.46 (s, 6 H).
22
OMe
13C NMR (100 MHz, CDCl3): d = 152.4, 150.4, 131.9, 131.1, 128.3,
OMe
OH
OH
127.9, 127.3, 124.6, 123.7, 116.1, 60.2, 55.8.
MS (EI, 70 eV): m/z = 367.0, 398.0 [M + H]+.
Anal. Calcd for C22H23O5P: C, 66.33; H, 5.82. Found: C, 66.31; H,
6.28.
O
Bis(2,3-dihydroxyphenyl)(phenyl)phosphane Oxide (3)
Phosphane oxide 6 (207 mg, 0.52 mmol) was dissolved in CH2Cl2
(20 mL). BBr3 (0.2 mL, 439.4 mg, 2.2 mmol) was added at 0 °C. Af-
ter overnight stirring at r.t., the mixture was quenched with MeOH
(4 mL) and concentrated under vacuum, and the residue was dis-
solved in EtOAc. After being washed with H2O, the organic phase
was dried (MgSO4), and the solvent was removed under vacuum.
This gave 3 as a beige solid.
P
OH
OH
18
OH
OH
Scheme 4 Preparation of triscatechol 18
Yield: 162 mg (92%); mp 70 °C.
We have presented reliable reaction sequences leading to
a new type of bis- and triscatechol ligands with a phospho-
ryl-functionalized center. Our synthetic approach allows
IR (KBr): 3850.8, 3745.3, 3676.9, 3442.9, 3185.1, 2964.4, 2518.7,
2361.5, 2338.6, 1913.1, 1590.4, 1381.7, 1340.9, 1256.6, 1087.8,
906.6, 822.3, 733.9, 658.6, 577.9, 532.2, 468.6 cm–1.
us to generate ligands with different symmetries and with 31P NMR (162 MHz, CDCl3): d = 49.9 (s).
1H NMR (400 MHz, CDCl3): d = 10.68 (s, 2 H), 7.64 (m, 3 H), 7.52
(m, 2 H), 7.10 (d, J = 8.0 Hz, 2 H), 6.82 (m, 2 H), 6.60 (m, 2 H),
5.80 (s, 2 H).
13C NMR (100 MHz, CD3OD): d = 163.3, 149.5, 145.7, 132.8,
131.1, 128.0, 123.0, 119.1, 114.8, 113.7.
different connecting units in the spacers. The compounds
should be appropriate building blocks for the metal-
directed self-assembly of supramolecular aggregates. The
coordination chemistry of the new ligands is currently be-
ing studied in our laboratories.
MS (EI, 70 eV): m/z = 342.0 [M + H]+.
Synthesis 2006, No. 18, 3037–3042 © Thieme Stuttgart · New York

3040
M. Albrecht, Y. Song
PAPER
Anal. Calcd for C18H15O5P·1.5EtOAc: C, 60.76; H, 5.74. Found: C,
60.49; H, 6.09.
MS (EI, 70 eV): m/z = 464.2 [M + H]+.
Anal. Calcd for C30H29N2OP·H2O: C, 74.67; H, 6.48; N, 5.81.
Found: C, 74.79; H, 6.33; N, 5.37.
1-(4-Bromophenyl)-2,5-dimethyl-1H-pyrrole (9)
4-Bromoaniline (8; 10.0 g, 58.5 mmol), hexane-2,5-dione (7.5 mL,
64.4 mmol), and TsOH (100.0 mg, 53.3 mmol) were dissolved in
toluene (100.0 mL), and the mixture was refluxed in a Dean–Stark
apparatus for 6 h. After the dark mixture had cooled down, it was
washed with sat. aq NaHCO3 (2 × 100 mL), H2O (5 × 100 mL), and
brine (100 mL), and decolorized with active carbon. After the soln
had been dried (MgSO4), the solvent was removed under vacuum;
this gave 9 as a brown solid.
Bis(4-aminophenyl)(phenyl)phosphane Oxide (11)
A mixture of compound 10 (570.0 mg, 1.23 mmol), NH2OH·HCl
(2.6 g, 37.4 mmol), Et3N (1.4 mL), EtOH (9.0 mL), and H2O (3.6
mL) was refluxed for 24 h. Then second portions of NH2OH·HCl
(2.6 g, 37.4 mmol) and Et3N (1.0 mL) were added, and the mixture
was refluxed for 30 h until TLC monitoring showed complete con-
sumption of 10. The reaction mixture was allowed to cool to r.t., its
pH was adjusted to 12.0 with aq NaOH, and it was stirred for 1 h.
The solvent was removed by rotary evaporation and the residue was
purified by column chromatography (silica gel, EtOAc–
MeOH, 10:1, Rf = 0.48); this gave 11 as a beige solid.
Yield: 13.2 g (90%).
1H NMR (300 MHz, CDCl3): d = 7.59 (d, J = 8.7 Hz, 2 H), 7.10 (d,
J = 8.7 Hz, 2 H), 5.90 (s, 2 H), 2.02 (s, 6 H).
Yield: 240 mg (63%).
1,1¢-[(Phenylphosphoryl)di-4,1-phenylene]bis(2,5-dimethyl-
1H-pyrrole) (10)
1P NMR (162 MHz, CDCl3): d = 30.1 (s).
1H NMR (400 MHz, CDCl3): d = 7.65 (m, 2 H), 7.48 (m, 1 H), 7.40
(m, 6 H), 6.68 (m, 4 H), 3.96 (br s, 4 H).
MS (EI, 70 eV): m/z = 308.0 [M + H]+.
Method A: A three-necked flask under N2 was charged with Mg
(80.0 mg, 6.7 mmol), dry THF (2 mL), and several drops of a soln
of pyrrole 9 (640 mg, 2.57 mmol) in dry THF (3 mL). Then I2 was
added to initiate the reaction under reflux temperature. When the re-
sulting mixture turned colorless, the THF soln of 9 was added con-
tinuously. After addition, the suspension turned a grape color and
was allowed to reflux for 2 h, after which it was cooled to 0 °C. At
this temperature, PhPCl2 (228.0 mg, 1.3 mmol) dissolved in dry
THF (3 mL) was added over 30 min. The mixture changed color
from brown to pale yellow, and was stirred at r.t. overnight. H2O
was added dropwise to quench the excess Grignard reagent. After
the aqueous phase had been extracted with EtOAc (3 × 20 mL), the
combined organic layer was concentrated by rotary evaporation.
The residue was dissolved in acetone (12 mL) to which of 30%
H2O2 (1.0 mL) had been added. The mixture was refluxed for 5 h,
and the solvent was removed. Then 10% NaOH (6.0 mL) was added
to the EtOAc soln of the residue. The organic layer was washed with
sat. aq NaCl (15 mL), and the aqueous layer was extracted with
EtOAc (2 × 20 mL). The combined organic phase was dried
(MgSO4) and the solvent was removed under vacuum. The crude
product was purified by column chromatography (silica gel,
EtOAc–hexane, 2.5:1, Rf = 0.43); this gave 10 as an off-white solid.
N,N¢-[(Phenylphosphoryl)di-4,1-phenylene]bis(2,3-dimethoxy-
benzamide) (13)
Benzoyl chloride 12 (184.0 mg, 0.92 mmol), 4-Å molecular sieves,
and HBTU (200.0 mg, 0.53 mmol) were added at 0 °C to py (15
mL). Then phosphane oxide 11 (130.0 mg, 0.42 mmol) dissolved in
MeCN (15 mL) was added dropwise. The mixture was stirred over-
night in an ice bath, and then at r.t. for 24 h. The solvent was re-
moved under reduced pressure, the residue was dissolved in
CH2Cl2, and the soln was washed with aq NH4Cl (20 mL), aq
NaHCO3 (20 mL), H2O (2 × 20 mL), and brine (20 mL). The organ-
ic layer was dried (MgSO4) and the solvent was removed. The resi-
due was purified by column chromatography (silica gel, CH2Cl2–
MeOH, 10:1, Rf = 0.51); this gave 13 as an off-white solid.
Yield: 161 mg (60%); mp 105–107 °C.
IR (KBr): 3764.6, 3306.3, 2937.4, 2835.2, 2347.4, 2295.7, 2193.6,
1395.2, 1259.1, 1174.1, 1111.4, 1054.9, 987.8, 922.3, 828.5, 529.5
cm–1.
31P NMR (162 MHz, CDCl3): d = 28.5 (s).
Yield: 87.0 mg (14.4%).
1H NMR (400 MHz, CDCl3): d = 10.22 (s, 2 H), 7.79 (m, 6 H), 7.68
(m, 6 H), 7.55 (m, 1 H), 7.47 (m, 2 H), 7.22 (t, J = 15.9 Hz, 2 H),
7.12 (m, 2 H), 4.00 (s, 6 H), 3.94 (s, 6 H).
13C NMR (75 MHz, CD3OD): d = 163.4, 152.6, 147.3, 141.7, 133.4,
132.1, 131.9, 128.5, 128.1, 126.6, 126.4, 124.8, 122.9, 119.7, 116.1,
61.7, 56.2.
Method B: A 1.6 M soln of n-BuLi in hexane (2.1 mL, 3.36 mmol)
was added to a soln of pyrrole 9 (790.0 mg, 3.18 mmol) in dry Et2O
(10 mL) under N2 at 0 °C. After the mixture had stirred for 2 h, a
soln of PhPCl2 (287.5 mg, 1.6 mmol) in dry Et2O (6 mL) was added
slowly. The resulting mixture was stirred overnight at r.t., and sat.
aq NH4Cl (10 mL) was added to terminate the reaction. After the
aqueous layer had been extracted with Et2O (3 × 15 mL), the com-
bined organic layer was concentrated (to 30 mL). A 30% soln of
H2O2 (1 mL) was added, and the mixture was refluxed for 4 h. Then
10% NaOH (10.0 mL) was added, and the organic layer was washed
with sat. aq NaCl (15 mL). The aqueous layer was extracted with
EtOAc (2 × 20 mL). The combined organic phase was dried
(MgSO4) and the solvent was removed. The crude product was pu-
rified by column chromatography (silica gel, EtOAc, Rf = 0.53);
this gave 10 as an off-white solid.
ESI-MS: m/z = 637.4 [M]+.
Anal. Calcd for C36H33N2O7P·3H2O: C, 62.60; H, 5.69; N, 4.06.
Found: C, 62.20; H, 5.22; N, 4.00.
N,N¢-[(Phenylphosphoryl)di-4,1-phenylene]bis(2,3-dihydroxy-
benzamide) (7)
Biscatechol 7 was prepared as a beige solid from protected precur-
sor 13 by the method employed for the synthesis of biscatechol 3.
Yield: 570.0 mg (76%); mp 83 °C.
Yield: 95%; mp 160 °C (dec.).
IR (KBr): 3865, 3744, 3431, 3054, 2917, 2543, 2364, 2343, 1922,
1733, 1651, 1594, 1503, 1318, 991, 842, 703, 617 cm–1.
IR (KBr): 3726, 3342, 3043, 2872, 2473, 2347, 2335, 2241, 1716,
1649, 1384, 1333, 1255, 955, 831, 583, 530 cm–1.
31P NMR (162 MHz, CDCl3): d = 28.5 (s).
1H NMR (400 MHz, CDCl3): d = 7.80 (m, 6 H), 7.62 (m, 1 H), 7.56
(m, 2 H), 7.36 (m, 4 H), 5.93 (s, 4 H), 2.06 (s, 12 H).
13C NMR (75 MHz, CDCl3): d = 142.5, 132.9, 132.3, 132.2, 132.0,
130.9, 128.8, 128.6, 128.3, 106.7, 13.2.
31P NMR (162 MHz, CD3OD): d = 31.9 (s).
1H NMR (400 MHz, CD3OD): d = 7.83 (m, 4 H), 7.56 (br, 8 H),
7.48 (m, 1 H), 7.34 (m, 2 H), 6.89 (m, 2 H), 6.71 (m, 2 H), 4.78 (s,
6 H).
Synthesis 2006, No. 18, 3037–3042 © Thieme Stuttgart · New York

PAPER
Synthesis of Phosphane Oxide Bridged Bis- and Triscatechol Derivatives
3041
13C NMR (75 MHz, CD3OD): d = 168.2, 148.1, 146.0, 142.1, 132.6,
131.7, 130.7, 128.5, 126.9, 125.4, 120.5, 118.7, 116.5; two signals
of carbon atoms were not observed.
was added dropwise. The mixture was stirred in an ice bath over-
night, and then at r.t. for 24 h. The solvent was removed under re-
duced pressure, the residue was dissolved in CH2Cl2, and the soln
was washed successively with aq NH4Cl (15 mL), aq NaHCO3 (15
mL), H2O (15 mL), and brine (15 mL). The organic layer was dried
(MgSO4) and the solvent was removed. The remaining residue was
purified by column chromatography (silica gel, EtOAc–MeOH, 8:1,
Rf = 0.51); this gave protected precursor 17 as an off-white solid.
ESI-MS: m/z = 579.4 [M]+.
Anal. Calcd for C32H25N2O7P·3.5H2O: C, 59.72; H, 5.01; N, 4.35.
Found: C, 59.73; H, 5.16; N, 4.08.
1,1¢,1¢¢-(Phosphoryltri-4,1-phenylene)tris(2,5-dimethyl-1H-pyr-
role) (15)
Yield: 79 mg (42%); mp 239 °C (dec.).
A 1.6 M soln of n-BuLi in hexane (2.1 mL, 3.36 mmol) was added
to a soln of pyrrole 9 (790.0 mg, 3.18 mmol) in dry Et2O (10 mL)
under N2 at 0 °C. After the mixture had stirred for 2 h, a soln of
POCl3 (136.8 mg, 0.9 mmol) in dry Et2O (5 mL) was added drop-
wise, and the mixture was stirred overnight at r.t. Then sat. aq
NH4Cl (15 mL) and EtOAc (20 mL) were added, and the organic
layer was washed with aq NH4Cl (15 mL), H2O (15 mL), and brine
(15 mL). Finally, the aqueous layer was extracted with EtOAc (2 ×
20 mL). The combined organic phase was dried (MgSO4) and the
solvent was removed. The crude product was purified by column
chromatography (silica gel, CH2Cl2–MeOH, 15:1, Rf = 0.69); this
gave pure 15 as an off-white solid.
IR (KBr): 3311.7, 2943.7, 2832.5, 2361.6, 2338.9, 1587.2, 1470.2,
1395.3, 1319.6, 1170.9, 1114.6, 1055.1, 989.8, 928.7, 825.1, 746.3,
689.4, 577.9, 535.5 cm–1.
31P NMR (162 MHz, CDCl3): d = 28.1 (s).
1H NMR (400 MHz, CDCl3): d = 10.23 (s, 3 H), 7.78 (m, 9 H), 7.70
(m, 6 H), 7.20 (t, J = 15.9 Hz, 3 H), 7.12 (m, 3 H), 4.01 (s, 9 H), 3.93
(s, 9 H).
13C NMR (100 MHz, CDCl3): d = 163.0, 152.4, 147.0, 141.5, 133.1,
128.0, 126.9, 124.7, 122.8, 119.4, 115.9, 61.7, 56.1.
ESI-MS: m/z = 816.3 [M + H]+.
Anal. Calcd for C45H42N3O10P·H2O: C, 64.82; H, 5.32; N, 5.04.
Found: C, 64.42; H, 5.32; N, 5.28.
Yield: 220 mg (36%); mp 205 °C (dec.).
IR (KBr): 3741.7, 3537.5, 3439.3, 3089.0, 2923.3, 2365.4, 2342.6,
2312.2, 2294.3, 1931.4, 1734.8, 1595.7, 1502.9, 1446.7, 1318.0,
1181.2, 1114.6, 994.1, 843.0, 621.4, 578.2, 492.2 cm–1.
31P NMR (122 MHz, CDCl3): d = 28.0 (s).
1H NMR (300 MHz, CDCl3): d = 7.83 (m, 6 H), 7.40 (m, 6 H), 5.94
(s, 6 H), 2.07 (s, 18 H).
13C NMR (75 MHz, CDCl3): d = 142.8, 132.9, 131.7, 130.3, 128.6,
106.8, 13.2.
MS (EI, 70 eV): m/z = 557.4 [M + H]+.
N,N¢,N¢¢-(Phosphoryltri-4,1-phenylene)tris(2,3-dihydroxy-
benzamide) (14)
Triscatechol 14 was prepared as a beige solid from protected pre-
cursor 17 by the method employed for the synthesis of biscatechol
3.
Yield: 90%; mp 175 °C (dec.).
IR (KBr): 3851.6, 3743.9, 3614.5, 3384.3, 2846.1, 2715.2, 1918.3,
1837.5, 1790.6, 1738.2, 1652.7, 1586.5, 1450.7, 1392.4, 1329.2,
1253.2, 1118.3, 956.3, 830.8, 741.9, 681.2, 586.3, 533.7 cm–1.
Anal. Calcd for C36H36N3OP·H2O: C, 74.64; H, 6.68; N, 7.25.
Found: C, 75.11; H, 6.65; N, 7.30.
31P NMR (162 MHz, CD3OD): d = 31.7 (s).
1H NMR (400 MHz, CD3OD): d = 7.92 (m, 6 H), 7.64 (m, 6 H), 7.42
(m, 3 H), 6.97 (m, 3 H), 6.78 (m, 3 H), 5.46 (s, 3 H).
13C NMR (100 MHz, CD3OD): d = 168.0, 148.0, 145.9, 142.0,
132.6, 129.2, 126.8, 125.7, 120.5, 118.7, 116.4.
ESI-MS: m/z = 730.3 [M]+.
4,4¢,4¢¢-Phosphoryltrianiline (16)
A mixture of phosphine oxide 15 (284.0 mg, 0.51 mmol),
NH2OH·HCl (1.6 g, 23.0 mmol), Et3N (0.9 mL), EtOH (21.0 mL),
and H2O (4.1 mL) was refluxed for 30 h. Second portions of
NH2OH·HCl (1.6 g, 23.0 mmol), Et3N (0.9 mL), and H2O (2.0 mL)
were added, and the mixture was refluxed for 24 h until TLC mon-
itoring revealed complete consumption of 15. After removal of the
solvents, the residue was poured into 30% NH3·H2O (15 mL) and
was stirred for 1 h. The pure product was collected by filtration and
dried under high vacuum; this gave 16 as a brown solid.
Anal. Calcd for C39H30N3O10P·3.5H2O: C, 58.94; H, 4.69; N, 5.29.
Found: C, 58.48; H, 4.88; N, 5.26.
Tris(4-bromophenyl)phosphane Oxide (20)14
A 1.51 M soln of n-BuLi in hexane (3.3 mL, 5.0 mmol) was added
slowly to a soln of 1,4-dibromobenzene (19; 1.18 g, 5.0 mmol) in
THF (5.0 mL) at –78 °C. A white suspension formed, to which PCl3
(0.14 mL, 0.23 g, 1.65 mmol) in THF (3.0 mL) was added dropwise
over 1 h. The suspension was allowed to warm to r.t. overnight, and
was stirred for another 30 min after the addition of 6% H2O2 (5.0
mL). The aqueous phase was extracted with CH2Cl2 (2 × 10 mL).
The organic phase was dried (MgSO4) and the solvent was re-
moved. The residue was purified by column chromatography (silica
gel, EtOAc, Rf = 0.63); this gave pure 20 as a white solid; yield:
493.6 mg (57%). However, under the same conditions, reaction of
the active organolithium intermediate with POCl3 afforded the pure
product 20 in only 19% yield.
Yield: 106 mg (43%); mp 175 °C (dec.).
IR (KBr): 3436.6, 3343.2, 3225.1, 3025.1, 2589.0, 2488.8, 2427.1,
2362.6, 2329.4, 1903.7, 1502.5, 1412.7, 1282.9, 824.1, 722.1,
670.1, 531.5, 479.1 cm–1.
31P NMR (162 MHz, CD3OD): d = 35.7 (s).
1H NMR (400 MHz, CD3OD): d = 7.21 (m, 6 H), 6.70 (m, 6 H), 4.79
(s, 6 H).
13C NMR (100 MHz, CD3OD): d = 151.7, 133.1, 118.7, 113.5.
MS (EI, 70 eV): m/z = 323.2 [M + H]+.
Anal. Calcd for C18H18N3OP·1.5H2O: C, 61.71; H, 6.04; N, 11.99.
Found: C, 61.46; H, 6.20; N, 12.24.
31P NMR (121 MHz, CDCl3): d = 27.4 (s).
1H NMR (400 MHz, CDCl3): d = 7.65 (m, 6 H), 7.52 (m, 6 H).
N,N¢,N¢¢-(Phosphoryltri-4,1-phenylene)tris(2,3-dimethoxy-
benzamide) (17)
Benzoyl chloride 12 (185.0 mg, 0.93 mmol), 4-Å molecular sieves,
and HBTU (150.0 mg, 0.39 mmol) were added at 0 °C to py (15
mL). A soln of triamine 16 (75.0 mg, 0.23 mmol) in DMF (15 mL)
Tris(2¢,3¢-dimethoxybiphenyl-4-yl)phosphine Oxide (22)
Phosphane oxide 20 (149 mg, 0.29 mmol) and Pd(PPh3)4 (48 mg,
0.042 mmol) were dissolved in toluene (10 mL) under N2. A mix-
ture of 2 M aq Na2CO3 (1.5 mL) and (2,3-dimethoxyphenyl)boronic
Synthesis 2006, No. 18, 3037–3042 © Thieme Stuttgart · New York

3042
M. Albrecht, Y. Song
PAPER
acid (21; 170.0 mg, 0.94 mmol) were added in several portions. The
mixture was refluxed for 2 d, and, after cooling to r.t., was washed
with aq Na2CO3 (4 × 20 mL). The organic phase was dried (MgSO4)
and the solvent was removed under vacuum. The residue was puri-
fied by column chromatograph (silica gel, EtOAc, Rf = 0.3); this
gave the protected ligand precursor 22 as a white solid.
Acknowledgment
Financial support by the Deutsche Forschungsgemeinschaft (SPP
1118), the Alexander von Humboldt Stiftung (AvH), and the young
teacher’s fund of Tianjin University (985200550) are gratefully
acknowledged.
Yield: 113 g (65%); mp 80–82 °C.
References
IR (KBr): 3720, 3434, 2935, 2832, 2348, 2292, 1732, 1670, 1585,
1387, 1313, 1188, 1122, 791, 645, 590, 546 cm–1.
(1) (a) Enemark, E. J.; Stack, T. D. P. Angew. Chem. Int. Ed.
Engl. 1995, 34, 996. (b) Kersting, B.; Meyer, M.; Powers, R.
E.; Raymond, K. N. J. Am. Chem. Soc. 1996, 118, 7221.
(c) Albrecht, M. Chem. Soc. Rev. 1998, 27, 281.
(d) Albrecht, M. Chem. Rev. 2001, 101, 3457.
(2) (a) Albrecht, M. Angew. Chem. Int. Ed. 1999, 38, 3463.
(b) Albrecht, M.; Janser, I.; Runsink, J.; Raabe, G.; Weis, P.;
Fröhlich, R. Angew. Chem. Int. Ed. 2004, 43, 6662.
(3) Albrecht, M.; Janser, I.; Meyer, S.; Weis, P.; Fröhlich, R.
Chem. Commun. 2003, 2854.
(4) Fiedler, D.; Bergman, R. G.; Raymond, K. N. Angew. Chem.
Int. Ed. 2006, 45, 745; Angew. Chem. 2006, 118, 759.
(5) Warmuth, R.; Kerdelhue, J.-L.; Carrera, S. S.; Langenwalter,
K. J.; Brown, N. Angew. Chem. Int. Ed. 2002, 41, 96.
(6) Warmuth, R. Chem. Commun. 1998, 59.
(7) (a) Albrecht, M.; Janser, I.; Houjou, H.; Fröhlich, R. Chem.
Eur. J. 2004, 10, 2839. (b) Albrecht, M.; Napp, M.;
Schneider, M.; Weis, P.; Fröhlich, R. Chem. Eur. J. 2001, 7,
3966. (c) Albrecht, M.; Mirtschin, S.; de Groot, M.; Janser,
I.; Runsink, J.; Raabe, G.; Kogej, M.; Schalley, C. A.;
Fröhlich, R. J. Am. Chem. Soc. 2005, 127, 10371.
(8) For related work on bipyridine derivatives, see: Ziessel, R.
F.; Charbonniere, L. J.; Mameri, S.; Camerel, F. J. Org.
Chem. 2005, 70, 9835.
31P NMR (162 MHz, CDCl3): d = 29.4 (s).
1H NMR (400 MHz, CDCl3): d = 7.82 (m, 6 H), 7.70 (m, 6 H), 7.12
(t, J = 10.9 Hz, 3 H), 6.96 (t, J = 13.5 Hz, 6 H), 3.91 (s, 9 H), 3.62
(s, 9 H).
13C NMR (100 MHz, CDCl3): d = 152.9, 146.4, 141.8, 134.5, 131.8,
131.4, 129.6, 124.1, 122.2, 112.1, 60.7, 55.9.
MS (EI, 70 eV): m/z = 686.3 [M + H]+.
Anal. Calcd for C42H39O7P·H2O: C, 71.58; H, 5.86. Found: C,
71.58; H, 6.36.
4¢,4¢¢,4¢¢¢-Phosphoryltribiphenyl-2,3-diol (18)
Triscatechol 18 was prepared as a beige solid from the protected
precursor 22 by the method employed for the synthesis of biscate-
chol 3.
Yield: 95%; mp 158 °C.
IR (KBr): 3478.2, 3189.4, 3046.4, 2926.2, 2849.9, 2683.9, 2365.3,
2341.7, 2233.8, 1832.0, 1701.8, 1592.2, 1463.8, 1357.8, 1210.4,
1070.4, 891.8, 827.9, 632.2, 541.5 cm–1.
31P NMR (162 MHz, CD3OD): d = 33.4 (s).
1H NMR (400 MHz, CD3OD): d = 7.67 (m, 6 H), 7.60 (m, 6 H), 6.72
(m, 6 H), 6.64 (m, 3 H).
13C NMR (100 MHz, CD3OD): d = 145.3, 143.3, 142.6, 130.2,
131.3, 129.3, 128.4, 127.1, 120.8, 114.5.
ESI-MS: m/z = 601.4 [M]+.
(9) Lützen, A.; Hapke, M. Eur. J. Org. Chem. 2002, 2292.
(10) Albrecht, M.; Janser, I.; Fröhlich, R. Synthesis 2004, 1977.
(11) Yeh, R. M.; Xu, J.; Seeber, G.; Raymond, K. N. Inorg.
Chem. 2005, 44, 6228.
(12) Whitaker, C. M.; Kott, K. L.; McMahon, R. J. J. Org. Chem.
1995, 60, 3499.
Anal. Calcd for C36H27O7P·2H2O: C, 67.71; H, 4.89. Found: C,
67.62; H, 5.14.
(13) Miyaura, N.; Ishiyama, T.; Sasaki, H.; Ishikawa, M.; Satoh,
M.; Suzuki, A. J. Am. Chem. Soc. 1989, 111, 314.
(14) Wende, M.; Seidel, F.; Gladysz, J. A. J. Fluorine Chem.
2003, 124, 45.
Synthesis 2006, No. 18, 3037–3042 © Thieme Stuttgart · New York