A facile synthesis of 2-oxo-cyclopentenylphosphonates by carbonylation of zirconacyclopentenylphosphonate with oxalyl chloride

Article abstract of DOI:10.1016/j.tetlet.2014.01.094

Addition of oxalyl chloride to zirconacycles prepared from 1-alkynylphosphonates 1 zirconocene dichloride, and two equivalents of EtMgBr smoothly produced novel 2-oxo-cyclopentenylphosphonates 6 in 58-81% isolated yields in the presence of a copper catalyst.

Full text of DOI:10.1016/j.tetlet.2014.01.094

Tetrahedron Letters 55 (2014) 1628–1630
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Tetrahedron Letters
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A facile synthesis of 2-oxo-cyclopentenylphosphonates
by carbonylation of zirconacyclopentenylphosphonate with oxalyl
chloride
⇑
Abed Al Aziz Al Quntar
Department of Material Engineering, Faculty of Engineering, Al Quds University, PO Box 51000, Abu Deis, Jerusalem, Palestine
a r t i c l e i n f o
a b s t r a c t
Article history:
Addition of oxalyl chloride to zirconacycles prepared from 1-alkynylphosphonates 1 zirconocene dichlo-
ride, and two equivalents of EtMgBr smoothly produced novel 2-oxo-cyclopentenylphosphonates 6 in
58–81% isolated yields in the presence of a copper catalyst.
Received 25 July 2013
Revised 5 January 2014
Accepted 22 January 2014
Available online 31 January 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
Vinylphosphonates
Cyclopentenone
Oxocyclopentenylphosphonates
Oxalyl chloride
Zirconacycle
Carbonylation
In addition to being important organic intermediates,1–3
vinylphosphonates are potential pharmaceutical compounds.4–6
In the last decade, we have investigated the synthesis of novel
vinylphosphonates utilizing three-membered ring metallacycles
of group 4 metals.7–13 Zirconacyclopentenylphosphonates, pre-
pared by the reaction of Cp2ZrCl2/2 EtMgBr with alkynylphopsho-
nates, proved interesting to us and were used to obtain other
Surprisingly, despite their interesting chemical and biological
properties, there are few methods in the literature reporting their
synthesis. For example, they were obtained by reaction of the
a
-phosphonovinyl anion with phenyl isocyanate,23 and by 1,3-die-
nyl phosphonate complexation to iron,24 the Arbuzov reaction of
-halogenated ketones with trialkyl phosphates,25 phosphoryla-
a
tion of cyclic ketones using electrophilic phosphorus reagents,26
and by rearrangement of furyl-hydroxymethylphosphonate.27
Initially, the synthesis of diethyl 2-octyl-5-oxocyclopent-1-eny-
lphosphonate (6a) was attempted by insertion of gaseous CO into
zirconacyclopentenylphosphonate 2, based on the reported reac-
tivities of small molecules such as isocyanates, CO and CO2 toward
metallacycles.28,29 However, unexpectedly, all efforts were unsuc-
cessful either by bubbling CO into the reaction mixture or under
a CO balloon atmosphere. Next, inspired by the research of Xi
and co-workers on the synthesis of cyclopentenones and cyclopen-
novel
vinylphosphonate
products,14
including
cyclo-
butenylphosphonates 4,15 and methylcyclopropylphosphonates 3
(Scheme 1).16
One particular class of vinylphosphonates that has attracted our
attention is the oxo-vinylphosphonates. Following on from the re-
ported synthesis of 3-oxo-vinylphosphonate by the addition of acyl
chlorides and nitriles to zirconacycles in the presence of a Cu cata-
lyst,17 and fused bicyclic 2-oxo-vinylphosphonate formation using
the Pauson–Khand reaction,18 herein the synthesis of another class
of cyclic 2-oxo-vinylphosphonates, 6, is reported. These novel com-
pounds are potential synthetic intermediates. For instance, they can
be used in the synthesis of thiazolehydroxyphosphonates and other
heterocycles,19 employed in asymmetric hydrogenations,20 or in
enantioselective reduction by Baker’s yeast,21 to provide interesting
biologically active products.22
tadienones,30 the oxocyclopent-1-enylphosphonate products
6
were obtained by reacting zirconacyclopentenylphosphonates 2
with oxalyl chloride in the presence of a catalytic amount of CuCl.
Thus, zirconacyclopentenylphosphonates 2, which were smoothly
prepared by reacting two equivalents of the Cp2ZrCl2/2 EtMgBr re-
agent with 1-alkynylphosphonates, were treated with 10 mol % of
CuCl and one equivalent of oxalyl chloride. In the absence of CuCl
or when other metal catalysts (Ni, Zn, Pt, Ce, Pd, etc.) were used in-
stead of CuCl, no traces of products 6 were detected, and only the
ethylated product 5 was obtained (Scheme 1).
⇑
Tel.: +970 2528437535; fax: +970 22797023.
E-mail address: abedalaziz@eng.alquds.edu
http://dx.doi.org/10.1016/j.tetlet.2014.01.094
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

A. A. A. Al Quntar / Tetrahedron Letters 55 (2014) 1628–1630
P(O)(OEt)2
1629
R
5
O
P
OEt
OEt
H
R
H
(1) 2 AlLn3
(2) H3O+
O
P
R
Cp2ZrCl2/2 EtMgBr
OEt
OEt
P(O)(OEt)2
R
ZrCp2
1
3
65%
95%
2
Ln = Me, Et
Ln = Cl
uCl
2 C
reflux, 3 h
R
P(O)(OEt)2
65-81%
4
Scheme 1. Reactions of zirconacyclopentenylphosphonates.
O
P(O)(OEt)2
R
OEt
OEt
P
Oxalyl chloride
Cp2ZrCl2
R
CuCl (10 mol%)
ZrCp2
R
P(O)(OEt)2
O
2 EtMgBr, THF
2
1
6
0 °C
58-81%
Scheme 2. Oxalyl chloride addition to zirconacyclopentenylphosphonates 2.
The oxocyclopent-1-enylphosphonate products 6 were isolated
by silica gel column chromatography in good yields (58–81%) and
were analyzed by NMR and GC/MS, and by elemental analysis
(Scheme 2).31 The broad triplet in the region ꢀ2.9 and the multi-
plet at ꢀ2.7 ppm in the 1H NMR spectra of compounds 6, along
with vinylic carbons at 128.8 and 195.6 ppm, respectively, and
the carbonyl carbon at 206.2 ppm in the 13C NMR spectra were
all indicative of oxocyclopentenylphosphonate structure 6. In addi-
tion, the 31P NMR chemical shifts of 6 in the region 11.0 ppm were
consistent with phosphorus attached to an sp2 carbon rather than
to an sp3 or sp carbon.
solvents. This efficient regio- and stereoselective intermolecular
cyclization reaction is also tolerant to alkyl (6a–d), phenyl (6h) si-
lyl (6g), and benzyloxy (6e–f) groups, as shown in Table 1.
The mechanism of this reaction is proposed to involve trans-
metallation of zirconacyclopentene 2 with CuCl followed by the
formation of a seven-membered ring by coordination with oxalyl
chloride and intramolecular cyclization with the elimination of
CO gas.30
In conclusion, a facile, general, regio-, and stereoselective syn-
thesis of novel oxocyclopentenylphosphonates has been accom-
plished in good yields by the addition of oxalyl chloride to
zirconacyclopentenylphosphonates in the presence of catalytic
CuCl. These products are of potential biological activity as anti-
inflammatory,5 and anticancer agents.4
This process represents a general and facile one-pot method for
the synthesis of novel cyclic 2-oxo-vinylphosphonates 6, which are
thermally- and air-stable compounds, and are soluble in most
Table 1
Diethyl oxocyclopentenylphosphonate products 6 obtained by carbonylation of zirconacyclopentenylphosphonates
Product
R
31P NMR (ppm)
Conversiona (%)
Yieldb (%)
6a
6b
6c
6d
6e
6f
n-C8H17
n-C5H11
n-C4H9
n-C10H21
PhCH2OCH2CH2
PhCH2OCHCH2CH2CH2CH2
(CH3)3Si
Ph
11.0
11.3
11.4
10.9
11.0
11.0
11.1
10.8
>95
>95
>95
90
>90
>90
90
81
80
78
62
68
58
70
78
6g
6h
93
a
Based on 31P NMR (121.4 MHz) and GC/MS analysis of the reaction mixture.
Yield of isolated product.
b

1630
A. A. A. Al Quntar / Tetrahedron Letters 55 (2014) 1628–1630
23. Kouno, R.; Tsubota, T.; Okauchi, T.; Minami, T. J. Org. Chem. 2000, 65, 4326–
Acknowledgment
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This Letter is dedicated to the memory of Professor M. Srebnik
who passed away in December 2011.
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References and notes
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31. Typical procedure and spectroscopic data for 6a: To zirconecene dichloride
(0.306 g, 1.05 mmol) dissolved in dry THF (6 ml) at À78 °C was added EtMgBr
(2 M, 1.05 ml, 2.1 mmol) dropwise in a 25 ml round-bottomed flask. After
stirring for 5 min at À78 °C, 1-decynylphosphonate (1 mmol) was added and
the mixture was gradually warmed to room temperature and stirred for 2 h.
Then, after cooling to À30 °C, CuCl (10 mol%) and oxalyl chloride (0.127 g,
1.0 mmol) were added successively. The reaction was again allowed to warm
to 0 °C and stirred for 1 h before being quenched with dilute HCl. The oily
products were extracted with EtOAc (2 Â 10 ml) and the combined organic
layers dried and evaporated. The residue was purified silica gel column
chromatography (70% petroleum ether: 30% EtOAc) to give the product in 81%
yield, which was analyzed by GC/MS, elemental analysis, and NMR
spectroscopy. 1H NMR (300 MHz, CDCl3): d 0.85 (t, 3H, JHH = 7.2 Hz), 1.10–
1.40 (overlap, 10H), 1.31 (t, 6H, JHH = 6.9 Hz), 1.55–1.65 (m, 2H), 2.44 (br t, 2H,
JHH = 5.4 Hz), 2.71 (m, 2H), 2.88 (br t, 2H, JHH = 8.4 Hz), 3.99 (m, 4H); 31P NMR
(121.4 MHz, CDCl3): d 11.02; 13C NMR (75.5 MHz, CDCl3): d 14.3, 16.6 (d,
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3
3JPC = 6.6 Hz), 22.8, 29.4, 29.6, 32.0, 32.4, 32.7, 32.5 (d, JPC = 18.7 Hz), 33.4 (d,
3
2
3JPC = 2.5 Hz), 35.5 (d, JPC = 11.2 Hz), 62.4 (d, JPC = 5.7 Hz), 128.8 (d,
2
2
1JPC = 192.5 Hz), 195.6 (d, JPC = 15.0 Hz), 206.2 (d, JPC = 12.7 Hz); MS(EI): m/z
(%) 330 (5.3), 301 (0.1), 287 (0.9), 259 (3.0), 245 (100), 232 (4.8), 217 (27.5),
204 (6.8), 189 (50.9), 171 (33.1), 133 (5.5), 106 (10.4), 91 (10.9), 79 (12.2), 55
(12.5); Anal. Calcd for C17H31O4P: C, 61.80; H, 9.46; P, 9.37. Found: C, 62.03; H,
9.53; P, 9.25.