Targeted synthesis of 2,3-disubstituted 2-phospholenes using catalytic cycloalumination of acetylenes

Article abstract of DOI:10.1016/j.tetlet.2014.05.029

A preparative one-pot method for the synthesis of 2,3-dialkyl-substituted phosphol-2-enes by catalytic cycloalumination of symmetric acetylenes with AlEt₃ catalyzed by Cp₂ZrCl₂ is developed. The reaction gives the corresponding aluminacyclopentenes, which then react in situ with phosphorus dihalides.

Full text of DOI:10.1016/j.tetlet.2014.05.029

Tetrahedron Letters xxx (2014) xxx–xxx
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Targeted synthesis of 2,3-disubstituted 2-phospholenes using
catalytic cycloalumination of acetylenes
⇑
Vladimir A. D’yakonov, Alevtina L. Makhamatkhanova , Rina A. Agliullina, Tat’yana V. Tyumkina,
Usein M. Dzhemilev
Institute of Petrochemistry and Catalysis of Russian Academy of Sciences, 141 Prospekt Oktyabrya, Ufa 450075, Russian Federation
a r t i c l e i n f o
a b s t r a c t
Article history:
A preparative one-pot method for the synthesis of 2,3-dialkyl-substituted phosphol-2-enes by catalytic
cycloalumination of symmetric acetylenes with AlEt3 catalyzed by Cp2ZrCl2 is developed. The reaction
gives the corresponding aluminacyclopentenes, which then react in situ with phosphorus dihalides.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 20 February 2014
Revised 17 April 2014
Accepted 7 May 2014
Available online xxxx
Keywords:
Aluminacyclopentenes
Phospholenes
Metal complex catalysis
Aluminum compounds
Zirconium complexes
Dzhemilev reaction
Organophosphorus compounds (OPC), in particular, cyclic OPCs,
have attracted significant attention from researchers engaged in
metal complex catalysis as highly efficient ligands.1
A recent trend in the synthesis of cyclic OPCs is via the direct
transformation of metallacarbocycles into the corresponding phos-
pholenes and phospholes.2 For example, a method for the direct
conversion of zirconacyclopentenes and zirconacyclopentadienes
into the corresponding substituted phosphacarbocycles has been
described.2a However, this approach requires the use of stoichiom-
studied for the first time the substitution of an Al atom with a P
atom in 2,3-disubstituted aluminacyclopent-2-enes.
It was found that 2,3-disubstituted aluminacyclopentenes 1a–
f,5 synthesized by Cp2ZrCl2-catalyzed cycloalumination of
symmetric alkynes with AlEt3, reacted with phenyl- and alkyldi-
chlorophosphines (ꢁ20 °C, 30 min) with the replacement of alumi-
num with phosphorus to give 2,3-disubstituted 2-phospholenes
2a–f in 80–88% yields (Scheme 1, Table 1).6
The phospholenes 2a–f thus formed were treated with H2O2
(chloroform, 1 h, rt) or S8 (toluene, 4 h, rt) to give the correspond-
ing phospholene 1-oxides 3a–f and phospholene 1-sulfides 4a–f in
quantitative yields (Scheme 2).7,8
etric amounts of expensive Zr-based
p-complexes and is encum-
bered with some preparative difficulties related to the synthesis
of zirconacarbocycles, in particular, the necessity to carry out these
reactions at low temperature (ꢀ90 to ꢀ78 °C), which prevents the
wide use of this method in organic and organometallic syntheses.
Thus, an alternative approach avoiding these drawbacks would
involve replacing zirconacarbocycles by cyclic organoaluminum
compounds (OACs), which can be obtained in one preparative step
by catalytic cycloalumination of unsaturated compounds with tri-
alkyl- or alkylhalolanes in the presence of zirconium complexes.3
Reports on the direct transformations of aluminacarbocycles
into cyclic OPCs are scarce in the literature.4 In order to continue
these studies and extend the scope of catalytic cycloalumination
of unsaturated compounds in the synthesis of cyclic OPCs, we have
The reaction between in situ generated bicyclic OAC9 1g and
PhPCl2 led to phospholene 2g with an annulated cyclic unit in
R
R
R1PCl2
ii
R
R
R
i
R
Al
P
R1
Et
2a-f
1a-f
R = Et, Pr, Bu
R1 = Me, Bu, Ph
Scheme 1. Synthesis of 2,3-disubstituted 2-phospholenes. Reagents and condi-
tions: (i) AlEt3, Cp2ZrCl2 (5 mol %), 40 °C, 2 h and (ii) toluene, 30 min, ꢀ5 °C to rt;
alkyne/[Al]/R1PCl2 = 1:1:1.
⇑
Corresponding author. Tel./fax: +7 3472842750.
E-mail address: ink@anrb.ru (A.L. Makhamatkhanova).
http://dx.doi.org/10.1016/j.tetlet.2014.05.029
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.
Please cite this article in press as: D’yakonov, V. A.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.05.029

2
V. A. D’yakonov et al. / Tetrahedron Letters xxx (2014) xxx–xxx
The 1H and 13C NMR chemical shifts of the five-membered
Table 1
Preparation of 2,3-disubstituted phosphol-2-enes 2a–g
rings in the series of compounds 2c, 2d, and 2f slightly varied
depending on the nature of the substituent on phosphorus. The
31P NMR chemical shift is more sensitive to the nature of the
substituent and varied from ꢀ6 to 10.6 ppm. Contrary to this,
the phosphorus chemical shifts in phospholene sulfides 4a–g are
about 66–74 ppm, while in phospholene oxide 3a–g, they range
from 63 to 75 ppm, which is in line with published data.2a,10
Entry
Alkyne
R1
Substrate
Product
Yielda (%)
1
2
3
4
5
6
7
Hex-3-yne
Oct-4-yne
Dec-5-yne
Dec-5-yne
Hex-3-yne
Dec-5-yne
Cyclododecyne
Ph
Ph
Ph
Me
Bu
Bu
Ph
1a
1b
1c
1d
1e
1f
2a
2b
2c
2d
2e
2f
80
85
88
86
80
85
81
Furthermore, the C–P coupling constants of the
a-carbon atoms
1g
2g
in the 13C NMR spectrum increased compared with the initial
a
The product yields were determined by GLC analysis using undecane as an
phospholenes 2a–g.11
internal standard.
In conclusion, the replacement of aluminum in aluminacycl-
opentanes by phosphorus has proved to be an efficient method
for one-pot construction of phosphol-2-enes.
81% yield (Scheme 3, Table 1). Derivatization of bicyclic phospho-
lene 2g gave rise to phospholene 1-oxide 3g and phospholene 1-
sulfide 4g in quantitative yields.
Acknowledgments
The structures of all compounds synthesized were established
by 1D (1H, 13C, DEPT 135) and 2D NMR spectroscopy [HSQC, HMBC
(C–H), HMBC (P–H), COSY (H–H)]. In the spectra of compounds 2a–
g, the signals at 135–136 ppm and 149–150 ppm were assigned to
the sp2-hybridized carbon atoms C-2 and C-3 in the phospholene
ring, respectively. This is confirmed by the rather large one-bond
spin–spin coupling constant between the phosphorus and C-2 car-
This work was supported financially by the Russian Foundation
for Basic Research (Grants 12-03-31259 and 14-03-31084) and
NSh-2136.2014.3 (Russian Federation).
Supplementary data
1
2
bon atoms, equal to JC–P = 8.1 Hz, (unlike JC–P = 6.0 Hz).
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2014.
05.029.
Characteristic interactions were observed in the HMBC spec-
trum of 2c (Fig. 1). In addition, the 13C NMR spectrum of compound
2c exhibited doublet splitting of the C-10 and C-20 carbon atom sig-
nals of the butyl group located at the
a position relative to the
References and notes
phosphorus. The 3JP–C coupling for C-20 is 5.0 Hz (22.97 ppm), while
2JP–C for C-10 reaches 21.1 Hz (30.8 ppm). The signal for this carbon
atom at 30.8 ppm was previously erroneously assigned to the ring
1. Kollar, L.; Keglevich, G. Chem. Rev. 2010, 110, 4257–4302.
2. (a) Zhou, Y.; Yan, X.; Xi, C. Tetrahedron Lett. 2010, 51, 6136–6138; (b) Oba, G.;
Phok, S.; Manuel, G.; Koenig, M. Tetrahedron 2000, 56, 121–127; (c) Fagan, P. J.;
Nugent, W. A.; Calabrese, J. C. J. Am. Chem. Soc. 1994, 116, 1880–1889; (d) Mao,
S. S. H.; Tilley, T. D. Macromolecules 1997, 30, 5566–5569; (e) Doherty, S.;
Eastham, G. R.; Tooze, R. P.; Scanlan, T. H.; Williams, D.; Elsegood, M. R. G.;
Clegg, W. Organometallics 1999, 18, 3558–3560; (f) Hydro, J.; Gouygou, M.;
Dallemer, F.; Daran, J.-C.; Balavoine, G. G. A. J. Organomet. Chem. 2000, 595,
261–277.
C-5 carbon.2a The signal of the C-5
a-carbon atom of the phospho-
lene ring actually occurs at 24.5 ppm, which was proven by means
of a homonuclear COSYHH experiment (Fig. 1). Indeed, the signals
of the diastereotopic –H2C protons of the ring at 1.7 and 2.2 ppm
correlated only with the vicinal partners at C-4 (2.6 and 2.9 ppm).
3. (a) Dzhemilev, U. M.; Ibragimov, A. G. Russ. Chem. Bull. 1998, 47, 786–794; (b)
Dzhemilev, U. M.; Ibragimov, A. G. J. Organomet. Chem. 2010, 695, 1085–1088.
4. MacKay, J. A.; Vedejs, E. J. Org. Chem. 2005, 71, 498–503.
5. (a) Dzhemilev, U. M.; Ibragimov, A. G.; Zolotarev, A. P. Mendeleev Commun.
1992, 2, 135–136; (b) Negishi, E.; Kondakov, D. Y.; Choueiry, D.; Kasai, K.;
Takahashi, T. J. Am. Chem. Soc. 1996, 118, 9577–9588; (c) D’yakonov, V. A.
Dzhemilev Reactions in Organic and Organometallic Synthesis; NOVA Science:
New York, 2010. p 96.
R
R
R
H2O2
S8
R
R
R
P
P
P
R'
R'
O
S
R'
2a-f
6. Synthesis of 2,3-disubstituted phosphol-2-enes (general procedure):
A round-
3a-f
4a-f
bottomed flask was charged successively with Cp2ZrCl2 (0.149 g, 0.5 mmol), an
alkyne (10 mmol), and AlEt3 (10 mmol) under a dry argon atmosphere with
stirring at 0 °C. The temperature was raised to 40 °C and the mixture was
stirred for 2 h. Next, toluene (20 ml) was added, and the mixture was cooled to
ꢀ5 °C, after which dichlorophenylphosphine or alkyldichlorophosphine
(10 mmol) was added dropwise. The mixture was stirred for an additional
Scheme 2. Synthesis of 2,3-disubstituted phosphol-2-ene 1-oxides and 1-sulfides.
30 min at room temperature and then treated with
a saturated aqueous
solution of NH4Cl. The reaction products were extracted with Et2O and dried
over MgSO4. The solvent was evaporated and the target phospholenes were
isolated by vacuum distillation. All operations were carried out under argon.
2,3-Dibutyl-1-phenylphosphol-2-ene (2c): Yield: 241 mg (88%), colorless oil, bp
214–216 °C (16 Topp); [found: 78.5; H, 9.6. C18H27P requires C, 78.79; H, 9.92];
nD20 = 1.5382; dH (400 MHz, CDCl3) 7.44–7.55, 7.24–7.38 (5H, m, Ph), 2.80–2.93
(1H, m, C(4)Hb), 2.56–2.69 (1H, m, C(4)Ha), 2.34–2.48 (1H, m, C(10)Hb), 2.23–
2.34 (2H, m, C(100)H2), 1.97–2.23 (2H, m, C(10)Ha, C(5)Hb), 1.71–1.81 (1H, m,
C(5)Ha), 1.21–1.57 (8H, m, C(20)H2, C(200)H2, C(30)H2, C(300)H2), 0.99 (3H, t, J
7.2 Hz, C(400)H3), 0.89 (3H, t, J 7.2 Hz, C(40)H3); dC (100.58 MHz, CDCl3) 149.12
(C(3), 2JPC = 5.0), 140.39 (C(6), 1JPC = 26.2), 135.48 (C(2), 1JPC = 8.1), 132.57 (C(7),
i
ii
iii
Al
Et
P
P
Ph
Ph
X
1g
2g
3g/4g
X = O, S
Scheme 3. Synthesis of 13-phenyl-13-phosphabicyclo[10.3.0]pentadec-1(12)-ene.
Reagents and conditions: (i) AlEt3, Cp2ZrCl2 (5 mol %), 40 °C, 2 h; (ii) PhPCl2, toluene,
30 min, ꢀ5 °C to rt; alkyne/[Al]/PhPCl2 = 1:1:1; and (iii) H2O2, chloroform, 1 h or S8,
chloroform, 4 h.
2
3
C(11), JPC = 19.1), 128.51 (C(9)), 128.17 (C(8), C(10), JPC = 7.0), 37.95 (C(4),
3
3
2JPC = 4.0), 31.94 (C(20), JPC = 6.0), 30.80 (C(200)), 29.86 (C(100), JPC = 3.0), 28.40
2
1
(C(10), JPC = 21.1), 24.53 (C(5), JPC = 5.0), 22.87 (C(300)), 22.78 (C(30)), 14.05
(C(400)), 13.93 (C(40)); dP (161.92 MHz, CDCl3) 10.48; GCMS m/z (Iony): 274
(28 M), 245 (35), 232 (11), 217 (24), 203 (20), 190 (100), 109 (30), 91 (26), 79
(13), 65 (8), 55 (11%).
HMBC
H H
H
H
1"
3"
2'
2"
4"
4
3
7. Synthesis of 2,3-disubstituted phosphol-2-ene 1-oxides 3 (general procedure): 30%
H2O2 (0.7 ml, 6 mmol) was slowly added dropwise to a vigorously stirred
solution of 2,3-dialkyl-1-alkyl(phenyl)-2-phospholene 2 (5 mmol) (prepared as
described above) in CHCl3 (10 ml), and the mixture was stirred for 1 h. The
mixture was washed with H2O (3 ꢂ 5 ml) and the organic layer was dried over
MgSO4. The solvent was evaporated.
COSYHH
4'
5
2
1
1'
3'
H
P
H
HH
Ph
Figure 1. Key correlations in the 2D spectra of compound 2c.
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V. A. D’yakonov et al. / Tetrahedron Letters xxx (2014) xxx–xxx
3
2,3-Dibutyl-1-phenylphosphol-2-ene 1-oxide (3c): [Found: C, 74.3; H, 9.0.
18H27PO requires C, 74.45; H, 9.37]; nD20 = 1.5225; dH (400 MHz, CDCl3)
2.12–2.32 (3H, m, C(100)Hb, C(10)H2), 2.00–2.12 (1H, m, C(100)Ha), 1.38–1.48
(2H, m, C(20)H2), 1.25–1.37 (2H, m, C(30)H2), 1.01–1.18 (4H, m, C(200)H2,
C
7.48–7.62, 7.24–7.43 (5H, m, Ph), 2.65–2.77 (1H, m, C(4)Hb), 2.48–2.58 (1H, m,
C(4)Ha), 2.17–2.28 (3H, m, C(100)Hb, C(10)H2), 1.95–2.10 (3H, m, C(100)Ha, C(5)Ha,
C(5)Hb), 1.04–1.47 (8H, m, C(20)H2, C(200)H2, C(30)H2, C(300)H2), 0.88 (3H, t, J
7.2 Hz, C(40)H3), 0.67 (3H, t, J 7.2 Hz, C(400)H3); dC (100.58 MHz, CDCl3) 158.30
(C(3), 2JPC = 31.2), 133.98 (C(6), 1JPC2 = 93.5), 131.36 (C(9), JPC = 3.0), 131.18 (C(2),
C(300)H2), 0.87 (3H,
J
7.2 Hz, C(40)H3), 0.62 (3H, t,
J
7.2 Hz, C(400)H3); dC
2
1
(100.58 MHz, CDCl3) 155.86 (C(3), JPC = 27.2), 133.78 (C(6), JPC = 71.4),
1
131.23 (C(2), JPC = 77.4), 131.23 (C(9), JPC = 2.0), 130.64 (C(7), C(11),
2JPC = 11.1), 128.27 (C(8), C(10), JPC = 12.1), 33.11 (C(4), JPC = 6.0), 31.72
3
2
1
2
(C(5), JPC = 56.3), 31.26 (C(200)), 31.01 (C(10), JPC = 14.1), 29.87 (C(20)), 25.09
3
3
1JPC = 94.5), 130.32 (C(7), C(11), JPC = 10.1), 128.40 (C(8), C(10), JPC = 12.1),
(C(100), JPC = 13.1), 22.78 (C(30)), 22.63 (C(300)), 13.89 (C(40)), 13.57 (C(400)); dP
2
2
31.18 (C(200)), 31.05 (C(4), JPC = 9.1), 30.89 (C(10), JPC = 14.1), 29.77 (C(20)),
(161.92 MHz, CDCl3) 68.91. MALDI TOF (m/z): [M+H]+, found 307.384.
3
1
25.38 (C(100), JPC =11.1), 25.30 (C(5), JPC =69.4), 22.73 (C(30)), 22.68 (C(300)),
13.81 (C(40)), 13.53 (C(400)); dP (161.92 MHz, CDCl3) 64.04. MALDI TOF (m/z):
[M+H]+, found 291.100. C18H27POH requires 290.380.
C18H27PSH requires 306.447.
9. (a) D’yakonov, V. A.; Tuktarova, R. A.; Dzhemilev, U. M. Tetrahedron Lett. 2010,
51, 5886–5888; (b) D’yakonov, V. A.; Tuktarova, R. A.; Khalilov, L. M.;
Dzhemilev, U. M. Tetrahedron Lett. 2011, 52, 4602–4605; (c) D’yakonov, V. A.;
Galimova, L. F.; Tyumkina, T. V.; Dzhemilev, U. M. Russ. J. Org. Chem. 2012, 48,
1–7.
8. Synthesis of 2,3-disubstituted phosphol-2-ene 1-sulfides 4 (general procedure):
Sulfur (0.16 g, 5 mmol) was added with cooling to a solution of 2,3-dialkyl-1-
alkyl(phenyl)-2-phospholene 2 (5 mmol) (prepared as described above) in
toluene (10 ml), and the mixture was stirred for 4 h. After filtration through a
thin layer of silica gel the solvent was evaporated.
10. Gorenstein, D. G. In Progress in NMR Spectroscopy; Pergamon Press, 1983; Vol.
16, pp 1–98.
2,3-Dibutyl-1-phenylphosphol-2-ene 1-sulfide (4c): [Found: C, 70.4; H, 8.6.
11. Kühl, O. Phosphorus-31 NMR Spectroscopy: A Concise Introduction for the
C
18H27PS requires C, 70.55; H, 8.88]; dH (400 MHz, CDCl3) 7.68–7.79, 7.30–7.42
Synthetic Organic and Organometallic Chemist; Springer: Berlin, Heidelberg,
(5H, m, Ph), 2.68–2.80 (2H, m, C(4)H2), 2.32–2.42 (2H, m, C(5)Ha, C(5)Hb),
2008. p 131.
Please cite this article in press as: D’yakonov, V. A.; et al. Tetrahedron Lett. (2014), http://dx.doi.org/10.1016/j.tetlet.2014.05.029