Reaction of 1-vinylpyrrole-2-carbaldehydes with phosphorus pentachloride: A stereoselective synthesis of E-2-(2-dichloromethylpyrrol-1-yl)vinylphosphonyl dichlorides

Article abstract of DOI:10.1016/j.tetlet.2011.01.072

1-Vinylpyrrole-2-carbaldehydes react with phosphorus pentachloride (benzene, 10-15°C) to afford E-2-(2-dichloromethylpyrrol-1-yl) vinylphosphonium hexachlorophosphates in up to 85% yield, which after treatment with SO₂ (benzene, rt) are convert

Full text of DOI:10.1016/j.tetlet.2011.01.072

Tetrahedron Letters 52 (2011) 1317–1319
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Tetrahedron Letters
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Reaction of 1-vinylpyrrole-2-carbaldehydes with phosphorus pentachloride:
a stereoselective synthesis of E-2-(2-dichloromethylpyrrol-1-yl)vinylphospho-
nyl dichlorides
M. Yu. Dmitrichenko a, , A. V. Ivanov b, I. A. Bidusenko b, I. A. Ushakov b, A. I. Mikhaleva b, B. A. Trofimov b,
⇑
a Irkutsk State University, Department of Chemistry, 126, Lermontov Str., RUS-664033 Irkutsk, Russia
b A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch of the Russian Academy of Sciences, 1, Favorsky Str., RUS-664033 Irkutsk, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
1-Vinylpyrrole-2-carbaldehydes react with phosphorus pentachloride (benzene, 10–15 °C) to afford E-2-
(2-dichloromethylpyrrol-1-yl)vinylphosphonium hexachlorophosphates in up to 85% yield, which after
treatment with SO2 (benzene, rt) are converted into E-2-(2-dichloromethylpyrrol-1-yl)vinylphosphonyl
dichlorides in 50–75% yields.
Received 18 October 2010
Revised 23 December 2010
Accepted 14 January 2011
Available online 20 January 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
1-Vinylpyrrole-2-carbaldehydes
Phosphorus pentachloride
E-2-(2-Dichloromethylpyrrol-1-
yl)vinylphosphonyl dichlorides
E-2-(2-Dichloromethylpyrrol-1-
yl)vinylphosphonium
hexachlorophosphates
Pyrroles with diverse phosphorus functions, for example, pyrr-
olylphosphines, which act as hybrid ligands combining soft and
hard donor sites, have attracted widespread attention in coordina-
tion and organometallic chemistry.1 This is due, to a large extent,
to the ability of these ligands to display hemilabile behavior
toward platinum group metal centers.2 As a result, new families
of pyrrole-substituted phosphines have been synthesized.3 Tertiary
phosphines bearing pyrrolyl substituents have been successfully
applied as ligands in a variety of transition metal catalyzed reac-
tions (hydrogenation of alkenes and arenes,4 allylic substitution,5
isomerization of alkenes,6 etc.). Tris(pyrrolyl)phosphine was
shown to be suitable for development into a solid phase linker.7
5-(Diethoxyphosphorylmethyl)-5-methyl-4,5-dihydro-3H-pyrrole
N-oxide was successfully employed as an efficient spin trap.8 The
combination of a pyrrole moiety with a phosphorus-containing
function is expected to result in high and specific biological activ-
ity. An example of such a combination is the natural compound
psilocybin (dimethyltryptamine-4-phosphate), which is the active
principle of Mexican mushrooms with strong hallucinogenic
activity.9
PCl5
benzene, 10-15 oC
R
CHO
R
CHCl2
N
N
PCl3PCl6
R = H (1); Ph (2)
R = H (4, 65%); Ph (5, 44%)
Scheme 1.
The most general synthetic route to dihalogeno-, halogeno-, and
tertiary pyrrolyl phosphines involves phosphorylation of N-substi-
tuted pyrroles with P(III) halides.10
For the synthesis of pyrrolylphosphonates, the Arbuzov rear-
rangement of trialkyl phosphites under the action of haloalkyl pyr-
roles was employed.8
A conceptually new approach to the
synthesis of phosphorus-containing pyrroles, which is developing
rapidly, is based on available11 1-vinylpyrroles. Thus, secondary
phosphines, under radical initiation, add readily to 1-vinylpyrroles
to give the anti-Markovnikov adducts, diorganyl-2-(1-pyrrolyl)eth-
ylphosphines, in 88–91% yields.12 The 1-vinylpyrroles were also
used for the synthesis of phosphorylated pyrroles via reaction with
phosphorus pentachloride, the process affording various phosphor-
ylationproducts, both on the pyrrole ring and vinyl group.13 1-Vinyl-
2-trifluoroacetylpyrroles were phosphorylated with phosphorus
⇑
Corresponding author. Fax: +7 3952 396046.
E-mail address: boris_trofimov@irioch.irk.ru (B.A. Trofimov).
Fax: +7 3952 425935.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.01.072

1318
M. Yu. Dmitrichenko et al. / Tetrahedron Letters 52 (2011) 1317–1319
CHCl2
CHCl2
PCl5
benzene, 10-15 oC
N
Cl6PCl2P
N
- HCl
CHO
CHCl2
N
N
Cl6PCl3P
7
Scheme 3.
PCl3PCl6
3
6, 85%
Scheme 2.
SO2
R
CHCl2
R
CHCl2
pentachloride selectively at the vinyl group tofurnish2-(2-trifluoro-
acetylpyrrol-1-yl)vinylphosphonium hexachlorophosphates in high
yields,14 which were further converted under the action of SO2 into
2-(2-trifluoroacetylpyrrol-1-yl)vinylphosphonyl dichlorides in al-
most quantitativeyields. Notably, in this case, the carbonyl group re-
mained intact.
N
N
benzene, r.t.
PCl3PCl6
POCl2
R = H (8, 75%); Ph (9, 50%)
4, 5
The purpose of the present work was to study the reaction of
1-vinylpyrrole-2-carbaldehydes 1–3 with phosphorus pentachlo-
ride and thereby synthesize new families of functionalized phos-
phorylated pyrroles. The starting pyrroles 1–3 were readily
accessible via the recently developed efficient selective formylation
of 1-vinylpyrroles.15 Pyrroles 1–3 were found to react smoothly and
stereoselectively with excess phosphorus pentachloride in benzene
(10–15 °C)16 involving both the formyl and vinyl groups to deliver E-
SO2
CHCl2
CHCl2
N
N
benzene, r.t.
PCl3PCl6
POCl2
6
10, 68%
Scheme 4.
2-(2-dichloromethylpyrrol-1-yl)vinylphosphonium
hexachloro-
phosphates 4–6 (Schemes 1 and 2; Table 1).
The best yield of the phosphorylated product was obtained with
the condensed pyrrole, 1-vinyl-4,5-dihydrobenz[g]indole-2-carb-
aldehyde (3) (Scheme 2).
spectrum (MeNO2) of salt 4, a multiplet appeared at 66.6 ppm,
where signals with 1JP–H = 25.7 and 7.9 Hz were present. The latter
were attributable,18 to 3,3-dichloro-6-(dichloromethyl)-1H-1k5-
In the 31P NMR spectra of salts 4–6, signals in the regions
pyrrolo-[1,2-a]-1,3-azaphospholidinium hexachlorophosphate
7
ꢀ
(approx. 8–10%, 31P NMR), which was probably formed via electro-
philic cyclization of the Z-isomer of 4 (Scheme 3).
ꢀ296.2 to ꢀ269.1 ppm and 89.7–93.9 ppm, assignable to PCl6
and PCl3þ, were observed. The signals for the trichlorophosphoni-
um cation (PCl3þ) appeared as doublets of doublets (1JP–H–2JP–H
=
The phenyl substituent, being an acceptor toward the 1-vinyl-
pyrrole moiety, decreases the nucleophilicity of the double bond,
which probably results in the lower yield of the corresponding salt
5. In the case of pyrrole 3, the adverse effect of the phenyl substi-
tuent is compensated by the saturated fragment (the alkyl substi-
tuent at pyrrole position 4), which increases the yield of salt 6.
13.2–33.8 Hz) indicating the E-configuration for the ethene moiety.
For E-isomers of similar compounds, J values are 18–30 Hz, while
for the corresponding Z-isomers, they can be up to 60 Hz.17 The
1H and 13C NMR spectra, as well as 2D HMBC, were in full agree-
ment with the assigned structures of salts 4–6. In the 31P NMR
Table 1
Spectroscopic data for compounds 4–6, 8–10 and 12
Producta Yield
(%)
NMR (DMSO-d6, d, ppm); 1H (400 MHz);13C (100 MHz); 31P (161.98 MHz)
13C
1H
31P
4
5
6
65
44
85
8.31 (m, 1H, N–CH@), 7.21 (m, 1H, H-5), 6.82 (s, 1H, CHCl2),
6.45 (m, 1H, H-3), 6.23 (m, 1H, H-4), 6.16 (m, 1H, P–CH@)
148.7 (d, 2JP–C = 37.5 Hz, N–CH@), 130.9 (C-2), 121.4 (C-5), 114.2 (C- ꢀ296.1
1
(PCl6ꢀþ) 92.1
3), 112.6 (C-4), 95.8 (d, JP–C = 180.0 Hz, P–CH@), 62.0 (CHCl2)
(PCl3
)
2
9.11 (m, 1H, N–CH@), 8.41–8.33 (m, 5H, Ph) 7.54 (m, 1H, H-3), 150.6 (d, JP–C = 38.0 Hz, N–CH@), 135.5 (C-2), 133.5 (C-5), 133.0,
7.22 (m, 1H, H-4), 7.10 (s, 1H, CHCl2), 6.59 (m, 1H, P–CH@)
ꢀ296.2
(PCl6ꢀþ) 89.7
132.8, 132.6, 131.9, 131.1, 130.9 (CPh), 119.5 (C-3), 118.4 (C-4),
1
102.3 (d, JP–C = 170.0 Hz, P–CH@), 62.5 (CHCl2)
(PCl3
)
2
8.89 (m, 1H, N–CH@), 8.20–8.01 (m, 4H, Ar) 7.49 (s, 1H, H-3), 147.6 (d, JP–C = 37.9 Hz, N–CH@), 139.8, 136.6 (CAr), 132.2 (C-2),
6.96 (s, 1H, CHCl2), 6.51 (m, 1H, P–CH@), 3.21 (m, 2H, CH2),
2.88 (m, 2H, CH2)
ꢀ296.1
(PCl6ꢀþ) 93.9
132.0 (C-5), 128.8, 127.7, 126.7, 126.1 (CAr), 125.5 (C-9a), 121.0 (C-
3a), 120.5 (C-3), 118.4 (C-4), 105.3 (d, 1JP–C = 171.3 Hz, P–CH@), 64.7
(CHCl2)
(PCl3
)
8
9
75
50
8.22 (m, 1H, N–CH@), 7.12 (m, 1H, H-5), 6.80 (s, 1H, CHCl2),
6.39 (m, 1H, H-3), 6.20 (m, 1H, H-4), 6.07 (m, 1H, P–CH@)
9.87 (m, 1H, N–CH@), 8.28–7.82 (m, 5H, Ph) 7.70 (m, 1H, H-3), 142.9 (d, JP–C = 19.9 Hz, N–CH@), 137.0 (C-2), 134.0 (C-5), 131.5,
141.3 (d, 2JP–C = 21.0 Hz, N–CH@), 131.5 (C-2), 128.7 (C-5), 114.0 (C- 31.9 (POCl2)
1
4), 112.3 (C-3), 106.5 (d, JP–C = 167.0 Hz, P–CH@), 61.8 (CHCl2)
2
33.7 (POCl2)
34.4 (POCl2)
6.97 (s, 1H, CHCl2), 6.81 (m, 1H, H-4), 5.73 (m, 1H, P–CH@)
130.4, 129.8, 129.6, 129.1, 128.0 (CPh), 124.1 (C-3), 117.9 (C-4),
1
112.5 (d, JP–C = 193.8 Hz, P–CH@), 62.9 (CHCl2)
2
10
12
68
41
8.81 (m, 1H, N–CH@), 8.29–7.98 (m, 4H, Ar) 7.50 (s, 1H, H-3), 141.5 (d, JP–C = 27.8 Hz, N–CH@), 139.5, 136.0 (CAr), 132.2 (C-2),
6.99 (s, 1H, CHCl2), 6.50 (m, 1H, P–CH@), 3.21 (m, 2H, CH2),
2.80 (m, 2H, CH2)
131.8 (C-5), 128.8, 127.1, 126.6, 126.7 (CAr), 125.3 (C-9a), 120.8 (C-
3a), 120.2 (C-3), 118.4 (C-4), 105.5 (d, 1JP–C = 191.3 Hz, P–CH@), 64.9
(CHCl2)
8.26 (m, 1H, N–CH@), 7.13 (m, 1H, H-5), 6.77 (s, 1H, CHCl2),
6.41 (m, 1H, H-3), 6.20 (m, 1H, H-4), 6.21 (m, 1H, P–CH@)
140.9 (d, 2JP–C = 25.8 Hz, N–CH@), 131.7 (C-2), 128.8 (C-5), 114.9 (C- 12.4
1
4), 111.9 (C-3), 107.1 (d, JP–C = 208.8 Hz, P–CH@), 61.8 (CHCl2)
(PO(OH)2)
a
Compounds 4–6 are deep-colored (from purple to dark-green) crystals, unstable in air. Compounds 8–10 and 12 are colored (from purple to brown) viscous oils.
Elemental analyses of compounds 5, 6, 9, 10 and 12 correspond well with calculated values.

M. Yu. Dmitrichenko et al. / Tetrahedron Letters 52 (2011) 1317–1319
1319
3. (a) Moloy, K. G.; Petersen, J. L. J. Am. Chem. Soc. 1995, 117, 7696; (b) Barnard, T.
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Luten, J.; Kamer, P. C. J.; van Leeuwen, P. W. N. M. Organometallics 2001, 21,
3873; (d) Jackstell, R.; Klein, H.; Beller, M.; Wiese, K. D.; Rottger, D. Eur. J. Org.
Chem. 2001, 3871; (e) Ahlers, W.; Paciello, R.; Vogt, D.; Hofmann, P. (BASF AG)
WO 02/83695 2002; Chem. Abstr. 2002, 137, 311033.
SO2
CHCl2
CHCl2
Cl6PCl2P
N
ClOP
N
benzene, r.t.
7
11
4. (a) Trzeciak, A. M.; Glowiak, T.; Ziolkowski, J. J. J. Organomet. Chem 1998, 552,
159; (b) Cozzi, P. G.; Zimmermann, N.; Hilgraf, R.; Schaffner, S.; Pfaltz, A. Adv.
Synth. Catal. 2001, 343, 450.
Scheme 5.
5. Mutt, P.; Pfaltz, A. Angew. Chem. 1993, 105, 614.
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Tunik, S. P. J. Am. Chem. Soc. 2002, 124, 8922.
7. Comely, A. C.; Gibson (née Thomas), S. E.; Sur, S. J. Chem. Soc., Perkin Trans. 1
2000, 109.
H2O
CHCl2
CHCl2
N
N
- 2HCl
8. Roubaud, V.; Mercier, A.; Olive, G.; Le Moigne, F.; Tordo, P. J. Chem. Soc., Perkin
Trans. 2 1997, 1827.
9. Gurevich, P. A.; Yaroshevskaya, V. A. Chem. Heterocycl. Comp. 2000, 36, 1361.
10. Chaikovskaya, A. A.; Dmytriev, Y. V.; Pinchuk, A. M.; Tolmachev, A. A.
Heteroatom Chem. 2008, 19, 93.
POCl2
PO(OH)2
12, 41%
8
11. (a) Abele, E.; Lucevics, E. Heterocycles 2000, 53, 2285; (b) Mikhaleva, A. I.;
Schmidt, E. Yu. In Selected Methods for Synthesis and Modification of
Heterocycles; Kartsev, V. G., Ed.; IBS Press: Moscow, 2002; Vol. 1, p 334; (c)
Tedeschi, R. J. Acetylene In Encyclopedia of Physical Science and Technology;
Meyers, R. A., Ed.; Acad. Press: San Diego, 2004; Vol. 1, p 55; (d)The Chemistry of
Hydroxylamines, Oximes and Hydroxamic Acids; Rappoport, Z., Liebman, J. F.,
Eds.; Wiley: Chichester, 2008; p 241; (e) Wang, Z. Comprehensive Organic Name
Reactions and Reagents; Wiley: London, 2009. Pt 3, Paragraph No. 626.
12. Trofimov, B. A.; Malysheva, S. F.; Sukhov, B. G.; Belogorlova, N. A.; Schmidt, E.
Yu.; Sobenina, L. N.; Kuimov, V. A.; Gusarova, N. K. Tetrahedron Lett. 2003, 44,
2629.
Scheme 6.
When salts 4–6 were subjected to a reaction with SO2 (benzene,
rt),19 E-2-(2-dichloromethyl-1-pyrrol-1-yl)vinylphosphonyldichlo-
rides 8–10 were formed in 50–75% yields (Scheme 4; Table 1).
In the 31P NMR spectra of dichlorides 8–10, signals in the region
1
31.9–34.4 ppm (dd, JP–H = 23.1–24.8 Hz) belonging to the POCl2
moiety were present. The 31P NMR spectrum of dichloride 8, exhib-
ited a low intensity signal at 20.7 ppm, which provided evidence
for the presence of the corresponding cyclic phosphinyl chloride
11 (6%, 31P NMR, Scheme 5).
13. Rozinov, V. G.; Pensionerova, G. A.; Donskih, V. I.; Sergienko, L. M.; Korostova, S.
E.; Mikhaleva, A. I.; Dolgushin, G. V. Zh. Obshch. Khim. 1986, 56, 790. Chem.
Abstr. 1987, 106, 50302c.
14. Rozinov, V. G.; Pensionerova, G. A.; Donskih, V. I.; Sergienko, L. M.; Petrova, O.
V.; Kalabina, A. V.; Mikhaleva, A. I. Zh. Obshch. Khim. 1984, 54, 2241. Chem.
Abstr. 1985, 102, 149358e.
Finally, phosphonyl chloride 8 is easily converted into the cor-
responding phosphonic acid (Scheme 6; Table 1).20
´
15. (a) Mikhaleva, A. I.; Zaitsev, A. B.; Ivanov, A. V.; Schmidt, E. Yu.; Vasiltsov, A. M.;
In summary, the stereoselective facile phosphorylation of
1-vinylpyrrole-2-carbaldehydes with phosphorus pentachloride
has been elaborated. The first representatives of novel families of
highly functionalized phosphorylated pyrroles, E-2-(2-dichlorom-
ethylpyrrol-1-yl)vinylphosphonyl dichlorides, E-2-(2-dichlorom-
ethylpyrrol-1-yl)vinylphosphonium hexachlorophosphates and
E-2-(2-dichloromethyl-1-pyrrol-1-yl)vinylphosphonic acids have
been synthesized. These compounds are promising intermediates
Trofimov, B. A. Tetrahedron Lett. 2006, 47, 3693; (b) Mikhaleva, A. I.; Ivanov, A.
V.; Skital’tseva, E. V.; Ushakov, I. A.; Vasil’tsov, A. M.; Trofimov, B. A. Synthesis
2009, 587.
16. PCl5 (1.56 g, 7.5 mmol) in benzene (15 mL) was heated at reflux to give a
homogeneous solution. This was cooled (10–15 °C) and
a solution of 1-
vinylpyrrole-2-carbaldehyde (2.5 mmol) in benzene (5 mL) was added
dropwise under stirring. After 20 min, the resulting precipitate was removed
by filtration and dried under vacuum to gave salts 4–6.
17. Rozinov, V. G.; Gluhih, V. I.; Rybkina, V. V.; Kalabina, A. V.; Lazareva, N. F. Zh.
Obshch. Khim. 1980, 50, 461. Chem. Abstr. 1980, 93, 114608e.
and building blocks for
pyrroles.
a variety of phosphorus-containing
18. Rozinov, V. G.; Rybkina, V. V.; Kalabina, A. V.; Gluhih, V. I.; Donskih, V. I.;
Seredkina, S. G. Zh. Obshch. Khim. 1981, 51, 1747. Chem. Abstr. 1982, 96, 52388.
19. A mixture of salt 4–6 (1 mmol) and benzene (2–3 mL) was treated (rt) with dry
SO2. After complete dissolution of the salt, the benzene was distilled and the
residue washed with hexane/Et2O (10:1, 3 ꢁ 6 mL). After removal of the
solvents, the dichlorides 8–10 were obtained.
20. A mixture of dichloride 8 (0.2 g, 0.7 mmol) and H2O (5 mL) was stirred (rt) for
5 d. After removal of H2O, the crude product was dried under vacuum to give
0.07 g of acid 12.
References and notes
1. Angurell, I.; Martínez-Ruiz, I.; Rossell, O.; Seco, M.; Gómez-Salb, P.; Martín, A.
Chem. Commun. 2004, 1712.
2. Burrows, A. D.; Harrington, R. W.; Mahon, M. F.; Palmer, M. T.; Senia, F.;
Varrone, M. Dalton Trans. 2003, 3717.