Electron-rich heteroaroylphosphonates and their reaction with trimethyl phosphite

Article abstract of DOI:10.1039/b717130g

Dialkyl heteroaroylphosphonates based on thiophene, pyrrole or furan have been prepared and their reactions with trimethyl phosphite investigated. Deoxygenation of the carbonyl groups in these heteroaroylphosphonates occurs to give carbene intermediates, which then undergo further reaction. In the case of the furan-3-oylphosphonates and those systems containing a thiophene or pyrrole ring, the major reaction pathway involves intermolecular trapping of the carbene intermediates by the trimethyl phosphite, leading to the formation of ylidic phosphonates that can be readily converted into the corresponding 1,1-bisphosphonates. However, in some furan-2-oylphosphonates the carbenes generated undergo ring-opening to initially give acyclic alkynylphosphonates which may react further to give other novel phosphorus compounds. The effects of substituents on the extent to which intermolecular trapping of the initially formed carbene competes with intramolecular rearrangement has been investigated. The latter process appears to be suppressed by a substituent at the 5-position of the furan ring, the resulting ylidic phosphonates being a rare example of an efficient intermolecular trapping of a furan-2-yl carbene. The Royal Society of Chemistry 2008.

Full text of DOI:10.1039/b717130g

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PAPER
www.rsc.org/obc | Organic & Biomolecular Chemistry
Electron-rich heteroaroylphosphonates and their reaction with
trimethyl phosphite†
D. Vaughan Griffiths,* Mohamad J. Al-Jeboori, Yuen-Ki Cheong, Philip Duncanson, Jayne E. Harris,
Michael C. Salt and Helen V. Taylor
Received 6th November 2007, Accepted 26th November 2007
First published as an Advance Article on the web 20th December 2007
DOI: 10.1039/b717130g
Dialkyl heteroaroylphosphonates based on thiophene, pyrrole or furan have been prepared and their
reactions with trimethyl phosphite investigated. Deoxygenation of the carbonyl groups in these
heteroaroylphosphonates occurs to give carbene intermediates, which then undergo further reaction. In
the case of the furan-3-oylphosphonates and those systems containing a thiophene or pyrrole ring, the
major reaction pathway involves intermolecular trapping of the carbene intermediates by the trimethyl
phosphite, leading to the formation of ylidic phosphonates that can be readily converted into the
corresponding 1,1-bisphosphonates. However, in some furan-2-oylphosphonates the carbenes
generated undergo ring-opening to initially give acyclic alkynylphosphonates which may react further
to give other novel phosphorus compounds. The effects of substituents on the extent to which
intermolecular trapping of the initially formed carbene competes with intramolecular rearrangement
has been investigated. The latter process appears to be suppressed by a substituent at the 5-position of
the furan ring, the resulting ylidic phosphonates being a rare example of an efficient intermolecular
trapping of a furan-2-yl carbene.
quantities for a meaningful study due to the tendency of the
Introduction
pyrrole-2-carbonyl chloride to decompose during its reaction with
The reactions of 2-substituted dialkyl benzoylphosphonates with
trimethyl phosphite. However, this problem did not arise with the
trialkyl phosphites have proved to be a fruitful area for research
N-substituted analogues 1f and 1g.
and have led to the formation of some novel compounds, often
The heteroaroylphosphonates all gave a characteristic low-field
large doublet in their 13C NMR spectra for the carbonyl carbon
adjacent to the phosphonate group and a 31P NMR chemical shift
around dP 0 ppm, although it is interesting to note that the 31P
NMR chemical shifts for the pyrrole systems 1f–h were about
1.5–2 ppm downfield of those for the other aroylphosphonates
studied to date. It is also interesting to note that some of the
heteroaroylphosphonates were sufficiently stable to enable them
to be purified by chromatography on silica. This contrasts with
the behaviour of the benzoylphosphonates we have studied which
usually readily hydrolyse and are thus difficult to purify if they
cannot be distilled.
via the intramolecular cyclisation of initially formed carbene
intermediates.1–5 In an attempt to broaden the scope of this
research and to investigate their synthetic potential, we have
now investigated the preparation and reactions of a range of
heterocyclic analogues of the benzoylphosphonates. In this paper
we report some of our studies on the reactions of trimethyl
phosphite with ‘electron-rich’ heteroaroylphosphonates based on
thiophene, pyrrole and furan.
Results and discussion
The heteroaroylphosphonates 1a–1g and 2a–2c were prepared
by the action of trimethyl phosphite on the corresponding acid
chlorides, sometimes in the presence of an inert solvent. In general
these reactions were carried out at room temperature, but, as
discussed later, in some cases it was desirable to cool the reaction to
avoid side reactions. Unfortunately, it proved to be very difficult to
prepare the parent pyrrole-based aroylphosphonate 1h in sufficient
School of Biological and Chemical Sciences, Queen Mary, Univer-
sity of London, Mile End Road, London, England E1 4NS. E-mail:
d.v.griffiths@qmul.ac.uk; Fax: +44 (0)20 7882 7427; Tel: +44 (0)20 7882
5389
† Electronic supplementary information (ESI) available: A. Additional
general details; B. Preparation, isolation and characterisation information
for 1a–h and 2a–c; C. NMR spectral data for 6a,c–g, 7a,d–f, 10, 15a–b,
16a–c, 17a, 18a–b, 19b, 19bꢀ, 2,4-DNPH derivatives of 20b, 20c, 23 and 25;
D. Crystal data and X-ray experimental data for 2,4-DNPH derivative of
20b. See DOI: 10.1039/b717130g
Moreover, although the deoxygenation reactions of the dialkyl
benzoylphosphonates with trimethyl phosphite usually required
heating before they proceeded at a reasonable rate, there was much
greater variability in the reactivities of the heteroaroyl systems.
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Thus, for example, while the reaction of the thiophene system
2a with trimethyl phosphite still required heating at 100 ◦C, that
involving the isomeric thiophene system 1a required cooling to
avoid overheating and charring.
However, providing the reaction of the aroylphosphonate 1a
with trimethyl phosphite was kept cool, it proceeded cleanly to
give the ylidic phosphonate 5a [dP 52.4 and 29.3 ppm, JPP 96 Hz]
and trimethyl phosphate as the major products. Since such ylidic
phosphonates have been shown to arise from the intermolecular
trapping of the corresponding carbene intermediates by trimethyl
phosphite,5 this indicates that the reaction follows the deoxy-
genation pathway shown in Scheme 1 which is analogous to that
previously observed for the benzoylphosphonates.
Scheme 2 X = S and Rꢀ = Rꢀꢀ = H shown to simplify structures.
The direct dealkylation of the quasiphosphonium salt 8a to give
the phosphate-phosphonate 11a [dP 2.3 and 18.7 ppm (d, JPP 32)]
(Scheme 3) was also observed in the presence of moisture, although
this was less favoured than the formation of 10 under the reaction
conditions used.
Scheme 3
In contrast, the 3-substituted thiophene system 2a behaved more
like the benzoylphosphonates in that it had to be heated with
trimethyl phosphite before the reaction proceeded at a reasonable
rate. Once again the reaction proceeded via a carbene intermediate
(Scheme 4) to give initially the ylide 14a, although prolonged
heating caused this material to rearrange to the bisphosphonate
15a. Attempts to purify the ylide 14a by chromatography led to
its decomposition and the isolation of its hydrolysis products, the
bisphosphonate 16a and the monophosphonate 17a.
If moisture is not fully excluded, the reaction of 2a with trimethyl
phosphite also generates some of the phosphate-phosphonate 18a.
Although the pyrrole-based heteroaroylphosphonates 1f and
1g both required heating with the trimethyl phosphite to achieve
deoxygenation, they behaved similarly to the thiophene system 1a
giving the ylidic phosphonates 5f and 5g as the major products.
There was no evidence for an intramolecular carbene insertion
reaction into the N-phenyl ring following the formation of the
carbene 4g. The ylidic phosphonates 5f and 5g were isolated as
their hydrolysis products, the corresponding bisphosphonates 6
and monophosphonates 7. A similar pathway appears to occur
with the parent system 1h.
Scheme 1
Decomposition of the ylidic phosphonate 5a in water pro-
duced a 2 : 1 mixture of the bisphosphonate 6a and the
monophosphonate 7a. The route by which this occurs has been
discussed previously for those ylidic phosphonates generated from
benzoylphosphonates.6
If moisture is not rigorously excluded during the reaction of the
aroylphosphonate 1a with trimethyl phosphite, two other products
are formed in addition to the ylidic phosphonate 5a. The first of
these is the novel bisphosphonate 10 (Scheme 2). The presence of a
methylene unit in this molecule clearly indicates the involvement of
a proton donor in its formation and this was confirmed by adding
a small quantity of water to the aroylphosphonate 1a immediately
prior to its reaction with trimethyl phosphite. This resulted in the
formation of the bisphosphonate 10 as the major reaction product.
The likely route to the bisphosphonate 10 is that shown in
Scheme 2. Under the reaction conditions it would seem that the
quasiphosphonium salt 8a, formed from the protonation of the
initially formed anionic intermediate 3a, preferentially undergoes
attack on the heterocyclic ring and that the resulting system 9 then
undergoes re-aromatisation and dealkylation to give the observed
bisphosphonate 10.
In contrast, the furan-2-oylphosphonate 1b showed quite dif-
ferent behaviour in its reaction with trialkyl phosphites to the
thiophene- and pyrrole-based aroylphosphonates.
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Scheme 5
The formation of analogous aldehydes has been observed
previously when attempts have been made to prepare other furan-
2-yl carbenes.8 Computational studies9 support the concept of a
spontaneous ring-opening of the furan-2-yl carbenes leading to
these aldehydes rather than the involvement of an intermediate
such as 21b. Furthermore, no experimental evidence has yet
been obtained to support the formation of such cyclopropene
intermediates.10
The reaction of the anionic intermediate 3b, initially formed
from the reaction of 1b with trimethyl phosphite, with the aldehyde
20b then explains the formation of the observed triphosphorus
compound 19b (Scheme 6).
Scheme 4
Firstly, the reaction needed to be carried out at low temperature
since at room temperature an exothermic reaction occurred
leading to extensive charring. Secondly, at low temperature and in
toluene, the reaction proceeded cleanly to give one major product,
a triphosphorus compound 19b [dP −48.3 (d, JPP 41), −3.4 (s) and
19.0 (d, JPP 41)] that can be seen to arise from two molecules of the
furanoylphosphonate 1b and one of the trimethyl phosphite. This
was confirmed by repeating the reaction using triethyl phosphite
which gave the corresponding triphosphorus compound 19bꢀ
[dP −51.4 (d, JPP 41), −3.4 (s) and 19.0 (d, JPP 41)]. A small quantity
of the ylidic phosphonate 5b was also produced under these
conditions [dP 28.9 (d, JPP 89) and 52.6 (d, JPP 89)] together with
other minor components including one [dP −4.9] later identified
as the aldehyde 20b.
The presence of the alkynylphosphonate portion of 19b was
confirmed from the high field shift of this phosphonate resonance
[dP −3.4 ppm] and by the exceptionally large coupling (JPC 298 Hz)
between the phosphonate group and the adjacent carbon atom.
A similar large coupling has been seen in related structures7 and
reflects the high degree of s character in this P–C bond. To explain
the formation of 19b we propose that the initially formed carbene
intermediate 4b undergoes ring opening to give the aldehyde 20b
(Scheme 5).
Scheme 6 X = O and Rꢀꢀ = H shown to simplify structures.
In an effort to obtain support for the involvement of the
intermediate aldehyde 20b in the formation of 19b, the reaction
of furan-2-oyl chloride with trimethyl phosphite was investigated
under a variety of conditions to see if the quantity of this aldehyde
in the reaction mixture could be increased. Fortunately, by using
low temperatures with acetonitrile as the solvent and by restricting
the quantity of trimethyl phosphite used, it was possible to obtain
a reaction mixture that contained a significant quantity of a
component [dP −4.9] that gave NMR spectra consistent with the
aldehyde 20b. This component was isolated from the reaction
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mixture as its 2,4-dinitrophenylhydrazone derivative, the structure
of which was determined using X-ray crystallography (Fig. 1).11
Fig. 1 X-ray structure of the 2,4-dinitrophenylhydrazone derivative
of 20b.
It is interesting to note that while the aldehyde 20b is initially
3
=
produced with a Z-configuration at the alkene (CH CH, JHH
11.2) it slowly isomerises under the reaction conditions to give the
corresponding E-configuration 22b (CH CH, JHH 16.2) as the
3
=
major component.
We have also investigated the influence of placing substituents
at the 3- and 5-positions on the furan ring. In particular we were
interested to see how this might affect the ease of ring opening of
the furan-2-yl carbenes 4c–e. We were also interested to see if it
might be possible to achieve an intramolecular insertion reaction
into a substituent at the 3-position on the ring as an alternative
reaction pathway for the carbene 4c.
Scheme 7
Interestingly, with the 3-benzyl-substituted system 1c there
was no evidence for the formation of any of the triphosphorus
compound analogous to 19b when it was reacted with trimethyl
phosphite, even though formation of the aldehyde 20c was
the major reaction pathway following carbene formation. The
benzyl substituent had thus clearly inhibited further reaction
of the aldehyde 20c with the anionic intermediate 3c. Some
intermolecular trapping of the carbene 4c by the trialkyl phosphite
to give the ylidic phosphonate 5c was also observed, suggesting
that this carbene intermediate is slightly longer-lived than that for
the unsubstituted system, but there was no evidence for products
arising from an interaction between the carbene centre and the
benzyl substituent in 4c.
We also observed that if a proton donor was present in the
reaction mixture the initially formed aldehyde could react with
further trimethyl phosphite to give a product giving two singlets
in the 31P NMR spectrum at dP −1.9 and 17.3 ppm. This product
was identified as the novel allene 23, the formation of which
can be rationalised as shown in Scheme 7. This allene showed a
characteristic resonance in the 13C NMR spectrum at dC 215.7 ppm
for the sp-hybridised carbon in an allene and a broad band in the
IR spectrum at mmax 1940 cm−1 typical of an allene.
Two other components were also produced small quantities
which arose as a result of traces of moisture in the reaction mixture,
the phosphate-phosphonate 11c and the bisphosphonate 25.
Although we earlier proposed that the formation of thiophene-
based bisphosphonate 10 involved attack by phosphite on the
quasiphosphonium salt 8a (Scheme 2), we believe that the forma-
tion of the furan-based system 25 is more likely to be derived from
the alternative mechanism shown in Scheme 8. This is supported by
the observation that treatment of the aldehyde 20c with trimethyl
phosphite without the rigorous exclusion of moisture leads to
cyclisation and formation of the bisphosphonate 25.
Scheme 8
Although the ring opening of thiophen-2-yl carbenes has been
reported12 we saw no evidence for this occurring with the thiophen-
2-yl carbene intermediate 4a generated by the action of trialkyl
phosphite on the aroylphosphonate 1a. We have therefore ruled
out a pathway analogous to that shown in Scheme 8 to explain
the formation of the corresponding thiophene-based bisphos-
phonate 10.
To investigate the influence of a substituent at the 5-position
on the furanyl carbenes 4 (X = O), we prepared the methyl- and
phenyl-substituted furanoylphosphonates 1d and 1e.
The reaction of the 5-methyl substituted system 1d with
trimethyl phosphite in toluene gave largely the ylidic phosphonate
5d, subsequently isolated as its decomposition products 6d and
7d, although a small quantity of the ring-opened ketone 20d
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(ca. 2%) was also produced. As with the aldehyde 20b previously
reaction mixture. The resulting ylidic phosphonates 5 and 14
can be used as precursors for the preparation of some novel 1,1-
bisphosphonates. In contrast, the major reaction pathway with the
furan-2-yl systems 1b and 1c, where there is no substituent on the
5-position of the furan ring, involves ring opening of the carbene
intermediates 4b,c to give novel alkynylphosphonates 20b,c and
22b. There was no evidence for any reaction between the benzyl
substituent in 4c and the carbene centre.
In the case of the unsubstituted furan-2-oylphosphonate 1b, the
initially formed anionic intermediate 3b reacts with the aldehyde
portion of the subsequently formed alkynylphosphonate 20b to
give the triphosphorus system 19b. However, with the benzyl-
substituted alkynylphosphonate 20c such a subsequent reaction
is inhibited. In contrast, the presence of a substituent at the
5-position on the furan ring in the carbene intermediates 4d
and 4e appears to discourage ring-opening, and trapping of the
carbene by trimethyl phosphite to give the ylidic phosphonates 5d
and 5e becomes the dominant reaction pathway. Indeed, in the
case of the 5-phenyl substituted carbene 4e this intermolecular
trapping pathway was the only carbene decomposition pathway
observed under the conditions used and as such it is a rare
example of a successful intermolecular trapping of a furan-2-yl
carbene.8
discussed, the ketone was initially produced as the Z-isomer
3
=
20d [CH CH, JHH 12 Hz] but subsequently isomerised under
the reaction conditions to give the corresponding E-form 22d
[CH CH, JHH 16.3 Hz] as the major isomer.
3
=
The ability of substituents at the 5-position on the furan ring
to affect the ease of ring-opening of the corresponding furanyl
carbene 4 was even more marked in the case of the 5-phenyl-
substituted furan-2-yl carbene 4e where no ring-opening to give
phenyl ketones analogous to 20d or 22d was observed under
the conditions used. In this case only intermolecular trapping
of the carbene intermediate 4e by the trialkyl phosphite was
observed leading to the formation of the ylidic phosphonate 5e.
It is interesting to note that early studies had concluded that
the presence of alkyl or aryl groups at the 5-position of some
simpler furan-2-yl carbenes had not had a significant effect on
the efficiency of ring opening although they had seen a marked
effect if an electron-withdrawing group was placed at the 5-
position.12 It is also interesting to note that it has proved extremely
difficult to intercept furan-2-yl carbene intermediates before ring
opening occurs.13 The formation of the ylidic phosphonate 5e in
the presence of trimethyl phosphite is therefore a rare example
of the efficient intermolecular trapping of such a carbene inter-
mediate.14
Finally, these studies have shown that some unexpected products
can be generated when the reaction of trimethyl phosphite with the
heteroaroylphosphonates occurs in the presence of a proton donor
such as moisture. Thus, for example, in the presence of moisture the
alkynylphosphonate 20c reacts with trimethyl phosphite to give the
novel allene 23 while the reaction of 1a with trimethyl phosphite
in the presence of moisture gave the unexpected bisphosphonate
10. Other reactions of this type will be the subject of a future
publication.15
The effect of moving the ketophosphonate group to the 3-
position on the furan ring was also investigated. Whereas the
reaction the furan-2-oylphosphonates 1b and 1e with trialkyl
phosphites had required cooling to avoid side reactions, the furan-
3-oylphosphonates 2b and 2c required heating with trimethyl
phosphite before the reaction occurred at any significant rate.
However, under these conditions both 2b and 2c reacted to give
the corresponding ylidic phosphonates 14b and 14c together with
trimethyl phosphate, indicating that these reactions too were
proceeding via carbene intermediates as had been observed with
the analogous thiophene system 2a (Scheme 4). In the case of the
parent furan system 2b, the initially formed ylidic phosphonate 14b
showed a tendency to rearrange to the corresponding bisphospho-
nate 15b if the reaction mixture was heated for an extended period,
but this was not observed with the 2-substituted system 14c. This
is consistent with the behaviour of the ylidic phosphonates from
benzoylphosphonates where the analogous rearrangement was
inhibited by the presence of an ortho substituent.5 Both ylidic
phosphonates could be readily converted into the corresponding
bisphosphonates 16b and 16c by the action of a suitable proton
donor such as hydrogen chloride. There was no evidence for
any interaction between the carbene centre and the adjacent
substituent in 13c.
Experimental
General details21
NMR spectra were recorded on JEOL EX-270, Bruker AMX400
and Bruker AV600 spectrometers. 31P NMR spectra are referenced
to 85% phosphoric acid, 1H NMR spectra to Me4Si, and 13C NMR
spectra to CDCl3 at 77.23 ppm. J values are given in Hz; ‘J’
indicates the apparent coupling in a second order spectrum.
The carboxylic acids used were either available commercially
or prepared by literature methods. 3-Benzylfuran-2-carboxylic
acid16 was prepared from 3-benzylfurfural,16 and 5-methylfuran-
2-carboxylic acid17 by the oxidation of 5-methylfurfural.17 5-Phe-
nylfuran-2-carboxylic acid18 was prepared from furan-2-carbo-
xylic acid, 1-phenylpyrrole-2-carboxylic acid19 from 1-phenyl-
pyrrole, and 2-(prop-2-ynyloxymethyl)furan-3-carboxylic acid20
from methyl 2-methylfuran-3-carboxylate.
Summary
The reactions of trimethyl phosphite with heteroaroylphospho-
nates 1a–h and 2a–c have been shown to proceed via deoxygenation
of the carbonyl group to give carbene intermediates 4a–h and
13a–c whose subsequent reactions depend on the nature of the
heterocyclic ring. With those 2-heteroaroyl systems 1a, 1f–h that
contained the more aromatic thiophene and pyrrole heterocyclic
systems, and with all the 3-heteroaroyl systems 2a–c studied,
the major reaction pathway involves the intermolecular trapping
of the carbene intermediates by the trimethyl phosphite in the
Typical procedure for the preparation of the aroylphosphonates
1a–h and 2a–c.21
The aroylphosphonates 1a–h and 2a–c were prepared by the action
of trimethyl phosphite on the corresponding acid chlorides, which
were usually prepared in situ by the action of thionyl chloride or
oxalyl chloride on the carboxylic acid.
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Dimethyl thiophene-2-carbonylphosphonate 1a
a period of 12 h 31P NMR spectroscopy showed the formation
of trimethyl phosphate, the ylidic phosphonate 5a [dP 29.3 and
52.4 ppm (d, JPP 96)] and a small quantity of the bisphosphonate
6a. Volatile components were then removed in vacuo (50 ◦C at
0.005 mmHg). Decomposition of the ylide 5a by the addition
of water resulted in the formation of the bisphosphonate 6a
and the monophosphonate 7a in a 5 : 1 ratio. Pure samples of
products in the residue were isolated by a combination of column
chromatography on silica gel using ethyl acetate as the eluent
and reverse-phase HPLC on a C18 column using water–methanol
mixtures as the eluent.
Tetramethyl thiophen-2-ylmethane-1,1-bisphosphonate 6a was
isolated as a pale yellow oil; dP(109.3 MHz, CDCl3) 19.7;
dH(400MHz, CDCl3) 4.12 (1 H, t, JPH 25.0, a-CH); dC(100.63 MHz,
CDCl3) 39.5 (t, JPC 136, a-C); m/z (EI) 314.0143 (M+. C9H16O6P2S
requires 314.0143).21
The phosphonate 1a was obtained as a pale yellow oil in essentially
quantitative yield; dP(109.3 MHz, CDCl3) 0.1; dC(67.9 MHz,
21
CDCl3) 188.6 (d, 1JPC 182, C O).
=
Dimethyl furan-2-carbonylphosphonate 1b
The phosphonate 1b (4.0 g, 58%) was isolated as a pale yellow
oil; dP(109.3 MHz, CDCl3) −0.1; dC(67.9 MHz, CDCl3) 183.7
21
=
(d, JPC 190, C O).
Dimethyl 3-benzylfuran-2-carbonylphosphonate 1c
A sample of the pure phosphonate 1c (1.2 g, 63%) was isolated as a
pale yellow oil; dP(109.3 MHz, CDCl3) 0.9; dC(67.9 MHz, CDCl3)
21
=
186.2 (d, JPC 186, C O).
Dimethyl 5-methylfuran-2-carbonylphosphonate 1d
Dimethyl thiophen-2-ylmethylphosphonate 7a was isolated as a
pale yellow oil; dP(109.3 MHz, CDCl3) 27.3; dH(400 MHz, CDCl3)
3.37 (2 H, d, JPH 20.8, CH2); dC(100.63 MHz, CDCl3) 27.1 (d, JPC
144, CH2); m/z (ESI) 229.0059 (M + Na+. C7H11O3PSNa requires
229.0064).21
The phosphonate 1d (5.1 g, 60%) was obtained as a pale yellow
oil; dP(109.3 MHz, CDCl3) 0.6; dC(67.9 MHz, CDCl3) 182.3
21
=
(d, JPC 189, C O).
Dimethyl 5-phenylfuran-2-carbonylphosphonate 1e
Dimethyl
5-(dimethoxyphosphorylmethyl)thiophen-2-ylphos-
phonate 10, was isolated as a pale yellow oil; dP(109.3 MHz,
CDCl3) 15.2 (d, JPP 3) and 26.3 (d, JPP 3); dH(400 MHz, CDCl3)
3.34 (2 H, d, JPH 21.2, CH2); dC(100.63 MHz, CDCl3) 26.3 (d, JPC
143, CH2), 124.7 (dd, JPC 211 and 4, C-2); m/z (EI) 314.0143 (M+.
C9H16O6P2S requires 314.0143).21
The phosphonate 1e (0.09 g, 20%) was isolated as a pale yellow
oil, bp 130 ◦C at 0.005 mmHg; dP(109.3 MHz, CDCl3) 0.6;
21
=
dC(67.9 MHz, CDCl3) 183.0 (d, JPC 189, C O).
Dimethyl 1-methylpyrrole-2-carbonylphosphonate 1f
The phosphonate ester 1f (1.04 g, 60%) was isolated as a pale
Reaction of dimethyl furan-2-carbonylphosphonate 1b with
trimethyl phosphite
yellow oil, bp 137 ◦C at 0.005 mmHg; dP(109.3 MHz, CDCl3) 2.5;
21
=
dC(67.9 MHz, CDCl3) 184.2 (d, JPC 183, C O).
Trimethyl phosphite (1.8 g, 14.7 mmol) was added dropwise to a
solution of the phosphonate 1b (1.0 g, 4.9 mmol) in dry toluene
(3 cm3) at −48 ◦C under an atmosphere of dry nitrogen. This
mixture was then allowed to warm to room temperature and
stirred for a further 16 h. Volatile components were then removed
in vacuo (55 ◦C at 0.005 mmHg). The NMR spectra of the
product confirmed the formation of the triphosphorus compound
19b, dP(109.3 MHz, CDCl3) −48.3 [d, JPP 41, P(OMe)3], −3.4
[s, CCP(O)(OMe)2] and 19.0 [d, JPP 41, P(O)(OMe)2],21 as the
major compound (ca. 90%) although small quantities of the ylidic
phosphonate 5b [dP 28.9 ppm (d, JPP 90) and 52.6 ppm (d, JPP
90)] and the aldehydes 20b and 22b [dP −4.8 and −4.9 ppm]
were also present. Attempts to obtain a pure sample of the
triphosphorus compound 19b by chromatography on silica led
to its decomposition.
Dimethyl 1-phenylpyrrole-2-carbonylphosphonate 1g
The phosphonate ester 1g was isolated as a pale yellow oil;
dP(109.3 MHz, CDCl3) 2.1; dC(100.63 MHz, CDCl3) 183.6
21
=
(d, JPC 184, C O).
Dimethyl thiophene-3-carbonylphosphonate 2a
The phosphonate 2a was isolated in essentially quantitative yield
as a pale yellow oil; dP(109.3 MHz, CDCl3) 0.75; dC (67.9 MHz,
21
=
CDCl3) 191.0 (d, JPC 178, C O).
Dimethyl furan-3-carbonylphosphonate 2b
The phosphonate 2b (12.4 g, 68%) was obtained as a pale yellow
oil; dP(109.3 MHz, CDCl3) −0.4; dC(67.9 MHz, CDCl3) 192.0
21
=
The reaction can also be carried out in the absence of a solvent
without any significant change in product.
Use of triethyl phosphite rather than trimethyl phosphite led
to the formation of 19bꢀin a good state of purity; dP(109.3 MHz,
CDCl3) 19.0 (d, JPP 41), −3.4 (s) and −51.4 (d, JPP 41).21
(d, JPC 183, C O).
Dimethyl 2-(prop-2-ynyloxymethyl)furan-3-carbonylphospho-
nate 2c
The phosphonate ester 2c was obtained as a pale yellow oil
in essentially quantitative yield; dP(109.3 MHz, CDCl3) 0.2;
Dimethyl (Z)-5-oxo-pent-3-en-1-ynylphosphonate 20b
21
=
dC(67.9 MHz, CDCl3) 193.9 (d, JPC 185, C O).
A solution of furan-2-carbonyl chloride (1.82 g, 14 mmol) in dry
acetonitrile (2 cm3) was cooled to −78 ◦C and trimethyl phosphite
(2.10 g, 16 mmol) added under an atmosphere of dry nitrogen. The
mixture was then allowed to warm to room temperature over a
period of 12 h. 31P NMR spectroscopy indicated that the reaction
had proceeded to form two products, the aroylphosphonate 1b
Reaction of dimethyl thiophene-2-carbonylphosphonate 1a with
trimethyl phosphite
Trimethyl phosphite (2.23 g, 18 mmol) was added slowly to a
stirred sample of the phosphonate 1a (1.32 g, 6 mmol) at 0 ◦C. The
solution was then allowed to warm to room temperature and after
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(ca. 60%) and the aldehyde 20b (ca. 40%). 20b: dP(109.3 MHz,
CDCl3) −4.9; dH(400 MHz, CDCl3) 3.85 (6 H, d, JHH 12.4, POMe),
6.47 (1 H, ddd, JHH 11.2 and 7.6, JPH 1.2, 4-H), 6.62 (1 H, dd, JHH
11.2, JPH ∼4, 3-H), 10.07 (1 H, d, JHH 7.6, CHO); dC(100.63 MHz,
CDCl3) 53.5 (x2)(d, JPC 6, POMe), 87.5 (d, JPC 293, C-1), 92.2
(d, JPC 51, C-2), 124.0 (d, JPC 6, C-3), 142.2 (d, JPC 3, C-4) and
189.8 (C-5). Under the reaction conditions 20b slowly isomerises
to give the (E)-isomer 22b as the major component (ca. 70%). 22b:
dP(109.3 MHz, CDCl3) −4.8 ppm; dH(400 MHz, CDCl3) 3.84 (6 H,
d, JHH 12.4, POMe), 6.56 (1 H, dd, JHH 16.2, JPH 3.2, 3-H), 6.62
(1 H, ddd, JHH 16.2 and 7.0, JPH 0.8, 4-H), 9.58 (1 H, d, JHH 7.0,
CHO); dC(100.63 MHz, CDCl3) 53.6 (x2)(d, JPC 6, POMe), 88.9
(d, JPC 294, C-1), 94.0 (d, JPC 51, C-2), 127.1 (d, JPC 6, C-3), 143.2
(d, JPC 3, C-4) and 191.8 (C-5).
JPH 6.6 and 3.2, 5-H); dC(100.63 MHz, CDCl3) 80.0 (d, JPC 199,
C-1), 100.3 (d, JPC 17.5, C-3), 107.1 (dd, JPC 10.2 and 9.8, C-
4), 137.7 (dd, JPC 5.3 and 5.1, C-5), 137.7 (d, JPC 4, C-1ꢀ), 215.7
(d, JPC 3, C-2); m/z (ESI) 389.0912 (M + H+. C16H23O7P2 requires
389.0919).21
Dimethyl 4-benzyl-5-(dimethoxyphosphorylmethyl)furan-2-yl-
phosphonate 25 was isolated as a pale yellow oil; dP(109.3 MHz,
CDCl3) 7.6, (d, JPP 4) and 25.1 (d, JPP 4); dH(400 MHz, CDCl3)
3.26 (2 H, d, JPH 21, PCH2); dC(100.63 MHz, CDCl3) 25.0 (d, JPC
143, PCH2), 141.6 (dd, JPC 245 and 4, C-2); m/z (EI) 388.0836
(M+. C16H22O7P2 requires, 388.0841).21
Reaction of (Z)-3-benzyl-5-oxo-pent-3-en-1-ynylphosphonate 20c
with trimethyl phosphite without the rigorous exclusion of moisture
Reaction of the initially formed aldehyde 20b with methanolic
2,4-dinitrophenylhydrazine solution gave an orange brown pre-
cipitate of the corresponding hydrazone which was purified by
chromatography on silica gel using ethyl acetate–petroleum ether
(bp 60–80 ◦C) as the eluent. Recrystallisation of this product
from hot methanol gave orange brown crystals suitable for X-
ray structure analysis;11 mp 151–153 ◦C; m/z (ESI) 391.0414 (M +
Na+. C13H13N4O7PNa requires 391.0419).21
Trimethyl phosphite (0.09 g, 0.72 mmol) was added to a solution
of dimethyl (Z)-3-benzyl-5-oxo-pent-3-en-1-ynylphosphonate 20c
(0.20 g, 0.72 mmol) in toluene (4 cm3) at −78 ◦C and the mixture
then allowed to warm to room temperature and monitored by
NMR spectroscopy. This showed the gradual formation of the
bisphosphonate 25. A sample of this was isolated by chromatog-
raphy and shown to be the same as the sample of 25 prepared and
characterised earlier.
Reaction of dimethyl 3-benzylfuran-2-carbonylphosphonate 1c with
trimethyl phosphite
Reaction of dimethyl 5-methylfuran-2-carbonylphosphonate 1d
with trimethyl phosphite
To a solution of 3-benzylfuran-2-carbonyl chloride (1 g, 4.5 mmol)
in deuterochloroform (2.5 cm3) cooled to −78 ◦C was added
trimethyl phosphite (0.56 g, 4.5 mmol). The mixture was then
allowed to warm to room temperature and 31P NMR spectroscopy
showed the formation of the phosphonate 1c (dP 0.9). A further
quantity of trimethyl phosphite (1.12 g, 9 mmol) was then
added and the reaction mixture left at room temperature until
the reaction was complete (ca. 1 h). Volatile components were
then removed from the reaction mixture in vacuo (40 ◦C at
0.005 mmHg). The 31P NMR spectrum of the residue showed the
formation of several components subsequently identified as the
ylidic phosphonate 5c [dP 28.5 ppm (d, JPP 102) and 53.7 ppm (d,
Trimethyl phosphite (6.2 g, 50 mmol) was added to a stirred
sample of the phosphonate 1d (4.36 g, 20 mmol) cooled to −78 ◦C
under an atmosphere of dry nitrogen. The mixture was then
allowed to warm to room temperature and the progress of the
reaction monitored by 31P NMR spectroscopy. When the reaction
of 1d was complete, the volatile components were removed under
reduced pressure (40 ◦C at 0.005 mmHg) to give a residue, which
contained the ylidic phosphonate 5d [dP 53.0 ppm (d, JPP 94) and
29.3 ppm (d, JPP 94)] (ca. 88%), together with its decomposition
products 6d (ca. 8%) and 7d (ca. 2%), and the ketone 20d (ca. 2%).
After decomposing the ylidic phosphonate 5d by the addition
of water, the products in the residue were isolated by column
chromatography on silica gel using petroleum ether (bp 40–60 ◦C)–
ethyl acetate mixtures as the eluent.
Dimethyl 5-oxo-hex-3-en-1-ynylphosphonate was isolated as a
mixture of the E and Z isomers 20d and 22d (60 : 40) as a yellow
oil; m/z (ESI) 203 (M + H+. C8H12O4P requires 203).
(Z)-Isomer 20d dP(109.3 MHz, CDCl3) −3.8; dH(400 MHz,
CDCl3) 2.34 (3 H, s, Me), 3.80 (6 H, d, JPH 12.2, POMe), 6.07
(1 H, dd, JHH 12, JPH 4.4, 3-H) and 6.54 (1 H, dd, JHH 12, JPH
1.2, 4-H); dC(100.63 MHz, CDCl3) 30.5 (Me), 53.9 (x2)(d, JPC 7,
POMe), 87.4 (d, JPC 296, C-1), 95.6 (d, JPC 51, C-2), 116.3 (d, JPC
6, C-3), 142.5 (d, JPC 3, C-4) and 195.9 (C-5);
J
PP 102)] (ca. 31%), the bisphosphonate 6c (ca. 16%), the allene 23
(ca. 33%), the bisphosphonate 25 (ca. 11%) and some aldehyde 20c
(ca. 9%).22 The major components in this residue were isolated by
chromatography on silica gel using mixtures of dichloromethane,
ethyl acetate and methanol of increasing polarity as the eluent.
Dimethyl (Z)-3-benzyl-5-oxo-pent-3-en-1-ynylphosphonate 20c
was isolated as a pale yellow oil; dP(109.3 MHz, CDCl3) −4.5;
=
dH(400 MHz, CDCl3) 6.34 (1 H, dq, J 8 and 1.2, CH ), and 10.05
(1 H, d, JHH 8, CHO); dC(100.63 MHz, CDCl3) 88.2 (d, JPC 291,
C-1), 94.1 (d, JPC 50, C-2), and 191.1 (s, C-5); m/z (ESI) 279.0781
(M + H+. C14H16O4P requires 279.0786).21
Tetramethyl 3-benzylfuran-2-ylmethane-1,1-bisphosphonate 6c
was isolated as a pale yellow oil; dP(109.3 MHz, CDCl3) 19.5;
dH(400 MHz, CDCl3) 4.03 (1 H, t, JPH 25.7, a-H); dC(100.63 MHz,
CDCl3) 37.5 (t, JPC 136, a-CH)); m/z (ESI) 411 (M + Na+.
C16H22O7P2Na requires 411).21
Dimethyl (Z)-3-benzyl-5-(dimethoxyphosphoryloxy)penta-1,2,
4-trienylphosphonate 23 was isolated as a pale yellow oil;
dP(109.3 MHz, CDCl3) −1.9 and 17.3; dH(400 MHz, CDCl3) 4.82
(1 H, ddt, JHH 6.4 and 1.6, JPH 2.7, 4-H), 5.35 (1 H, tddd, JHH
2.7, 1.6 and 1.6, JPH 1.4, 1-H), 6.46 (1 H, dddd, JHH 6.4 and 1.6,
(E)-Isomer 22d dP(109.3 MHz, CDCl3) −4.0; dH(400 MHz,
CDCl3) 2.25 (3 H, s, Me), 3.77 (6 H, d, JPH 12.2, POMe), 6.55
(1 H, dd, JHH 16.3, JPH 3.7, 3-H) and 6.68 (1 H, dd, JHH 16.3, JPH
1.0, 4-H); dC(100.63 MHz, CDCl3) 31.1 (Me), 53.8 (x2)(d, JPC 7,
POMe), 85.5 (d, JPC 297, C-1), 95.7 (d, JPC 52, C-2), 119.47 (d, JPC
7, C-3), 142.0 (d, JPC 3, C-4) and 195.9 (C-5); mmax(CH2Cl2)/cm−1
=
=
1716 C O, 1257 P O, 1039 P–O.
Dimethyl 5-methylfuran-2-ylmethylphosphonate 7d, from the
hydrolysis of 5d, was isolated as a colourless oil; dP(109.3 MHz,
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CDCl3) 26.7; dH(400 MHz, CDCl3) 2.26 (3 H, d, JPH 2, Me), 3.21
(2 H, d, JPH 20.8, CH2); dC(100.63 MHz, CDCl3) 25.7 (d, JPC
144, CH2); m/z (ESI) 227.0424 (M + Na+. C8H13O4PNa requires
227.0449).21
Tetramethyl 5-methylfuran-2-ylmethane-1,1-bisphosphonate 6d
was isolated as a pale yellow oil; dP(109.3 MHz, CDCl3) 19.0;
dH(400 MHz, CDCl3) 4.04 (1 H, t, JPH 25.2, a-CH); dC(100.63MHz,
CDCl3) 37.7 (t, JPC 136, a-CH); m/z (ESI) 335.0427 (M + Na+.
C10H18O7P2Na requires 335.0425).21
d, JPH 20, CH2); dC(100.63 MHz, CDCl3) 24.1 (d, JPC 144, CH2);
m/z (ESI) 204.0779 (M + H+. C8H15NO3P requires 204.0789).21
Tetramethyl 1-methylpyrrol-2-ylmethane-1,1-bisphosphonate 6f
(0.22 g) was isolated as a pale yellow oil; dP(109.3 MHz, CDCl3)
20.0; dH(270 MHz, CDCl3) 3.72 (1 H, br t, JPH 25, a-CH);
dC(100.63 MHz, CDCl3) 36.1 (t, JPC 133, a-CH); m/z (ESI)
334.0579 (M + Na+. C10H19NO6P2Na requires 334.0585).21
Reaction of dimethyl 1-phenylpyrrole-2-carbonylphosphonate 1g
with trimethyl phosphite
Reaction of dimethyl 5-phenylfuran-2-carbonylphosphonate 1e
with trimethyl phosphite
A solution of trimethyl phosphite (1.90 g, 15 mmol) and the
phosphonate 1g (2.22 g, 7.95 mmol) in dry toluene (10 cm3) was
To a solution of 5-phenylfuran-2-carbonyl chloride (0.5 g,
2.4 mmol) in dry toluene (30 cm3), cooled to −78 ◦C under
an atmosphere of dry nitrogen, was added trimethyl phosphite
(1.0 g, 8 mmol). The mixture was then allowed to warm to
room temperature and the progress of the reaction monitored
by 31P NMR spectroscopy. This showed the initial formation
of the aroylphosphonate 1e [dP (CDCl3–PhMe) 0.4 ppm] which
then reacted further. When the reaction was complete (ca. 12 h)
volatile components were removed under reduced pressure (40 ◦C
at 0.005 mmHg) and the residue analysed by NMR spectroscopy.
This showed the aroylphosphonate 1e had been converted into the
ylidic phosphonate 5e [dP (CDCl3–PhMe) 53.9 (d, JPP 84) and 27.9
(d, JPP 84)] (ca. 60%), some of which had decomposed to give the
bisphosphonate 6e [dP 19.0 ppm] (ca. 40%). Decomposition the
remaining ylide 5e resulted in the formation of more bisphospho-
nate 6e together with a limited quantity of the monophosphonate
7e. Samples of these hydrolysis products were isolated by column
chromatography on silica gel using petroleum ether (bp 40–60 ◦C)–
ethyl acetate mixtures as the eluent.
heated at 100 ◦C for 6 h under an atmosphere of dry nitrogen. 31
P
NMR spectroscopy showed that ca. 50% of the starting materials
had reacted and that the reaction had proceeded cleanly to give
the ylidic phosphonate 5g [dP 51.8 (d, JPP 109) and 28.5 ppm (d, JPP
109)] and some of its hydrolysis product 6g [dP 20.1]. The mixture
was subjected to column chromatography on silica gel using ethyl
acetate–methanol mixtures as the eluent.
The unreacted dimethyl 1-phenylpyrrole-2-carbonylphospho-
nate 1g was isolated as a pale yellow oil.
Tetramethyl 1-phenylpyrrol-2-ylmethane-1,1-bisphosphonate 6g
was isolated as a pale yellow oil; dP(109.3 MHz, CDCl3) 20.1;
dH(400MHz, CDCl3) 3.87 (1 H, t, JPH 25.7, a-CH); dC(100.63 MHz,
CDCl3) 35.9 (t, JPC 139, a-CH); m/z (ESI) 396.0735 (M + Na+.
C15H21NO6P2Na requires 396.0741).21
Reaction of dimethyl thiophene-3-carbonylphosphonate 2a with
trimethyl phosphite
Trimethyl phosphite (2.34 g, 19.0 mmol) was added dropwise to
phosphonate 2a (2 g, 9 mmol) at room temperature with stirring.
The mixture was then heated at 100 ◦C under an atmosphere
Dimethyl 5-phenylfuran-2-ylmethylphosphonate 7e was isolated
as a pale yellow oil; dP(109.3 MHz, CDCl3) 26.1; dH(400 MHz,
CDCl3) 3.33 (2 H, d, JPH 21, CH2); dC(100.63 MHz, CDCl3) 26.1
(d, JPC 144, CH2); m/z (ESI) 267 (M + H+. C13H16O4P requires
267).21
of dry nitrogen and the progress of the reaction monitored by 31
P
NMR spectroscopy. This showed the initial formation of the ylidic
phosphonate 14a [dP 55.5 and 30.0 ppm (d, JPP 90)] together with
small quantity of the phosphate-phosphonate 18a. After 12 h,
the reaction was complete and the ylide had largely decomposed
(>90%) to give either the rearrangement product 15a (75%) or the
hydrolysis product 16a (15%). Decomposition of the remaining
ylide by the addition of water led to the formation of both the
bisphosphonate 16a and the monophosphonate 17a. Samples of
the major reaction products were isolated by chromatography on
silica gel using ethyl acetate–methanol mixtures as the eluent.
Dimethyl thiophen-3-ylmethylphosphonate 17a was isolated as a
pale yellow oil; dP(109.3 MHz, CDCl3) 28.8; dH(400 MHz, CDCl3)
3.22 (2 H, d, JPH 20.9, CH2); dC(100.63 MHz, CDCl3) 27.3 (d,
JPC 141, a-CH2); m/z (ESI) 229.0059 (M + Na+. C7H11O3PSNa
requires 229.0064).21
Tetramethyl 5-phenylfuran-2-ylmethane-1,1-bisphosphonate 6e
was isolated as a pale yellow oil; dP(109.3 MHz, CDCl3) 18.8;
dH(400 MHz, CDCl3) 4.16 (1 H, t, JPH 25.5, a-CH); dC(100.63MHz,
+
CDCl3) 38.9 (t, JPC 136, a-CH); m/z (ESI) 397.0564 (M + Na .
C15H20O7P2Na requires 397.0582).21
Reaction of dimethyl 1-methylpyrrole-2-carbonylphosphonate 1f
with trimethyl phosphite
A solution of trimethyl phosphite (0.57 g, 4.6 mmol) and the
phosphonate 1f (0.5 g, 2.3 mmol) in dry toluene (20 cm3)
was heated at 60 ◦C for 48 h under an atmosphere of dry
nitrogen. Volatile components were then removed in vacuo (50 ◦C
at 0.005 mmHg) to give a residue that was shown by NMR
spectroscopy to contain the ylidic phosphonate 5f [dP 52.6 (d, JPP
116) and 30.1 (d, JPP 116)] together with one of its decomposition
products, the bisphosphonate 6f. The ylidic phosphonate was
decomposed by the addition of water and samples of the resulting
products isolated by column chromatography on silica gel using
ethyl acetate–methanol mixtures as the eluent.
Dimethyl 1-(dimethoxyphosphoryloxy)-1-(thiophen-3-yl)me-
thylphosphonate 18a was isolated as
a pale yellow oil;
dP(109.3 MHz, CDCl3) 2.0 (d, JPP 32), 19.2 (d, JPP 32);
dH(400 MHz, CDCl3) 5.72 (1 H, dd, JPH 10 and 13, a-CH);
dC(100.63 MHz, CDCl3) 70.4 (dd, JPC 176 and 7, a-CH); m/z
(ESI) 352.9981 (M + Na+. C9H16O7P2SNa requires 352.9989).21
Tetramethyl thiophen-3-ylmethane-1,1-bisphosphonate 16a was
isolated as a pale yellow oil; dP(109.3 MHz, CDCl3) 20.8;
dH(400MHz, CDCl3) 4.02 (1 H, t, JPH 24.7, a-CH); dC(100.63 MHz,
Dimethyl 1-methylpyrrol-2-ylmethylphosphonate 7f (0.15 g), gen-
erated after the addition of the water, was isolated as a colourless
oil; dP(109.3 MHz, CDCl3) 27.4; dH(400 MHz, CDCl3) 3.12 (2 H,
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CDCl3) 40.1 (t, JPC 134, a-CH); m/z (EI) 314.0143 (M+.
C9H16O6P2S requires 314.0143).21
Tetramethyl 1-(thiophen-3-yl)ethane-1,1-bisphosphonate 15a
was isolated as a pale yellow oil; dP(109.3 MHz, CDCl3) 24.7;
dH(270 MHz, CDCl3) 1.86 (3 H, t, JPH 16, Me); dC(67.9 MHz,
CDCl3) 18.0 (t, JPC 6, Me), 44.3 (t, JPC 140, a-C); m/z (EI) 328.0299
(M+. C10H18O6P2S requires 328.0299).21
3-ylmethane-1,1-bisphosphonate 16c to be isolated as a pale yellow
oil; dP(109.3 MHz, CDCl3) 21.2; dH(400 MHz, CDCl3) 3.97 (1 H, t,
JPH 24.6, a-CH); dC(100.63 MHz, CDCl3) 34.9 (t, JPC 136, a-CH);
mmax(CH2Cl2)/cm−1 2957 cm−1 C≡C–H, 2853 cm−1 CH2OCH2,
−1
1254 cm−1 P O, 1031 cm P–O; m/z (ESI) 389.0531 (M + Na+.
=
C13H20O8P2Na requires 389.0531).21
X-Ray crystallography
Reaction of dimethyl furan-3-carbonylphosphonate 2b with
trimethyl phosphite
Further details are provided within the ESI.† CCDC reference
numbers 648419. For crystallographic data in CIF or other
electronic format, see DOI: 10.1039/b717130g
A solution of trimethyl phosphite (2.38 g, 19 mmol) and the
phosphonate 2b (1.90 g, 9.3 mmol) in dry toluene (30 cm3) was
◦
heated at 100 C for 12 h under an atmosphere of dry nitrogen.
Acknowledgements
Volatile components were then removed in vacuo (50 ◦C at
0.005 mmHg). 31P NMR spectroscopy showed the major products
to be the ylidic phosphonate 14b [dP(CDCl3) 53.6 ppm (d, JPP
92) and 31.8 ppm (d, JPP 92)] (ca. 45%) and its decomposition
products 15b (ca. 12%) and 16b (ca. 22%). A small quantity
of the phosphate-phosphonate 18b (ca. 10%) had also been
formed. After decomposing the ylide 14b by the addition of
water, the reaction products were isolated by column chromatog-
raphy on silica gel using ethyl acetate–methanol mixtures as the
eluent.
We thank the EPSRC National Crystallography Service,
Southampton for data collection and Mr Majid Motevalli for
his help in determining the X-ray crystal structure of the 2,4-DNP
derivative of 20b.
Notes and references
1 D. V. Griffiths, J. E. Harris, K. Karim and B. J. Whitehead, ARKIVOC,
2000, 1, 304.
2 D. V. Griffiths, P. A. Griffiths, K. Karim and B. J. Whitehead, J. Chem.
Soc., Perkin Trans. 1, 1996, 555.
3 D. V. Griffiths, K. Karim and B. J. Whitehead, Zh. Obshch. Khim., 1993,
63, 2245.
4 D. V. Griffiths, P. A. Griffiths, K. Karim and B. J. Whitehead, J. Chem.
Res., Synop., 1996, 176, (J. Chem. Res, Miniprint, 1996, 901).
5 D. V. Griffiths, P. A. Griffiths, B. J. Whitehead and J. C. Tebby, J. Chem.
Soc., Perkin Trans. 1, 1992, 479.
6 D. V. Griffiths, K. Karim and J. E. Harris, J. Chem. Soc., Perkin Trans.
1, 1997, 2539.
7 X. Jiao and W. G. Bentrude, J. Am. Chem. Soc., 1999, 121, 6088
(supporting information JA984460S).
8 R. V. Hoffman and H. Shechter, J. Am. Chem. Soc., 1971, 93, 5940;
R. V. Hoffman and H. Shechter, J. Am. Chem. Soc., 1978, 100, 7934.
9 R. Herges, Angew. Chem., Int. Ed. Engl., 1994, 33, 255; D. M. Benoit,
University of Ulm, Germany, personal communication.
10 R. Albers and W. Sander, Liebigs Ann./Recl., 1997, 897.
11 Data have been deposited with the Cambridge Crystallographic Data
Centre as CCDC 648419; for crystallographic data in CIF or other
electronic format, see DOI: 10.1039/b717130g.
Dimethyl 1-(dimethoxyphosphoryloxy)-1-(furan-3-yl)methyl-
phosphonate 18b was isolated as a pale yellow oil; dP(109.3 MHz,
CDCl3) 1.7 (d, JPP 33) and 19.3 (d, JPP 33); dH(400 MHz, CDCl3)
5.62 (1 H, dd, JPH 13 and 10, a-CH); dC(100.63 MHz, CDCl3)
67.0 (dd, JPC 180 and 6, a-CH); m/z (ESI) 337.0217 (M + Na+.
C9H16O8P2Na requires 337.0218).21
Tetramethyl furan-3-ylmethane-1,1-bisphosphonate 16b was iso-
lated as a viscous pale yellow oil (found: C, 36.5; H, 5.4%.
C9H16O7P2 requires C, 36.25; H, 5.41%); dP(109.3 MHz, CDCl3)
21.2; dH(400 MHz, CDCl3) 3.77 (1 H, t, JPH ∼24,23 a-CH);
dC(100.63 MHz, CDCl3) 34.9 (t, JPC 136, a-CH); m/z (ESI)
321.0263 (M + Na+. C9H16O7P2Na requires 321.0269).21
Tetramethyl 1-(furan-3-yl)ethane-1,1-bisphosphonate 15b was
isolated as a viscous pale yellow oil; dP(109.3 MHz, CDCl3) 24.6;
dH(270 MHz, CDCl3) 1.73 (3 H, t, JPH 16, Me); dC(69.7 MHz,
CDCl3) 16.2 (t, JPC 6, Me), 39.4 (t, JPC 136, a-C); m/z (EI) 312
(M +. C10H18O7P2 requires 312).21
12 R. V. Hoffman, G. G. Orphanides and H. Shechter, J. Am. Chem. Soc.,
1978, 100, 7927.
13 D. M. Birney, J. Am. Chem. Soc., 2000, 122, 10917; T. Khasanova and
R. S. Sheridan, J. Am. Chem. Soc., 1998, 120, 233.
Reaction of dimethyl 2-(prop-2-ynyloxymethyl)furan-3-
carbonylphosphonate 2c with trimethyl phosphite
14 Our studies of the carbenes generated from dialkyl benzoylphospho-
nates have shown that intermolecular trapping by trialkyl phosphites
can even compete effectively with intramolecular insertion into an
adjacent substituent if the quantity of solvent present is limited.
15 D. V. Griffiths, Y.-K. Cheong, P. Duncanson, J. E. Harris, H. V. Taylor,
manuscript in preparation.
16 O. E. O. Hormi and R. Sjholm, Synth. Commun., 1990, 20, 3015.
17 J. E. Semple, P. C. Wang, Z. Lysenko and M. M. Joullie, J. Am. Chem.
Soc., 1980, 102, 7505.
To a solution of the phosphonate 2c (3.0 g, 11 mmol) in
dry toluene (30 cm3) was added trimethyl phosphite (2.72 g,
22 mmol) and the mixture heated at 100 ◦C for 12 h under
an atmosphere of dry nitrogen. Volatile components were then
removed under reduced pressure (40 ◦C at 0.005 mmHg) and
the residue analysed by 31P NMR spectroscopy. This showed the
formation of the ylidic phosphonate 14c [dP(CDCl3) 52.1 ppm
(d, JPP 98) and 30.6 ppm (d, JPP 98)] together with some of
its hydrolysis product 16c. A small quantity of the phosphate-
phosphonate 18c [dP(CDCl3) 19.3 ppm (d, JPP 34) and 1.9 ppm
(d, JPP 34)] had also been formed. Column chromatography on
silica gel using ethyl acetate–methanol mixtures as the eluent
enabled a sample of tetramethyl 2-(prop-2-ynyloxymethyl)furan-
18 A. Krutosˇ´ıkova´, J. Kova´c, J. Rentka and M. Cakrt, Collect. Czech.
Chem. Commun., 1974, 39, 767.
19 F. Faigl and M. Schlosser, Tetrahedron, 1993, 49, 10271.
20 M. Curini, F. Epifano, M. Marcotullio, O. Rosati, Y. Guan and E.
Wenkert, Helv. Chim. Acta, 2000, 83, 755.
21 Further relevant information available in ESI†.
22 Several of these components require the presence of traces of moisture
in the reaction mixture so their formation can be suppressed by the
rigorous exclusion of moisture.
23 Signal partially obscured.
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