Desymmetrization by direct cross-metathesis producing hitherto unreachable P-stereogenic phosphine oxides

Article abstract of DOI:10.1016/j.tet.2005.01.019

Desymmetrization of prochiral di- and trialkenyl phosphine oxides by cross-metathesis with various olefinic partners allowed direct access to novel racemic P-stereogenic products featuring two or three different alkenyl groups. The excellent control of product selectivity and E/Z selectivity allowed the preparation of desymmetrized products in good yields from readily available precursors. These are the first examples of desymmetrization of prochiral substrates by direct cross-metathesis.

Full text of DOI:10.1016/j.tet.2005.01.019

Tetrahedron 61 (2005) 2395–2400
Desymmetrization by direct cross-metathesis producing hitherto
unreachable P-stereogenic phosphine oxides
*
´
Fabrice Bisaro and Veronique Gouverneur
Chemistry Research Laboratory, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK
Received 14 October 2004; revised 26 November 2004; accepted 7 January 2005
Available online 27 January 2005
Abstract—Desymmetrization of prochiral di- and trialkenyl phosphine oxides by cross-metathesis with various olefinic partners allowed
direct access to novel racemic P-stereogenic products featuring two or three different alkenyl groups. The excellent control of product
selectivity and E/Z selectivity allowed the preparation of desymmetrized products in good yields from readily available precursors. These are
the first examples of desymmetrization of prochiral substrates by direct cross-metathesis.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
With the appearance of functional group-compatible
transition-metal catalysts over the past decade, olefin
metathesis has rapidly become a powerful transformation
widely used in organic synthesis.1 Recently, we have shown
that ring closing metathesis (RCM) and cross-metathesis
(CM) are effective methods for the construction of various
phosphine oxides and borane-stabilized phosphines.2 As
part of our program aimed at developing transition metal-
catalyzed transformations for the construction of diverse
phosphorus-containing compounds, we herein report how
the cross-metathesis reaction can provide a direct entry to
structurally diverse P-stereogenic phosphine oxides featur-
ing two or three different alkenyl groups. These compounds
could be regarded as valuable building blocks for the
preparation of numerous targets upon functional group
manipulation of the double bonds. These targets could
include mixed phosphine–phosphine oxide ligands that
seem to hold special promise for a wide variety of reactions
catalyzed by late transition metals.3 A survey of the
literature revealed that, in contrast to a,b-unsaturated
monoalkenyl analogues, phosphine oxides possessing two
or three different alkenyl groups are virtually unknown,
probably due to the lack of general synthetic methodologies
for their preparation.4 Herein we disclose a conceptually
novel approach toward the preparation of unsymmetrical
racemic P-stereogenic dienes and trienes, a desymmetriza-
tion process that relies upon the cross-metathesis coupling
of prochiral phosphine oxides with various olefinic partners.
The desymmetrization of prochiral phosphine oxides by
cross-metathesis with an olefinic partner is a complex
problem as one needs to control selectivity at different
levels. Indeed, the challenge is to achieve high yield of the
cross-product with minimal amounts of competing self-
metathesis product. In addition, the methodology should
favor the formation of the product resulting from a single
cross-metathesis reaction, minimizing as much as possible
the formation of achiral products resulting from a double
cross-metathesis. Finally, E/Z selectivity is also a critical
issue particularly if the newly formed double bond requires
further stereoselective manipulation. Therefore, it is not
surprising that the possibility to use a cross-metathesis
reaction for the desymmetrization of a prochiral diene has
hardly been investigated5 and to the best of our knowledge,
trienes have never been desymmetrized using this tech-
nology (Eqs. 1 and 2, Fig. 1).
The unprecedented activity of catalyst 16 in the presence of
conjugated electron-deficient olefins including a,b-unsatu-
rated phosphine oxides has allowed the formation of
products with high CM selectivity and excellent E/Z
selectivity.2d,7 The high cross-product/dimer ratio is due to
the slow rate of dimerization of these substrates with these
catalysts. It was therefore anticipated that phenyldivinyl-
phosphine oxide 3 and trivinylphosphine oxide 4 were ideal
candidates for desymmetrization (Eqs. 1 and 2, Fig. 1). They
were easily prepared by treatment of the commercially
available PhPOCl2 or POCl3 with vinylmagnesium bromide
in good isolated yields (76 and 70%, respectively). A
preliminary study revealed that compounds 3 and 4 are
reluctant to homodimerize in the presence of up to 4 mol%
Keywords: Cross-Metathesis; Desymmetrization; Phosphine oxide.
* Corresponding author. Tel./fax: C44 1865 275 644;
e-mail: veronique.gouverneur@chem.ox.ac.uk
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.01.019

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F. Bisaro, V. Gouverneur / Tetrahedron 61 (2005) 2395–2400
Figure 1. Desymmetrization of P-templates by CM.
of catalysts 1 or 26 in DCM at reflux (3 and 4 are therefore
type III olefins, according to the classification of Grubbs8),
auguring high CM selectivity in the presence of olefinic
partners of type I or type II.
noted that the excess diene 3 was recovered for recycling
after purification.
This positive result led us to examine the cross-metathesis
of 3 with various olefinic partners including 4-methoxy-
styrene, trimethylallylsilane and 6-bromohexene in the
presence of 2 mol% of 1 (Table 1, entries 3–5). Particularly,
noteworthy are the good yields attained for these reactions
reflecting good control of selectivities under these con-
ditions. The stereoselectivity of these transformations in
favor of the E-isomer is excellent making them synthetically
practical. Indeed, no trace of the Z-isomer could be detected
in the crude reaction mixtures except for product 5d. For
this compound, less than 10% of the minor Z-isomer was
formed.
In the exploration of a variety of reaction conditions to
optimize the metathesis of diene 3 with dodecene, a
representative type I olefin, we discovered that the best
product distribution was obtained using 1 equiv of the
olefinic partner (0.3 M) and 3 equiv of the diene in DCM
under reflux in the presence of 2 mol% of catalyst 1
(Table 1, entries 1 and 2). Under these conditions, the crude
mixture revealed the presence of products 5a and 6a in a 4:1
ratio with the exclusive formation of E-isomers. No trace of
product resulting from a homodimerization process of the
diene 3 was detected in the reaction mixture, confirming that
the combination of olefinic partners of type I and type III led
to selective CM reactions. Clearly, the use of an excess of
the diene minimizes the formation of the undesired
achiral product 6a. Under these conditions, the desired
desymmetrized P-stereogenic phosphine oxide 5a was
isolated as a pure compound in 79% yield. It should be
Further functionalization of compound 5a by CM with
styrene in the presence of 5 mol% of 1 afforded (E,E)-7 in
up to 69% isolated yield (Table 2). This reaction is best
performed in the presence of 3 equiv of 5a. The crude
mixture of this reaction revealed the formation of several
side products identified as compounds 8, 6a and 3 in
Table 1. Desymmetrization of the prochiral diene 3
Entry
Conditions
Yield 5 (%)
Yield 6 (%)
1
2
3
4
5
1 equiv 3, 1 equiv dodecene, 2 mol% 1, 24 h
3 equiv 3, 1 equiv dodecene, 2 mol% 1, 24 h
3 equiv 3, 4-methoxystyrene, 2 mol% 1, 24 h
3 equiv 3, CH2]CHCH2Si(CH3)3, 2 mol% 1, 24 h
3 equiv 3, CH2]CH(CH2)4Br, 2 mol% 1, 24 h
5a 47
5a 79
5b 68
5c 72
5d 86
6a 23
6a 14
6b —a
6c —a
6d —a
a Less than 5% of this product was detected in the crude mixture.

F. Bisaro, V. Gouverneur / Tetrahedron 61 (2005) 2395–2400
Table 2. Optimization of the CM of 5a with styrene
2397
Reaction conditlions
Ratio 5a/7/8/6a/3
Isolated yield 7 (%)
1 equiv 5a, 3 equiv styrene
1 equiv 5a, 1 equiv styrene
2 equiv 5a, 1 equiv styrene
3 equiv 5a, 1 equiv styrene
0:4:4:1:0
0:2:1:1:0
8:6:1:3:2
15:8:1:5:4
36
47
59
69
addition to unreacted starting material 5a. All these
side-products could be separated from the desired
desymmetrized phosphine oxide 7 by silica gel chromato-
graphy. The formation of compound 8 suggests that capping
one of the double bond with an alkyl chain was not sufficient
to prevent its reaction with styrene upon CM. In this
process, the resulting Ru-carbenoid species bearing the
alkyl chain can further react to afford minor quantities of 6a.
The presence of these side products demonstrated that
alkene group exchange is possible under these conditions.
three different E-alkenyl groups was successfully prepared
in 65% by reacting 10a (3 equiv) with 3-phenylpropene
(1 equiv) for 24 h in CH2Cl2 at reflux with 4 mol% of
catalyst 1. If this reaction is left stirring for extended
reaction time (up to 48 h), only 32% of the desired product
could be isolated suggesting that the catalyst mediated
alkene group exchanges leading to mixture of products, as
previously observed with substrate 5a (Scheme 1).
3. Conclusion
The possibility to desymmetrize the triene 4 was investi-
gated next. This overall process involves two or three
sequential cross-metathesis reactions as illustrated in
Scheme 1. Triene 4 (3 equiv) was firstly reacted with
dodecene (1 equiv) in the presence of 4 mol % of catalyst 1
to afford 75% of the triene 9a as a single E-isomer. We were
pleased to discover that triene 9a (3 equiv) reacted further in
the presence of styrene (1 equiv) and this CM reaction
allowed the formation of 87% of compound 10a and only
traces of the undesired product resulting from a double
cross-metathesis reaction. In addition, compound 10a was
formed as the sole E-isomer. By reversing the order of the
two CM reactions, 10a could be obtained with an overall
chemical yield of 48% instead of 65%, suggesting that the
order of introduction of the two olefinic partners is
important. Finally, the phosphine oxide 11 substituted by
In conclusion, we have demonstrated that phosphine oxides
3 and 4 could be successfully desymmetrized using CM
leading to a series of P-stereogenic phosphine oxides. This
unprecedented strategy allows direct access to these
compounds that were never prepared before, probably due
to the difficulties associated with their syntheses using more
traditional synthetic strategies. This novel desymmetriza-
tion process on phosphorus templates illustrates how
molecular symmetry can be exploited for the construction
of P-stereogenic compounds that are not heterocyclic.
Current efforts aimed at studying the reactivity of these
novel compounds and at developing an enantioselective
desymmetrization process for the preparation of nonracemic
P-stereogenic targets are underway in our laboratory.
Scheme 1. Desymmetrization of the pro-prochiral triene 4.

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F. Bisaro, V. Gouverneur / Tetrahedron 61 (2005) 2395–2400
4. Experimental
CDCl3, ppm): d 6.10–6.34 (9H, system (ABC)3X). 13C NMR
(100.6 MHz, CDCl3, ppm): d 134.0 (s), 130.4 (d, JPZ
99.9 Hz). 31P NMR (162.0 MHz, CDCl3, ppm): d 17.6 Hz.
IR (film, cmK1): 1169, 1396, 1601, 2962, 3003, 3031, 3082.
MpZ96–98 8C (lit.,10 mpZ99–101 8C). HRMS: (CIC)
C6H10OP (MCHC), calcd 129.0469, found 129.0467.
4.1. General procedures
1H NMR spectra were recorded at 400 and 500 MHz on a
Bruker DPX400 and Bruker AMX500 spectrometers,
respectively. 13C NMR spectra were recorded on the same
spectrometers at 100 and 125 MHz respecively. Proton
decoupled 31P NMR spectra were recorded on a Bruker
AMX500 spectrometer at 202 MHz. Chemical shifts (d) are
quoted in parts per million (ppm) and are referenced to the
residual solvent peak. Multiplicities are reported as broad
(br), singlet (s), doublet (d), triplet (t), quartet (q), multiplet
(m), or as a combination of these. Coupling constants (J) are
reported to the nearest 0.1 Hertz (Hz). Infra-red spectra
were recorded as thin films using a Perkin–Elmer Paragon
1000FT-IR spectrometer. Absorption peaks are reported in
wavenumbers (cmK1). High resolution mass spectra (m/z)
were recorded on micro-mass GCT in chemical ionisation
(NH3, CIC) or on a AutoSpec-oaTof instruments (CIC).
Melting points (mp) were obtained using standard melting
point apparatus and are uncorrected. Flash chromatography
was accomplished on silica gel using Merck silica gel C60
(40–60m). The solvents were dried before use; tetrahydro-
furan (THF) by distillation over sodium/benzophenone
ketyl; dichloromethane (DCM) over calcium hydride. All
other reagents were purified in accordance with the
instructions in ‘Purification of Laboratory Chemicals’,
D.D. Perrin and W.L.F. Armarego, Pergamon Press, Third
Edition, 1998, or used as obtained from chemical sources.
4.2. General procedure for cross-metathesis between two
alkenes a and b using catalyst 1
A solution of alkenes a and b in DCM was heated to reflux
under argon. Catalyst 1 (2 mol%) was then added as a solid
every 24 h. The reaction was followed by TLC. The mixture
was then concentrated in vacuo and the product purified by
silica gel chromatography.
4.2.1. (Dodec-1-enyl-vinyl-phosphinoyl)-benzene 5a.
General procedure with 3 (200 mg, 1.12 mmol) and
dodecene (83 mL, 0.375 mmol, cZ0.3 M) in DCM
(1.25 mL) using 2 mol% of catalyst 1 (6.3 mg, 7.49 mmol)
for 24 h. Purification of the residue by silica gel chroma-
tography (98/01/01: chloroform/AcOEt/MeOH) allowed
isolation of 94.5 mg of 5a as a colourless oil (0.297 mmol,
yieldZ79%), and 12.2 mg of (di-dodec-1-enyl-phos-
phinoyl)-benzene 6a as a colourless oil (0.027 mmol,
1
yieldZ14%). 5a: H NMR (400.1 MHz, CDCl3, ppm): d
3
7.64–7.70 (2H, m), 7.39–7.48 (3H, m), 6.67 (1H, ddt, JZ
6.7, 17.1 Hz, JPZ19.5 Hz), 6.07–6.47 (3H, system ABCX),
5.97 (1H, ddt, 4JZ1.5 Hz, 3JZ17.1 Hz, JPZ24.2 Hz),
2.19–2.25 (2H, m), 1.38–1.45 (2H, m), 1.15–1.30 (14H,
m), 0.83 (3H, t, 3JZ6.8 Hz). 13C NMR (100.6 MHz, CDCl3,
ppm): d 152.3 (d, JPZ2.0 Hz), 133.2 (s), 132.6 (d, JPZ
105.4 Hz), 131.7 (d, JPZ98.9 Hz), 131.6 (d, JPZ2.7 Hz),
130.6 (d, JPZ9.8 Hz), 128.5 (d, JPZ12.0 Hz), 121.3 (d,
JPZ104.1 Hz), 34.4 (d, JPZ16.9 Hz), 31.8 (s), 29.5 (s),
29.4 (s), 29.3 (s), 29.2 (s), 29.0 (s), 27.8 (d, JPZ1.2 Hz),
22.6 (s), 14.0 (s). 31P NMR (202.4 MHz, CDCl3, ppm): 21.2
(s). IR (film, cmK1): 1185, 1437, 1465, 1630, 2854, 2925.
HRMS: (CIC) C20H32OP (MCHC), calcd 319.2191, found
319.2190. 6a: 1H NMR (400.2 MHz, CDCl3, ppm): d 7.67–
4.1.1. (Divinyl-phosphinoyl)-benzene 3. A solution of
phenylphosphonic dichloride (1 mL, 7.07 mmol) in a
mixture of THF (35 mL) and ether (35 mL) was cooled to
K70 8C and vinylmagnesium bromide (1 M in THF,
14.1 mL, 14.1 mmol) was then added slowly. The solution
was stirred at K70 8C for 3 h then poured into a mixture of
HCl 12 M (21 mL) and ice water (140 mL). The mixture
was extracted with DCM, dried over MgSO4 and concen-
trated in vacuo. Purification of this residue by silica gel
chromatography (98/02: AcOEt/MeOH) allowed isolation
3
7.72 (2H, m), 7.43–7.52 (3H, m), 6.67 (2H, ddt, JZ6.6,
1
of 960 mg of a white solid (5.39 mmol, yieldZ76%). H
16.9 Hz, JPZ19.7 Hz), 5.98 (2H, ddt, 4JZ1.5 Hz, 3JZ
16.9 Hz, JPZ24.0 Hz), 2.27–2.22 (2H, m), 1.49–1.42 (2H,
NMR (400.2 MHz, CDCl3, ppm): d 7.62–7.67 (2H, m),
7.38–7.49 (3H, m), 6.46–6.10 (6H, system (ABC)2X). 13C
NMR (100.6 MHz, CDCl3, ppm): d 134.2 (s), 131.9 (d, JPZ
2.4 Hz), 131.5 (d, JPZ105.5 Hz), 130.7 (d, JPZ99.1 Hz),
130.7 (d, JPZ9.6 Hz), 128.6 (d, JPZ12.0 Hz). 31P NMR
(162.0 MHz, CDCl3, ppm): d 20.4 (s). IR (film, cmK1):
1180, 1392, 1438, 1603, 3000, 3027, 3056, 3078. MpZ48–
49 8C (lit.,9 mpZ50–51 8C). HRMS: (CIC) C10H12OP
(MCHC), calcd 179.0626, found 179.0626.
3
m), 1.20–1.35 (2H,m), 0.88 (6H, t, JZ6.9 Hz). 13C NMR
(100.6 MHz, CDCl3, ppm): d 151.6 (d, JPZ2.4 Hz), 133.6
(d, JPZ104.7 Hz), 131.4 (d, JPZ2.4 Hz), 130.7 (d, JPZ
9.6 Hz), 128.4 (d, JPZ12.0 Hz), 122.2 (d, JPZ103.9 Hz),
34.4 (d, JPZ16.8 Hz), 31,9 (s), 29.6 (s), 29,5 (s), 29.4 (s),
29.3 (s), 29.1 (s), 27.9 (d, JPZ1.2 Hz), 22.7 (s), 14.1 (s). 31
P
NMR (162.0 MHz, CDCl3, ppm): 20.0 (s). IR (film, cmK1):
1176, 1442, 1470, 1635, 2849, 2913. HRMS: (CIC)
C30H52OP (MCHC), Calcd. 459.3756, found 459.3757.
4.1.2. (Divinyl-phosphinoyl)-ethene 4. A solution of
phosphorus oxychloride (1 mL, 10.7 mmol) in a mixture
of THF (50 mL) and ether (50 mL) was cooled to K70 8C
and vinylmagnesium bromide (1 M in THF, 32.2 mL,
32.2 mmol) was added slowly. The solution was stirred at
K70 8C for 3 h then poured into a mixture of HCl 12 M
(30 mL) and ice water (200 mL). The mixture was extracted
with DCM, dried over MgSO4 and concentrated in vacuo.
Purification of this residue by silica gel chromatography
(98/02: AcOEt/MeOH) allowed isolation of 961 mg of a
white solid (7.51 mmol, yieldZ70%). 1H NMR (400.2 MHz,
4.2.2.
1-Methoxy-4-[2-(phenyl-vinyl-phosphinoyl)-
vinyl]-benzene 5b. General procedure with 3 (200 mg,
1.12 mmol), and p-methoxystyrene (50 mL, 0.375 mmol,
cZ0.3 M) in DCM (1.25 mL) using 2 mol% catalyst 1
(6.3 mg, 7.49 mmol) for 24 h. Purification of the residue by
silica gel chromatography (98/02: AcOEt/MeOH) allowed
isolation of 72.0 mg of 5b as a yellow oil (0.254 mmol,
1
yieldZ68%). 5b: H NMR (400.1 MHz, CDCl3, ppm): d
7.72–7.78 (2, m), 7.34–7.52 (6H, m), 6.87 (2H, d, 3JZ
8.5 Hz), 6.14–6.58 (4H, m) which could be described as

F. Bisaro, V. Gouverneur / Tetrahedron 61 (2005) 2395–2400
2399
3
6.14–6.58 (3H, system ABCX) overlapping with 6.44 (1H,
dd, 3JZ17.4 Hz, JPZ22.2 Hz), 3.79 (3H, s). 13C NMR
(100.6 MHz, CDCl3, ppm): 161.1 (s), 146.6 (d, JPZ4.0 Hz),
133.6, (s), 132.7 (d, JPZ105.8 Hz), 131.7 (d, JPZ2.7 Hz),
131.7 (d, JPZ99.7 Hz), 130.7 (d, JPZ9.9 Hz), 129.2 (d, JPZ
1.0 Hz),128.6(d, JPZ12.1 Hz),127.9(d, JPZ18.4 Hz),115.8
(d, JPZ107.1 Hz), 114.2 (s), 55.3 (s). 31P NMR (162.0 MHz,
CDCl3, ppm): 22.5 (s). IR (film, cmK1): 1174, 1398, 1421,
1438, 1464, 1604, 2838, 2960. HRMS: (CIC) C17H18O2P
(MCHC), calcd 285.1044, found 285.1043.
(1H, dd, JZ17.1 Hz, JPZ24.4 Hz), 2.26–2.31 (2H, m),
3
1.44–1.51 (2H, m), 1.24–1.35 (14H, m), 0.87 (3H, t, JZ
6.8 Hz). 13C NMR (100.6 MHz, CDCl3, ppm): d 152.3 (d,
JPZ2.0 Hz), 146.4 (d, JPZ3.8 Hz), 135.2 (d, JPZ17.8 Hz),
133.3 (d, JPZ106.6 Hz), 131.6 (d, JPZ2.7 Hz), 130.7 (d,
JPZ9.8 Hz), 129.9 (s), 128.8 (s), 128.6 (d, JPZ12.0 Hz),
127.6 (d, JPZ0.8 Hz), 121.8 (d, JPZ105.2 Hz), 119.8 (d,
JPZ105.1 Hz), 34.5 (d, JPZ17.0 Hz), 31.9 (s), 29.6 (s),
29.5 (s), 29.4 (s), 29.3 (s), 29.1 (s), 27.9 (d, JPZ1.1 Hz),
22.7 (s), 14.1 (s). 31P NMR (162.0 MHz, CDCl3, ppm): 20.9
(s). IR (film, cmK1): 1179, 1437, 1612, 2854, 2926. HRMS:
(CIC) C26H36OP (MCHC), calcd 395. 2504, found
4.2.3. Trimethyl-[3-(phenyl-vinyl-phosphinoyl)-allyl]-
silane 5c. General procedure using 3 (200 mg, 1.12 mmol)
and allyltrimethylsilane (59 mL, 0.375 mmol, cZ0.3 M) in
DCM (1.25 mL) with 2 mol% of catalyst 1 (6.3 mg,
7.49 mmol) for 24 h. Purification of the residue by silica
gel chromatography (98/01/01: chloroform/AcOEt/MeOH)
allowed isolation of 71.0 mg of 5c as a colourless oil
(0.269 mmol, yield 72%). 5c 1H NMR (400.1 MHz, CDCl3,
ppm): d 7.66–7.72 (2H, m), 7.40–7.51 (3H,m), 6.69 (1H,
ddt, 3JZ8.5, 16.9 Hz, JPZ19.3 Hz), 6.49–6.08 (3H, system
ABCX), 5.78 (1H, ddt, 4JZ1.2 Hz, 3JZ16.9 Hz, JPZ
24.4 Hz), 1.80–1.82 (2H, m), 0.03 (9H, s). 13C NMR
(100.6 MHz, CDCl3, ppm): d 150.3 (d, JPZ2.4 Hz), 133.1
(d, JPZ105.5 Hz), 132.9 (s), 132.2 (d, JPZ99.0 Hz), 131.5
(d, JPZ2.4 Hz), 130.7 (d, JPZ9.7 Hz), 128.4 (d, JPZ
11.4 Hz), 118.7 (d, JPZ107.1 Hz), 27.4 (d, JPZ16.2 Hz),
K1.9 (s). 31P NMR (202.4 MHz, CDCl3, ppm): 21.3 (s). IR
(film, cmK1): 1170, 1393, 1438, 1637, 2853, 2925, 3058.
1
395.2513. 8: H NMR (400.2 MHz, CDCl3, ppm): d 7.27–
3
7.86 (17H, m), 6.72 (2H, dd, JZ17.4 Hz, JPZ22.2 Hz).
13C NMR (100.6 MHz, CDCl3, ppm): d 146.9 (d, JPZ
3.7 Hz), 135.2 (d, JPZ18.0 Hz), 133.1 (d, JPZ107.7 Hz),
131.9(d, JPZ2.6 Hz), 130.8(d, JPZ10.0 Hz), 130.1(s), 128.9
(s),128.8(d,JPZ12.1 Hz),127.7(s), 119.4(d, JPZ106.2 Hz).
31P NMR (162.0 MHz, CDCl3, ppm): 21.7 (s). IR (film,
cmK1): 1169, 1216, 1438, 1493, 1574, 1608, 2993. HRMS:
(CIC) C22H20OP (MCHC), calcd 331.1252, found 331.1256.
4.2.6. 1-(Divinyl-phosphinoyl)-dodec-1-ene 9a. General
procedure with 4 (200 mg, 1.56 mmol) and dodecene
(116 mL, 0.521 mmol, cZ0.3 M) in DCM (1.74 mL) using
5 mol% of catalyst 1 (22.1 mg, 26.0 mmol) for 48 h.
Purification of the residue by silica gel chromatography
(90/10: chloroform/AcOEt) allowed isolation of 105.0 mg
of 9a as a colourless oil (0.392 mmol, yieldZ75%). 9a: 1H
NMR (400.2 MHz, CDCl3, ppm): d 6.69 (1H, ddt, 3JZ6.6,
17.2 Hz, JPZ20.0 Hz), 6.08–6.35 (6H, system (ABC)2X),
5.83 (1H, ddt, 4JZ1.5 Hz, 3JZ17.2 Hz, JPZ24.5 Hz),
2.21–2.27 (2H, m), 1.41–1.49 (2H, m), 1.20–1.35 (14H,
m), 0.9 (3H, t, 3JZ6.8 Hz). 13C NMR (100.6 MHz, CDCl3,
ppm): d 152.2 (d, JPZ1.9 Hz), 133.2 (s), 131.2 (d, JPZ
99.8 Hz), 120.7 (d, JPZ105.2 Hz), 34.5 (d, JPZ16.8 Hz),
31.9 (s), 29.6 (s), 29.5 (s), 29.4 (s), 29.3 (s), 29.1 (s), 27.8 (d,
JPZ1.2 Hz), 22.7 (s), 14.1 (s). 31P NMR (162.0 MHz,
CDCl3, ppm): 17.6 (s). IR (film, cmK1): 1173, 1392, 1466,
1603, 1638, 2851, 2922. HRMS: (CIC) C16H30OP (MC
HC), calcd 269.2034, found 269.2029.
4.2.4. [(6-Bromo-hex-1-enyl)-vinyl-phosphinoyl]-ben-
zene 5d. General procedure with 3 (200 mg, 1.12 mmol)
and bromohexene (50 mL, 0.375 mmol, cZ0.3 M) in DCM
(1.25 mL) using 2 mol% of catalyst 1 (6.3 mg, 7.49 mmol)
for 24 h. Purification of the residue by silica gel chroma-
tography (98/02: AcOEt/MeOH) allowed isolation of
101.0 mg of 5d as a brown oil (0.323 mmol, yieldZ86%).
1
5d: H NMR (400.1 MHz, CDCl3, ppm): d 7.64–7.69 (2H,
3
m), 7.41–7.50 (3H, m), 6.67 (1H, ddt, JZ6.5, 17.1 Hz,
JPZ19.5 Hz), 6.10–6.48 (3H, system ABCX), 6.02 (1H,
2
3
ddt, JZ1.4 Hz, JZ17.1 Hz, JPZ24.2 Hz), 3.36 (2H, t,
3JZ6.7 Hz), 2.24–2.30 (2H, m), 1.81–1.88 (2H–m), 1.56–
1.64 (2H, m). 13C NMR (100.6 MHz, CDCl3, ppm): d 153.7
(d, JPZ1.7 Hz), 136.3 (s), 135.1 (d, JPZ105.5 Hz), 134.4
(d, JPZ2.4 Hz), 134.3 (d, JPZ99.0 Hz), 133.4 (d, JPZ
9.7 Hz), 131.3 (d, JPZ12.2 Hz), 124.9 (d, JPZ103.1 Hz),
36.1 (d, JPZ17.0 Hz), 35.9 (s), 34.7 (s), 29.1 (s). 31P NMR
(202.4 MHz, CDCl3, ppm): 20.9 (s). IR (film, cmK1): 1173,
1397, 1437, 1623, 2860, 2933. HRMS: (CIC) C14H19OPBr
(MCHC), calcd 313.0357, found 313.0360.
4.2.7. [2-(Divinyl-phosphinoyl)-vinyl]-benzene 9b.
General procedure starting from 4 (160 mg, 0.125 mmol)
and styrene (48 mL, 0.417 mmol, cZ0.3 M) in DCM
(1.4 mL) using 5 mol% catalyst 1 (17.6 mg, 20.8 mmol)
for 24 h. Purification of the residue by silica gel chroma-
tography (98/02: AcOEt/MeOH) allowed isolation of
57.6 mg of 9b as a colourless oil (0.282 mmol, yieldZ
68%). 9b: 1H NMR (400.2 MHz, CDCl3, ppm): d 7.35–7.50
(6H, m), 6.12–6.49 (7H, m which could be analysed as 6.44
(1H, dd, 3JZ17.4 Hz, JPZ22.2 Hz) overlapping with 6.12–
6.42 (6H, system (ABC)2X). 13C NMR (100.6 MHz, CDCl3,
ppm): d 147,0 (d, JPZ3.2 Hz), 135.0 (d, JPZ18.4 Hz),
133.7 (s), 130.9 (d, JPZ100.7 Hz), 130.1 (s), 128.8 (s),
127.6 (s), 118.2 (d, JPZ106.3 Hz). 31P NMR (162.0 MHz,
CDCl3, ppm): 18.5 (s). IR (film, cmK1): 1171, 1393, 1449,
1495, 1604, 2853, 2924, 3000, 3026. HRMS: (CIC)
C12H14OP (MCHC), calcd 205.0782, found 205.0787.
4.2.5. [(2-Phenyl-vinyl)-dodec-1-enyl-phosphinoyl]-ben-
zene 7. General procedure with 5a (154.2 mg, 0.485 mmol)
and styrene (18 mL, 0.162 mmol, cZ0.3 M) in DCM
(0.5 mL) using 5 mol% of catalyst 1 (6.8 mg, 8.08 mmol)
for 48 h. Purification of the residue by silica gel chroma-
tography (90/10: chloroform/AcOEt) allowed isolation of
44.0 mg of 7 as a colourless oil (0.112 mmol, yieldZ69%),
as well as 28.4 mg of 6a, 5.0 mg of [bis-(2-phenyl-vinyl)-
phosphinoyl]-benzene 8, 63.7 mg of 5a and 10.0 mg of 3. 7
1H NMR (400.2 MHz, CDCl3, ppm): d 7.74–7.79 (2H, m),
4.2.8. [2-(Dodec-1-enyl-vinyl-phosphinoyl)-vinyl]-ben-
zene 10a. General procedure starting from 9b (45.0 mg,
0.221 mmol) and dodecene (16 mL, 0.074 mmol, cZ0.3 M)
3
7.35–7.52 (9H, m), 6.76 (1H, ddt, JZ6.6, 16.9 Hz, JPZ
3
19.7 Hz), 6.61 (1H, dd, JZ17.4 Hz, JPZ22.0 Hz), 6.09

2400
F. Bisaro, V. Gouverneur / Tetrahedron 61 (2005) 2395–2400
in DCM (0.25 mL) using 5 mol% of catalyst 1 (3.1 mg,
3.68 mmol) for 48 h. Purification of the residue by silica gel
chromatography (98/02: AcOEt/MeOH) allowed isolation
of 18.0 mg of 10a as a colourless oil (0.052 mmol, yieldZ
References and notes
1. For reviews and key papers on ring-closing metathesis and
cross-metathesis, see: (a) Chatterjee, A. K.; Morgan, J. P.;
Scholl, M.; Grubbs, R. H. J. Am. Chem. Soc. 2000, 122, 3783.
(b) Chatterjee, A. K.; Choi, T.-L.; Sanders, D. P.; Grubbs,
R. H. J. Am. Chem. Soc. 2003, 125, 11360. (c) Connon, S. J.;
Blechert, S. Angew. Chem., Int. Ed. 2003, 42, 1900.
(d) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413.
(e) Blechert, S.; Schuster, M. Angew. Chem., Int. Ed. Engl.
1997, 36, 2035. (f) Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc.
Chem. Res. 1995, 28, 446. (g) Gibson, S. E.; Keen, S. P. Top.
Organomet. Chem. 1998, 1, 155. (h) Schrock, R. R.; Hoveyda,
A. H. Angew. Chem., Int. Ed. 2003, 42, 4592.
1
71%). 10a: H NMR (400.2 MHz, CDCl3, ppm): d 7.31–
7.49 (6H, m), 6.70 (1H, ddt, 3JZ6.6, 17.1 Hz, JPZ20.0 Hz),
6.50–6.07 (4H, m which could be analysed as 6.43 (1H, 3JZ
17.4 Hz, JPZ22.0 Hz) overlapping with 6.41–6.07 (3H,
4
3
system ABCX)), 5.89 (1H, ddt, JZ1.5 Hz, JZ17.1 Hz,
JPZ24.4 Hz), 2.21–2.27 (2H, m), 1.41–1.48 (2H, m), 1.18–
1.35 (14H, m), 0.86 (3H, t, 3JZ6.8 Hz). 13C NMR
(100.6 MHz, CDCl3, ppm): d 151.9 (d, JPZ2.4 Hz), 146.2
(d, JPZ4.0 Hz), 135.2 (d, JPZ17.6 Hz), 132.9 (s), 131.7 (d,
JPZ100.7 Hz), 129.9 (s), 128.8 (s), 127.5 (s), 121.3 (d, JPZ
105.5 Hz), 119.2 (d, JPZ105.5 Hz), 34.5 (d, JPZ16.8 Hz),
31.8 (s), 29.6 (s), 29.5 (s), 29.4 (s), 29.3 (s), 29.1 (s), 27.8 (d,
JPZ1.6 Hz), 22.6 (s), 14.1 (s). 31P NMR (162.0 MHz,
CDCl3, ppm): 18.3 (s). IR (film, cmK1): 1174, 1449, 1465,
1625, 2854, 2925. HRMS: (CIC) C22H34OP (MCHC),
calcd 345.2347, found 345.2351. 10a was also synthesized
using the general procedure starting from 9a (118 mg,
0.440 mmol) and styrene (17 mL, 0.147 mmol, cZ0.3 M) in
DCM (0.5 mL) using 5 mol% catalyst 1 (6.2 mg, 7.34 mmol)
for 48 h. Purification of the residue by silica gel chroma-
tography (98/02: AcOEt/MeOH) allowed isolation of 44.0 mg
of 10a as a colourless oil (0.128 mmol, yieldZ87%).
2. (a) Trevitt, M.; Gouverneur, V. Tetrahedron Lett. 1999, 40,
7333. (b) Schuman, M.; Trevitt, M.; Redd, A.; Gouverneur, V.
Angew. Chem., Int. Ed. 2000, 39, 2491. (c) Slinn, C. A.; Edlin,
C.; Redgrave, A. J.; Hind, S. L.; Nolan, S. P.; Gouverneur, V.
Org. Biomol. Chem. 2003, 1, 3820. (d) Bisaro, F.; Gouverneur,
V. Tetrahedron Lett. 2003, 44, 7133. For an excellent review
on the synthesis of phosphorus heterocycles via RCM, see
(e) Reynolds, M. D.; Dougherty, J. M.; Hanson, P. R. Chem.
Rev. 2004, 104, 2239.
3. Grushin, V. V. Chem. Rev. 2004, 104, 1629.
4. For monoalkenyl phosphine oxides: (a) Organic Phosphorus
Compounds; Kosolapoff, G. M., Maier, L., Eds.; Wiley-
Interscience: New York, 1972. (b) Goldwhite, H. Introduction
to Phosphorus Chemistry; Cambridge University Press: Cam-
bridge, 1981. (c) Takaki, K.; Koshoji, G.; Komeyana, K.;
Takeda, M.; Shishido, T.; Kitanin, A.; Takeshira, K. J. Org.
Chem. 2003, 68, 6554 and references therein. For unsymmetical
di- and trialkenyl phosphine oxides, see: (d) Gnon, J.-F.; Pilard,
K.; Tantaoui, A.-C.; Gaumont, J.-M.; Denis Tetrahedron Lett.
1995, 36, 4421. (e) Trofimov, B. A.; Gusarova, N. K.;
Malysheva, S. F.; Dmitriev, V. I.; Rakhmatulina, T. N.;
Voronkov, M. G. Phosphorus, Sulfur Silicon Relat. Elem.
1990, 51/52, 713. (f) Prishchenko, A. A.; Livantsov, M. V.;
Lutsenko, I. F. J. Gen. Chem. USSR (Engl. Transl.) 1987,57, 1256.
5. To the best of our knowledge, there are no examples in the
literature of desymmetrization of prochiral substrates by direct
cross-metathesis leading to racemic or enantioenriched
products. For an abstract presenting the concept, see: (a)
Goldberg, S. D.; Ward, D. W.; Berlin, J. M.; Toste, F. D.;
Grubbs, R.H. Abstracts of Papers, 224th ACS National
Meeting, Boston, MA, USA, August 18–22, 2002 (2002),
ORGN-216. For a paper reporting on a ‘net’ cross-metathesis
according to an in situ ARCM/ring opening process leading to
enantioenriched products, see: (b) Jernelius, A.; Schrock,
R. R.; Hoveyda, A. H. Tetrahedron 2004, 60, 7345.
4.2.9.
{2-[(3-Phenyl-propenyl)-dodec-1-enyl-phos-
phinoyl]-vinyl}-benzene 11. General procedure starting
from 10a (56.5 mg, 0.164 mmol) and 3-phenylpropene
(7 mL, 0.055 mmol, cZ0.3 M) in DCM (0.2 mL) using
5 mol% catalyst 1 (2.3 mg, 2.74 mmol) for 24 h. Purification
of the residue by silica gel chromatography (90/10:
chloroform/AcOEt) allowed isolation of 15.5 mg of 11 as
1
a colourless oil (0.036 mmol, yieldZ65%). 11: H NMR
(500.0 MHz, CDCl3, ppm): d 7.22–7.54 (11H, m), 6.87 (1H,
ddt, 3JZ6.2, 17.0 Hz, JPZ19.2 Hz), 6.72 (1H, ddt, 3JZ6.5,
17.1 Hz, JPZ19.8 Hz), 6.47 (1H, dd, 3JZ17.5 Hz, JPZ
21.8 Hz), 5,89–5.97 (2H, m), 3.63 (2H, d, 3JZ6.2 Hz),
2.27–2.31 (2H, m), 1.47–1.53 (2H, m), 1;29–1.38 (14H, m),
0.93 (3H, t; JZ7.0 Hz). 13C NMR (125.7 MHz, CDCl3,
3
ppm): d 151.4 (s), 148.9 (s), 145.8 (s), 137.5 (s), 135.2 (d,
JPZ18.9 Hz), 129.7 (s), 128.8 (s), 128.7 (s), 128.5 (s), 127.5
(s), 126.5 (s), 123.7 (d, JPZ105.6 Hz), 121.7 (d, JPZ
106.9 Hz), 119.7 (d, JPZ110.6 Hz), 40.5 (d, JPZ17.6 Hz),
34.4 (d, JPZ16.3 Hz), 31.7 (s), 29.4 (s), 29.3 (s), 29.2 (s),
29.0 (s), 27.8 (s), 22.5 (s), 14.0 (s). 31P NMR (202.4 MHz,
CDCl3, ppm): 19.1 (s). IR (film, cmK1): 1170, 1452, 1495,
1576, 1624, 2855, 2926. HRMS: (CIC) C29H40OP (MC
HC), calcd 435.2817, found 435.2824.
6. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999,
1, 955. Chatterjee, A. K.; Grubbs, R. G. Org. Lett. 1999, 1, 1751.
7. Demchuk, O. M.; Pietrusiewicz, K. M.; Michrowska, A.;
Grela, K. Org. Lett. 2003, 5, 3217.
Acknowledgements
We thank the EPSRC (GR/N34901/01) for generous
financial support (F. B.).
8. For the definition of types I–IV olefins, see Ref. 1(b).
9. Monkowius, U.; Nogai, S.; Schmidbaur, H. Organometallics
2003, 22, 145.
10. Weiner, M. A.; Pasternack, G. J. Org. Chem. 1967, 32, 3707.
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.tet.2005.01.019