Stobbe-like condensation reactions of the anion of diethyl (2-carboethoxy)benzylphosphonate with some aromatic and heterocyclic aldehydes

Article abstract of DOI:10.1016/j.tet.2014.07.001

Deprotonation of diethyl (2-carboethoxy)benzylphosphonate using sodium ethoxide followed by reaction of the carbanion with furfural or aryl aldehydes gives diethyl (E)-1-(2′-carboxyphenyl)-1-phosphono-2-arylethenes that are formed via intramolecular Stobb

Full text of DOI:10.1016/j.tet.2014.07.001

Tetrahedron 70 (2014) 7241e7244
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Stobbe-like condensation reactions of the anion of diethyl (2-
carboethoxy)benzylphosphonate with some aromatic and
heterocyclic aldehydes
*
Matthias C. Eichler, David H. Grayson , Jonathan Huddleston, Joseph P. O’Neill
School of Chemistry, Trinity Biomedical Sciences Institute, Trinity College Dublin, 152-160 Pearse Street, Dublin 2, Ireland
a r t i c l e i n f o
a b s t r a c t
Article history:
Deprotonation of diethyl (2-carboethoxy)benzylphosphonate using sodium ethoxide followed by re-
action of the carbanion with furfural or aryl aldehydes gives diethyl (E)-1-(20-carboxyphenyl)-1-
phosphono-2-arylethenes that are formed via intramolecular Stobbe-like condensation reactions.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 24 April 2014
Received in revised form 26 June 2014
Accepted 1 July 2014
Available online 9 July 2014
Keywords:
Condensation
Aldehyde
Stobbe
Vinyl phosphonate
R
1. Introduction
O
The HornereEmmons condensation reactions of phosph-
onate-stabilised anions with aldehydes and ketones find wide-
spread use in the synthesis of alkenes.1 In connection with other
work we sought to synthesise the ester 1 via the apparently
simple HornereEmmons condensation of furfuraldehyde 2 with
the carbanion derived from the benzylic phosphonate 3. Very
poor yields of the desired ester 1 were obtained from this re-
action, and we were led to investigate the alkaline aqueous
phase that remained after extraction of the neutral ester from
the reaction mixture. Here we found a novel product, formed by
Stobbe-like reaction of the anion of the phosphonate 3 with the
aldehyde 2. In this paper, we provide evidence for the structure
of this unexpected product, propose a mechanism for its for-
mation and describe a number of analogous compounds that can
be obtained by reaction of the anion of the phosphonate 3 with
a range of different aldehydes.
CHO
O
CO Et
2
CO Et
2
3 R = PO(OEt)
4 R = Br
1
2
2
was deprotonated using ethanolic sodium ethoxide in dime-
thylformamide and then reacted with furfuraldehyde 2. The usual
work-up afforded ethyl (E)-2-[2-(2-furyl)ethenyl]benzoate 1 in
only w10% yield. However, acidification of the bright yellow
aqueous washings gave a solid product (64% after recrystallisation)
that was identified as being diethyl (E)-1-(20-carboxyphenyl)-1-
phosphono-2-(200-furyl)ethene 5.
HO C
PO(OEt)
2
2
2. Results and discussion
The phosphonate 3, which was prepared in the conventional
way from ethyl (2-bromomethyl)benzoate 4 and triethyl phosphite,
O
* Corresponding author. Tel.: þ353 (0)1 896 2021; e-mail address: dgrayson@tcd.
ie (D.H. Grayson).
http://dx.doi.org/10.1016/j.tet.2014.07.001
0040-4020/Ó 2014 Elsevier Ltd. All rights reserved.

7242
M.C. Eichler et al. / Tetrahedron 70 (2014) 7241e7244
The infrared spectrum of the vinylic phosphonate 5 shows nmax
9e12 by reacting the carbanion derived from the phosphonate 2
with, respectively, each of thiophene-2-carboxaldehyde, benzal-
dehyde, 4-methoxybenzaldehyde and 4-fluorobenzaldehyde. None
of these reactions yielded detectable quantities of the ‘normal’
HornereEmmons products.
1712 (C]O) and 1197 (PeO) cmꢀ1. The 1H NMR spectrum confirms
the presence of the phosphonate ester function and of the
substituted aryl and furyl ring systems, and shows a 1H doublet at
dH 7.18 ppm that can be assigned to the vinylic proton
b to the
phosphonate group. The 31P NMR spectrum of 5 exhibits a single
resonance at dP 17.8 ppm.
H CO C
PO(OEt)
R
HO C
3
2
PO(OEt)
2
2
2
There are a number of literature reports2e6 concerning the re-
lationship between JHeP and double bond geometry in vinyl phos-
phonates. For example, typical values that have been measured by Xu
et al.3 for JHeP in a series of vinyl phosphonates that are geometrical
isomersare 10e30Hzforcompoundswhere the vicinalvinylic proton
is cis to the phosphonate group and 30e50 Hz where it is trans.
The doublet due to the vinylic proton of the phosphonate 5 has
JHeP 23.6 Hz, falling clearly into the observed range for protons that
are cis to the phosphorus atom, hence we are confident in con-
cluding that the magnitude of this coupling constant is consistent
with the assigned (E)-geometry.
R
13 R = 4-MeO-C H
9
R = 2-thenyl
6
4
10 R = C H
14 R = 4-F-C H
6
5
6
4
11 R = 4-MeO-C H
6
4
12 R = 4-F-C H
6
4
15 R = (E)-C H CH=CH
6
5
We rationalise the formation of the vinylic phosphonate 5 on
the basis of the mechanism outlined in Scheme 1. Here, conden-
sation of the anion of the phosphonate 3 with furfuraldehyde 2
The vinyl phosphonates 11 and 12 that were obtained from 4-
methoxybenzaldehyde and from 4-fluorobenzaldehyde were not
at first obtained as solids, and were initially characterised by con-
version into their methyl esters 13 and 14 using diazomethane.
These esters were much more easily purified than the corre-
sponding acids. However, after standing for several months each of
the acids 11 and 12 solidified and could then be recrystallised.
Cinnamaldehyde also reacted with the anion of the phosphonate 3,
yielding the (E,E)-dienyl phosphonate 15, but pivalaldehyde failed
to react, and neither did pyrrole-2-carboxaldehyde or
cyclohexanone.
gives an intermediate
6 whose oxy-anion undergoes intra-
molecular reaction with the carboxylic rather than with the phos-
phonic ester function, to give the intermediate lactone 7. In a final
step, that is, reminiscent of the classical Stobbe condensation re-
action, b-elimination of carboxylate ion from 7 yields the sodium
salt 8 of the observed product 5.
O
O
NaO C
(EtO) P
2
H
PO(OEt)
2
2
P
(EtO)
2
PO(OEt)
2
O
O
O
-
S
O
O
CO Et
2
O
CO H
2
CO H
8
2
16
17
Scheme 1.
In principle, the intermediate 6 should possess the erythro-
configuration in order to deliver (E)-8. Bearing in mind that the
initial carbonecarbon bond-forming step is reversible,7 the oxy-
anion of the b-hydroxyphosphonate 6 (which is likely formed un-
der kinetic control) would then have to very quickly undergo
The formation of the thenyl-substituted vinylic phosphonate 9 is
of interest. Murty et al.9 have reported that when the benzylic
phosphonate 16, closely related to the phosphonate 3, is reacted
with thiophene-2-carboxaldehyde in THF in the presence of 2 equiv
of potassium hydroxide, the ‘normal’ HornereEmmons acid 17 is
formed in 80% yield. In this instance the course of the reaction is
dictated by the fact that the carboxylate ion already present in the
deprotonated phosphonate 16 does not act as an internal electro-
phile towards the oxy-anion intermediate formed during the
reaction.
intramolecular cyclisation to lactone 7 since the thermodynami-
cally more stable threo-configured
b-hydroxyphosphonate oxy-
anion usually8 prevails in HornereEmmons reactions, leading to
the formation of trans-alkenes. Alternatively, an E1CB pathway
proceeding from either stereochemistry of the initial adduct 6 via
a phosphonate anion derived from lactone 7 is plausible, although
this then requires that the product 8 represents the thermody-
namic outcome, as must the analogous products 9e12.
3. Conclusions
The reaction appears to be fairly general for heteroaryl and aryl
aldehydes, since we have obtained (Table 1) the analogous products
Intramolecular trapping by a neighbouring carboethoxy group
of the intermediate oxy-anion formed in the first stage of a Hor-
nereEmmons reaction between an aldehyde and the anion of
diethyl (2-carboethoxy)benzylphosphonate 3 diverts the reaction
from its normal course, and leads to the formation of Stobbe-like
products via the intervention of a presumed intermediate lactone.
Table 1
Reactions of aldehydes with the anion of diethyl (2-carboethoxy)benzylphospho-
nate to yield vinylic phosphonates
Aldehyde
Vinyl phosphonate
% Yielda
Furan-2-carboxaldehyde
Thiophene-2-carboxaldehyde
Benzaldehyde
4-Methoxybenzaldehyde
4-Fluorobenzaldehyde
Cinnamaldehyde
5
9
64
70
89
79
87
53
0
4. Experimental
4.1. General
10
11
12
15
d
d
2,2-Dimethylpropanal
Pyrrole-2-carboxaldehyde
Unless otherwise stated, 1H, 13C, 19F and 31P NMR spectra were
recorded for solutions in CDCl3 using a Bruker Avance DPX
400 MHz spectrometer. Coupling constants are recorded in hertz.
0
a
Yields of analytically pure materials after recrystallisation.

M.C. Eichler et al. / Tetrahedron 70 (2014) 7241e7244
7243
Assignments were verified where appropriate by 1He1H COSY,
1He13C COSY, HMBC and DEPT experiments. IR spectra were
recorded for Nujol mulls (N) or liquid films (L) between sodium
chloride plates using a Mattson FT-IR spectrometer. Mass spectra
were obtained under electrospray conditions using a Micromass
time-of-flight instrument. Melting points (uncorrected) were
measured in unsealed capillary tubes using an Electrothermal
IA9100 apparatus. Thin layer chromatography was carried out using
Merck Kieselgel 60F254 0.2 mm silica gel plates. Column chroma-
tography was carried out using Merck Kieselgel 60 (70e230 mesh)
silica gel. All solvents were dried and distilled before use. Organic
extracts of reaction products were dried over anhydrous magne-
sium sulfate. Combustion analyses were obtained from the Micro-
analytical Laboratory, University College, Dublin.
H-40 aryl and H-500 furyl), 7.97 (1H, d, J 8.0, H-60) and 12.70 (1H, s,
exch D2O, CO2H) ppm; dC (100.6 MHz) 16.1 (d, 3JCeP 6.8, OCH2CH3),
2
2
61.4 (d, JCeP 5.8, OCH2CH3), 61.9 (d, JCeP 5.8, OCH2CH3), 112.1 (C-
400), 113.6 (C-300), 128.0 (d, 1JCeP 187.6, C-1), 128.01 (C-50), 128.3 (d,
3
3
2JCeP 11.7, C-2), 130.3 (d, JCeP 4.9, C-30), 130.5 (C-60), 131.0 (d, JCeP
4.9, C-10), 132.1 (C-40), 136.6 (d, 2JCeP 5.8, C-20), 144.6 (C-500), 150.6 (d,
3JCeP 27.2, C-200) and 167.4 (CO2H) ppm; dP (162 MHz) 17.8 ppm.
Ethyl (E)-2-[2-(2-furyl)ethenyl]benzoate12 1 (0.1 g; 10%) was
obtained from the neutral extract as an oil, nmax (L) 1720 cmꢀ1
; dH
(300 MHz) 3.90 (3H, s, CO2CH3), 6.41 (2H, overlapping ms, H-30 and
H-40), 6.80 (1H, J 18.0, vinyl) and 7.21e7.90 (6H, ms, vinyl H, ArH and
H-50) ppm.
4.6. Diethyl (E)-[1-(o-carboxyphenyl)-2-(20-thenyl)vinyl]
phosphonate 9
4.2. Ethyl (2-bromomethyl)benzoate 4
From thiophene-2-carboxaldehyde (0.42 g; 4 mmol) there was
obtained, after recrystallisation from acetone, the title compound 9
(1.02 g; 70%) as a solid, mp 197e200 ꢁC; [Found C 55.54, H 5.33%.
A mixture of ethyl o-toluate (15 g, 91.5 mmol), N-bromosucci-
nimide (19.6 g, 110 mmol) and AIBN (60 mg) was refluxed in CCl4
(250 mL) for 2 h to give the bromo-ester 4 as a colourless oil,
bp 92e94 ꢁC/0.1 mmHg (lit.10 bp 100e105 ꢁC/1.0 mmHg), nmax (L)
C
17H19O5PS requires C 55.74, H 5.19%]; nmax (N) 1713, 1605, 1570,
1203,1161,1138,1058,1027 cmꢀ1
;
dH 1.15 (3H, t, J 7.5, OCH2CH3),1.19
1730 cmꢀ1
;
dH 1.44 (3H, t, J 7.3, CO2CH2CH3), 4.43 (2H, q, J 7.3,
(3H, t, J 7.5, OCH2CH3), 3.90e4.10 (4H, m, OCH2CH3), 6.99 (1H, ap-
parent t, J 4.4, H-400), 7.18 (1H, d, J 7.5, H-30), 7.33 (1H, d, J 3.4, H-300),
7.46 (1H, d, J 4.8, H-500), 7.50e7.70 (3H, m, H-2, H-40 and H-50), 8.01
(1H, d, J 7.5, H-60) and 12.65 (1H, s, exch D2O, CO2H) ppm; dC
CO2CH2CH3), 4.98 (2H, s, CH2Br), 7.35e7.43 (1H, m, H-5), 7.44e7.53
(2H, m, H-3 and H-4) and 7.98 (1H, d, J 7.5, H-6) ppm.
3
2
4.3. Diethyl (2-carboethoxy)benzylphosphonate 3
(100.6 MHz): d 16.1 (d, JCeP 5.8, OCH2CH3), 61.3 (d, JCeP 4.9,
OCH2CH3), 61.8 (d, 2JCeP 5.8, OCH2CH3), 126.6 (C-400), 127.8 (C-1, 1JCeP
188), 128.7 (C-50), 130.6 (C-500), 131.0 (C-60), 131.3 (d, 3JCeP 4.9, C-30),
Ethyl (2-bromomethyl)benzoate 4 (15 g; 62 mmol) and triethyl
phosphite (11 g; 66 mmol) were heated together without solvent at
160 ꢁC during 24 h. Distillation yielded diethyl (2-carboethoxy)
3
2
131.7 (d, JCeP 4.9, C-10), 132.6 (C-40), 132.8 (C-300), 134.1 (d, JCeP
2
3
12.6, C-2), 135.7 (d, JCeP 6.8, C-20), 138.4 (d, JCeP 25.3, C-200) and
167.2 (CO2H) ppm; dP (162 MHz) 18.1 ppm.
benzylphosphonate
bp 138e140 ꢁC/0.1 mmHg (lit.11 bp 170e174 ꢁC/0.1 mmHg), nmax (L)
1718 and 1267 cmꢀ1
dH 1.21 (6H, t, J 7.2, OCH2CH3), 1.40 (3H, t, J 7.3,
3
(13.6 g; 90%) as
a
colourless oil,
;
4.7. Diethyl (E)-[1-o-carboxyphenyl-2-phenylvinyl]phospho-
nate 10
2
CO2CH2CH3), 3.81 (2H, d, JHeP 23.2, ePCH2), 3.93e4.05 (4H, m,
OCH2CH3), 4.36 (2H, q, J 7.2, CO2CH2CH3), 7.27e7.34 (1H, m, H-5),
7.35e7.48 (2H, m, H-3 and H-4) and 7.87 (1H, d, J 8.0, H-6) ppm.
Following the general procedure, benzaldehyde (0.42 g;
4 mmol) gave a crude acidic product that was recrystallised from
acetone to afford the title compound 10 (1.29 g; 89%) as a solid,
mp 181e183 ꢁC; [Found C 63.12, H 5.90%. C20H23O5P requires C
63.33, H 5.83%]; nmax (N) 1716, 1615, 1593, 1570, 1201, 1162, 1139,
4.4. General procedure for reactions between diethyl (2-
carboethoxy)benzylphosphonate 3 and an aldehyde
Diethyl (2-carboethoxy)benzylphosphonate 3 (1.2 g; 4 mmol) in
dry DMF (5 mL) was added to ethanolic sodium ethoxide (1 M;
12 mmol; 12 mL) at room temperature under nitrogen. After 5 min
an aldehyde (4 mmol; neat or dissolved in a little DMF) was added
and the mixture was stirred during 1 h. It was then diluted with
water, and neutral products and residual starting materials were
extracted using ether. The aqueous phase was then acidified to
pH¼1 using concentrated hydrochloric acid and extracted using
ethyl acetate to give acidic products. Each of these organic extracts
was washed with brine, dried and evaporated. The crude neutral
fraction was analysed by means of 1H NMR spectroscopy. The acidic
product generally solidified and was then further purified by
recrystallisation, except where noted below.
1061, 1031 cmꢀ1
; dH 1.13e1.22 (6H, m, OCH2CH3), 3.90e4.05 (4H, m,
OCH2CH3), 7.00e7.13 (3H, m, H-30, H-200 and H-600), 7.15e7.25 (3H,
m, H-300, H-400 and H-500), 7.38 (1H, d, 3JHeP 24.6, H-2 vinyl), 7.48 (1H,
t, J 7.5, H-50), 7.54 (1H, t, J 7.5, H-40), 7.95 (1H, d, J 7.5, H-60) and 12.80
3
(1H, s, exch D2O, CO2H) ppm; dC (100.6 MHz) 16.1 (d, JCeP 5.8,
OCH2CH3), 61.4 (d, 2JCeP 5.8, OCH2CH3), 61.8 (d, 2JCeP 5.8, OCH2CH3),
128.0 (C-50), 128.3 (C-300 and C-500), 128.8 (C-400), 129.7 (C-200 and C-
3
1
600), 130.5 (C-30 and C-60), 131.8 (d, JCeP 3.9, C-10), 131.83 (d, JCeP
182.7, C-1), 132.3 (C-40), 134.8 (d, 3JCeP 22.4, C-100), 136.5 (d, 2JCeP 6.8,
2
C-20), 140.3 (d, JCeP 9.7, C-2) and 167.7 (CO2H) ppm; dP (162 MHz)
17.9 ppm.
4.8. Diethyl (E)-[1-(o-carboxyphenyl)-2-(4-methoxyphenyl)
vinyl]phosphonate 11
4.5. Diethyl (E)-[1-o-carboxyphenyl-2-(20-furyl)vinyl]phos-
phonate 5
From 4-methoxybenzaldehyde (0.54 g; 4 mmol) there was ob-
tained the title compound 11 as a viscous oil (1.24 g; 79%) that very
slowly solidified and that could then be recrystallised from EtOAc/
Et2O, mp 118e120 ꢁC; nmax (N) 1711, 1616, 1605, 1571, 1178, 1128,
Following the general procedure, 2-furaldehyde (0.38 g;
4 mmol) gave a crude acidic product that was recrystallised from
acetone to afford the title compound 5 (0.89 g; 64%) as a solid,
mp 208e210 ꢁC; [Found C 58.20, H 5.51%. C17H19O6P requires C
58.27, H 5.47%]; nmax (N) 1712, 1614, 1593, 1571, 1209, 1162, 1141,
1052,1024, 991 cmꢀ1
; dH 1.16 (3H, t, J 7.0, OCH2CH3),1.29 (3H, t, J 7.0,
OCH2CH3), 3.69 (3H, s, eOCH3), 3.90e4.20 (4H, m, OCH2CH3), 6.75
(2H, d, J 8.8, H-300 and H-500), 6.97 (2H, d, J 8.8, H-300 and H-500), 7.09
(1H, d, J 8, H-30), 7.31 (1H, d, 3JPeH 24.6, H-2), 7.48 (1H, t, J 7.5, H-50),
7.56 (1H, t, J 7.5, H-40), 7.95 (1H, d, J 7, H-60) and 12.74 (1H, s,
exch D2O, eCO2H) ppm; dC (100.6 MHz) 16.1 (d, 3JPeC 5.8, CH3), 55.1
1054, 1024 cmꢀ1
; dH 1.15 (3H, t, J 7.0, OCH2CH3), 1.19 (3H, t, J 7.0,
OCH2CH3), 3.90e4.05 (4H, m, OCH2CH3), 5.86 (1H, d, J 3.5, H-300
furyl), 6.40 (1H, dd, J 3.5 and 2.0, H-400 furyl), 7.18 (1H, d, 3JHeP 23.6,
H-2), 7.18 (1H, d, J 7.5, H-30), 7.50 (1H, t, J 7.5, H-50), 7.55e7.67 (2H, m,
2
2
(OCH3), 61.2 (d, JPeC 4.9, CH2), 61.7 (d, JPeC 5.8, CH2), 113.8 (C-300

7244
M.C. Eichler et al. / Tetrahedron 70 (2014) 7241e7244
3
1
and C-500), 127.3 (d, JPeC 23.3, C-100), 128.0 (C-50), 128.7 (d, JPeC
1570, 1192, 1161, 1132, 1051, 1024 cmꢀ1
; dH 1.25 (6H, m, OCH2CH3),
184.6, C-1), 130.5 (C-60), 130.6 (d, 3JPeC 5.8, C-30), 131.4 (C-200 and C-
3.78 (3H, s, CO2CH3), 4.08 (4H, m, OCH2CH3), 6.84 (2H, t, J 8.5, H-300
and H-50), 7.03 (2H, dd, J 8.5 and 5.8, H-200 and H-600), 7.18 (1H, d, J
7.5, H-30), 7.40e7.70 (3H, m, H-2, H-40 and H-50) and 7.98 (1H, d, J
7.5, H-60) ppm; dC2(100.6 MHz) 15.8 (d, 3JCeP 5.8, OCH2CH3), 51.6 (s,
3
2
600), 131.9 (d, JPeC 3.9, C-10), 132.3 (C-40), 136.8 (d, JPeC 6.8, C-20),
2
140.1 (d, JPeC 10.7, C-2), 159.7 (C-400) and 167.7 (C]O) ppm; dP
(162 MHz) 18.6 ppm; HRMS (ESI): MHþ, found 391.1314. C20H24O6P
requires 391.1311.
2
CO2CH3), 61.6 (d, JCeP 5.8, OCH2CH3), 61.9 (d, JCeP 5.8, OCH2CH3),
2
4
114.9 (d, JCeF 21.4, C-300 and C-500), 127.6 (d, JCeP 2.9, C-50), 129.1
(part of d for C-1), 130.2e130.5 (m, C-30 and C-60), 130.6e131 (m, C-
10 and C-100), 131.4 (d, 3JCeF 8.7, C-200 and C-600) 131.9 (d, 5JCeP 1.9, C-
4.9. Diethyl (E)-[1-(o-carbomethoxyphenyl)-2-(4-
methoxyphenyl)vinyl]phosphonate 13
40), 135.9 (d, JCeP 6.8, C-20), 140.5 (d, JCeP 9.7, C-2), 162.2 (d, 1JCeF
250.7, C-400) and 166.9 (CO2CH3) ppm; dP (162 MHz) 18.2 ppm; dF
(376.4 MHz) ꢀ111.8 ppm; HRMS (ESI): MHþ, found 393.1277.
2
2
A portion of the acid 11 (1.0 g, 2.55 mmol) was dissolved in ethyl
acetate and methylated using a slight excess of ethereal diazo-
methane. Column chromatography of the oily product afforded the
title compound 13 as a colourless oil (0.36 g); nmax (L) 1726, 1604,
C
20H23FO5P requires 393.1267.
1572, 1180, 1130, 1051, 1026 cmꢀ1
; dH 1.25 (6H, m, OCH2CH3), 3.74
4.12. Diethyl (E,E)-[1-o-carboxyphenyl-4-phenyl-buta-1,3-di-
enyl]phosphonate 15
(3H, s, OCH3), 3.77 (3H, s, CO2CH3), 4.08 (4H, m, OCH2CH3), 6.68 (2H,
d, J 8.5, H-300 and H-500), 6.98 (2H, d, J 8.5, H-200 and H-600), 7.20 (1H, d,
J 7.5, H-30), 7.43 (1H, t, J 7.5, H-50) 7.47e7.60 (2H, m, H-2 and H-40)
From cinnamaldehyde (0.53 g; 4 mmol) there was obtained after
recrystallisation from acetone the title compound 15 (0.82 g; 53%) as
a solid, mp 184e186 ꢁC; [Found C 64.19, H 6.11%. C20H23O5P requires
C 64.17, H 6.15%]; nmax (N) 1718, 1620, 1561, 1207, 1163, 1139, 1061,
and 7.98 (1H, d, J 7.5, H-60) ppm; dC (100.6 MHz): 15.8 (d, 3JCeP 6.8,
d
OCH2CH3), 51.5 (CO2CH3), 54.7 (OCH3), 61.5 (d, 2JCeP 5.8, OCH2CH3),
61.8 (d, 2JCeP 6.8, OCH2CH3), 113.2 (C-300 and C-5),127.1 (d, 3JCeP 23.3,
C-100), 127.3 (d, 1JCeP 186.6, C-1), 127.4 (C-50), 130.3 (C-60), 130.6 (d,
4JCeP 5.8, C-30), 131.0 (d, 3JCeP 4.9, C-10), 131.3 (C-200 and C-600), 131.9
(C-40), 136.4 (d, 2JCeP 7.8, C-20), 141.5 (d, 2JCeP 10.7, C-2), 159.6 (C-400)
and 167.1 (CO2CH3) ppm; dP (162 MHz) 19.0 ppm; HRMS (ESI):
MHþ, found 405.1462. C21H26O6P requires 405.1468.
1035 cmꢀ1
; dH 1.15 (3H, t, J 7.0, OCH2CH3), 1.20 (3H, t, J 7.0,
OCH2CH3), 3.90e4.05 (4H, m, OCH2CH3), 6.41 (1H, ddd, J 15.6, 11.0
and 2.5, H-3), 7.08 (1H, d, J 15.6, H-4), 7.12e7.24 (2H, m, H-2 and H-
30), 7.25e7.35 (5H, m, H-200, H-300, H-400, H-500 and H-600), 7.50 (1H, dt,
J 7.5, 7.5 and 1.0, H-50), 7.61 (1H, t, J 7.5, H-40), 7.91 (1H, d, J 7.5, H-60)
and 12.78 (1H, s, exch D2O, CO2H) ppm; dC (100.6 MHz) 16.1 (d, 3JCeP
4.10. Diethyl (E)-[1-(o-carboxyphenyl)-2-(4-fluorophenyl)vi-
nyl]phosphonate 12
2
2
5.8, OCH2CH3), 61.3 (d, JCeP 5.8, OCH2CH3), 61.7 (d, JCeP 5.8,
OCH2CH3), 123.8 (d, 3JCeP 21.4, C-3), 126.9 (C-300 and C-500), 128.0 (C-
50), 128.9 (C-200, C-400 and C-600), 130.1 (C-60), 131.0 (d, 1JCeP 186.6, C-
4-Fluorobenzaldehyde (0.5 g; 4 mmol) gave the title compound
12 as a viscous oil (1.31 g; 87%), which very slowly became a solid
that could be recrystallised from CH2Cl2, mp 176e178 ꢁC; nmax (N)
3
3
1), 131.1 (d, JCeP 4.9, C-30), 131.5 (C-40), 132.2 (d, JCeP 4.9, C-10),
135.3 (d, 2JCeP 7.8, C-20), 135.9 (C-100), 139.0 (C-4), 141.4 (d, 2JCeP 9.7,
C-2), 167.9 (CO2H) ppm; dP (162 MHz) 17.9 ppm.
1711, 1615, 1593, 1569, 1201, 1162, 1139, 1060 cmꢀ1
; dH 1.17 (3H, t, J
7.2, OCH2CH3), 1.31 (3H, t, J 7.2, OCH2CH3), 3.98e4.12 (2H, m,
OCH2CH3), 4.16 (2H, apparent quintet, J 7.2, OCH2CH3), 6.82 (2H,
apparent t, J 8.5, H-300 and H-500), 7.00 (2H, dd, J 8.9 and 5.5, H-200 and
H-600), 7.13 (1H, d, J 7.5, H-30), 7.43e7.55 (3H, m, H-2, H-40 and H-50)
Acknowledgements
We thank Trinity College Dublin for financial support to M.C.E.,
Dr. Martin Feeney for the HRMS data and Dr. John O’Brien for the
NMR spectra.
3
and 8.08 (1H, d, J 7.5, H-6) ppm; dC (100.6 MHz) 15.7 (d, JCeP 6.8,
OCH2CH3), 15.8 (d, 3JCeP 6.8, OCH2CH3), 62.3 (d, 2JCeP 5.8, OCH2CH3),
2
2
62.7 (d, JCeP 5.8, OCH2CH3), 114.9 (d, JCeF 22.2, C-300 and C-500),
127.9 (d, 5JCeP 2.9, C-50), 129.4 (d, 1JCeP 187.6, C-1), 130.1 (d, 3JCeP 4.9,
3
4
C-30), 130.3 (dd, JCeP 22.8 and JCeF 3.4, C-100), 131.0 (s, C-60), 131.5
(d, 3JCeF 8.7, C-200 and C-600: C-10 obscured by these signals), 132.2 (s,
C-40),135.2 (d, 2JCeP 6.8, C-20),140.6 (d, 2JCeP 10.7, C-2),162.3 (d, 1JCeF
250.7, C-400) and 169.3 (C]O) ppm; dP (162 MHz) 18.2 ppm; dF
(376.4 MHz) ꢀ111.4 ppm; HRMS (ESI): MHþ, found 379.1108.
References and notes
1. For a comprehensive review see: Savignac, P.; Iorga, B. Modern Phosphonate
Chemistry; CRC: Boca Raton, 2003.
2. Goulioukina, S.; Doligna, T. M.; Beletskaya, I. P.; Henry, J.-C.; Lavergne, D.; Ra-
tovelomanana-Vidal, V.; Genet, J.-P. Tetrahedron: Asymmetry 2001, 319e327.
3. Xu, X.; Flavin, M. T.; Xu, Z.-Q. J. Org. Chem. 1996, 61, 7697e7701.
C
19H21FO5P requires 379.1111.
ꢀ
4. Aboujaoude, E. E.; Lietje, S.; Collignon, N.; Teulade, M. P.; Savignac, P. Tetrahe-
dron Lett. 1985, 26, 4435e4438.
5. Tavs, P.; Weitkamp, H. Tetrahedron 1970, 26, 5529e5534.
4.11. Diethyl (E)-[1-(o-carbomethoxyphenyl)-2-(4-
fluorophenyl)vinyl]phosphonate 14
6. Griffin, C. E.; Mitchell, T. D. J. Org. Chem. 1965, 30, 1935e1939.
ꢁ
7. Lefebvre, G.; Seyden-Penne, J. J. Chem. Soc. D 1970, 1308e1309.
8. Stec, W. J. Acc. Chem. Res. 1983, 16, 411e417.
9. Murty, M. S. R.; Ramalingam, T.; Sabitha, G.; Yadav, J. S. Heterocycl. Commun.
2001, 7, 449e454.
10. Tobia, D.; Baranski, J.; Rickborn, B. J. Org. Chem. 1989, 54, 4253e4256.
11. Kaur, K.; Lan, M. J. K.; Pratt, R. F. J. Am. Chem. Soc. 2001, 123, 10436e10443.
12. O’Neill, J. P. Ph.D. Thesis; University of Dublin, 1995.
A portion of 12 (0.74 g, 1.95 mmol) was dissolved in ethyl acetate
and methylated using a slight excess of ethereal diazomethane.
Column chromatography of the crude oily product afforded the title
compound 14 as a colourless oil (0.45 g); nmax (L) 1726, 1622, 1601,