Site-selective phosphorylation of arylphospholes through reaction with phosphorus tribromide

Article abstract of DOI:10.1016/S0022-328X(01)01119-6

The reaction of 1-(tri-tert-butylphenyl)phosphole (1) with phosphorus tribromide gave the 3-dibromophosphino intermediate (2) selectively that was useful in the synthesis of phosphonic amides 4, H-phosphinic amide 6 and H-phosphinates 8. A similar transformation of the 1-(triisopropylphenyl)phosphole (9) led to a 2-substitution furnishing phosphonic amides 12 or H-phosphinates 14. The phosphorylated phospholes (4, 6, 8) were tested as ligands of transition metal complexes in hydroformylation.

Full text of DOI:10.1016/S0022-328X(01)01119-6

Journal of Organometallic Chemistry 643–644 (2002) 32–38
www.elsevier.com/locate/jorganchem
Site-selective phosphorylation of arylphospholes through reaction
with phosphorus tribromide 1
Gyo¨rgy Keglevich a,*, Tungalag Chuluunbaatar a, Bea´ta Dajka a, Krisztina Luda´nyi b,
Gyula Parlagh c, Tama´s Ke´gl d, La´szlo´ Kolla´r e, La´szlo´ Toke f
3
a Department of Organic Chemical Technology, Budapest Uni6ersity of Technology and Economics, 1521 Budapest, Hungary
b Hungarian Academy of Sciences, Chemical Research Center, 1525 Budapest, Hungary
c Department of Physical Chemistry, Budapest Uni6ersity of Technology and Economics, 1521 Budapest, Hungary
d Research Group for Petrochemistry of the Hungarian Academy of Sciences, 8200 Veszpre´m, Hungary
e Department of Inorganic Chemistry, Uni6ersity of Pe´cs, 7624 Pe´cs, Hungary
f Research Group of the Hungarian Academy of Sciences at the Department of Organic Chemical Technology,
Budapest Uni6ersity of Technology and Economics, 1521 Budapest, Hungary
Received 21 May 2001; accepted 16 July 2001
Dedicated to Professor Dr Franc¸ois Mathey on the occasion of his 60th birthday
Abstract
The reaction of 1-(tri-tert-butylphenyl)phosphole (1) with phosphorus tribromide gave the 3-dibromophosphino intermediate
(2) selectively that was useful in the synthesis of phosphonic amides 4, H-phosphinic amide 6 and H-phosphinates 8. A similar
transformation of the 1-(triisopropylphenyl)phosphole (9) led to a 2-substitution furnishing phosphonic amides 12 or H-phosphi-
nates 14. The phosphorylated phospholes (4, 6, 8) were tested as ligands of transition metal complexes in hydroformylation.
© 2002 Elsevier Science B.V. All rights reserved.
Keywords: Arylphospholes; Phosphorylation; Selectivity; Hydroformylation
of phospholes and their reactivity in aromatic elec-
trophilic substitutions encountered a significant electron
1. Introduction
delocalization [7–10].
In this paper, we report a new reaction of tri-
Phospholes, perhaps the most representative class of
P-heterocycles, have attracted much attention recently
alkylphenylphospholes; their site-selective phosphoryla-
[2–4]; they are widely used as ligands in transition
tion via reaction with phosphorus tribromide is a good
metal complexes applied in hydroformylations [5]. On
means for the preparation of modified phospholes.
the other hand, the controversy over the aromaticity of
phospholes stimulated an intensive study of the prob-
lem [6]. It is now clear that the ‘‘common or garden’’
variety phospholes are not aromatic due to the pyrami-
2. Results and discussion
dal character of the phosphorus atom. The 1-(2,4,6-tri-
The reaction of 1-(2,4,6-tri-tert-butylphenyl)-
alkylphenyl)phospholes
exhibiting
a
flattened
phosphole (1) with phosphorus tribromide, which was
found to be an efficient reactant for the introduction of
the dibromophosphino group into N-heterocycles [11–
14], led to the 3-dibromophosphinophosphole (2) after
48 h reflux in chloroform, in the presence of one
equivalent of pyridine. The unstable intermediate (2)
was immediately converted to phosphonous amides (3a
P-pyramid were found, however, to be of aromatic
character. Both the bond-equalization in the hetero ring
* Corresponding author. Tel.: +36-1-463-1111/5883; fax: +36-1-
463-3648.
E-mail address: keglevich@oct.bme.hu (G. Keglevich).
1 Preliminary communication: [1].
0022-328X/02/$ - see front matter © 2002 Elsevier Science B.V. All rights reserved.
PII: S0022-328X(01)01119-6

G. Kegle6ich et al. / Journal of Organometallic Chemistry 643–644 (2002) 32–38
33
Scheme 1.
1
and 3b) by reaction with morpholine or diethylamine in
benzene solution. To obtain even more stable products,
the phosphonous amides (3a and 3b) were oxidized by
hydrogen peroxide to phosphonic amides (4a and 4b,
respectively) (Scheme 1).
supported by the JPH coupling of 499 Hz obtained
from the proton coupled 31P-NMR spectrum.
Intermediate 2 was also utilized in the synthesis of
H-phosphinates; its reaction with simple alcohols in
boiling benzene in the presence of triethylamine fol-
lowed by hydrolysis gave rise to products 8a–c (Scheme
3).
The power of the above reaction sequence is the
site-selective substitution of the phosphole moiety in
position 3. The reaction site must be controlled by the
steric hindrance around the phosphorus atom. It is
worthy of mention that the oxidation of intermediate 3
affected only the phosphonous function, the phospho-
rus atom of the phosphole ring remaining intact. This is
obviously the consequence of the appropriate 3-substi-
tution, as the trialkylphenylphospholes (e.g. 1 and 9),
are known to undergo oxidation to afford phosphole
oxides that are subsequently dimerized [8,15]. The oxi-
dation of sterically hindered phospholes (e.g. 1 and 9)
was, however, reported to proceed significantly slower
than that of other phospholes [8,15].
The phosphinates (8a–c) isolated in ca. 72% yield
after chromatography were identified by 31P-, 13C- and
1H-NMR, as well as high resolution mass spectrometry.
The 13C-NMR spectral parameters are listed in Table 1.
The 3JPP couplings (ca. 27 Hz), the 1JPC couplings of ca.
2
130 Hz obtained on C3 and the JPH couplings detected
on C2ꢀH and C5ꢀH (ca. 26 and 36 Hz, respectively)
were in accord with the 3-substitution. The P(O)H
moiety of the products (8a–c) was confirmed by the
1JPH couplings of ca. 550 Hz obtained from the proton
coupled 31P-NMR spectrum.
Intermediates 3a and 3b were characterized by 31P-
NMR spectroscopy and their elemental composition
was confirmed by high resolution mass spectrometry.
The structure of products 4a and 4b obtained in ca.
56% yield after purification by column chromatography
was supported by 31P-, 13C- and 1H-NMR spec-
troscopy, as well as high resolution mass spectrometry.
The 13C-NMR spectral parameters are listed in Table 1.
3
Species 3 and 4 were characterized by JPP couplings of
1
ca. 34 and 22 Hz, respectively. The JPC coupling of ca.
Scheme 2.
155 Hz detected on C3 of the phosphole ring of 4a and
1
4b was in agreement with the 3-substitution. The H-
2
NMR spectrum of phospholes 4 revealed a JPH cou-
pling for both C5ꢀH and C2ꢀH (ca. 36 and 30 Hz,
respectively), the latter signal also being coupled by the
C3ꢀP atom (3JPh ca. 12).
The reaction of dibromophosphine 2 with diiso-
propylamine, as a consequence of steric hindrance, led
only to monosubstitution (Scheme 2). The H-phos-
phinic amide (6) obtained after hydrolysis was charac-
terized by 31P- and 13C-NMR, as well as mass
spectrometry. The 13C-NMR spectral parameters are
shown in Table 1. The P(O)H unit in compound 6 was
Scheme 3.

34
G. Kegle6ich et al. / Journal of Organometallic Chemistry 643–644 (2002) 32–38

G. Kegle6ich et al. / Journal of Organometallic Chemistry 643–644 (2002) 32–38
35

36
G. Kegle6ich et al. / Journal of Organometallic Chemistry 643–644 (2002) 32–38
Scheme 4.
Obviously, the reaction of 1-(2,4,6-triisopropy-
(Scheme 6). All the in situ catalysts formed from
[Rh(nbd)Cl]2 and the above phospholes are active un-
der the given conditions (Table 3). Practically complete
conversions have been obtained in up to 4 h at 100 °C.
(The blank experiment with [Rh(nbd)Cl]2 as the only
catalyst shows that the addition of phospholes resulted
in more active and more regioselective catalytic systems
except for 4a.) It is worth noting that the reaction can
almost be considered to be chemospecific: the chemose-
lphenyl)phosphole (9) with phosphorus tribromide led
to a 2-substitution, as the steric hindrance was not, in
this case, significant. Reaction of intermediate 10 with
morpholine furnished phosphonous amide 11, whose
oxidation, in turn, yielded phosphonic amide 12
(Scheme 4).
Phosphonous amide 11 was characterized by 31P-
NMR spectra and high resolution mass spectrometry.
The structure of product 12 was confirmed by 31P-, 13C-
1
and H-NMR, as well as mass spectrometry. The 13C-
NMR spectral parameters are listed in Table 2. Species
2
11 and 12 were characterized by JPP couplings of 71
and 49 Hz, respectively.
The reaction of the mixture of dibromophos-
phinophosphole (10) with methanol followed by hy-
drolysis resulted in the formation of H-phosphinate 14
(Scheme 5). The product (14) was identified by 31P-,
13C- and 1H-NMR, as well as high resolution mass
spectrometry. The 13C-NMR spectral parameters are
listed in Table 2. Product 14 exhibited a significant JPP
coupling of 58 Hz.
Scheme 5.
The substitution of triisopropylphenylphosphole 9
was not so efficient, as that of tri-tert-butylphenyl
derivative 1, products 12 and 14 were obtained in ca.
41% yield after chromatography. The side-reactions
were not evaluated. It seems to be probable that the
aromaticity of the phosphole ring promotes the reac-
tion with phosphorus tribromide.
Scheme 6.
Table 3
2.1. Hydroformylation in the presence of 4a, 4b, 6, 8a
and 8b
Hydroformylation of styrene (15) in the presence of [Rh(nbd)Cl]2+
4 L in situ catalysts (L=a sterically hindered phosphole ligand) a
b
Styrene (15), as the model substrate, was reacted in
the presence of in situ rhodium catalysts containing one
of the sterically hindered phospholes 4a, 4b, 6, 8a, 8b
with CO/H2 (1/1) at 100 °C at a pressure of 100 bar.
Although the activity of the tested rhodium catalysts
falls slightly behind the best rhodium–phosphine cata-
lysts, the catalytic test of the hindered phosphole-based
catalysts proved to be of interest from a theoretical
point of view.
L
Reaction time (h)
Conversion (%)
Rbr (%)
4a
4b
6
8a
8b
-
3.5
4
2.5
2
2
4
95
99
69
98
99
99
57
70
72
75
80
58
a Reaction conditions: 0.05 mmol catalyst; Rh/P=1/2; 100 mmol
styrene; toluene solvent; p(CO)=p(H2)=40 bar; 100 °C; the
chemoselectivity (RC=(mol 16+mol 17)/(mol 16+mol 17+mol
18)×100) was higher than 99% in all cases.
In addition to the formyl regioisomers, 2-phenyl-
propanal (16) and 3-phenyl-propanal (17), the hydro-
genation product, ethylbenzene (18) was also formed
b Regioselectivity Rbr=(mol 16)/(mol 16+mol 17)×100.

G. Kegle6ich et al. / Journal of Organometallic Chemistry 643–644 (2002) 32–38
37
lectivity of the hydroformylation is excellent in all cases
(higher than 99%) by the prevailing formation of alde-
hydes (16, 17) over the hydrogenated side-product (18).
Moderate regioselectivities (57–80%) have been ob-
tained. However, the preliminary experiments at low
temperature (40 °C) show high regioselectivities by the
prevailing formation of the branched aldehyde (Rbr\
99%). The systematic investigation of the temperature
dependence of the catalytic characteristics, as well as
that of the structure–reactivity relationship are in
progress.
No reaction between the phospholes possessing
P(O)H functionality (e.g. 8a) and styrene has been
observed either in the presence or in the absence of the
rhodium-containing precursor, [Rh(nbd)Cl]2. A five-
membered ring H-phosphonate was, however, reported
to react with 1-octene in the presence of a palladium
complex [16].
In summary, it was found that the phospholes bear-
ing a tri-tert-butylphenyl- or a triisopropylphenyl sub-
stituent on the phosphorus atom react with phosphorus
tribromide in a site-selective manner to afford a 3- or a
2-substitution, respectively. The dibromophosphino
derivatives are excellent intermediates in the prepara-
tion of phosphorylated phospholes that may be ligands
in the transition metal catalysts of hydroformylation.
mmol of morpholine or diethylamine at 0 °C. After
stirring at room temperature (r.t.) for 3 h, the amine
salt was filtered off and the solvent of the filtrate
evaporated to yield 3a,b, or 11, respectively.
The 40 ml CHCl3 solution of the ca. 1.17 mmol of
phosphonous amide 3a, 3b or 11 was treated with 0.27
ml (2.34 mmol) of 30% H2O2 at 0 °C with intensive
stirring. Then, the contents of the flask were stirred at
r.t. for 1 h. The mixture was extracted with 3×20 ml of
water, the organic phase was dried (Na2SO4) and the
solvent evaporated. The crude product so obtained was
purified by column chromatography (silica gel, 3%
MeOH in CHCl3) to furnish phosphorylphospholes
4a,b, or 12.
3.2.3. The preparation of
alkoxy-H-phosphonylphospholes (8 and 14)
The solution of ca. 1.17 mmol of the intermediate 2
or 10, 3.5 mmol of the alcohol (MeOH, EtOH or
isopropanol) and 0.33 ml (2.34 mmol) of Et3N in 50 ml
of dry benzene was stirred at boiling point for 3 h. The
amine salt was removed by filtration and the solvent of
the filtrate evaporated. The residue was taken up in 40
ml of CHCl3 and stirred with 1.5 ml of water for 10
min. The organic phase was dried (Na2SO4) and the
solvent evaporated. The crude product so obtained was
purified by column chromatography as above to afford
8a–c, or 14, respectively.
Product 6 was prepared similarly, using diisopropy-
lamine instead of the alcohol.
3. Experimental
3a: Yield: 79%; 31P-NMR lP (CDCl3) 3.4 (P1), 90.7
3.1. General
(C3ꢀP), 3JPP=33.6; HR-FAB [M+H]+measured
=
544.3323, C31H50N2O2P2 requires 544.3348.
The 31P-, 13C- and H-NMR spectra were taken on a
1
4a: Yield: 60%; 31P-NMR, lP (CDCl3) 7.1 (P1), 23.4
Bruker DRX-500 spectrometer operating at 202.4,
125.7 and 500 MHz, respectively. Chemical shifts are
downfield relative to 85% H3PO4 or Me4Si. The cou-
plings are given in Hz. Mass spectrometry was per-
formed on a ZAB-2SEQ instrument.
3
1
(C3ꢀP), JPP=21.8; 13C-NMR, Table 1; H-NMR lH
(CDCl3) 6.66 (dm, JPH=35.5, C5ꢀH), 7.37 (ddd,
J
PH=28.1, JP%H=12.1, JHH=2.5, C2ꢀH); HR-FAB
[M+H]m+easured=560.3292, C31H50N2O3P2 requires
560.3297.
3b: Yield: 71%; 31P-NMR, lP (CDCl3) −1.8 (P1),
91.7 (C3ꢀP), 3JPP=33.2; HR-FAB [M+H]+measured
=
3.2. General procedure for the phosphorylation of
phospholes (1 and 9)
517.3731, C31H55N2P2 requires 517.3841.
4b: Yield: 52%; 31P-NMR, lP (CDCl3) 4.12 (P1),
27.02 (C3ꢀP), 3JPP=21.7; 13C-NMR, Table 1; 1H-NMR
lH (CDCl3) 6.51 (dm, JPH=36.2, C5ꢀH), 7.16 (ddd,
3.2.1. The preparation of dibromophosphinophospholes
(2 and 10)
To 1.17 mmol of phosphole (1 or 9) in 50 ml of dry
CHCl3 was added 0.12 ml (1.26 mmol) of phosphorus
tribromide and 0.10 ml (1.24 mmol) of Py and the
solution was stirred at boiling point for 48 h under a
nitrogen atmosphere. The volatile components were
removed in vacuo to give 2 or 10, respectively, practi-
cally in quantitative yield.
J
PH=31.3, JP%H=12.4, JHH=1.9, C2ꢀH); HR-FAB
[M+H]+measured=533.3701,
C31H55N2OP2
requires
533.3790.
8a: Yield: 71%; 31P-NMR, lP (CDCl3) 11.32 (P1),
23.82 (C3ꢀP), 3JPP=27.5; 13C-NMR, Table 1; 1H-NMR
lH (CDCl3) 6.56 (dm, JPH=35.8, C5ꢀH), 7.66 (ddd,
J
PH=26.5, JP%H=13.6, JHH=2.4, C2ꢀH); HR-FAB
[M+H]+measured=421.2355,
C24H39O2P2
requires
3.2.2. The preparation of diaminophosphorylphospholes
(4 and 12)
The ca. 1.17 mmol of the intermediate (2 or 10) was
taken up in 50 ml of dry benzene and treated with 4.7
421.2425.
8b: Yield: 76%; 31P-NMR, lP (CDCl3) 10.72 (P1),
21.32 (C3ꢀP), 3JPP=27.2; 13C-NMR, Table 1; 1H-NMR
lH (CDCl3) 6.55 (dm, JPH=35.8, C5ꢀH), 7.65 (ddd,

38
G. Kegle6ich et al. / Journal of Organometallic Chemistry 643–644 (2002) 32–38
the pale yellow solution was removed and immediately
analyzed by GC.
J
PH=25.4, JP%H=14.8, JHH=2.1, C2ꢀH); HR-FAB
[M+H]+measured=435.2502,
C25H41O2P2
requires
435.2582.
8c: Yield: 69%; 31P-NMR, lP (CDCl3) 10.02 (P1),
18.82 (C3ꢀP), 3JPP=26.9; 13C-NMR, Table 1; 1H-NMR
lH (CDCl3) 6.54 (dm, JPH=35.8, C5ꢀH), 7.64 (ddd,
Acknowledgements
The authors thank the Hungarian National Science
Foundation (OTKA T029039 and T035347) for finan-
cial support.
J
PH=27.0, JP%H=13.6, JHH=2.2, C2ꢀH); HR-FAB
[M+H]+measured=449.2603,
C26H43O2P2
requires
449.2738.
6: Yield: 44%; 31P-NMR, lP (CDCl3) 8.02 (P1), 5.02
3
1
(C3ꢀP), JPP=26.5; 13C-NMR, Table 1; H-NMR lH
References
(CDCl3) 6.62 (dm, JPH=32.0, C5ꢀH), 7.74 (ddd, JPH
=
28.4,
J
P%H=13.2,
JHH=2.4, C2ꢀH); HR-FAB
[1] Gy. Keglevich, T. Chuluunbaatar, A. Dobo´, L. To
3 ke, J. Chem.
[M+H]+measured=490.3257,
C29H50N1OP2
requires
Soc. Perkin Trans. 1 (2000) 1495.
[2] K.B. Dillon, F. Mathey, J.F. Nixon, Phosphorus: the Carbon
Copy, from Organophosphorus to Phospha-Organic Chemistry,
Wiley, Chichester, 1998, p. 203 chapter 8.
[3] L.D. Quin, Phospholes, in: A.R. Katritzky, C.W. Rees, E.F.V.
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[4] L.D. Quin, in: F. Mathey (Ed.), Phosphorus–Carbon Hetero-
cyclic Chemistry. The Rise of a New Domain, Elsevier, 2001
chapter 4, in press.
[5] I. Ojima, C.-Y. Tsai, M. Tzamarioudaki, D. Bonafoux, in: L.E.
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Organic Reactions, Vol. 56, Wiley, 2000, pp. 1–354.
[6] L. Nyula´szi, Chem. Rev. 101 (2001) 1229.
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490.3368.
11: Yield: 90%; 31P-NMR lP (CDCl3) 0.2 (P1), 94.1
(C2ꢀP), 2JPP=70.6; HR-FAB [M+H]+measured
=
502.2870, C28H44N2O2P2 requires 502.2878.
12: Yield: 38%; 31P-NMR, lP (CDCl3) 0.9 (P1), 24.1
2
1
(C2ꢀP), JPP=49.4; 13C-NMR, Table 2; H-NMR lH
(CDCl3) 7.04 (dm, JPH=38.2, C5ꢀH), 7.42 (ddd, JPH
=
JP%Hꢀ13.0,
J
HH=1.2,
C3ꢀH);
HR-FAB
[M+H]+measured=518.2832, C28H44N2O3P2 requires
518.2827.
14: Yield: 43%; 31P-NMR lP (CDCl3) 2.92 (P1), 22.52
2
1
(C2ꢀP), JPP=58.4; 13C-NMR, Table 2; H-NMR lH
[8] Gy. Keglevich, L.D. Quin, Zs. Bo¨cskei, Gy.M. Keseru3 , R.
(CDCl3) 6.82 (dm, JPH=38.1, C5ꢀH), 7.43 (ddd,
Kalgutkar, P.M. Lahti, J. Organomet. Chem. 532 (1997) 109.
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[9] Gy. Keglevich, Zs. Bo¨cskei, Gy.M. Keseru
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Szo¨llosy, L. Toke, J. Chem. Soc. Perkin Trans. 1 (2000) 2895.
3
, K. Ujsza´szy, L.D.
J
PH=JP%Hꢀ12.1,
JHHꢀ1,
C3ꢀH);
C21H33O2P2
HR-FAB
requires
[M+H]+measured=379.1878,
´
379.1956.
3
3
[11] S.P. Ivonin, T.E. Terikovska, A.A. Chaikovskaya, A.P.
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3.3. Hydroformylation experiments
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eroatom Chem. 10 (1999) 585.
In a typical experiment a solution of 0.0125 mmol of
[Rh(nbd)Cl]2, 0.05 mmol of substituted phospholes 4, 6
or 8 in 7.5 ml toluene containing 25 mmol of styrene
was transferred under Ar into a 20 ml stainless steel
autoclave. The reaction vessel was pressurized to 100
bar total pressure (CO/H2=1/1) and placed in an oil
bath and the mixture was stirred with a magnetic
stirrer. The pressure was monitored throughout the
reaction. After cooling and venting of the autoclave,
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machev, Heteroatom Chem. 9 (1998) 559.
[15] Gy. Keglevich, Zs. Bo¨cskei, V. Harmat, L. To
3 ke, Heteroatom
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[16] L.-B. Han, F. Mirzaei, C.-Q. Zhao, M. Tanaka, J. Am. Chem.
Soc. 122 (2000) 5407.