Synthesis, derivatisation and structural characterisation of a new macrobicyclic phosphane oxide cryptand

Article abstract of DOI:10.1002/ejoc.200800630

Following a tripod-coupling strategy a new phosphane oxide cage compound was synthesised in comparatively high yield. The X-ray crystal structure obtained shows a large cavity and an out-positioned P=O moiety in the solid state. A stable in-isomer was not

Full text of DOI:10.1002/ejoc.200800630

FULL PAPER
DOI: 10.1002/ejoc.200800630
Synthesis, Derivatisation and Structural Characterisation of a New
Macrobicyclic Phosphane Oxide Cryptand
Frank Däbritz,[a] Anne Jäger,[a] and Ingmar Bauer*[a]
Keywords: Macrobicycles / Cryptands / Homeomorphic isomers / Phosphanes / Phosphane oxides
Following a tripod-coupling strategy a new phosphane oxide
cage compound was synthesised in comparatively high yield.
The X-ray crystal structure obtained shows a large cavity and
an out-positioned P=O moiety in the solid state. A stable in-
isomer was not detected, either during synthesis or by iso-
merisation. We attribute this fact to homeomorphic isomeri-
sation in solution at room temperature.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
sponding benzylic alcohol and subsequent bromination
with SOBr2 (Scheme 1). All steps could be realised on a
large scale. Direct Wohl–Ziegler bromination of 1 led only
to an inseparable mixture containing compounds of dif-
ferent bromination degree.
Introduction
The motive of our work was the interest in in-function-
alised macrobicycles with large cavities. Bearing a phos-
phane moiety, such structures could potentially act as li-
gands for metal-catalysed reactions[1] or as organocata-
lysts.[2] The exceptional location of the donor centre inside
the cavity might give rise to increased regio- and stereospec-
ificity. The corresponding phosphane oxides could also play
a role as ionophores.[3] Tsuji et al. pointed out that large
bowl-shaped phosphane ligands were highly effective in
C–C bond forming reactions, and the depth of the bowl af-
fected the catalytic activity considerably; in general, the
deeper bowl ligands were more effective than the shallower
ones.[1] The application of chiral phosphane ligands with a
pronounced cavity has also been reported for asymmetric
metal-catalysed allylic alkylations.[4] In our previous work
we investigated the in/out-isomerism of phosphorus bridge-
head cage compounds in the form of phosphites and phos-
phates.[5–9] The studies presented here deal with related
phosphane and phosphane oxide macrobicycles bearing one
phosphorus bridgehead atom. Corresponding phosphane
and phosphane oxides with two P-bridgeheads are de-
scribed elsewhere.[10]
Scheme 1. Synthesis of 2: a) 3.3 equiv. p-bromotoluene, Mg,
1 equiv. POCl3, THF, reflux, 2 h, 43%; b) 12 equiv. KMnO4, pyr-
idine/water = 1:2, reflux, 20 h, 99%; c) 6 equiv. SOCl2, EtOH, re-
flux, 9 h, 87%; d) 9.6 equiv. LiAlH4, THF, reflux, 18 h, 54%; e)
SOBr2, 2 drops DMF, room temp., 19 h, 67%.
We were able to determine the crystal structure of 2 by
X-ray diffraction (Figure 1).
Results and Discussion
We intended to assemble a macrobicyclic phosphane ox-
ide cryptand applying a tripod-coupling method.[11] Benzyl
bromide 2 as a basic building block was synthesised in 13%
overall yield over five steps starting from p-bromotoluene
and POCl3 by a Grignard coupling,[12] followed by oxi-
dation with KMnO4, esterification, reduction to the corre-
Figure 1. X-ray crystal structure of 2.
Mono-O-acetylated product 3 was obtained from the
corresponding, commercially available bisphenol. William-
son ether synthesis using 3 and benzyl bromide 2 followed
by in situ deprotection of the ester moieties provided the
tripodal compound 4 in 45% yield (Scheme 2).
[a] Department Chemie, Technische Universität Dresden,
Bergstrasse 66, 01062 Dresden, Germany
Fax: +49-351-46335515
E-mail: ingmar.bauer@chemie.tu-dresden.de
Eur. J. Org. Chem. 2008, 5571–5576
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F. Däbritz, A. Jäger, I. Bauer
FULL PAPER
Scheme 2. Synthesis of capping reagent 4 via Williamson ether synthesis and subsequent tripod-coupling of 4 and 5.
The synthesis of the macrobicyclic product 6 was ac-
complished by a tripod-coupling reaction of 4 and 5 under
dilute conditions (Scheme 2). The phosphane oxide 6 was
formed in a comparatively high yield of 52% as a single
isomer. To our delight, we obtained single crystals and de-
termined the crystal structure (Figures 2 and 3) showing a
huge hole and a distance between the bridgehead fragments
of about 11 Å. The P=O moiety is clearly out-positioned in
the crystalline state. Our primary aim, however, was to gain
access to a macrobicyclic phosphane with the phosphorus
lone pair directing into the cavity, thus being prepared for
ligation inside the macrobicycle. Therefore we applied a re-
duction protocol to phosphane oxide 6 using trichlorosilane
Figure 2. X-ray crystal structure of 6. Front view into the cavity.
and triethylamine, which is known to lead to inversion of Hydrogen atoms are omitted for clarity.
the configuration at the phosphorus.[13–15] Complete con-
version was verified by 31P NMR spectroscopy. The
31P NMR peak of starting phosphane oxide 6 at δ =
28.5 ppm had disappeared completely in favour of a peak at
–7.3 ppm, corresponding to the phosphane. Due to a high
tendency for oxidation during workup and purification, we
reoxidised the crude phosphane with H2O2 with retention
(Scheme 3).[15–18] Thus, we could investigate the stereo-
chemical outcome of the reductive step by making use of
the phosphane oxide product distribution. To our surprise,
after this reduction/oxidation procedure we exclusively ob-
tained a single product which turned out to be identical
with the starting phosphane oxide 6 (Scheme 3).
In contrast to our previously described less flexible
macrobicyclic systems[5–9] it was not possible to isolate
stable homeomorphic isomers, either during synthesis or by
isomerisation. We tentatively attribute this fact to a rapid
homeomorphic isomerisation in solution,[19] which is made
Figure 3. X-ray crystal structure of 6. Top view along the bridge-
head segments. Hydrogen atoms are omitted for clarity.
possible by the long and flexible arms of the macrobicyclic chlorosilane proceeding with retention of the configuration
cage. The derivative phosphane-borane complex 7 was syn- at the phosphorus,[12–14] and subsequent quenching with
thesised from phosphane oxide 6 via reduction with tri- borane-tetrahydrofuran complex (Scheme 3).[13]
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Eur. J. Org. Chem. 2008, 5571–5576

A New Macrobicyclic Phosphane Oxide Cryptand
Scheme 3. Isomerisation experiment of 6 (left) and synthesis of phosphane-borane complex 7 (right).
and POCl3 (75.52 g, 45.9 mL, 0.493 mol) was added slowly. After
Conclusions
refluxing for 1 h, the mixture was cooled to room temperature and
then quenched with water and concentrated HCl. After extraction
with dichloromethane and washing with NaHCO3, NaCl and 2 
NaOH, the combined organic layers were dried with MgSO4. The
solvent was removed under reduced pressure. Recrystallisation of
the residue from ethyl acetate/pentane gave product 1 (74.97 g,
We synthesised a new phosphane oxide macrobicycle in
high yield by a tripod-coupling strategy. The X-ray struc-
ture of this new cryptand reveals an out-position of the
P=O moiety in the solid state; however, in solution we as-
sume a fast homeomorphic isomerisation at room tempera-
ture which prevents the isolation of a stable in-isomer.
0.234 mol, 43%) as a colourless solid; m.p. 140 °C. 1H NMR
4
(300 MHz, CDCl3, 25 °C): δ = 2.37 (s, 9 H, 5-H), 7.23 (dd, JPH
=
2.4, 3JHH = 7.9 Hz, 6 H, 3-H), 7.52 (dd, 3JPH = 11.8, 3JHH = 8.1 Hz,
6 H, 2-H) ppm. 13C NMR (76 MHz, CDCl3, 25 °C): δ = 21.53 (C-
3
1
Experimental Section
5), 129.10 (d, JPC = 12.5 Hz, C-3), 129.57 (d, JPC = 106.5 Hz, C-
2
4
1), 132.03 (d, JPC = 10.2 Hz, C-2), 142.16 (d, JPC = 3.0 Hz, C-4)
ppm. 31P NMR (122 MHz, CDCl3, 25 °C): δ = 29.40 (s) ppm. ESI-
MS (10 V): m/z (%) = 321.4 (100) [M + H]+.
General: Melting points were determined on a Boëtius melting
point apparatus. 1H NMR (TMS internal reference), 13C NMR
(TMS internal reference) and 31P NMR spectra (85% H3PO4 exter-
nal reference) were recorded with Bruker DRX-500 and AC300-P
spectrometers. For detailed assignment of the NMR peaks based
on 2D NMR measurements of 4, 6 and 7 see numbering in
Scheme 2 and Scheme 3. ESI-MS spectra were determined with a
Bruker Esquire mass spectrometer with an ion trap detector. Ele-
mental analysis was carried out with a Hekatech EA 3000 Euro
Vector instrument. IR spectra were recorded with a Thermo Nico-
let Avatar 260 FT-IR instrument. Thin-layer chromatography
(TLC) was carried out on aluminum sheets coated with silica gel
obtained from Merck. Plates were visualised by UV irradiation.
Column chromatography was performed using silica gel (Merck,
0.040–0.063 mm). All reactions were carried out in dry solvents
under argon. The solvents were dried using a solvent purification
system (MBraun-SPS). Chemicals were used as received from com-
mercial sources. Reagent 5 was synthesised according to a literature
procedure.[20]
Tri(p-carboxyphenyl)phosphane
Oxide:
KMnO4
(118.40 g,
749.150 mmol) was added in small portions to a refluxing solution
of 1 (20.00 g, 64.429 mmol) in pyridine/water (150 mL, 1:2). After
each portion, the reaction mixture was kept stirring under reflux
for 1 h until the colour changed from violet to brown. After 20 h,
the hot suspension was filtered. The residual MnO2 was washed
with hot water. After acidification of the aqueous phase with semi-
concentrated H2SO4, the crude product precipitated. The solid was
separated and dissolved in NaOH (10%), and the solution was ex-
tracted with THF and EtOAc to remove residual starting material
1. The aqueous phase was again treated with semiconcentrated
H2SO4 to precipitate the product. This procedure was repeated.
The product was powdered and dried at 70 °C under vacuum to
obtain the title phosphane oxide compound (25.28 g, 61.611 mmol,
99%) as a colourless solid; m.p. 365 °C. 1H NMR (300 MHz, [D6]-
3
3
DMSO, 25 °C): δ = 7.80 (dd, JPH = 11.6, JHH = 8.3 Hz, 6 H, 2-
Tri(p-tolyl)phosphane Oxide (1): The synthesis was accomplished
according to ref.[12] In a dry flask (1 L), magnesium splints (43.64 g,
1.788 mol) and dry THF (100 mL) were combined under argon. p-
Bromotoluene (278.00 g, 200 mL, 1.625 mol) was added slowly un-
til the reaction started. The reaction mixture was cooled to 0 °C,
and the residual p-bromotoluene dissolved in dry THF (300 mL)
was added. After 1 h at reflux, the mixture was cooled to 0 °C again
H), 8.11 (dd, 4JPH = 2.5, 3JHH = 8.3 Hz, 6 H, 3-H) ppm. 13C NMR
(76 MHz, [D6]DMSO, 25 °C): δ = 129.60 (d, JPC = 12.2 Hz, C-3),
3
2
4
131.96 (d, JPC = 10.3 Hz, C-2), 134.29 (d, JPC = 2.7 Hz, C-4),
136.16 (d, JPC = 101.1 Hz, C-1), 166.58 (COOH) ppm. 31P NMR
1
(122 MHz, [D6]DMSO, 25 °C): δ = 24.69 (s) ppm. ESI-MS (25 V):
m/z (%) = 843.1 (34) [2M + Na]+, 821.2 (100) [2M + H]+, 433 (5)
[M + Na]+, 411.1 (38) [M + H]+. IR (ATR): ν = 2880 (w, br, O–
˜
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5573

F. Däbritz, A. Jäger, I. Bauer
FULL PAPER
HH-linked), 2619 (w, br), 2500 (w, br), 1690 (st, C=O), 1396, 1235 Tri(p-bromomethylphenyl)phosphane Oxide (2): Under argon,
(P=O), 1162 (st), 1100 (st), 1016, 856, 762, 695 (st) cm–1.
SOBr2 (6 mL, 16.10 g, 77.330 mmol) was added at room tempera-
ture to tri(p-hydroxymethylphenyl)phosphane oxide (100.0 mg,
0.272 mmol) and dry DMF (2 drops). After stirring for 19 h at
room temperature, the solution was slowly diluted with CH2Cl2
(50 mL) and water (50 mL). NaOH (40%) was added until the solu-
tion reached pH 11. After separation of the phases, the aqueous
layer was extracted with CH2Cl2. The combined organic layers were
dried with MgSO4, and the solvent was evaporated under reduced
pressure. After column chromatography on silica gel eluting with
EtOAc/CH2Cl2 = 1:2, product 2 was obtained as a colourless, crys-
Tri(p-ethoxycarbonyl)phosphane Oxide: SOCl2 (70.72 mL, 115.30 g,
0.949 mol) was slowly added to a suspension of tri(p-carb-
oxyphenyl)phosphane oxide (64.94 g, 0.158 mol) in EtOH (1 L).
The solution was kept stirring under reflux until HCl formation
finished (≈ 9 h). The progress of the reaction was monitored by
thin-layer chromatography with EtOAc (product: Rf = 0.5). The
solution was cooled to room temperature, and the solid precipitate
was separated and dissolved in dichloromethane. The solution was
washed with water and a saturated NaCl solution and dried with
MgSO4. After removal of the solvent under vacuum, the crude
product was separated from by-products by column chromatog-
raphy on silica gel, eluting with CH2Cl2, followed by EtOAc to
release the product. After removal of the solvent under vacuum,
the title ester was obtained as a colourless solid (67.88 g, 0.137 mol,
87%); m.p. 79 °C. 1H NMR (300 MHz, CDCl3, 25 °C): δ = 1.39 (t,
1
talline solid (101.8 mg, 0.183 mmol, 67%); m.p. 176 °C. H NMR
4
(300 MHz, CDCl3, 25 °C): δ = 4.42 (s, 6 H, 5-H), 7.42 (dd, JPH
=
2.6, 3JHH = 8.3 Hz, 6 H, 3-H), 7.57 (dd, 3JPH = 11.7, 3JHH = 8.2 Hz,
6 H, 2-H) ppm. 13C NMR (76 MHz, CDCl3, 25 °C): δ = 32.03 (d,
5JPC = 1.2 Hz, C-5), 129.17 (d, JPC = 12.6 Hz, C-3), 132.09 (d,
3
1JPC = 104.7 Hz, C-1), 132.49 (d, JPC = 10.4 Hz, C-2), 141.93 (d,
2
4JPC = 2.9 Hz, C-4) ppm. 31P NMR (122 MHz, CDCl3, 25 °C): δ
= 27.45 (s) ppm. ESI-MS (10 V): m/z (%) = 561.8 (7) [M(3·81Br/
1·13C)+H]+, 560.8 (33) [M(3·81Br/12C)+H]+, 559.8 (22) [M(1·79Br/
2·81Br/1·13C)+H]+, 558.8 (100) [M(1·79Br/2·81Br/12C)+H]+, 557.8
(23) [M(2·79Br/1·81Br/1·13C)+H]+, 556.8 (99) [M(2·79Br/1·81Br/12C)
+H]+, 555.8 (7) [M(3·79Br/1·13C)+H]+, 554.8 (31) [M(3·79Br/12C)
3
3JHH = 7.2 Hz, 9 H, –COOCH2CH3), 4.40 (q, JHH = 7.1 Hz, 6
3
3
H, –COOCH2CH3), 7.73 (dd, JPH = 11.8, JHH = 8.5 Hz, 6 H, 2-
H), 8.13 (dd, 4JPC = 2.6, 3JHH = 8.4 Hz, 6 H, 3-H) ppm. 13C NMR
(76 MHz, CDCl3, 25 °C): δ = 14.25 (–COOCH2CH3), 61.57 (–CO-
3
2
OCH2CH3), 129.62 (d, JPC = 12.4 Hz, C-3), 132.02 (d, JPC
=
=
4
1
10.2 Hz, C-2), 134.09 (d, JPC = 2.4 Hz, C-4), 136.10 (d, JPC
+H]+. IR (ATR): ν = 1600 (νC=C), 1402 (P-phenyl), 1232 (P=O),
˜
101.8 Hz, C-1), 165.52 (–COOEt) ppm. 31P NMR (122 MHz,
CDCl3, 25 °C): δ = 26.98 (s) ppm. ESI-MS (25 V): m/z (%) = 533.0
(16) [M + K]+, 517.1 (6) [M + Na]+, 495.2 (100) [M + H]+. IR
1201, 1178 (st), 1112 (st), 1090, 833, 817, 660 (st, C–Br), 607 (st,
C–Br) cm–1. C21H18Br3OP (557.05): calcd. C 45.28, H 3.26; found
C 45.45, H 3.16.
(ATR): ν = 2983 (w), 1712 (st, C=O), 1397, 1366, 1270 (st, CO–
˜
O), 1197, 1095 (st, CO–O), 1016 (st), 856, 764, 733 (st), 696 (st) Mono-O-acetylated Bisphenol 3: Under argon, Ac2O (0.78 mL,
cm–1. C27H27O7P (494.47): calcd. C 65.58, H 5.50; found C 65.55,
H 5.53.
0.85 g, 8.326 mmol) was added dropwise (over 1 h) at room tem-
perature with vigorous stirring to a solution of 4,4Ј-(1,4-phenylene-
dipropane-2,2-diyl)diphenol (5.71 g, 16.490 mmol) and dry pyr-
idine (3.32 mL, 3.27 g, 41.210 mmol) in dry THF (300 mL). The
solution was stirred for 45 min, and the reaction mixture was
quenched with water and extracted with CH2Cl2. The combined
organic layers were washed with saturated solutions of NH4Cl and
NaCl. After drying with MgSO4 and solvent evaporation under
vacuum, the crude product was purified by column chromatog-
raphy on silica gel with pentane/diethyl ether = 2:1. Compound 3
was obtained in 72% yield (Ac2O was the limiting reagent) as a
Tri(p-hydroxymethylphenyl)phosphane Oxide: A solution of tri(p-
ethoxycarbonyl)phosphane oxide (67.88 g, 0.137 mol) in dry THF
(500 mL) was added dropwise under argon to a refluxing suspen-
sion of LiAlH4 (50.02 g, 1.317 mol) in dry THF (800 mL). The pro-
gress of the reaction was monitored by thin-layer chromatography
with EtOH. After quenching with water and acidification with
H2SO4 (25%) the solvents (EtOH, water) were removed under re-
duced pressure. The residue was dissolved in EtOH, and the solu-
tion was dried with MgSO4. The product mixture contained about
13% of the corresponding phosphane according to 31P NMR spec-
troscopy. In order to oxidize the phosphane to the desired product,
the solution was treated at room temp. with H2O2 (30%, 2 mL) for
30 min. After evaporation of the solvent under reduced pressure,
the product was purified by chromatography on silica gel. Elution
with CH2Cl2 removed nonpolar by-products. Subsequently, the
product was eluted with EtOH. The solvent was removed under
reduced pressure, and the residue was dried at 75 °C for 10 h under
vacuum. Tri(p-hydroxymethylphenyl)phosphane oxide was ob-
tained as a yellow, hygroscopic powder (27.32 g, 0.074 mol, 54%);
1
colourless solid (2.30 g, 5.928 mmol, 72%); m.p. 112 °C. H NMR
(300 MHz, CDCl3, 25 °C): δ = 1.56 (s, 6 H, 15-H or 16-H), 1.57 (s,
3
6 H, 15-H or 16-H), 2.21 (s, 3 H, 18-H), 6.65 (d, JHH = 8.8 Hz, 2
3
H, 2-H), 6.89 (d, JHH = 8.7 Hz, 2 H, 3-H), 7.03 (s, 4 H, 7/8-H),
3
3
7.03 (d, JHH = 8.8 Hz, 2 H, 13-H), 7.15 (d, JHH = 8.8 Hz, 2 H,
12-H) ppm. 13C NMR (76 MHz, [D6]DMSO, 25 °C): δ = 20.87
(C-18), 30.43 (C-15 or C-16), 30.62 (C-15 or C-16), 41.27 (C-5 or
C-10), 41.77 (C-5 or C-10), 114.67 (C-2 or C-13), 121.20 (C-2 or
C-13), 125.95 (C-7 or C-8), 126.07 (C-7 or C-8), 127.37 (C-3 or C-
12), 127.48 (C-3 or C-12), 140.42 (C-4 or C-6 or C-9 or C-11 or C-
14), 146.84 (C-4 or C-6 or C-9 or C-11 or C-14), 147.73 (C-4 or
C-6 or C-9 or C-11 or C-14), 147.99 (C-4 or C-6 or C-9 or C-11
or C-14), 148.24 (C-4 or C-6 or C-9 or C-11 or C-14), 155.04 (C-
1), 169.28 (C-17) ppm. ESI-MS (25 V): m/z (%) = 406.2 (100) [M
1
m.p. 230 °C. H NMR (300 MHz, [D6]DMSO, 25 °C): δ = 4.57 (d,
3
3JHH = 5.5 Hz, 6 H, 5-H), 5.36 (t, JHH = 5.7 Hz, 3 H, –OH), 7.48
4
3
3
(dd, JPH = 2.4, JHH = 7.8 Hz, 6 H, 3-H), 7.56 (dd, JPH = 11.2,
3JHH = 8.0 Hz, 6 H, 2-H) ppm. 13C NMR (126 MHz, [D6]DMSO,
25 °C): δ = 62.47 (C-5), 126.46 (d, 3JPC = 12.0 Hz, C-3), 131.23 (d,
+ NH ]+. IR (ATR): ν = 3472, 3422 (br., νO–H), 2965 (st), 1732 (st,
˜
4
C=O), 1612, 1506 (st), 1433, 1368, 1269 (st), 1231 (st, CO–O), 1203
(st, CO–O), 1089, 1016 (st), 916, 844, 830 (st, p-disubst. aromatics),
810, 603 cm–1. C26H28O3 (388.50): calcd. C 80.38, H 7.26; found C
80.48, H 7.39.
1JPC = 104.1 Hz, C-1), 131.42 (d, JPC = 9.9 Hz, C-2), 146.85 (d,
2
4JPC = 2.4 Hz, C-4) ppm. 31P NMR (122 MHz, [D6]DMSO, 25 °C):
δ = 25.70 (s) ppm. ESI-MS (10 V): m/z (%) = 759.2 (100) [2M +
Na]+, 757.1 (24), 743.2 (42), 737.2 (12) [2M + H]+, 735.2 (10), 655.2
(27), 639.2 (18), 633.2 (20), 623.2 (6), 617.2 (11), 607.1 (4), 497.1
(2), 475.1 (4), 391.1 (12) [M + Na]+, 383.1 (4), 369.1 (43)
Phosphane Oxide 4: In a flask (100 mL) under argon, compound 3
(251.1 mg, 0.646 mmol) was dissolved in dry acetone (50 mL). Dry
NaI (5.8 mg, 0.039 mmol), dry K2CO3 (71.5 mg, 0.517 mmol) and
benzyl bromide 2 (72.0 mg, 0.129 mmol) were added. After stirring
15 h at room temperature, the solvent was evaporated under re-
[M + H]+, 260.9 (5). IR (ATR): ν = 3267 (st, br, νO–H), 2914 (w),
˜
2856 (w), 1602, 1400 (P–phenyl), 1162, 1114 (st), 1014 (st), 804 670
(st) cm–1.
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A New Macrobicyclic Phosphane Oxide Cryptand
duced pressure. The residue was dissolved in THF, and after ad-
dition of NaOH (4%, 10 mL), the solution was stirred for an ad-
ditional 30 min at room temperature. The solvent was evaporated,
and the crude product was dissolved in CH2Cl2 and washed with
water. After separation of the phases, extraction of the aqueous
phase with CH2Cl2, treatment of the combined organic layers with
saturated solutions of NaHCO3, NH4Cl and NaCl, and drying with
MgSO4, the solvent was evaporated. After column chromatography
on silica gel with EtOAc/CH2Cl2 = 1:4, compound 4 was obtained
as a yellow solid (78.3 mg, 0.058 mmol, 45%); m.p. 126 °C. 1H
NMR (500 MHz, [D6]DMSO, 25 °C): δ = 1.54 (s, 18 H, 16-H), 1.56
147.76 (C-6 or C-9), 156.28 (C-14), 156.50 (C-1) ppm. 31P NMR
(122 MHz, CDCl3, 25 °C): δ = 28.48 (s) ppm. ESI-MS (100 V):
m/z (%) = 1467.8 (100) [M + H]+. IR (ATR): ν = 2962, 2927, 2866,
˜
1605, 1507, 1459, 1401, 1360, 1297, 1221, 1180, 1113, 1014, 827,
677 cm–1.
Phosphane–Borane Complex 7: The following reaction procedure is
based on a method described by Odinets et al. for the reduction of
phosphane oxides with trichlorosilane and subsequent trapping of
the products as phosphane–borane complexes.[12] In
a flask
(25 mL) under argon, macrobicycle 6 (95.4 mg, 0.065 mmol) was
dissolved in dry benzene. HSiCl3 (0.07 mL, 88.9 mg, 0.650 mmol)
was added. The reaction mixture was stirred for 24 h at room tem-
perature, and the progress of the reaction was followed by thin-
layer chromatography with CH2Cl2 (phosphane: Rf ≈ 1, phosphane
oxide: Rf ≈ 0.4). Subsequently, the reaction was quenched with a
1  solution of BH3–THF (0.97 mL, 83.8 mg, 0.975 mmol) in THF
and stirred for 15 min at room temperature. After addition of water
and extraction with EtOAc, the combined organic layers were
washed with a saturated NaCl solution and dried with MgSO4.
After solvent removal and column chromatography on silica gel
with pentane/diethyl ether = 3:1, the phospane–borane complex 7
was obtained as a yellow solid (19.8 mg, 0.014 mmol, 21%);
m.p. 184 °C. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 1.64 (s, 36
H, 15/16-H), 5.01 (s, 6 H, 17-H), 5.02 (s, 6 H, 20-H), 6.81 (d, 3JHH
3
(s, 18 H, 15-H), 5.12 (s, 6 H, 17-H), 6.64 (d, JHH = 8.6 Hz, 6 H,
3
3
2-H), 6.89 (d, JHH = 8.7 Hz, 6 H, 13-H), 6.99 (d, JHH = 8.6 Hz,
3
6 H, 3-H), 7.07 (s, 12 H, 7/8-H), 7.11 (d, JHH = 8.7 Hz, 6 H, 12-
H), 7.59 (dd, 4JPH = 1.9, 3JHH = 8.2 Hz, 6 H, 19-H), 7.65 (dd, 3JPH
3
= 11.4, JHH = 8.2 Hz, 6 H, 20-H), 9.18 (s, 3 H, OH), 11.68 (s,
hydrogen bonding, ≈ 0.12 H, weakens after dehydration in the vac-
uum oven) ppm. 13C NMR (126 MHz, [D6]DMSO, 25 °C): δ =
30.55 (C-15), 30.64 (C-16), 41.25 (C-5), 41.40 (C-10), 68.58 (C-17),
114.17 (C-13), 114.68 (C-2), 125.93 (C-7 or C-8), 125.97 (C-7 or C-
3
8), 127.38 (C-3), 127.57 (C-12), 127.60 (d, JPC = 12.1 Hz, C-19,
signal partially overlapped by C-12), 131.75 (d, 2JPC = 10.0 Hz, C-
20), 132.05 (d, 1JPC = 103.4 Hz, C-21), 140.46 (C-4), 141.62 (C-18),
142.78 (C-11), 147.33 (C-6), 147.80 (C-9), 155.06 (C-1), 156.03 (C-
14) ppm. 31P NMR (203 MHz, [D6]DMSO, 25 °C): δ = 25.00 (s)
ppm. ESI-MS (–75 V): m/z (%) = 1351.2 (100) [M – H]– found,
3
= 8.8 Hz, 6 H, 13-H), 6.83 (d, JHH = 8.9 Hz, 6 H, 2-H), 7.10–7.11
4
(m, 24 H, 3/7/8/12-H), 7.42 (s, 3 H, 19-H), 7.45 (dd, JPH = 1.8,
1351.7 [M – H]– calcd. IR (ATR): ν = 3037 (w, br), 2961, 2924,
˜
3
3
3JHH = 8.1 Hz, 6 H, 22-H), 7.55 (dd, JPH = 10.6, JHH = 8.3 Hz,
6 H, 23-H) ppm. 13C NMR (76 MHz, CDCl3, 25 °C): δ = 30.68
(C-15 or C-16), 30.77 (C-15 or C-16), 41.85 (C-5/10), 69.27 (C-20),
2852, 1607, 1508 (st, P-phenyl), 1460, 1402, 1361, 1297, 1225 (st,
P=O), 1178 (st), 1117, 1089, 1015, 828 (st, p-disubst. aromatics),
679 cm–1. C93H93O7P (1353.70): calcd. C 82.51, H 6.92; found C
82.48, H 6.94.
69.72 (C-17), 114.04 (C-2 or C-13), 114.09 (C-2 or C-13), 125.83
3
(C-19), 126.22 (C-7 or C-8), 126.24 (C-7 or C-8), 127.53 (d, JPC
=
1
10.4 Hz, C-22), 127.77 (C-3/12), 128.52 (d, JPC = 58.4 Hz, C-24),
133.40 (d, JPC = 10.0 Hz, C-23), 138.00 (C-18), 140.83 (C-21),
Macrobicyclic Phosphane Oxide (6): In a flask (1 L) under argon,
a suspension of dry K2CO3 (7.96 g, 57.620 mmol) and KI (0.024 g,
0.144 mmol) in dry DMF (650 mL) was provided. After heating to
110 °C, a solution of alcohol 4 (0.65 g, 0.480 mmol) in dry DMF
(50 mL) and simultaneously a solution of 1,3,5-tri(bromomethyl)-
benzene 5[20] (0.171 g, 0.480 mmol) in dry DMF (50 mL) were
added dropwise with two perfusors over about 2 h with equal drop
speeds. The reaction mixture was stirred at 110 °C for 42 h, during
which the solution colour changed from pink to grey. The reaction
was quenched with a saturated NaHCO3 solution, stirred for ad-
ditional 10 min at 110 °C, and then cooled to room temperature.
The solvent was evaporated under reduced pressure, and the resi-
due was dissolved in THF. The organic phase was washed with
saturated solutions of NH4Cl and NaCl, and dried with MgSO4.
After evaporation of the solvent and column chromatography on
silica gel with CH2Cl2/EtOH = 100:5, the product 6 was obtained
as a yellow solid (0.364 g, 0.248 mmol, 52%). Compound 6 could
be recrystallised from CH2Cl2/acetone to form thin plates;
m.p. 170 °C. 1H NMR (300 MHz, CDCl3, 25 °C): δ = 1.58 (s, 36
H, 15/16-H), 4.94 (s, 6 H, 17-H), 4.97 (s, 6 H, 20-H), 6.74* (dd,
3JHH = 8.7, 4JHH = 1.9 Hz, 6 H, 13-H), 6.76* (dd, 3JHH = 8.9, 4JHH
2
143.43 (C-4 or C-11), 143.67 (C-4 or C-11), 147.75 (C-6 or C-9),
147.77 (C-6 or C-9), 156.34 (C-14), 156.53 (C-11) ppm. 31P NMR
(203 MHz, CDCl3, 25 °C): δ = 19.67 (s) ppm. ESI-MS (25 V):
m/z (%) = 1483.6 (88) [M(1·11B/1·13C) + NH4]+, 1482.6 (100)
[M(1·11B/12C) + NH4]+, 1481.6 (29) [M(1·10B/12C)+NH4]+. ESI-MS
(100 V): m/z (%) = 1503.7 (34) [M + K]+, 1489.7 (75) [M – BH3+
K]+, 1487.7 (42) [M + Na]+, 1482.7 (18) [M + NH4]+, 1473.7 (79)
[M – BH3+Na]+, 1465.8 (19) [M + H]+, 1451.8 (100) [M –
BH +H]+. IR (ATR): ν = 2959, 2922, 2852, 1509, 1462, 1378, 1243,
˜
3
1182, 1018, 829, 739 cm–1.
Crystal Data of 2: C21H18Br3OP, Mr = 557.05 gmol–1, colourless
crystal 0.20ϫ0.10ϫ0.07 mm3, monoclinic, space group P21/c
(No. 14), a = 17.0513(5) Å, b = 11.4785(3) Å, c = 10.5829(2) Å, α
= 90°, β = 96.511(1)°, γ = 90°, V = 2057.96(9) Å3, Z = 4, ρcalcd.
=
1.798 gcm–3, µ = 5.966 mm–1, empirical absorption correction from
SORTAV (0.382ՅTՅ0.680), λ = 0.71073 Å, T = 223(2) K, ω and
φ scans, 11364 reflections collected (Ϯ h, Ϯ k, Ϯ l), [sinθ/λ] =
0.60 Å–1, 3635 independent (Rint = 0.075) and 2239 observed reflec-
tions [IՆ2σ(I)], 255 refined parameters, R = 0.071, wR2 = 0.172,
max./min. residual electron density 1.53/–0.90 e·Å–3. The structure
was solved by direct methods and refined by full-matrix least-
squares on F2. Hydrogen atoms were calculated and refined as ri-
ding atoms. Br was disordered and refined with split positions.
3
= 1.9 Hz, 6 H, 2-H), 7.03* (s, 12 H, 7/8-H), 7.04* (dd, JHH = 8.5,
4
4JHH = 1.9 Hz, 12 H, 3/12-H), 7.35 (s, 3 H, 19-H), 7.41 (dd, JPH
3
3
3
= 2.4, JHH = 8.2 Hz, 6 H, 22-H), 7.58 (dd, JPH = 11.7, JHH
=
8.2 Hz, 6 H, 23-H) ppm. * signal partially superposed. 13C NMR
(126 MHz, CDCl3, 25 °C): δ = 30.65 (C-15 or C-16), 30.76 (C-15
or C-16), 41.82 (C-5/10), 69.27 (C-20), 69.67 (C-17), 114.02 (C-2
or C-13), 114.05 (C-2 or C-13), 125.80 (C-19), 126.19 (C-7 or C-
Crystal Data of 6: C102H99O7P, Mr = 1467.78 gmol–1, colourless
3
¯
crystal 0.60ϫ0.25ϫ0.10 mm , triclinic, space group P1 (No. 2),
3
8), 126.22 (C-7 or C-8), 127.19 (d, JPC = 12.2 Hz, C-22), 127.76
a = 15.214(3) Å, b = 19.131(1) Å, c = 19.787(4) Å, α = 117.15(1)°,
1
2
(C-3/12), 131.75 (d, JPC = 104.2 Hz, C-24), 132.34 (d, JPC
=
β = 108.52(2)°, γ = 94.98(1)°, V = 4672.3(13) Å3, Z = 2, ρcalcd.
=
10.1 Hz, C-23), 137.97 (C-18), 141.53 (d, JPC = 2.4 Hz, C-21), 1.043 gcm–3,
µ =
0.080 mm–1, absorption correction from
4
143.38 (C-4 or C-11), 143.64 (C-4 or C-11), 147.73 (C-6 or C-9), SADABS (0.795ՅTՅ0.992), λ = 0.71073 Å, T = 198(2) K, φ
Eur. J. Org. Chem. 2008, 5571–5576
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5575

F. Däbritz, A. Jäger, I. Bauer
FULL PAPER
[8] I. Bauer, M. Gruner, S. Goutal, W. D. Habicher, Chem. Eur. J.
2004, 10, 4011–4016.
[9] I. Bauer, G. G. Sergeenko, I. y. S. Nizamov, G. Theumer, R.
Fröhlich, A. R. Burilov, V. I. Maslennikova, W. D. Habicher,
ARKIVOC 2004, xii, 38–46.
[10] F. Däbritz, G. Theumer, M. Gruner, I. Bauer, Tetrahedron
2008, submitted.
scans, 110134 reflections collected (Ϯ h, Ϯ k, Ϯ l), [sinθ/λ] =
0.61 Å–1, 17041 independent (Rint = 0.104) and 9763 observed re-
flections [IՆ2σ(I)], 973 refined parameters, R = 0.086, wR2
=
0.212, max./min. residual electron density 0.47/–0.31 e·Å–3. The
structure was solved by direct methods and refined by full-matrix
least-squares on F2. Hydrogen atoms were calculated and refined
as riding atoms. Solvent free reflection dataset was produced by
PLATON/SQUEEZE.
[11]
[12]
[13]
B. Dietrich, P. Viout, J.-M. Lehn, Macrocyclic Chemistry, VCH,
Weinheim, 1992.
W.-N. Chou, M. Pomerantz, J. Org. Chem. 1991, 56, 2762–
2769.
I. L. Odinets, N. M. Vinogradova, E. V. Matveeva, D. D. Golo-
vanov, K. A. Lyssenko, G. Keglevich, L. Kollár, G.-V. Roesch-
enthaler, T. A. Mastryukova, J. Organomet. Chem. 2005, 690,
2559–2570.
CCDC-685055 (for 2) and -685056 (for 6) contain the supplemen-
tary crystallographic data for this paper. These data can be ob-
tained free of charge from The Cambridge Crystallographic Data
Centre via www.ccdc.cam.ac.uk/data_request/cif.
[14]
[1] H. Ohta, M. Tokunaga, Y. Obora, T. Iwai, I. Tetsuo, T.
Fujihara, Y. Tsuji, Org. Lett. 2007, 9, 89–92.
L. Horner, W. D. Balzer, Tetrahedron Lett. 1965, 1157–1162.
[15] L. D. Quin, A Guide to Organophosphorus Chemistry, Wiley In-
[2] J. L. Methot, W. R. Roush, Adv. Synth. Catal. 2004, 346, 1035–
tersience, New York, 2000.
1050.
[16] L. Horner, H. Winkler, A. Rapp, A. Mentrup, H. Hoffmann,
P. Beck, Tetrahedron Lett. 1961, 161–166.
[17] L. Horner, Pure Appl. Chem. 1964, 9, 225–244.
[18] K. M. Pietrusiewicz, M. Zablocka, Chem. Rev. 1994, 94, 1375–
1411.
[3] G. G. Talanova, Ind. Eng. Chem. Res. 2000, 39, 3550–3565.
[4] B. M. Trost, D. L. Van Vranken, Chem. Rev. 1996, 96, 395–422.
[5] I. Bauer, W. D. Habicher, I. S. Antipin, O. G. Sinyashin, Russ.
Chem. Bull. Int. Ed. 2004, 53, 1402–1416.
[6] I. Bauer, O. Rademacher, M. Gruner, W. D. Habicher, Chem.
Eur. J. 2000, 6, 3043–3051.
[7] I. Bauer, R. Fröhlich, A. Y. Ziganshina, A. V. Prosvirkin, M.
Gruner, E. K. Kazakova, W. D. Habicher, Chem. Eur. J. 2002,
8, 5622–5629.
[19] R. W. Alder, S. P. East, Chem. Rev. 1996, 96, 2097–2111.
[20] F. Vögtle, M. Zuber, R. G. Lichtenthaler, Chem. Ber. 1973, 106,
717–719.
Received: June 25, 2008
Published Online: October 10, 2008
5576
www.eurjoc.org
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 5571–5576