A new synthesis of α-ketophosphonates

Article abstract of DOI:10.1055/s-2003-37341

α-Ketophosphonates are prepared from 2-alkyl-2-phosphonyl-1,3-dithianes.

Full text of DOI:10.1055/s-2003-37341

PAPER
357
A New Synthesis of -Ketophosphonates
a
b
a
A
K
N
ew Synthesis
o
a
f
α
-Ketoph
m
osphonates yar Afarinkia,* Andrew Faller, Andrew J. Twist
a
Department of Chemistry, King’s College, Strand, London WC2R 2LS, UK
Fax +44(20)78482810; E-mail: kamyar.afarinkia@kcl.ac.uk
b
GlaxoSmithKline, New Frontiers Science Park (North), Harlow, Essex CM19 5AW, UK
Received 22 November 2002
H
R
Abstract: α-Ketophosphonates are prepared from 2-alkyl-2-phos-
phonyl-1,3-dithianes.
a
S
S
P(O)(OEt)2
P(O)(OEt)2
S
S
Keywords: α-ketophosphonates, hydrolysis, 1,3-dithiane, phos-
phorus, alkylations
1
2
R = Me (2a, 78%); R = Et (2b, 76%); R = CH2Ph (2c, 80%); R = n-C6H13
2d, 74%); R = CH2CH=CH2 (2e, 75%); R = CH2CH2CH=CH2 (2f, 74%);
(
R = CH2CO2Et (2g, 81%); R = CH2CH2CH(OCH2CH2CH2O) (2h, 34%).
α-Ketophosphonates are one of the most interesting class-
Scheme 2 Reaction conditions: a) LDA, THF, –78 °C, Ar; then R-
Hal
es of organophosphorus compounds with many useful
1
synthetic applications. There are, however, only two gen-
eral methods for the preparation of α-ketophosphonates in
the literature. The first method is the Arbuzov reaction be-
its 2-position with a variety of electrophiles to afford 2a–
h (Scheme 2).
tween the corresponding acid chloride and alkylphospho-
1
nites or alkylphosphites. This is a useful method; Although α-ketophosphonates are generally speaking sta-
however, it is restricted in so far as only commercially or ble, lower molecular weight analogues are quite suscepti-
synthetically available acid chlorides can be used. The ble to hydrolysis. Therefore, we required a general
second method is the oxidation of the corresponding α- method for the hydrolysis of dithianes 2a–g, which did not
2
hydroxyphosphonates. This method is more general but cause a concurrent hydrolysis of the α-ketophosphonate
is still limited in the range of substrates that can be em- group. A number of methods failed to give satisfactory
ployed. As a result, the vast majority of preparations of α- means of hydrolysing the dithiane group. These included
ketophosphonates to date are restricted to those, which cerium ammonium nitrate (CAN), mercuric dichloride
5
lack complex molecular architecture and functional (HgCl ), various aqueous acids and wet silica gel. How-
2
groups.
ever, we discovered that dithianes 2a–g can be easily con-
verted into their corresponding α-ketophosphonates 3a–g
by careful hydrolysis using bromine and silver nitrate in
Here, we report a new and versatile synthesis under mild,
non-thermal conditions which cleanly and efficiently af-
fords a diverse range of α-ketophosphonates. The key ad-
vantage of this method is that a number of functional
groups are tolerated at the side chain. Therefore, a wider
and more functionally complex range of α-ketophospho-
nates can be prepared by this method.
6
aqueous acetonitrile (Scheme 3). These reactions afford-
ed satisfactory yields both on small scale (200 mg) and
medium scale (1 g). No chromatographic purification of
the α-ketophosphonate products was necessary as in all
cases, after the recommended workup procedure the prod-
1
13
31
ucts were obtained in pure form ( H, C and P NMR).
O
S
S
R
P(O)(OEt)2
R
S
S
P(O)(OEt)2
P(O)(OEt)2
Scheme 1
The procedure involves the alkylation of 2-(diethylphos-
3
,4
phonyl)-1,3-dithiane (1) followed by hydrolysis of the
corresponding dithiane to afford the required α-ketophos-
phonates (Scheme 1).
2
-(Diethylphosphonyl)-1,3-dithiane (1) is prepared on a
large scale from 1,3-dithiane in a one-pot two-step proce-
3
,4
dure. Compound 1 is easily and efficiently alkylated at
Synthesis 2003, No. 3, Print: 28 02 03.
Art Id.1437-210X,E;2003,0,03,0357,0360,ftx,en;P06402SS.pdf.
Scheme 3
©
Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

3
58
K. Afarinkia et al.
PAPER
A number of functional groups are compatible under these Diethyl 2-Methyl-1,3-dithian-2-ylphosphonate (2a)
Orange oil; yield: 2.11 g (78%).
conditions (Scheme 3). However, side-chains containing
an alkene functionality undergo concurrent bromination IR (liquid): 2978, 2925, 1239, 1053, 1022 (P–O, s), 964 (O–P–O,
–
1
bend) cm .
1
of the double bond. This can be avoided by using N-chlo-
rosuccinimide (NCS) in place of bromine. The use of this
6
H NMR (CDCl ): δ = 1.36 (t, 6 H, J = 7 Hz, OCH CH ), 1.52 (d,
3
HH
2
3
reagent is quite satisfactory; however, since succinimde is 3 H, JPH = 14 Hz, PCCH ), 1.76 (m, 1 H, 5-Hax), 2.14 (m, 1 H, 5-
3
H ), 2.54 (m, 2 H, 4-H and 6-H ), 3.67 (m, 2 H, 4-H and 6-H ),
obtained as an organic by-product, chromatographic sep-
aration of the desired α-ketophosphonates becomes nec-
eq
eq
eq
ax
ax
4
.26 (m, 4 H, CH CH ).
2 3
essary. When iodine is used in place of bromine the 13C NMR (CDCl
): δ = 16.9 (JPC = 6 Hz, CH
CH
), 24.4
3
2
3
(
CH CH CH ), 25.1 (J = 4 Hz, CCH ), 28.4 (SCH ), 40.9 (J
=
reactions are sluggish and afforded more impurities.
Therefore, chromatographic methods for purification are
necessary and the procedure is ultimately less efficient.
2
2
2
PC
3
2
PC
1
61 Hz, PC), 64.4 (JPC = 7 Hz, OCH2).
3
1
P NMR (CDCl ): δ = 20.7.
3
+
MS (EI): m/z = 270 (M , 56), 237 (15), 197 (6), 135 (34), 81 (15),
In summary, we have developed a method for the prepa-
ration of α-ketophosphonates starting from 2-(dieth-
ylphosphonyl)-1,3-dithiane. The method is general, very
mild and can be used to efficiently prepare a range of
functionalised α-ketophosphonates.
5
9 (100).
HRMS: m/z calcd for C H PO S : 270.0513; found: 270.0512.
9
19
3 2
Diethyl 2-Ethyl-1,3-dithian-2-ylphosphonate (2b)
Orange solid; yield: 2.16 g (76%); mp 50.5–52 ºC.
IR (CCl ): 2977, 2930 (C–H, s), 1284, 1239, 1059, 1026 (P–O, s),
952 (O–P–O, bend) cm .
4
NMR spectra were obtained in CDCl on Bruker AMX360 and
–1
3
AMX400 spectrometers operating respectively at 360 and 400 MHz
1H NMR (CDCl
H, JHH = 7 Hz, OCH CH ), 1.74 (m, 1 H, 5-H ), 1.90 (dq, 2 H,
): δ = 1.12 (t, 3 H, JHH = 7 Hz, CCH CH ), 1.35 (t,
3 2 3
1
13
31
for H, 90.6 and 101 MHz for C and 146 and 162 MHz for
P
6
2
3
ax
NMR spectroscopy. Chemical shifts are reported in ppm. Mass
spectra were obtained on a Jeol AX505W mass spectrometer using
electron impact (EI) and chemical ionisation (CI) techniques. Infra-
red spectra were recorded on a Perkin-Elmer 1600 FTIR instrument.
JHH = 7.5 Hz, JPH = 11 Hz, PCCH CH ), 2.11 (m, 1 H, 5-H ), 2.55
2
3
eq
(
m, 2 H, 4-Heq and 6-H ), 3.69 (m, 2 H, 4-H and 6-H ), 4.26 (m,
eq ax ax
4
H, OCH CH ).
2 3
1
3
C NMR (CDCl ): δ = 8.6 (J = 6 Hz, CCH CH ), 16.9 (J = 6
3
PC
2
3
PC
2
-Diethylphosphonate-1,3-dithiane (1)3,4
Hz, CH CH ), 24.6 (CH CH CH ), 27.8 (SCH ), 30.5 (J = 3 Hz,
2 3 2 2 2 2 PC
A solution of dithiane (6.00g, 0.05 mol) in benzene (50 mL) was
CCH CH ), 46.7 (J = 160 Hz, PC), 64.3 (JPC = 7.5 Hz, OCH2).
2 3 PC
added via a cannula to a stirred solution of N-chlorosuccinimide
31
P NMR (CDCl ): δ = 20.4.
3
(
6.70g, 0.05 mol) in benzene (100 mL) at r.t. and the resulting solu-
+
MS (EI): m/z = 284 (M , 25), 251 (6), 147 (100), 83 (35), 73 (52).
HRMS: m/z calcd for C H PO S : 284.0670; found: 84.0677.
tion was stirred overnight. Triethylphosphite (10.3 mL, 0.06 mol)
was added and the reaction mixture was warmed to 60 °C and main-
tained at that temperature for 4 h. The precipitate (succinimide) was
filtered off and the solvent was removed from the filtrate in vacuo.
1
0
21
3 2
Diethyl 2-Benzyl-1,3-dithian-2-ylphosphonate (2c)
Light-orange, low-melting solid; yield: 2.76 g (80%).
Et O was added to the resultant orange oil and last traces of succin-
2
imide were removed by filtration. The filtrate was concentrated in
vacuo and was purified by column chromatography (eluent:
EtOAc–petroleum ether, 1:1).
IR (CCl ): 2977, 2924 (C–H, s), 1733, 1239, 1054, 1024 (P–O, s),
4
–
1
9
64 (O–P–O, bend) cm .
1
H NMR (CDCl ): δ = 1.24 (t, 6 H, J = 7.0 Hz, OCH CH ), 1.53
3
HH
2
3
Yield: 8.71 g (68%).
(
m, 1 H, 5-H ), 1.94 (m, 1 H, 5-H ), 2.41 (m, 2 H, 4-H and 6-H ),
ax eq eq eq
1
H NMR (CDCl ): δ = 1.37 (t, 6 H, J = 7 Hz, 2 × OCH CH ), 1.99
3.06 (d, 2 H, JPH = 10.0 Hz, CH Ph), 3.61 (m, 2 H, 4-H and 6-Hax),
3
HH
2
3
2
a
x
(
m, 1 H, 5-H ), 2.11 (m, 1 H, 5-H ), 2.55 (m, 2 H, 4-H and 6-H ),
ax eq eq eq
4.18 (m, 4 H, CH CH ), 7.18–7.27 (m, 5 H, aromatic H).
2 3
3
.51 (m, 2 H, 4-H and 6-H ), 3.60 (d, 1 H, J = 19 Hz, PCH), 4.26
ax ax PH
13
C NMR (CDCl ): δ = 16.9 (J 5.8 Hz, CH CH ), 24.0
3
PC
2
3
(
m, 4 H, 2 × OCH2).
(
CH CH CH ), 28.0 (SCH ), 43.2 (J = 2.5 Hz, CH Ph), 46.7 (J
2 2 2 2 PC 2 PC
1
3
C NMR (CDCl ): δ = 16.9 (J = 6 Hz, CH CH ), 25.4
= 158.5 Hz, PC), 64.5 (JPC = 7.5 Hz, OCH ), 127.6 (aromatic CH),
3
PC
2
3
2
(
CH CH CH ), 26.5 (SCH ), 34.5 (J = 161 Hz, PC), 64.4 (JPC = 7
2 2 2 2 PC
127.8 (aromatic CH), 132.2 (aromatic CH), 134.7 (aromatic C).
Hz, OCH2).
31
P NMR (CDCl , 162 MHz): δ = 19.3.
3
3
1
4
P NMR (CDCl ): δ = 19.2 (Lit. 18.7 ppm).
3
+
MS (EI): m/z = 346 (M , 9), 255 (100), 209 (97), 135 (29), 91 (42).
Preparation of 2-Alkyl-2-diethylphosphonate-1,3-dithiane;
General Procedure
HRMS: m/z calcd for C15H23PO S : 346.0826; found: 346.0819.
3 2
LDA (0.02 mol, from commercially available solution in hexane–
THF) was added to a stirred solution of 2-diethylphosphonate-1,3-
dithiane (2.56 g, 0.01 mol) in THF (20 mL) maintained under anhyd
conditions at –78 °C. After 5 min the alkylating agent was added
Diethyl 2-Hexyl-1,3-dithian-2-ylphosphonate (2d)
Orange liquid; yield: 2.52 g (74%).
IR (film): 2955, 2924, 2855, (C–H, s), 1239, 1054, 1025 (P–O, s),
–1
9
82 (O–P–O, bend) cm .
(0.02 mol) and the reaction was stirred for further 30 min before be-
1
H NMR (CDCl ): δ = 1.03 (t, 3 H, J = 6.8 Hz, CH CH CH ),
ing allowed to warm to r.t. H O (10 mL) was added and the organic
3
HH
2
2
3
2
1
.43–1.51 (overlapping m, 8 H, CH CH CH CH CH ), 1.51 (t, 6 H,
products were extracted with Et O (2 × 10 mL). The combined ex-
2 2 2 2 3
2
JHH = 7.1 Hz, OCH CH ), 1.87–2.00 (overlapping m, 3 H, PCCH
tracts were dried over MgSO and concentrated in vacuo. The prod-
2
3
2
4
and 5-H ), 2.26 (m, 1 H, 5-H ), 2.69 (m, 2 H, 4-H and 6-Heq),
uct was purified by column chromatography (eluent: EtOAc).
ax
eq
eq
3
.85 (m, 2 H, 4-Hax and 6-H ), 4.40 (m, 4 H, CH CH ).
ax 2 3
1
3
C NMR (CDCl , 100 MHz): δ = 14.1 (J = 5.9 Hz, CH CH CH ),
3
PC
2
2
3
1
6.6 (JPC = 5.6 Hz, CH CH ), 22.6 (CH CH CH CH ), 23.4
2 3 2 2 2 3
Synthesis 2003, No. 3, 357–360 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
A New Synthesis of α-Ketophosphonates
359
+
(
(
(
3
CH CH CH CH CH ), 24.3 (SCH CH ), 27.6 (SCH ), 29.7
MS (EI): m/z = 342 (M , 7), 309 (18), 205 (100), 109 (15), 91 (53),
59 (27)
2
2
2
2
3
2
2
2
CH CH CH -CH CH ), 31.6 (CH CH CH CH CH ), 37.0
2
2
2
2
3
2
2
2
2
3
CCH CH ), 46.7 (J = 159.2 Hz, PC), 64.0 (JPC = 7.4 Hz, OCH2).
2
2
PC
HRMS: m/z calcd for C12H PO S : 342.0725; found: 342.0729.
2
3
5 2
1
P NMR (CDCl ): δ = 20.3.
3
+
Preparation of (1-Oxoalkyl)-diethylphosphonates; General
Procedure
MS (EI): m/z = 340 (M , 9), 203 (81), 119 (16), 83 (100).
HRMS: m/z calcd for C H PO S : 340.1296; found: 340.1298.
1
4
29
3
2
AgNO (0.760 g, 4.5 mmol) was added to a stirred solution of bro-
3
mine (0.64 g, 4.0 mmol) in CH CN (20 mL, 0.2 M solution) at 0 °C
3
Diethyl 2-[2-(1,3-Dioxolan-2-yl)ethyl]-1,3-dithian-2-ylphospho-
nate (2e)
Orange liquid; yield: 1.25 g (34%).
and stirred so that it formed a suspension. A mixture of CH CN–
3
H O (2mL–2mL) was added followed by the 2-alkyl-2-diethylphos-
2
phonate-1,3-dithiane (1.0 mmol). The solution was stirred for 30
min at 0 °C and then allowed to warm to r.t. and stirred for further
30 min. The solution was filtered and to the filtrate was added 10%
aqueous ammonium acetate (10 mL) and 10% aqueous sodium thio-
sulfate solutions (10 mL). The aqueous layer was extracted with
IR (film): 2974, 2924, 2851 (C–H, s), 12.38, 1053, 1022 (P–O, s),
–
1
9
53 (O–P–O, bend) cm .
1
H NMR (CDCl ): δ = 1.36 (t, 6 H, J = 7.1 Hz, OCH CH ), 1.72
3
HH
2
3
(
m, 1 H, 5-H ), 1.91–1.98 (overlapping m, 4 H, CCH CH ), 2.02–
a
x
2
2
Et O (3 × 20 mL) and the combined extracts were washed with
2
2
.16 (overlapping m, 3 H, 5 -H , 5 -H and 5-H ), 2.53 (m, 2 H, 4-
eq ax eq
brine (20 mL), H O (20 mL) and dried (MgSO ). The product was
2
4
Heq and 6-H ), 3.62–3.79 (overlapping m, 4 H, 4 -H and 6 -Heq
eq
eq
obtained after removal of the solvent in vacuo.
and 4-Hax and 6-H ), 4.09 (overlapping m, 2 H, 4 -Hax and 6 -Hax),
ax
4
.25 (m, 4 H, OCH CH ), 4.51 (t, 1 H, J = 2.3 Hz, OCHO).
2 3 HH
Diethyl Acetylphosphonate (3a)
Pale yellow liquid; yield: 141 mg (78%).
1
3
C NMR (CDCl ): δ = 17.0 (J = 5.5 Hz, CH CH ), 24.6
3
PC
2
3
(
CH CH CH ), 26.2 (C′H C′H C′H ), 27.9 (SCH ), 29.7 (J = 5.8
2 2 2 2 2 2 2 PC
IR (film): 2986 (C–H, s), 1711 (C=O, s), 1224 (P=O), 1023 (O–P,
s), 978 (O–P–O, bend) cm .
Hz, PCCH CH ), 31.5 (J = 2.4 Hz, PCCH CH ), 45.8 (J = 160.8
Hz, PC), 64.5 (JPC = 7.5 Hz, OCH CH ,), 67.3 (O′C′H C′H ), 102.5
OCO).
3
–1
2
2
PC
2
2
PC
2
3
2
2
1
H NMR (CDCl ): δ = 1.32 (t, 6 H, J = 7.1 Hz, OCH CH ), 2.43
3
HH
2
3
(
d, 3 H, JPH = 5.2 Hz, PCOCH ), 4.17 (m, 4 H, OCH ).
1
3
2
P NMR (CDCl ): δ = 20.1.
3
1
3
C NMR (CDCl ): δ = 16.8 (J = 5.6 Hz, OCH CH ), 31.0 (J =
PC
+
3
PC
2
3
MS (EI): m/z = 370 (M , 30), 337 (14), 233 (100), 175 (47), 147
5
9.6 Hz, PCOCH ), 64.3 (J = 7.3 Hz, OCH ), 209.2 (J = 171.6
3 PC 2 PC
(17), 127 (26), 100 (35), 87 (70).
Hz, CO).
HRMS: m/z calcd for C H PO S : 370.1037; found: 370.1039.
31
1
4
27
5 2
P NMR (CDCl ): δ = –1.9.
3
+
MS (EI): m/z = 180 (M , 18), 169 (16), 149 (41), 135 (100), 109
Diethyl 2-But-3-enyl-1,3-dithian-2-ylphosphonate (2f)
Orange liquid; yield: 2.29 g (74%).
(
79), 91 (53), 81 (83).
7
HRMS: m/z calcd C H PO : 180.0551; found: 180.0565.
IR (film): 2975, 2926 (C–H, s), 1285, 12.38, 1059, 1024 (P–O, s),
6
13
4
–
1
9
63 (O–P–O, bend) cm .
Diethyl Propionylphosphonate (3b)
Pale yellow liquid; yield: 154 mg (79%).
1
H NMR (CDCl ): δ = 1.36 (t, 6 H, J = 7.1 Hz, OCH CH ), 1.75
3
HH
2
3
(
m, 1 H, 5-H ), 1.90 (m, 2 H, CCH CH ), 2.12 (m, 1 H, 5-H ), 2.40
ax 2 2 eq
IR (film): 2983, 2939 (C–H, s), 1696 (C=O, s), 1253, 1023 (O–P, s),
(
m, 2 H, CH CH CH), 2.55 (m, 2 H, 4-H and 6-H ), 3.70 (m, 2 H,
2 2 eq eq
–
1
9
77 (O–P–O, bend) cm .
4
5
-H and 6-H ), 4.26 (m, 4 H, OCH CH ), 5.05 (m, 2 H, CHCH ),
ax
.77 (m, 1 H, CHCH2).
ax 2 3 2
1
H NMR (CDCl ): δ = 1.11 (dt, 3 H, J = 0.7 Hz, JHH = 7.1 Hz,
3
PH
1
3
COCH CH ), 1.38 (t, 6 H, J = 7.1 Hz, OCH CH ), 2.88 (dq, 2 H,
C NMR (CDCl ): δ = 16.9 (J = 5.6 Hz, CH CH ), 24.6
2 3 HH 2 3
3
PC
2
3
JPH = 5.1 Hz, JHH = 6.0 Hz, PCOCH ), 4.23 (m, 4 H, OCH ).
(
CH CH CH ), 27.9 (SCH ), 28.2 (CCH CH ), 36.4 (J = 2.8 Hz,
2
2
2
2
2
2
2
2
PC
CCH CH ), 46.0 (J = 139.9 Hz, PC), 64.4 (JPC = 7.5 Hz, OCH2),
13
2
2
PC
C NMR (CDCl ): δ = 4.5 (J = 4.3 Hz, COCH CH ), 14.5 (J
=
PC
3
PC
2
3
1
19.5 (CH=CH ), 138.2 (CH=CH ).
2
2
5.6 Hz, OCH CH ), 34.9 (J = 66.1 Hz, PCOCH ), 61.9 (J = 7.3
2 3 PC 2 PC
3
1
Hz, OCH ), 209.6 (J 166.3 Hz, CO).
2 PC
P NMR (CDCl ): δ = 20.0.
3
3
1
+
P NMR (CDCl ): δ = –1.5.
MS (EI): m/z = 310 (M , 11), 210 (8), 173 (100), 147 (56), 132 (22),
3
1
09 (24), 99 (42), 91 (41), 81 (39).
+
MS (EI): m/z = 194 (M , 30), 166 (15), 138 (100), 111 (84), 109
(
68), 91 (21), 81 (51).
HRMS: m/z calcd for C H PO S : 310.0826; found: 310.0829.
1
2
23
3 2
7
HRMS: m/z calcd for C H PO : 194.0708; found: 194.0710.
7
15
4
Ethyl [2-(Diethoxyphosphoryl)-1,3-dithian-2-yl]acetate (2g)
Orange oil; yield: 2.77g (81%).
Diethyl Phenylacetylphosphonate (3c)
exists in keto and stabilized enol form)
(
IR (film): 2980, 2931 (C–H, s), 1737 (C=O, s), 1242, 1185, 1050,
–
1
1
024 (P–O, s), 968 (O–P–O, bend) cm .
Pale yellow liquid; yield: 150 mg (77%).
1
H NMR (CDCl ): δ = 1.28 (t, 3 H, J = 7.1 Hz, CO CH CH ) 1.35
3
HH
2
2
3
IR (film): 2983, 2939 (C–H, s), 1696 (C=O, s), 1253, 1023 (O–P, s),
(
t, 6 H, JHH = 7.1 Hz, OCH CH ), 1.81 (m, 1 H, 5-H ), 2.11 (m, 1
–1
2
3
ax
977 (O–P–O, bend) cm .
H, 5-H ), 2.58 (m, 2 H, 4-H and 6-H ), 2.77 (d, 2 H, J = 11.1,
eq
eq
eq
PH
1
H NMR (CDCl ): δ = 1.31 (t, 6 H, J = 7.1 Hz, OCH CH ), 1.37
3
HH
2
3
CCH CO Et), 3.71 (m, 2 H, 4-H and 6-H ), 4.18 (m, 2 H,
2
2
ax
ax
(
t, 6 H′, JHH = 6.8 Hz, OCH CH ), 4.12 (d, 2 H, J = 0.9 Hz,
2 3 PH
CO CH CH ), 4.28 (m, 4 H, POCH CH ).
2
2
3
2
3
PCOCH ), 4.14 (overlapping m, 4 H + 4 H′, OCH ), 6.09 (d, 1 H′,
2
2
1
3
C NMR (CDCl ): δ = 14.6 (CO CH CH ), 16.9 (J = 5.5 Hz,
3
2
2
3
PC
JPH = 12.4 Hz, COHCHPh), 7.20–7.77 (m, 5 H + 5 H′, Ph).
POCH CH ), 24.2 (CH CH CH ), 28.2 (SCH ), 42.5 (J = 2.1 Hz,
2
3
2
2
2
2
PC
13
C NMR (CDCl ): δ = 4.5 (J = 4.3 Hz, COCH CH ), 14.5 (J =
PC
3
PC
2
3
PCCH ), 43.0 (J = 159.0 Hz, PC), 61.3 (CO CH CH ), 64.8
2
PC
2
2
3
5
.6 Hz, OCH CH ), 34.9 (J = 66.1 Hz, PCOCH ), 61.9 (J = 7.3
2 3 PC 3 PC
(
JPC = 8.5 Hz, POCH ), 168.1 (J = 2.3 Hz, CO2).
2
PC
Hz, OCH ), 209.6 (J = 166.3 Hz, CO).
2
PC
3
1
P NMR (CDCl ): δ = 18.3.
3
Synthesis 2003, No. 3, 357–360 ISSN 0039-7881 © Thieme Stuttgart · New York

3
60
K. Afarinkia et al.
PAPER
3
1
13
P NMR (CDCl ): δ = –1.5.
C NMR (CDCl ): δ = 16.4 (J = 5.6 Hz, CH CH ), 29.61
3
3
PC
2
3
+
(CH
2
CH=), 42.3 (JPC = 55 Hz, CH CO), 63.9 (JPC = 7.5 Hz, OCH ),
2
2
MS (EI): m/z = 256 (M , 28), 228 (14), 164 (12), 136 (59), 118, (48),
1
1
15.8 (CH=CH ), 136.1 (CH=CH ), 205.25 (J = 69 Hz, CO).
2
2
PC
09 (79), 105 (50), 91 (100), 81 (40).
3
1
P NMR (CDCl ): δ = –2.48.
3
HRMS: m/z calcd for C H PO : 194.0708; found: 194.0710.
1
2
17
4
+
MS (ESI): m/z [M + Na] calcd for C H PO Na: 243.0762; found:
9
17
4
Diethyl Heptanoylphosphonate (3d)
423.0679.
Pale yellow liquid; yield: 200 mg (80%).
Ethyl 3-(Diethoxyphosphoryl)-3-oxopropanoate (3g)
Pale yellow liquid, yield: 187 mg (74%).
IR (film): 2957, 2931, 2859 (C–H, s), 1697 (C=O, s), 1254, 1021
–
1
(
O–P, s), 975 (O–P–O, bend) cm .
1
IR (film): 3067(C–H, s), 1772, 1733 (C=O, s), 1204, 1027 (O–P, s),
H NMR (CDCl ): δ = 0.88 (t, 3 H, J = 7 Hz, CH CH CH ), 1.29
3
HH
2
2
3
–1
9
78 (O–P–O, bend) cm .
(
overlapping m, 4 H, CH CH CH ), 1.38 (overlapping m, 8 H,
2 2 3
1
OCH CH3
and
CH CH CH CH ),
1.61
(m,
2
H,
H NMR (CDCl ): δ = 1.32 (t, 3 H, J = 7 Hz, CO CH CH ), 1.38
3 HH 2 2 3
2
2
2
2
3
CH CH CH CH CH ), 2.84 (t, 2 H, J = 7 Hz, PCOCH ), 4.23 (m,
(t, 6 H, JHH = 7 Hz, POCH CH ), 2.02 (s, 2 H, PCOCH ), 4.25 (over-
2
2
2
2
3
HH
2
2
3
2
4
H, OCH2).
lapping m, 4 H, POCH and CO CH ).
2 2 2
1
3
13
C NMR (CDCl ): δ = 14.4 (CH CH CH ), 16.8 (J = 6 Hz,
C NMR (CDCl ): δ = 14.4 (CO CH CH ), 16.6 (J = 6 Hz,
3 2 2 3 PC
3
2
2
3
PC
OCH CH ), 22.7 (CH CH CH ), 22.8 (CH CH CH ), 28.9
POCH CH ), 43.3 (PCOCH CO ), 62.8 (CO CH ), 65.5 (J = 7
2
3
2
2
3
2
2
3
2 3 2 2 2 2 PC
(
CH CH CH CH ), 31.8 (PCOCH CH ), 43.7 (J = 54 Hz,
Hz, POCH ), 166.2 (CO ), 209.1 (J = 169 Hz, CO).
2 2 PC
2
2
2
3
2
2
PC
PCOCH ), 64.2 (J = 7 Hz, OCH ), 211.4 (J = 155 Hz, CO).
31
2
PC
2
PC
P NMR (CDCl ): δ = –1.2.
3
3
1
P NMR (CDCl ): δ = –1.7.
+
3
MS (EI): m/z = 252 (M , 37), 221 (43), 164 (27), 138 (100), 91 (76),
81(32).
+
MS (EI): m/z = 251 (M , 79), 243 (15), 159 (30), 137 (16), 121
(
100), 113 (41).
HRMS: m/z calcd for C9H PO : 252.2014; found: 252.2008.
1
7
6
HRMS: m/z calcd for C H PO : 250.1334; found: 250.1341.
1
1
23
4
Acknowledgement
Diethyl [3-(1,3-Dioxan-2-yl)propanoyl]phosphonate (3e)
Pale yellow liquid; yield: 216 mg (77%).
We would like to thank the EPSRC and GlaxoSmithKline for a
CASE-Quota studentship award to AJT.
IR (film): 2976, 2867 (C–H, s), 1698 (C=O, s), 1251, 1015 (O–P, s),
–
1
9
74 (O–P–O, bend) cm .
1
H NMR (CDCl ): δ = 1.40 (t, 6 H, J = 7 Hz, OCH CH ), 1.93 (dt,
3
HH
2
3
References
2
H, JHH = 5 Hz, JHH = 7 Hz, COCH CH ), 2.05 (m, 2 H,
2 2
CH CH CH ), 2.98 (dt, 2 H, J = 7 Hz, JPH = 1 Hz, PCOCH ), 3.73
(1) For a review see: Afarinkia K., Vinader M. V.; In Organic
Functional Group Transformations; Moody C. J. Ed.;
Pergamon: London, 1995; Vol. 5: 393.
2
2
2
HH
3
(
(
1
m, 2 H, CH HCH CH H), 4.07 (m, 2 H, CH HCH CH H), 4.22
eq 2 eq ax 2 ax
m, 4 H, POCH ), 4.59 (t, 1 H, J = 5 Hz, OCH O).
2
HH
2
3
(2) (a) Using CrO : Liao, Y.; Shabany, H.; Spilling, C. D.
C NMR (CDCl ): δ = 16.7 (J = 6 Hz, OCH CH ), 26.0
2
3
PC
2
3
Tetrahedron Lett. 1998, 39, 8389. (b) Using CrO3/
(
CH CH CH), 28.1 (CH CH CH ), 37.7 (J = 57 Hz, PCOCH3),
2 2 2 2 2 PC
Alumina: Kaboudin, B. Tetrahedron Lett. 2000, 41, 3169.
6
4.3 (JPC = 7 Hz, POCH ), 67.2 (OCH CH ), 100.6 (CHO), 210.6
2
2
2
(
c) Using MnO : Smyth, M. S.; Ford, H. J.; Burke, T. R. J.
(
JPC = 169 Hz, CO).
2
Tetrahedron Lett. 1992, 33, 4137. (d) Using Zinc chromate:
Firouzabadi, H.; Iranpoor, N.; Sobhani, S.; Sardarian, A. R.
Tetrahedron Lett. 2001, 42, 4369.
3
1
P NMR (CDCl ): δ = –1.9.
3
+
MS (EI): m/z = 280 (M , 20), 235 (17), 223 (16), 191 (21), 171 (27),
1
65 (45), 143 (100), 137 (53), 129 (17), 109 (80), 91 (46), 81 (84).
(3) Iogra, B.; Mouriés, V.; Savignac, P. Bull. Soc. Chim. Fr.
1
997, 134.
HRMS: m/z calcd for C H PO : 280.1076; found: 280.1085.
1
1
21
6
(
4) Aggarwal, V. K.; Barrell, J. K.; Worrall, J. M.; Alexander,
R. J. Org. Chem. 1998, 63, 7128.
5) Gröbels, B.-T.; Seebach, D. Synthesis 1977, 357.
6) Corey, E. J.; Crouse, D. J. Org. Chem. 1968, 33, 298.
(7) Berlin, K. D.; Hellwege, D. M.; Nagabhushanam, M. J. Org.
Chem. 1965, 30, 1265.
Diethyl Pent-4-enoylphosphonate (3f)
Yellow liquid; yield: (76%).
(
(
IR (film): 2982, 2931 (C–H, s), 1714 (C=O, s), 1251 (P=O, s), 1023,
–
1
9
77 (O–P–O, bend) cm .
1
H NMR (CDCl ): δ = 1.38 (t, 6 H, J = 7.1 Hz, OCH CH ), 2.37
3
HH
2
3
(
m, 2 H, CH CO), 2.94 (m, 2 H, CH CH=), 4.23 (m, 4 H,
2
2
OCH CH ), 5.06 (m, 2 H, CH=CH ), 5.82 (m, 1 H, CH=CH ).
2
3
2
2
Synthesis 2003, No. 3, 357–360 ISSN 0039-7881 © Thieme Stuttgart · New York