Acetylene-substituted phosphane oxides: Building blocks for macrocycles

Article abstract of DOI:10.1002/ejoc.200600877

Phosphorus-based macrocycles with acetylenic scaffolds have been built from acetylene-substituted phosphane oxides that were formed from diisopropylphosphoramidic dibromide (3) and an acetylenic Grignard reagent. The four-and six-edged macrocycles 15 and

Full text of DOI:10.1002/ejoc.200600877

FULL PAPER
DOI: 10.1002/ejoc.200600877
Acetylene-Substituted Phosphane Oxides: Building Blocks for Macrocycles
Sander G. A. van Assema,[a] G. Bas de Jong,[a] Andreas W. Ehlers,[a] Frans J. J. de Kanter,[a]
Marius Schakel,[a] Anthony L. Spek,[b] Martin Lutz,[b] and Koop Lammertsma*[a]
Keywords: Phosphorus heterocycles / Alkynes / Macrocycles / Cross-coupling / Phosphanes
Phosphorus-based macrocycles with acetylenic scaffolds
have been built from acetylene-substituted phosphane ox-
ides that were formed from diisopropylphosphoramidic di-
bromide (3) and an acetylenic Grignard reagent. The four-
and six-edged macrocycles 15 and 16, in which the iPr2NP(O)
units are connected through 1,3-butadiyne rods, were ob-
tained from the monosilylated derivative of iPr2NP(O)(C2H)2
(7) by multiple acetylene coupling reactions under oxidative
Hay conditions. Reaction of iPr2NP(O)(Br)2 (3) with lithiated
1,2-diethynylbenzene gave a mixture of cis and trans mono-
cyclic bis(phosphane oxide) 18. An X-ray crystal structure
determination of the trans isomer shows the ring structure to
adopt a puckered form.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2007)
In the study reported herein we used ethynylphosphane
oxides as the starting point for the synthesis of cyclic
P/C frames to simplify product handling. These oxides are
commonly generated from air-sensitive ethynylphosphanes
by peroxide oxidation.[7] However, we have used a diethyn-
ylphosphane oxide with an amine substituent, which has
the advantage over P-alkyl and P-aryl groups in that it en-
ables further functionalization.[8]
Introduction
Acetylenic scaffolds have been heavily pursued over the
past decade, mainly because of their optoelectronic proper-
ties.[1] From the perspective of carbon networks, beautifully
designed one-, two-, and three-dimensional scaffolds have
been prepared.[2] Remarkably, with the exception of sulfur-
based molecules, heteroatoms have rarely been embedded
in these rigid wires, rings, boxes, and cages. Especially in
the context of the special P/C relationship,[3] it is surprising
that hardly any attention has been paid to the incorporation
of phosphorus atoms. Examples of their potential are the
thiophene- and pyridine-conjugated phospholes that pos-
sess optical and electrochemical properties.[4]
Only a few examples are known of phosphorus-contain-
ing carbon skeletons. In 1990 Scott and co-workers[5] re-
ported on alkynyl-conjugated organophosphorus ring
structures such as 1. Later, Märkl et al.[6] reported on the
synthesis of cyclic ethynylphosphanes like 2.
Results and Discussion
The synthesis and manipulation of the building blocks
will be discussed first, followed by an evaluation of the
Grignard and oxidative Hay coupling reactions in the con-
struction of P/C macrocycles. A P/C ring structure obtained
from 1,2-diethynylbenzene and diisopropylphosphoramidic
dibromide is described in the final section.
Building Blocks
Diisopropylphosphoramidic dibromide [iPr2NP(O)Br2]
(3) (Scheme 1), a potential corner unit of P/C rings, can
be generated from oxygen- and moisture-sensitive
iPr2NPBr2,[9] obtained from the addition of diisopropyl-
amine to PBr3 (85%), by reaction with ozone at –78 °C in
[a] Department of Organic and Inorganic Chemistry, Faculty of
Sciences, Vrije Universiteit,
De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands
[b] Bijvoet Center for Biomolecular Research, Crystal and Struc-
tural Chemistry, Utrecht University,
Padualaan 8, 3584 CH Utrecht The Netherlands
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Scheme 1. Synthesis of iPr2NP(O)Br2 (3).
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K. Lammertsma et al.
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dichloromethane (70%), as monitored by 31P NMR spec- Grignard Reactions
troscopy (+174.3 Ǟ –34.1 ppm) for maximum conversion.
Our first approach was to use both building blocks 3 and
7 to form cyclic P/C frames in a single step. Bis-Grignard
reagent 9 could be formed from 7 and EtMgBr (or n-BuLi),
as quenching with TMSCl to give 6 suggests, but reaction
with 3 at –78 °C Ǟ room temp. did not give the desired
ring products. Instead, rapid polymerization occurred above
–20 °C. 31P NMR analysis showed the presence of some
unreacted 7 in the reaction mixture. Since the same polyme-
rization reaction occurred in the absence of 3, it would ap-
pear that bis-Grignard reagent 9 is unstable under the reac-
tion conditions and presumably reacts faster intermo-
lecularly with a P=O group than with 3. Likewise, reaction
of a mono-Grignard reagent, generated from 10, with 3 also
resulted in a black insoluble material instead of giving tri-
phosphinoyl coupling product 11 (Scheme 3). Compound
10 was obtained from the mono-anion of 7 by Et3SiCl
quenching, giving a mixture, separable by chromatography,
of the product (53%), starting material (17%), and a di-
silylated product (trace).[15]
Replacing the bromines of 3 by acetylene units gives a
potentially even better building block, but reaction with
HCϵC–MgBr (2 equiv.) mainly resulted in a black un-
identified (polymeric) material with only trace amounts of
the dialkynylated phosphane oxide. Apparently, the Grig-
nard reagent (or the product) is not stable under the reac-
tion conditions. Use of the silyl-protected Grignard reagent
BrMgCϵCTMS (4) gave dialkynylphosphinic amide 6
(80%) via nonisolable monoalkynylated intermediate 5
[δ(31P) = –15 ppm] (Scheme 2). Purification of 6 by column
chromatography with either silica gel or aluminium oxide
led to partial desilylation,[7a] whereas tetrabutylammonium
fluoride (TBAF) on silica in wet THF at –78 °C gave full
conversion into 7 (68% isolated yield) (Scheme 2) which is
a stable solid that can be kept for months when stored be-
low 0 °C. Related building blocks such as sterically pro-
tected diethynylphosphanes and butadiynylphosphanes
have been reported by Yoshifuji and co-workers.[10]
Scheme 2. Synthesis of phosphinic amide 7 and phosphinate 8.
Whereas 7 did not hydrolyze with HCl(g)/Et2O nor with
conc. HCl,[11] the amine substituent could be replaced by a
methoxy group by reaction with BF3·OEt2 in methanol to
give phosphinate 8 (50%) as a volatile light-yellow liquid
(Scheme 2).[12] 31P NMR monitoring of the reaction
showed the clean conversion of 7 (δ = –21.5 ppm) into
product 8 (δ = –19.6 ppm). The presence of the MeO group
is evident from the signals at δ(1H) = 3.87 ppm [3J(P,H) =
13.9 Hz] and δ(13C) = 53.3 ppm [2J(P,C) = 5.8 Hz]. There
are many methods for converting phosphinates into phos-
phinic chlorides, for example, with PCl5, SOCl2, COCl2,[13]
enabling further substitution. Instead of dibromide 3 we
Scheme 3. Attempted Grignard condensation reactions.
The unwanted behavior of the acetylenic phosphane ox-
ides[16] suggests that the acetylide attacks the acetylenic
phosphorus atom rather than the P–Br bond of 3, which
relates to the dephosphinylation of N-(diphenylphos-
phanyl)aziridines by organometallic reagents like PhLi.[12]
Acetylene Self-Coupling Reactions
Our next approach was to use a single building block,
also explored the potential of iPr2NP(O)Cl2, synthesized ethynylphosphinic amide 10, to form the P/C cycles by
from iPr2NPCl2 by ozone oxidation,[14] as a precursor to 6, intermolecular coupling of acetylenic groups. Various coup-
but reaction with BrMgCϵCTMS (4) required tempera- ling procedures may be considered such as the Glaser,[17]
tures above 50 °C, causing degradation of the Grignard rea- Englinton,[18] and Hay[19] reactions which are well known
gent.
in the formation of acetylene scaffolds of carbon analogues.
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Acetylene-Substituted Phosphane Oxides
FULL PAPER
However, only the Pericàs modification of the oxidative symmetry has three nonequivalent phosphorus centers,
Hay coupling reaction, which is also used to synthesize di- while each of the other three isomers 15a,c,d has four equiv-
alkoxybutadiynes from alkoxyacetylenes,[20] gave coupling alent phosphorus centers.[6]
product 12 in 67% yield (Scheme 4). The protective silyl
groups of 12, which slowly degrades in CDCl3, turning
brown, were removed at –78 °C with TBAF on silica to give
13 (60%), which may exist in two diastereomeric (racemic
and meso) forms. Hence, while two 31P NMR chemical
shifts would be expected,[6] the observed single one at δ =
–21.9 ppm may indicate that the difference between them is
too small to detect.
Scheme 5. Dimerization of 15 under oxidative Hay conditions.
The second fraction (12%, Rf = 0.38–0.48) showed a
sharp singlet at δ(31P) = –24.1 ppm (16%) and broad unre-
solved resonances from δ = –23.5 to –23.2 ppm (84%).
High-resolution mass spectrometry indicated the mixture
Scheme 4. Oxidative Hay coupling of 10.
likely consists of isomers of trimer 16 (Scheme 6). We
speculatively assign the singlet at δ = –24.1 ppm to a single
Cyclic products may be obtained from 13 either by a
isomer with the phosphorus substituents being either all-cis
double-oxidative Hay coupling reaction (“shot-gun” ap-
proach) or in a stepwise manner. The latter requires mono-
silylation (14), coupling, deprotection, and cyclization steps.
However, treatment of 13 with EtMgBr or n-BuLi at –78 °C
or all-trans. Crystallization from a dichloromethane/hexane
solvent mixture provided a “hair”-like solid that slowly de-
composed above 150 °C. Unfortunately, the “hairs”, with
lengths up to 2 cm, were bent and twisted and not suitable
Ǟ –30 °C followed by Et3SiCl quenching gave 14 in only
for X-ray crystal structure analysis. These types of hairs are
13% yield as a moderately stable pale-white solid [δ(31P)
also known as “whiskers” and can be regarded as a solid
= –23.2 ppm (Si–CϵC–P), –22.2 ppm (HCϵC–P)], which
makes the stepwise route impractical for the synthesis of
macrocycles.
equivalent of nanotubes.[21] Such an arrangement would be
possible through stacking of the macrocycles through hy-
drogen bonding of the amine substituents to the polar P=O
groups.
The intermolecular coupling of 13 proved to be more
successful. Use of the high-dilution Pericàs modification of
the oxidative Hay coupling gave two sets of products that
could be isolated by chromatography over silica gel. The 1H
NMR spectra of the two sets of products showed the ab-
sence of acetylenic proton resonances, thereby suggesting
Mixed Acetylene Coupling Reactions
Our final approach to the construction of P/C cycles was
that cyclic products had been formed. Both sets of com- to couple 3 with a non-phosphorus-containing linker. The
pounds are stable when obtained as solids, but slowly de- objectives were a more selective process than the self-coup-
compose in solution. The fraction (18%) that eluted first ling of 13 and to circumvent the ill-fated Grignard reaction
from the column (silica, ethyl acetate/hexane 2:1, Rf = 0.63– of 7 with 3. We opted for 1,2-diethynylbenzene (17) that
0.73) showed four distinct 31P NMR single resonances with has, like 7, an acute angle between the conjugated acetylenic
different intensities, [δ(31P) (CDCl3) = –23.7 (18%), –23.9 groups and is readily accessible from commercially available
(30%), –24.1 (19%), –24.2 (33%)]. High-resolution mass ophthalaldehyde.[22] Intermolecular cyclization of building
spectrometry confirmed the mixture consists of isomers of blocks 3 and 17 indeed proved successful (Scheme 7). Thus,
structure 15 (Scheme 5). We were unable to separate the addition of the diacetylide 17, along with n-BuLi, to a THF
isomers by chromatographic techniques. Given that 13 may solution of 3 gave both the cis and trans isomers of cyclic
exist as two diastereomers, cross-coupling may lead to four bis(phosphane oxide) 18 (25%) in a 2:3 ratio, as determined
isomers that could display a total of six resonances in the by integration of their 31P NMR resonances [cis: δ(31P) =
31P NMR spectrum, that is, isomer 15b with the lowest –20.4 ppm; trans: δ(31P) = –20.2 ppm].
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Scheme 7. Synthesis of cyclic ethynylphosphane oxide 18.
The single-crystal X-ray structure of the trans isomer
(Figure 1) confirmed the formation of the cyclic structure.
The pyramidal nature of the phosphorus centers [N1–P1–
C1 106.37(14)°, O1–P1–C1 113.098(13)°] causes the ring to
be puckered. This is reflected in the dihedral angles of
127.71(17)° for C1–P1–P2–C11 and 116.07(16)° for C20–
P1–P2–C10. The acetylene bonds are only marginally bent
[P1–C1–C2 178.4(3)°, C1–C2–C3 178.9(3)°]. As expected,
the aliphatic ring C–C bonds are shortened [C2–C3
1.435(5) Å] relative to regular sp3–sp3 C–C single bonds.
The crystal structure displays normal bond lengths for the
CϵC triple bonds [C1–C2 1.206(4) Å] and aromatic phenyl
Scheme 6. Trimerization of 13 under oxidative Hay conditions.
Figure 1. Displacement ellipsoid plot of trans-18 in the crystal form, drawn at the 50% probability level. Hydrogen atoms and disordered
solvent molecules have been omitted for clarity. Selected bond lengths [Å], bond angles [°], and torsion angles [°]: P1–O1 1.464(2), P1–
N1 1.630(3), P1–C1 1.753(4), P1–C20 1.760(3), P2–O2 1.468(2), P2–N2 1.622(2), P2–C10 1.753(3), P2–C11 1.765(3), C1–C2 1.206(4),
C2–C3 1.435(5), C3–C8 1.406(4), C8–C9 1.442(4), C9–C10 1.202(4), C11–C12 1.206(4), C12–C13 1.434(5), C13–C18 1.402(4), C18–C19
1.442(4), C19–C20 1.201(4); O1–P1–N1 115.71(13), O1–P1–C1 113.09(13), N1–P1–C1 106.37(14), C1–P1–C20 100.73(15), P1–C1–C2
178.4(3), C1–C2–C3 178.9(3), C2–C3–C8 119.8(3), C3–C8–C9 119.4(3), C8–C9–C10 178.7(3), C9–C10–P2 176.2(3), O1–P1–N1–C21
8.7(3), C1–P1–N1–C21 135.2(2), C20–P1–N1–C21 –118.0(2), C2–C3–C8–C9 0.9(5).
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Acetylene-Substituted Phosphane Oxides
FULL PAPER
tive and slowly decomposes with a color change to yellow/orange,
bonds [C3–C4 1.390(4) Å and C3–C8 1.406(4) Å]. The P–C
[P1–C1 1.753(4) Å], P–N [P1–N1 1.630(3) Å], and P–O [P1–
O1 1.464(2) Å] bond lengths are in the expected range. The
sulfide and silane analogues have also been reported: They
were synthesized by the reaction of 1,2-diethynylbenzene
with either bis(phenylsulfonyl) sulfide (for sulfurization) or
dichlorophenylsilane (for silylation).[23] The reported crystal
structures of these compounds differ considerably from that
of bis(phosphane oxide) 18. The silicon analogue was found
to be almost planar, while the sulfur analogue was only
slightly puckered.
requiring storage below –20 °C. 31P{1H} NMR (101 MHz, CDCl3,
1
27 °C): δ = 174.3 (s) ppm. H NMR (250 MHz, CDCl3, 27 °C): δ
3
3
= 1.26 (d, JH,H = 6.9 Hz, 12 H, CH3), 3.87–4.05 (m, JH,H
=
6.9 Hz, 2 H, CH) ppm. 13C{1H} NMR (63 MHz, CDCl3, 27 °C): δ
= 22.9 (d, 3JP,C = 8.6 Hz, CH3), 50.8 (d, 2JP,C = 13.7 Hz, CH) ppm.
HRMS: calcd. for C6H14Br2NP 288.9230; found 288.9233 for the
79Br79Br isotope; this isotope is given because it does not interfere
with the reference peak.
Oxidation of (iPr)2NPBr2 with Ozone to (iPr)2NP(O)Br2 (3):
(iPr)2NPBr2 (2.84 g, 9.76 mmol) was dissolved in CH2Cl2 (100 mL)
and cooled to –78 °C. Dry ozone was bubbled through the reaction
mixture for several hours during which time it slowly turned yellow/
orange. The 31P NMR spectrum indicated complete conversion of
the starting material to a new product. Evaporation of CH2Cl2 and
extraction with hexane (2ϫ50 mL) afforded a solution of nearly
pure (iPr)2NP(O)Br2 (3). Crystallization from hexane gave 3
(2.40 g, 80%) as a moisture-sensitive white solid that required stor-
age below –20 °C. Compound 3 slowly decomposed at tempera-
tures Ն–20 °C with a color change to yellow/orange. M.p. 51–
52 °C. 31P{1H} NMR (101 MHz, CDCl3, 27 °C): δ = –34.1 (s) ppm.
Conclusions
We have demonstrated that amino-containing acetylene-
substituted phosphane oxides can function as building
blocks in the construction of novel P/C frames. The build-
ing blocks are readily accessible from 3 and acetylenic Grig-
nard reagent 4. Under oxidative Hay conditions dimeric
unit 13, obtained from monosilylated 10, couples in modest
yields to give complex mixtures of the 20- and 30-mem-
3
1H NMR (250 MHz, CDCl3. 27 °C): δ = 1.37 (d, JH,H = 6.8 Hz,
3
3
12 H, CH3), 3.68–3.80 (m, JP,H = 30.3 Hz, JH,H = 6.8 Hz, 2 H,
bered macrocycles 15 and 16. Coupling of phosphorus units CH) ppm. 13C{1H} NMR (63 MHz, CDCl3, 27 °C): δ = 21.7 (d,
3JP,C = 2.4 Hz, CH3), 49.8 (d, JP,C = 5.3 Hz, CH) ppm. HRMS:
2
3 and 7 by way of a Grignard reaction did not lead to any
ring structures, but coupling of 3 with lithiated 1,2-diethyn-
ylbenzene resulted in a cis/trans mixture of the 14-mem-
calcd. for C6H14Br2NOP 306.9159; found 306.9169 (this is the most
abundant 79Br81Br combination).
bered puckered macrocyclic system 18.
Synthesis of (iPr)2NP(O)(CϵCH)2 (7): TMS–CϵC–MgBr
(2 equiv., ~0.4  in THF) was added dropwise at 0 °C to a solution
of (iPr)2NP(O)Br2 (950 mg, 3.1 mmol) in THF (10 mL) and was
slowly warm to room temperature; the 31P NMR spectrum showed
complete conversion to the product. The light-brown residual oil,
obtained after solvent evaporation, was dissolved in diethyl ether
(400 mL), washed with H2O, and dried with MgSO4. The crude
product was dissolved in wet THF (50 mL), cooled to 0 °C, and
TBAF on silica (250 mg, 1–1.5 mol-% fluoride per gram) was
added. The reaction mixture was stirred for 1 h and quenched with
H2O. Column chromatography (silica gel, ethyl acetate/hexane, 1:1)
yielded 7 (415 mg, 68%) as a light-yellow solid. M.p: 134–135 °C.
31P{1H} NMR (101 MHz, CDCl3, 27 °C): δ = –21.4 (s) ppm. 1H
Experimental Section
[24]
BrMg–CϵC–SiMe3
and 1,2-diethynylbenzene[22] were prepared
according to literature procedures. All experiments, except for the
oxidative Hay coupling reactions, were performed under dry nitro-
gen. Solvents were purified, dried, and degassed by standard tech-
niques. In reactions with wet THF, a few drops of H2O were added
to THF. NMR spectra were recorded (T = 300 K) with a Bruker
Advance 250 or MSL 400 spectrometer (31P: 85% H3PO4; 1H, 13C:
internally referenced to residual solvent resonances). High-resolu-
tion mass spectra (HRMS) were recorded with a Finnigan Mat
900 spectrometer (EI, 70 eV). Fast atom bombardment (FAB) mass
spectrometry was carried out using a JEOL JMS SX/SX 102A four-
sector mass spectrometer, coupled to a JEOL MS-MP9021D/UPD
system program. Samples were loaded in a matrix solution (3-ni-
trobenzyl alcohol) onto a stainless steel probe and bombarded with
Xenon atoms with an energy of 3 keV. During the high-resolution
FAB-MS measurements a resolving power of 10000 (10% valley
definition) was used. IR spectra were recorded with a Mattson 6030
Galaxy spectrometer. Elemental analyses were performed by the
Microanalytical Laboratory of the Laboratorium für Organische
Chemie, ETH, Zürich. Melting points were measured on samples
in unsealed capillaries and are uncorrected.
3
NMR (250 MHz, CDCl3, 27 °C): δ = 1.31 (d, JH,H = 6.8 Hz, 12
3
H, CH3), 3.05 (d, JP,H = 11.6 Hz, 2 H, ϵC–H), 3.60–3.74 (m,
3JP,H = 21.2 Hz, 3JH,H = 6.8 Hz, 2 H, N–CH) ppm. 13C{1H} NMR
3
(63 MHz, CDCl3, 27 °C): δ = 22.5 (d, JP,C = 2.1 Hz, CH3), 46.9
2
1
(d, JP,C = 6.9 Hz, N–CH), 81.1 (d, JP,C = 224.7 Hz, P–Cϵ), 88.3
2
(d, JP,C = 41.5 Hz, ϵCH) ppm. HRMS: calcd. for C10H16NOP
197.0970; found 197.0969.
Synthesis of MeO–P(O)(CϵCH)2 (8): (iPr)2NP(O)(CϵCH)2 (7)
(195 mg, 1.0 mmol) was dissolved in a 1:1 mixture of MeOH and
CH2Cl2 (40 mL) and cooled to 0 °C. BF3·Et2O (600 µL, 4.0 mmol)
was added at once and the reaction mixture was stirred at room
temperature for 48 h. The yellow solution was evaporated at re-
duced pressure and the resulting yellow oil was purified by column
chromatography (silica gel, ethyl acetate). MeOP(O)(CϵCH)2
Synthesis of (iPr)2NPBr2: PBr3 (6.77 g, 25.0 mmol) was dissolved
in dry diethyl ether (60 mL) and cooled to –78 °C. Whilst stirring
rapidly, (iPr)2NH (5.06 g, 50.0 mmol) was added over 30 minutes. (50 mg, 40%) was isolated as a volatile yellow liquid. 31P{1H}
The reaction mixture was allowed to warm to room temperature
and stirred overnight after which it was filtered and the salts
washed with diethyl ether. Evaporation of the solvents afforded a
yellow oil. Distillation (4ϫ10–2 mbar) gave (iPr)2NPBr2 at 55–
60 °C as a colorless liquid, which solidified upon cooling to give a
yield of 6.16 g (85%). The product is very air- and moisture-sensi-
NMR (101 MHz, CDCl3, 27 °C): δ = –19.7 (s) ppm. 1H NMR
3
(250 MHz, CDCl3, 27 °C): δ = 3.12 (d, JP,H = 12.7 Hz, 2 H, ϵC–
3
H), 3.87 (d, JP,H = 13.9 Hz, 3 H, OCH3) ppm. 13C{1H} NMR
2
(63 MHz, CDCl3, 27 °C): δ = 53.3 (d, JP,C = 5.8 Hz, OCH3), 76.2
1
2
(d, JP,C = 259.4 Hz, P–Cϵ), 90.6 (d, JP,C = 48.1 Hz, P–
CϵC) ppm.
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K. Lammertsma et al.
Synthesis of (iPr)2NP(O)(CϵCH)(CϵCSiEt3) (10): (iPr)2NP- P–CϵC–Cϵ), 89.8 (d, JP,C = 42.8 Hz, P–CϵCH) ppm. HRMS:
FULL PAPER
2
(O)(CϵCH)2 (7) (3.00 g, 15.2 mmol) was dissolved in THF
(150 mL) and cooled to –78 °C. EtMgBr (1.05 equivalent, 16 mL,
1  in THF) was added over a period of 15 min and the cloudy
reaction mixture was stirred for an additional hour before warming
it to –30 °C. Et3SiCl (2.52 g, 16.7 mmol) was added dropwise and
the light-yellow mixture was slowly warmed to room temperature.
The solvent was evaporated and the yellow oil with white salts was
filtered through a short silica gel column using ethyl acetate/hexane
(1:1). Column chromatography (silica gel, ethyl acetate/hexane, 3:1)
afforded monosilylated 10 (2.50 g, 53%) followed by unreacted
starting material 7 (500 mg, 17%). M.p. 94–95 °C. 31P{1H} NMR
calcd.
for
C20H30N2O2P2
392.1783;
found
392.1765.
C20H30N2O2P2: calcd. C 61.22, H 7.71, N 7.14; found C 61.30, H
7.70, N 7.08.
Monosilylation of 13 to 14: Compound 13 (392 mg, 1.0 mmol) was
dissolved in THF (10 mL) and cooled to –78 °C. A solution of
EtMgBr (1 mL, 1  in THF) was added dropwise over 30 min and
the reaction mixture was stirred at –78 °C for 1 h before being al-
lowed to warm to –30 °C where it was kept for 30 min and
quenched with Et3SiCl (0.2 mL, 1.2 mmol). The black residue that
resulted on evaporation of the solvent was purified by column
chromatography (silica gel, ethyl acetate/hexane, 1:1) to give 14 as
a pale white powder (50 mg, 13%) that slowly decomposed on ex-
posure to light. Only a 31P NMR spectrum was recorded. A pure
1H NMR spectrum was not obtained because of residual solvents
and decomposition products present in the sample. 31P{1H} NMR
(101 MHz, CDCl3, 27 °C): δ = –23.2 (s, Si–CϵC–P), –22.2 (s, H–
CϵC–P) ppm.
1
(101 MHz, CDCl3, 27 °C): δ = –22.3 (s) ppm. H NMR (CDCl3):
3
3
δ = 0.64 (q, JH,H = 7.9 Hz, 6 H, CH2), 0.70 (t, JH,H = 7.9 Hz, 9
3
H, CH2–CH3), 1.31 (d, JH,H = 6.8 Hz, 12 H, CH–CH3), 2.98 (d,
3JP,H = 11.3 Hz, 1 H, ϵCH), 3.62–3.75 (m, JP,H = 20.8 Hz, JH,H
= 6.8 Hz, 2 H, N–CH) ppm. 13C{1H} NMR (63 MHz, CDCl3,
27 °C): δ = 3.7 (s, SiCH2), 7.2 (s, CH2CH3), 22.2 (d, 3JP,C = 1.6 Hz,
3
3
2
1
CH–CH3), 46.5 (d, JP,C = 6.9 Hz, N–CH), 81.6 (d, JP,C
=
2
Cyclization by Oxidative Hay Coupling of 13 to 15 and 16: Com-
pound 13 (500 mg, 1.27 mmol) was dissolved in dry acetone
(250 mL) and protected from light. A freshly prepared solution of
2 mol-% CuI (12 mg) and 4 mol-% TMEDA (18 µL) in dry acetone
(25 mL) was added at once. Upon addition of the catalyst, the color
of the reaction mixture turned light-yellow. Air was then bubbled
through the reaction mixture for 10 h. Every 2 h, another portion
of catalyst (1 mol-% CuI and 2 mol% TMEDA in 10 mL dry ace-
tone) was added. The reaction was followed by TLC. After full
conversion of the starting material, the solvent was evaporated un-
der reduced pressure and the dark-brown residue purified by col-
umn chromatography (silica gel, ethyl acetate/hexane, 1:1 and 2:1)
to give two sets of products with Rf = 0.63–0.73 for 15 (91 mg,
18%) and Rf = 0.38–0.48 for 16 (60 mg, 12%).
220.0 Hz, P–CϵCH), 87.1 (d, JP,C = 40.7 Hz, ϵCH), 102.5 (d,
1JP,C = 212.3 Hz, P–CϵCSi), 107.3 (d, 2JP,C = 30.4 Hz, ϵCSi) ppm.
HRMS: calcd. for C16H30NOPSi 311.1834; found 311.1843.
Oxidative Hay Coupling of 10 to 12: Compound 10 (150 mg,
0.48 mmol) was dissolved in dry acetone (10 mL) and protected
from light. A freshly prepared solution of 5 mol-% CuI and 10 mol-
% TMEDA in dry acetone (10 mL) was added. Air was bubbled
through the clear green reaction mixture for 5 h and dry acetone
was added to compensate for solvent evaporation. When the reac-
tion stopped, as indicated by the blue color of the reaction mixture,
another portion of 5 mol-% CuI and 10 mol-% TMEDA in dry
acetone was added. The solvent was evaporated after full conver-
sion was observed (as monitored by 31P NMR spectroscopy) and
the green/blue residue was dissolved in diethyl ether (10 mL),
washed with water, and dried with MgSO4. Column chromatog-
raphy (silica gel, ethyl acetate/hexane, 1:2) afforded 12 (100 mg,
67%) as a white solid. M.p. 117–118 °C. 31P{1H} NMR (101 MHz,
C6D6, 27 °C): δ = –23.9 (s) ppm. 1H NMR (250 MHz, C6D6,
15 (mixture of isomers): M.p. Ͼ175 °C (decomp.). 31P{1H} NMR
(101 MHz, CDCl3, 27 °C): δ = –23.1 (s, 18%), –23.3 (s, 30%), –23.5
(s, 19%), –23.6 (s, 33%) ppm. 1H NMR (250 MHz, CDCl3, 27 °C):
3
δ = 1.33 (d, JH,H = 6.7 Hz, 48 H, CH3), 3.61–3.78 (m, 8 H, N–
27 °C): δ = 0.45 (br. q, JH,H = 7.5 Hz, 12 H, Si–CH2), 0.91 (br. t,
CH) ppm. 13C{1H} NMR (63 MHz, C6D6, 27 °C): δ = 20.2 (br.
s, CH3), 45.1 (br., N–CH), 78.5–81.9 (P–CϵC and P–CϵC) ppm.
3
3
3JH,H = 7.5 Hz, 18 H, CH2–CH3), 1.35 (d, JH,H = 6.7 Hz, 12 H,
3
CH–CH3), 1.44 (d, JH,H = 6.6 Hz, 12 H, CH–CH3), 3.60–3.80 (m, HRMS (FAB+): calcd. for C40H57N4O4P4 [M + H] 781.3330; found
3
3JP,H = 21.4 Hz, JH,H = 6.7 Hz, 4 H, CH) ppm. 13C{1H} NMR
781.3336.
(63 MHz, C6D6, 27 °C): δ = 4.0 (s, Si–CH2), 7.5 (s, Si–CH2–CH3),
16 (single isomer isolated from crystallization in CH2Cl2/hexane):
M.p. Ͼ150 °C (decomp.). 31P{1H} NMR (101 MHz, CDCl3, 27 °C)
2
22.0 (s, CH–CH3), 22.6 (s, CH–CH3), 46.9 (d, JP,C = 7.0 Hz, N–
2
3
CH), 79.6 (dd, JP,C = 40.2 Hz, JP,C = 7.4 Hz, P–CϵC–Cϵ), 82.0
(dd, 1JP,C = 206.8 Hz, 4JP,C = 2.2 Hz, P–CϵC–Cϵ), 103.5 (dd, 1JP,C
= 214.4 Hz, 6JP,C = 3.8 Hz, P–CϵC–Si), 108.0 (dd, 2JP,C = 30.4 Hz,
1
(mixture of isomers): δ = –24.1 (s, 16%), –23.3 (br., 84%) ppm. H
3
NMR (CDCl3) (single isomer): δ = 1.35 (d, JH,H = 6.6 Hz, 72 H,
3
3
CH3), 3.60–3.74 (m, JP,H = 21.6 Hz, JH,H = 6.6 Hz, 12 H, N–
7JP,C
=
6.9 Hz, P–CϵC–Si) ppm. HRMS: calcd. for
CH) ppm. 13C{1H} NMR (100 MHz, CDCl3, 27 °C) (single iso-
mer): δ = 22.4 (s, CH3), 47.2 (d, JP,C = 6.77 Hz, N–CH); CϵC
C32H58N2O2P2Si2 620.3512; found 620.3519.
2
Desilylation of 12 to HCϵC–P(O)[N(iPr)2]–CϵC–CϵC–P(O)-
[N(iPr)2]–CϵCH (13): A solution of 12 (500 mg, 0.81 mmol) in wet
THF (40 mL) was cooled to –78 °C. TBAF on silica (110 mg, 1.0–
1.5 mmol fluoride/g) was added and the reaction mixture stirred at
–78 °C for 2 h, slowly turning black, after which it was quenched
with a few drops of water. The black oil that resulted on evapora-
tion of the solvent was purified by column chromatography (silica
gel, ethyl acetate/hexane, 1:1) to give 13 (190 mg, 60%) as a white
resonances too weak to be observed. HRMS (FAB+): calcd. for
C60H85N6O6P6 [M + H] 1171.4956; found 1171.5002.
The HRMS FAB spectrum indicates that a small amount of tetra-
mer C80H112N8O8P8 (m/z = 1561.7 [M+1]) is present in the second
set of products after column chromatography.
Cyclization of 1,2-Diethynylbenzene (17) with (iPr)2NP(O)Br2: 1,2-
Diethynylbenzene (380 mg, 3.0 mmol) was dissolved in THF
crystalline solid. M.p. Ͼ140 °C (decomp.). 31P{1H} NMR (20 mL) and cooled to –78 °C. n-BuLi (3.75 mL, 1.6  in hexanes)
(101 MHz, CDCl3, 27 °C): δ = –21.9 (s) ppm. 1H NMR (250 MHz,
was added dropwise and the cloudy white solution was stirred for
1.5 h at –78 °C after which time it was added over a period of
3
CDCl3, 27 °C): δ = 1.31 (d, JH,H = 6.8 Hz, 24 H, CH3), 3.14 (d,
3
3
3JP,H = 11.9 Hz, 2 H, ϵCH), 3.56–3.75 (m, JP,H = 21.5 Hz, JH,H 30 min to a solution of (iPr)2NP(O)Br2 (920 mg, 3.0 mmol) in THF
= 6.8 Hz, 4 H, N–CH) ppm. 13C{1H} NMR (100 MHz, CDCl3,
27 °C): δ = 22.6 (m, CH3), 47.1 (m, N–CH), 80.1 (m, P–CϵCH), 1 h at –15 °C the reaction mixture was warmed to room tempera-
80.2 (m, P–CϵC–Cϵ), 80.3 (dd, JP,C = 42.4 Hz, JP,C = 7.8 Hz,
(100 mL) at –15 °C which turned from orange to dark green. After
2
3
ture and the solvent evaporated. Column chromatography (silica
2410
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© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2007, 2405–2412

Acetylene-Substituted Phosphane Oxides
FULL PAPER
gel, ethyl acetate/hexane, 1:1 to pure ethyl acetate) afforded pure
trans isomer 18 (120 mg, 15%) followed by the cis isomer (80 mg,
10%) contaminated with three minor products as UV-sensitive
white solids. Crystals of the trans isomer suitable for X-ray diffrac-
tion were obtained by crystallization from ethyl acetate/hexane.
[1]
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18 (trans isomer): M.p 325 °C (decomp.). 31P{1H} NMR
(101 MHz, CDCl3, 27 °C): δ = –20.2 (s) ppm. 1H NMR (250 MHz,
3
CDCl3, 27 °C): δ = 1.42 (d, JH,H = 6.8 Hz, 24 H, CH3), 3.83–3.97
3
3
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(m, JP,H = 21.5 Hz, JH,H = 6.8 Hz, 4 H, N–CH), 7.38–7.43 (m, 4
H, Ar), 7.50–7.55 (m, 4 H, Ar) ppm. 13C{1H} NMR (63 MHz,
CDCl3, 27 °C): δ = 22.9 (d, JP,C = 1.9 Hz, CH3), 47.2 (d, JP,C
7.0 Hz, N–CH), 90.6 (d, JP,C = 229.8 Hz, P–Cϵ), 95.9 (d, JP,C
42.8 Hz, P–CϵC), 124.4 (dd, JP,C = 4.9 Hz, JP,C = 2.2 Hz, i-Ph),
3
2
=
=
1
2
3
4
4
130.5 (s, Ph), 133.0 (d, JP,C = 2.0 Hz, Ph) ppm. HRMS: calcd. for
C32H36N2O2P2 542.2252; found 542.2259. C32H36N2O2P2: calcd. C
70.84, H 6.69, N 5.16; found C 70.75, H 6.54, N 5.15.
18 (cis isomer): 31P NMR (101 MHz, CDCl3, 27 °C): δ = –20.4
1
(s) ppm. H NMR (250 MHz, CDCl3, 27 °C): δ = 1.42 (m, 24 H,
CH3), 3.75–3.96 (m, 4 H, N–CH), 7.30–7.46 (m, 4 H, Ar), 7.48–
7.64 (m, 4 H, Ar) ppm.
Crystal Structure Data for 18: C32H36N2O2P2 + disordered solvent,
Mw = 542.57*, colorless needle, 0.27ϫ0.09ϫ0.03 mm3, mono-
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24.2849(5) Å, β = 94.7219(12)°, V = 3762.18(11) Å3, Z = 4, Dx =
0.958 gcm–3 *, µ = 0.14 mm–1 *. (Derived parameters marked with
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[8]
chromator, λ = 0.71073 Å) up to a resolution of (sin θ/λ)max
=
0.56 Å–1 at a temperature of 150 K. The reflections were corrected
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tions with the SADABS program [25] (0.83–1.00 correction range).
5597 Reflections were unique (Rint = 0.0837). The structure was
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gram[27] against F2 for all reflections. The crystal structure contains
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ment parameters. All hydrogen atoms were introduced in geometri-
cally optimized positions and refined with a riding model. 351 Pa-
rameters were refined with no restraints. R1/wR2 [I Ͼ 2σ(I)] =
0.0553/0.1458. R1/wR2 [all reflections] = 0.0841/0.1566, S = 1.066.
Residual electron density is between –0.30 and 0.34 eÅ–3. Geome-
try calculations and the check for higher symmetry were performed
with the PLATON program.[28]
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[14]
[15]
Supporting Information (see footnote on the first page of this arti-
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[16]
Acknowledgments
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This work was supported by the Council for Chemical Sciences of
the Netherlands Organization for Scientific Research (NWO/CW).
We thank Prof. L. T. Scott of Boston College for insightful infor-
mation.
Eur. J. Org. Chem. 2007, 2405–2412
© 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
2411

K. Lammertsma et al.
FULL PAPER
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Received: October 6, 2006
Published Online: January 8, 2007
2412
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Eur. J. Org. Chem. 2007, 2405–2412