Electrophilic alkylation of electron-rich arenes by phosphacymantrenylcarbenium ions

Article abstract of DOI:10.1021/om020981j

Phosphacymantren-2-ylcarbinol 1 is transformed into the corresponding carbenium ion by reaction with AlCl₃ in CH₂Cl₂ at 0°C. This ion is able to alkylate ferrocene and electron-rich arenes such as anisole and 1,3-dimethoxy

Full text of DOI:10.1021/om020981j

1340
Organometallics 2003, 22, 1340-1342
Notes
Electr op h ilic Alk yla tion of Electr on -Rich Ar en es by
P h osp h a cym a n tr en ylca r ben iu m Ion s
Patrick Toullec, Louis Ricard, and Franc¸ois Mathey*
Laboratoire ‘He´te´roe´le´ments et Coordination’ UMR CNRS 7653, DCPH, Ecole Polytechnique,
91128 Palaiseau Cedex, France
Received December 3, 2002
Summary: Phosphacymantren-2-ylcarbinol 1 is trans-
formed into the corresponding carbenium ion by reaction
with AlCl3 in CH2Cl2 at 0 °C. This ion is able to alkylate
ferrocene and electron-rich arenes such as anisole and
1,3-dimethoxybenzene. One isomer of the double-alkyla-
tion product derived from 1,3-dimethoxybenzene has
been characterized by X-ray crystal structure analysis.
It derives from the carbenium ion with the E-stereo-
chemistry.
Lewis acid, the expected para-alkylation product 2 was
obtained in satisfactory yield (eq 1).
In tr od u ction
Recent work by Ganter1 has demonstrated that the
replacement of an η5-cyclopentadienyl ligand by an η5-
phospholyl group does not significantly alter the ability
of a ferrocene derivative to stabilize a ferrocenylcarbe-
nium ion. It is also known from pKR+ measurements2
that benchrotrenyl- and cymantrenylcarbenium ions
display almost equal stabilities. Despite their stabiliza-
tion by the [Cr(CO)3] group, benchrotrenylcarbenium
ions remain sufficiently electrophilic to alkylate electron-
rich arenes, and this property has found some use in
organic synthesis.3 These various data led us to wonder
whether the phosphacymantrenylcarbenium ions could
enter into a similar chemistry with electron-rich arenes,
thus providing an access to hitherto unaccessible phos-
phole-containing molecules.
Other Lewis acids such as H2SO4 or HBF4 are also
effective, but F3B‚OEt2, ZnCl2, and CF3SO3H proved to
be useless. Compound 2 was obtained as a 80:20 mixture
of two diastereomers (δ31P -40.1 (2a , major), -31.7 (2b,
minor) (CDCl3)), which could not be separated. Mass
spectrometry confirmed the formulation of 2 (m/z 384,
M+), and a complete characterization of each isomer by
1H and 13C NMR spectroscopy proved possible. The most
striking difference between the spectra of both com-
1
pounds concerns the H resonance of the methyl group
located on the â-carbon of the phospholyl ring. In 2a
(major), it is found at higher field, δ Me(â) 1.75, δ
Me(â′) 2.01; in 2b (minor), δ Me(â) 2.07, δ Me(â′) 2.14.
The stereochemical origin of this effect will be discussed
later.
Resu lts a n d Discu ssion
All our experiments were conducted with the easily
available secondary phosphacymantrenylcarbinol 1.4
Compound 1 is prepared by reduction of the correspond-
ing 2-acetyl derivative by NaBH4 in ethanol and is
obtained as a 85:15 mixture of two diastereomers: δ31P
-48.2 (major) and -41.4 (minor) in CDCl3. The more
shielded major isomer 1a is assigned the configuration
shown in eq 1 by analogy with the work of Ganter on
the analogous phosphaferrocene derivative.1 The test
reaction was conducted with anisole. Using AlCl3 as the
We then attempted to reproduce this reaction using
ferrocene in place of anisole. Once again, two isomers
were obtained (δ31P -35.1 (3a , 80%), -28.8 (3b, 20%)),
and the major isomer shows some shielding of the
methyl protons on Câ (3a , δ Me(â) 1.99, δ Me(â′) 2.07;
3b, δ Me(â) 2.05, δ Me(â′) 2.10).
The next step was an application of this methodology
to build a more sophisticated, potentially chelating, bis-
phosphacymantrenyl structure. The attempt was car-
ried out with 1,3-dimethoxybenzene (eq 2).
Here of course, with two chiral sp3-carbons and two
planar chiral η5-units, several diastereomers should be
formed, and these were indeed observed when monitor-
ing the reaction mixture by 31P NMR. We were able to
isolate the two major ones, 4a and 4b, in the pure state
by chromatography on silica gel. Both feature the high
(1) Brassat, L.; Ganter, B.; Ganter, C. Chem. Eur. J . 1998, 4, 2148.
(2) Watts, W. E. In Comprehensive Organometallic Chemistry;
Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.; Pergamon: Oxford,
1982; Vol. 8, p 1052.
(3) Davies, S. G.; Donohoe, T. J . Synlett 1993, 323.
(4) Breque, A.; Mathey, F.; Santini, C. J . Organomet. Chem. 1979,
165, 129.
10.1021/om020981j CCC: $25.00 © 2003 American Chemical Society
Publication on Web 02/11/2003

Notes
Organometallics, Vol. 22, No. 6, 2003 1341
F igu r e 1. Crystal structure of 4b.
de microanalyse du CNRS, Gif-sur-Yvette, France. High-reso-
lution mass spectra were recorded by Service de spectrome´trie
de masse, De´partement de chimie, Ecole Normale Supe´rieure,
Paris, France.
field shifted Me(â) protons already observed for 2a and
3a . We have been able to get good crystals of 4b and to
determine its X-ray crystal structure (Figure 1). Given
the high degree of steric crowding and restricted rota-
tion, this structure is probably not very different from
the structure in solution. On this basis, the shielding
of the Me(â) protons could result from a through-space
interaction with the methyl groups of the CHMe linkers.
From another standpoint, the two former phosphacy-
mantrenylcarbenium units in 4b (P1, C5) and (P2, C12)
display the (S)-P, (R)-C or (R)-P, (S)-C stereochemistry.
If we admit, for obvious steric reasons, that the elec-
tron-rich arene attacks the carbenium ion from the exo-
side, the carbocation (Z)-5 will give the diastereomeric
unit with the (R)-P, (R)-C + (S)-P, (S)-C stereochemis-
try, whereas (E)-5 will give the observed stereochem-
istry (eq 3).
2-(4′-Meth oxyph en yl)eth yl-3,4-dim eth ylph osph acym an -
t r en e, 2. 2-(1′-Hydroxyethyl)-3,4-dimethylphosphacyman-
trene, 1 (300 mg, 1 mmol), and 108 mg of anisole (1 mmol)
were placed in a Schlenk tube under nitrogen atmosphere, and
20 mL of distilled dichoromethane was added via a septum.
The yellow solution was cooled to 0 °C, and 145 mg of
aluminum chloride (1 mmol) was added. The solution turned
dark brown after 15 min. The consumption of the starting
phosphacymantrene was monitored by 31P NMR spectroscopy
after 2 h of reaction. The reaction medium was diluted by 50
mL of dichloromethane, and the solution was hydrolyzed using
100 mL of a saturated sodium hydrogen carbonate aqueous
solution and washed with 100 mL of brine. The organic layer
was collected and dried with magnesium sulfate, and the
solvents were removed under vacuum to give the crude
products as an orange oil. Chromatography over silica gel was
carried out with a 90:10 hexane/ether mixture as the eluent.
The two diastereoisomers 2a and 2b (265 mg) of the final
product were isolated as a mixture (80:20): 69% yield; MS m/z
384 (M+, 10), 300 (M+ - 3CO, 100), 245 (M+ - 3CO - Mn,
11); HRMS for the mixture 2a +2b calcd 384.0323, found
384.0320.
1
4
2a : H NMR (CDCl3) δ 1.34 (d, J H-P ) 7 Hz, 3H, benzylic
CH3), 1.75 (s, 3H, Câ-CH3), 2.01 (s, 3H, Câ-CH3), 3.41 (m, 1H,
2
benzylic proton), 3.69 (s, 3H, CH3-O), 4.12 (d, J H-P ) 36 Hz,
1H, C5-H), 6.73 (d, J H-H ) 8 Hz, 2H, C2′-H), 7.03 (d, J H-H
)
3
3
8 Hz, 2H, C3′-H); {1H}13C NMR (CDCl3) δ 13.61 (s), 16.41 (s),
3
2
25.26 (d, J C-P ) 17 Hz, benzylic CH3), 40.50 (d, J C-P ) 13
Hz, benzylic C), 55.85 (s, CH3-O), 90.78 (d, 1J C-P ) 59 Hz, C5),
Cation (E)-5 is probably formed by abstraction of OH-
from 1a on the exo-side (see the work of Ganter on the
analogous phosphaferrocenylcarbenium ions).1 Quite
logically, (E)-5 is less stable than (Z)-5, and thus our
observation means that the rate of the reaction of (E)-5
with the electron-rich arene is higher than the rate of
the conversion of (E)-5 into (Z)-5. From a purely practi-
cal standpoint, the synthesis of 4a ,b opens the possibil-
ity of synthesizing various flexible rings containing
several phosphole units.5 Only a few such species are
presently known.6
109.85 (d, J C-P ) 6 Hz, C4), 114.54 (s, Cmeta), 115.17 (d, J C-P
) 6 Hz, C3), 128.70 (s, Cortho), 138.27 (s, Cipso), 158.66 (s, Cpara),
225.05 (s, CO); {1H}31P NMR (CDCl3) δ -40.14.
2
2
1
4
2b: H NMR (CDCl3) δ 1.39 (d, J H-P ) 7 Hz, 3H, benzylic
CH3), 2.07 (s, 3H, Câ-CH3), 2.14 (s, 3H, Câ-CH3), 3.41 (m, 1H,
2
benzylic proton), 3.72 (s, 3H, CH3-O), 4.17 (d, J H-P ) 36 Hz,
1H), 6.79 (d, J A-B ) 8 Hz, 2H, C2′-H), 7.14 (d, J A-B ) 8 Hz,
3
3
2H, C3′-H); {1H}13C NMR (CDCl3) δ 13.55 (s), 16.45 (s), 24.79
2
(s, benzylic CH3), 39.97 (d, J C-P ) 15 Hz, benzylic C), 55.85
(s, CH3-O), 91.11 (d, J C-P ) 60 Hz, C5), 110.71 (d, J C-P ) 6
1
2
Hz, C4), 113.75 (d, J C-P ) 6 Hz, C3), 114.16 (s, Cmeta), 129.66
2
(d, J ) 4 Hz, Cortho), 136.90 (d, J ) 3 Hz, Cipso), 159.20 (s, Cpara),
225.05 (s, CO); {1H}31P NMR (CDCl3) δ -31,74.
Exp er im en ta l Section
2-(1′-F e r r oce n yl)e t h yl-3,4-d im e t h ylp h osp h a cym a n -
t r en e, 3. 2-(1′-Hydroxyethyl)-3,4-dimethylphosphacyman-
trene, 1 (330 mg, 1.12 mmol), and 186 mg of ferrocene (1 mmol)
were placed in a Schlenk tube under nitrogen atmosphere, and
20 mL of distilled dichoromethane was added via a septum.
The yellow solution was cooled to 0 °C, and 160 mg of
aluminum chloride (1.2 mmol) was added. The solution turned
NMR spectra were recorded on a multinuclear Bruker
AVANCE 300 MHz spectrometer operating at 300.13 for 1H,
75.47 for 13C, and 121.50 MHz for 31P. Chemical shifts are
expressed in parts per million (ppm) downfield from inter-
nal tetramethylsilane (1H and 13C) and external 85% aqueous
H3PO4(31P). Elemental analyses were performed by the Service
(5) The transformation of phosphacymantrenes into phospholes is
described in: Deschamps, B.; Toullec, P.; Ricard, L.; Mathey, F. J .
Organomet. Chem. 2001, 634, 131.
(6) Laporte, F.; Mercier, F.; Ricard, L.; Mathey, F. J . Am. Chem.
Soc. 1994, 116, 3306. Deschamps, E.; Ricard, L.; Mathey, F. J . Chem.
Soc., Chem. Commun. 1995, 1561.

1342 Organometallics, Vol. 22, No. 6, 2003
Notes
dark brown after 15 mn. The consumption of the starting
phosphacymantrene was monitored by 31P NMR spectroscopy
after 2 h of reaction. The reaction medium was diluted by 50
mL of dichloromethane, and the solution was hydrolyzed using
100 mL of a saturated sodium hydrogen carbonate aqueous
solution and washed with 100 mL of brine. The organic layer
was collected and dried with magnesium sulfate, and the
solvents were removed under vacuum to give the crude
products as an orange oil. Chromatography over silica gel was
carried out with a 90:10 hexane/ether mixture as the eluent.
The two diastereoisomers 3a and 3b of the final product (180
mg) were isolated as a mixture (80:20): 40% yield; MS m/z
463 (M+, 39), 378 (M+ - 3CO + 1, 100), 312 (M+ - 3CO -
C5H5, 9), 258 (M+ - 3CO - C5H5 - Mn, 36); HRMS for the
mixture 3a +3b calcd 461.9880, found 461.9880.
the final product (480 mg) was isolated in 70% total yield. A
second chromatography over silica gel carried out with the
same eluent mixture led to the isolation of 80 mg of the isomer
4a and 100 mg of the isomer 4b as yellow solids.
4a : 1H NMR (CDCl3) δ 1.27 (dd, J H-P ) 7 Hz, 6H, benzylic
4
CH3), 1.71 (s, 6H, C3′′-CH3), 2.12 (s, 6H, C4′′-CH3), 3.75 (m, 2H,
2
benzylic proton), 3.82 (s, 6H, CH3-O), 4.24 (d, J H-P ) 36 Hz,
2H, C5′′-H), 6.34 (s, 1H, C2-H), 6.74 (s, 1H, C5-H); {1H}13C NMR
(CDCl3) δ 12.46 (s, C3′′-CH3), 15.70 (s, C4′′-CH3), 22.24 (d, 3J C-P
2
) 17 Hz, benzylic CH3), 33.07 (d, J C-P ) 13 Hz, benzylic C),
1
55.32 (s, CH3-O), 90.62 (d, J C-P ) 60 Hz, C5′′), 94.46 (s, C2),
2
2
109.24 (d, J C-P ) 5 Hz, C4′′), 113.92 (d, J C-P ) 7 Hz, C3′′),
127.00 (s, C5), 127.90 (d, J C-P ) 63 Hz, C2′′), 155.28 (s, C1,
1
C3), 224.42 (s, CO); {1H}31P NMR (CH2Cl2) δ -39.95; HRMS
for 4a calcd 690.0177, found 690.0182.
1
4
3a : H NMR (CDCl3) δ 1.50 (d, J H-P ) 7 Hz, 3H, benzylic
CH3), 1.99 (s, 3H, Câ-CH3), 2.07 (s, 3H, Câ-CH3), 3.20 (m, 1H,
benzylic proton), 4.1-4.25 (m, 9H, Cp et Cp′); {1H}13C NMR
4b: 1H NMR (CDCl3) δ 1.32 (dd, J H-P ) 6 Hz, 6H, benzylic
4
CH3), 1.59 (s, 6H, C3′′-CH3), 2.06 (s, 6H, C4′′-CH3), 3.83 (m, 2H,
2
benzylic proton), 3.85 (s, 6H, CH3-O), 4.23 (d, J H-P ) 35 Hz,
3
(CDCl3) δ 13.76 (s, Câ-CH3), 16.55 (s, Câ-CH3), 24.28 (d, J C-P
2H, C5′′-H), 6.36 (s, C2-H), 6.73 (s, C5-H); {1H}13C NMR (CDCl3)
2
) 13 Hz, benzylic CH3), 33.10 (d, J C-P ) 15 Hz, benzylic C),
3
δ 12.30 (s), 15.65 (s), 22.18 (d, J C-P ) 17 Hz, benzylic CH3),
66.90 (s, Cp), 67.72 (s, Cp), 67.89 (s, Cp), 69.28 (s, Cp), 90.31
2
32.32 (d, J C-P ) 14 Hz, benzylic C), 55.44 (s, CH3-O), 90.83
1
2
(d, J C-P ) 59 Hz, C5), 110.23 (d, J C-P ) 6 Hz, C4), 113.99 (d,
(d, J C-P ) 60 Hz, C5′′), 94.14 (s, C2), 109.13 (d, J C-P ) 7 Hz,
1
2
2J C-P ) 7 Hz, C3), 128.15 (d, J C-P ) 63 Hz, C2), 225.18 (s,
1
C4′′), 113.20 (d, J C-P ) 7 Hz, C3′′), 125.48 (s, C5), 126.54 (s,
2
CO); {1H}31P NMR (CDCl3) δ -35.10.
C4), 128.47 (d, 1J C-P ) 64 Hz, C2′′) 155.05 (s, C1, C3), 224.30 (s,
CO); {1H}31P NMR (CH2Cl2) δ -40.79. MS m/z 691 (M+ + 1,
4), 606 (M+ - 3CO, 53), 522 (M+ - 6CO, 100), 467 (M+ - 6CO
- Mn, 25); HRMS for 4b calcd 690.0177, found 690.0182.
1
4
3b: H NMR (CDCl3) δ 1.45 (d, J H-P ) 7 Hz, 3H, benzylic
CH3), 2.05 (s, 3H, Câ-CH3), 2.10 (s, 3H, Câ-CH3); {1H}13C NMR
(CDCl3) δ 13.53 (s, Câ-CH3), 16.46 (s, Câ-CH3), 23.35 (m,
2
benzylic CH3), 34.58 (d, J C-P ) 15 Hz, benzylic C), 67.17 (d,
Crystallographic data for C30H30Mn2O8P2 (4b): M ) 690.36
g/mol; triclinic; space group P1h; a ) 9.383(5) Å, b ) 12.956(5)
Å, c ) 14.152(5) Å, R ) 67.370(5)°, â ) 71.510(5)°, γ ) 82.330-
(5)°, V ) 1505.8(11) Å3; Z ) 2; D ) 1.523 g cm-3; µ ) 0.994
cm-1; F(000) ) 708. Crystal dimensions 0.20 × 0.14 × 0.10
J ) 6 Hz, Cp), 67.68 (s, Cp), 68.34 (s, Cp), 69.16 (s, Cp), 88.74
(d, 1J C-P ) 60 Hz, C5′), 109.76 (d, 2J C-P ) 6 Hz, C4′), 114.84 (d,
2J C-P ) 6 Hz, C3′), 130.16 (d, J C-P ) 62 Hz, C2′), 225.18 (s,
1
CO); {1H}31P NMR (CDCl3) δ -28.80.
1,3-Dim eth oxy-4,6-bis[1′-(3′′,4′′-dim eth ylph osph acym an -
t r en yl)et h yl]b en zen e, 4. 2-(1′-Hydroxyethyl)-3,4-dimeth-
ylphosphacymantrene, 1 (620 mg, 2.1 mmol), and 140 mg of
1,3-dimethoxybenzene (1 mmol) were placed in a Schlenk tube
under nitrogen atmosphere, and 20 mL of distilled di-
choromethane was added via a septum. The yellow solution
was cooled to 0°C and 300 mg of aluminum chloride (2.24
mmol) were added. The solution turned dark brown after 15
mn. The consumption of the starting phosphacymantrene was
monitored by 31P NMR spectroscopy after 2 h of reaction. The
reaction medium was diluted by 50 mL of dichloromethane,
the solution was hydrolyzed using 100 mL of a saturated
sodium hydrogen carbonate aqueous solution and washed with
100 mL of brine. The organic layer was collected and dried
with magnesium sulfate, and the solvents were removed under
vacuum to give the crude products as a yellow oil. A first
chromatography over silica gel was carried out with a 90:10
hexane/ether mixture as the eluent. A mixture of isomers of
mm. Total reflections collected 13 387 and 6947 with
I
> 2σ(I). Goodness of fit on F2 1.047; R(I>2σ(I)) ) 0.0362, wR2
) 0.0902(all data); maximum/minimum residual density
0.404(0.063)/-0.502(0.063) e Å-3. Data were collected on a
KappaCCD diffractometer at 150.0(1) K with Mo KR radiation
(λ ) 0.71073 Å). Full details of the crystallographic analysis
are described in the Supporting Information.
Ack n ow led gm en t. The authors thank BASF for the
financial support of P.T. and of this research program.
Su p p or tin g In for m a tion Ava ila ble: Crystallographic
data for 4b and {1H}13C NMR spectra of 2a +b, 3a +b, and
4b. This material is available free of charge via the Internet
at http://pubs.acs.org.
OM020981J