Diethyl [Nitro(diazo)methyl]phosphonate: Synthesis and reactivity towards alkenes

Article abstract of DOI:10.1055/s-0029-1217103

A novel and convenient synthesis of diethyl [nitro(di-azo)methyl] phosphonate and its reactions with various alkenes are described. The reactivity of diethyl [nitro(diazo)methyl]phosphonate is shown to be dependent on the structure of the alkene. A number of cyclopropyl-nitrophosphonates were obtained. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1217103

PAPER
259
Diethyl [Nitro(diazo)methyl]phosphonate: Synthesis and Reactivity towards
Alkenes
D
iethyl [Nitro(diaz
n
o)methyl]ph
d
osphonate rey V. Chemagin,a Nikolai V. Yashin,*a,b Yuri K. Grishin,a Tamara S. Kuznetsova,a,b Nikolai S. Zefirova,b
a
Lomonosov Moscow State University, Department of Chemistry, Leninskie Gory, 1-3, Moscow 119991, Russian Federation
Fax +7(495)9393969; E-mail: yashin-n@org.chem.msu.ru
b
IPhAC RAS, Severnyi Proezd, 1, Chernogolovka, Moscow Region, 142432, Russian Federation
Received 4 September 2009; revised 9 September 2009
use of diethyl [nitro(diazo)methyl]phosphonate (NDMP)
as a potential synthetic precursor, that would represent an
equivalent of an amino acid upon reduction of the nitro
group. Herein, we report an improved procedure for the
preparation of this reagent and its application to the syn-
thesis of a number of structurally diverse (1-nitrocyclo-
propane)phosphonates.
Abstract: A novel and convenient synthesis of diethyl [nitro(di-
azo)methyl]phosphonate and its reactions with various alkenes are
described. The reactivity of diethyl [nitro(diazo)methyl]phospho-
nate is shown to be dependent on the structure of the alkene. A num-
ber of cyclopropyl a-nitrophosphonates were obtained.
Key words: diazo compounds, phosphonates, alkenes, cyclopropa-
nation, carbenes
Although the preparation of diethyl [nitro(diazo)meth-
yl]phosphonate has already been described,8 the proce-
dure is inconvenient due to the requirement for dinitrogen
pentoxide which is unstable and dangerous to handle.
Moreover, diethyl [nitro(diazo)methyl]phosphonate is
formed as a mixture of products under the reported condi-
tions, separation of which is required. Hence, the reactivity
and synthetic potential of diethyl [nitro(diazo)meth-
yl]phosphonate has not been investigated in detail. We
have developed an alternative route to this reagent starting
from commercially available 1-chloroacetone (Scheme 1).
The synthetic protocol involves sequential Finkelstein
and Arbuzov reactions, followed by nitration9 of the re-
sulting phosphonoacetone using nitric acid–acetic anhy-
dride to afford nitrophosphonate 1 in a moderate yield. It
is essential that the appropriate azide is used in order to
successfully perform the subsequent diazo transfer reac-
tion. We found that the reaction of nitrophosphonate 1
with triflic azide in the presence of pyridine afforded the
target, diethyl [nitro(diazo)methyl]phosphonate in a good
yield. Triflic azide has earlier been reported to give excel-
lent results in the synthesis of a-diazo-a-nitroacetates
from the corresponding nitroesters.10
a-Aminophosphonic acids serve as bioisosteres1 of the
corresponding amino acids and are of interest as enzyme
inhibitors, herbicides, antibacterial agents, fungicides,
plant growth regulators, etc.2 The tetrahedral structure of
the phosphonic acid moiety allows their possible action as
‘transition-state analogues’.2c Cyclopropane a-amino-
phosphonic acids are promising structures (Figure 1), but
as yet, they have not received the same attention as cyclo-
propane amino acids3 or acyclic aminophosphonates. Al-
though syntheses of cyclopropane a-aminophosphonic
acids have been reported,4 a general route still needs to be
developed.
NH2
NH2
COOH
P(O)(OH)2
Figure 1 A cyclopropane amino acid and the corresponding phos-
phonic acid analogue
We have previously reported simple and convenient syn-
theses of various polycyclic cyclopropane amino acids via
rhodium(II)-catalyzed cyclopropanation of alkenes con-
taining small rings with a-diazoacetates.5
We have studied the reactivity of diethyl [nitro(diazo)meth-
yl]phosphonate towards various alkenes in order to pre-
pare a new group of cyclopropane a-nitrophosphonates.
Methylenecyclobutane (2a) was chosen as a model com-
pound for optimization of the reaction conditions
(Table 1).
As a part of our ongoing research program aimed at the
development of new methods for the synthesis of unnatu-
ral cyclopropane amino acids,5,6 as well as their bioisos-
teric phosphonic analogues,7 we became interested in the
N2
O
TfN3, py
1. KI, acetone, 95%
Cl
O2N
P(O)(OEt)2
2. P(OEt)3, Et2O, 75%
3. HNO3, Ac2O, 40%
O2N
P(O)(OEt)2
MeCN
hexanes
63%
NDMP
1
Scheme 1 A novel straightforward synthesis of diethyl [nitro(diazo)methyl]phosphonate
SYNTHESIS 2010, No. 2, pp 0259–0266
x
x
.
x
x
.2
0
0
9
Advanced online publication: 06.11.2009
DOI: 10.1055/s-0029-1217103; Art ID: Z18809SS
© Georg Thieme Verlag Stuttgart · New York

260
A. V. Chemagin et al.
PAPER
Table 1 Optimization of the Reaction Conditions for the Cyclo-
propanation of Methylenecyclobutane (2a) with Diethyl [Nitro(di-
azo)methyl]phosphonate
As the structure of the alkene became more crowded the
cyclopropane yield decreased and the formation of
alternative products was observed. The acylnitroso inter-
mediate C (Scheme 2), derived from (diethoxyphosphor-
yl)nitrocarbene A, participated in an ene reaction with
several alkenes to yield the corresponding hydroxycar-
bamoylphosphonic acid of type III (pathway c,
Scheme 2). Reaction of hex-1-ene (2g) with diethyl [ni-
tro(diazo)methyl]phosphonate gave cyclopropane 3g and
the ene-product 4g in yields of 22% and 30%, respectively
(Table 2). In contrast, reaction of 1,1¢-bi(cyclobutylidene)
(2h) gave the hydroxycarbamoylphosphonate 3h in 50%
yield as the only product.
NDMP
Rh2(OAc)4
P(O)(OEt)2
3a
O2N
2a
Entry Alkene Solvent
(equiv)
Temp
Catalyst
Yield
(%)a
1
2
5
10
10
10
10
10
10
10
10
10
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
DCE
0 °C
0 °C
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
CuOTf
30
45
53
70
62
32
0
3
25 °C
42 °C
60 °C
80 °C
0 °C
We were surprised to find that with donor alkenes such as
enol ethers 2j–l the reactions proceeded via [3+2] cy-
cloaddition to form the corresponding isoxazoline N-ox-
ides 3j–l in moderate to excellent yields. The reaction of
alkene 2i with diethyl [nitro(diazo)methyl]phosphonate
gave cyclopropane 3i and N-oxide 4i in yields of 33% and
38%, respectively, as determined by 31P NMR spectrosco-
py. Following silica gel column chromatography, no cy-
clopropane product was isolated, and the yield of N-oxide
4i increased to 65%. This shows that cyclopropane 3i un-
dergoes rearrangement on silica gel, the driving force be-
ing release of ring-strain in the nitro-substituted three-
membered ring.
4
5
6
C6H6
7
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
8
42 °C
0 °C
CuOTf
0
9
CuI
0
10
42 °C
CuI
0
a Yield determined from the 31P NMR spectrum.
The rearrangement of (1-nitrocyclopropane)phosphonates
into isoxazoline N-oxides is known for several other nitro-
cyclopropanes containing an electron-withdrawing moi-
ety a to the nitro group.5a,12
The highest yield in the [1+2]-cycloaddition reaction was
obtained in dichloromethane at reflux using a ten-fold ex-
cess of the alkene in the presence of rhodium(II) acetate (5
mol%) as catalyst. In the case of the expensive substrates
2c–e,h,i, the excess unreacted alkene was recovered after
column chromatography. We also tested copper catalysts
which are reported to be active in [1+2]-cycloaddition re-
actions.11 However, no cyclopropanes were formed under
these conditions, even after extended heating in dichlo-
romethane at reflux; in each case, the starting diazo com-
pound remained unchanged.
Thus, three pathways for the reaction of diethyl [nitro(di-
azo)methyl]phosphonate with alkenes are possible
(Scheme 2). Initially, diethyl [nitro(diazo)methyl]phos-
phonate undergoes nitrogen extrusion to form nitro(di-
ethoxyphosphoryl)carbene A. The main pathway for this
reaction involves [1+2] cycloaddition of carbene A to the
alkene leading to (1-nitrocyclopropane)phosphonates of
type I (pathway a). Alternatively, the carbene A may act
as a 1,3-dipole (B) which undergoes reaction with the alk-
A number of alkenes were submitted to the optimized re-
action conditions (Table 2). The behavior of alkenes con-
taining small rings was of interest for the preparation of
polyspirocyclic cyclopropane nitrophosphonates. The
mode of reaction was found to be highly dependent on the
substitution pattern of the alkene. Terminal alkenes such
as methylenecycloalkanes 2a–e and styrene (2f) were
converted into cyclopropanes 3a–f in moderate to good
yields.
P(O)(OEt)2
N2
NO2
NDMP
– N2 Rh(II)
(EtO)2(O)P
N
O
••
O
(EtO)2(O)P
N
O
(EtO)2(O)P
NO2
O
The reactions were not diastereoselective; the cyclopro-
panes were formed in diastereoisomeric ratios ranging
from 73:27 to 56:44. Products 3d,e derived from methyl-
enecycloalkanecarboxylates 2d,e are interesting as pre-
cursors of conformationally constrained bioisosteric
glutamate analogues. Methyl 2-methylenecyclopropane-
carboxylate (2d) gave a low yield of product 3d due to the
electron-withdrawing character and bulky nature of the
carbomethoxy group in proximity to the double bond.
A
B
C
a
b
c
OH
N
P(O)(OEt)2
O
NO2
P(O)(OEt)2
(EtO)2(O)P
N
O
O
I
II
III
Scheme 2 Reactivity of diethyl [nitro(diazo)methyl]phosphonate
towards alkenes
Synthesis 2010, No. 2, 259–266 © Thieme Stuttgart · New York

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Diethyl [Nitro(diazo)methyl]phosphonate
261
Table 2 Scope of the Rh2(OAc)4-Catalyzed Reactions of Diethyl [Nitro(diazo)methyl]phosphonate with Various Alkenes
Entry
1
Alkene
Product
Yield (%)a
65
2a
3a
P(O)(OEt)2
P(O)(OEt)2
P(O)(OEt)2
O2N
2
3
4
2b
2c
2d
3b
3c
3d
45b
O2N
54
(dr = 73:27)c
O2N
25
P(O)(OEt)2
(dr = 56:44)c
MeO2C
MeO2C
MeO2C
MeO2C
O2N
50
NO2
5
2e
3e
(dr = 60:40)c
P(O)(OEt)2
73b
Ph
6
7
2f
3f
(dr = 59:41)c
Ph
P(O)(OEt)2
O2N
25
n-Bu
2g
3g
(dr = 73:27)c
n-Bu
P(O)(OEt)2
O2N
n-Pr
O
30
4g
3h
(dr = 82:18)c
N
P(O)(OEt)2
OH
8
9
2h
2i
50
N
P(O)(OEt)2
HO
O
33d
P(O)(OEt)2
NO2
3i
4i
(dr = 50:50)c
P(O)(OEt)2
38d (65a)
N
O
O
P(O)(OEt)2
10
11
2j
3j
93
60
EtO
N
EtO
O
O
P(O)(OEt)2
2k
3k
PhO
N
PhO
O
O
P(O)(OEt)2
12
2l
3l
43
N
O
O
O
O
a Yield of isolated product.
b Reaction was carried out at 0 °C.
c Diastereoisomeric ratio determined from the 31P NMR spectrum.
d Yield determined from the 31P NMR spectrum.
ene to yield isoxazoline N-oxides of type II (pathway b), carbamoylphosphonic acid derivatives of type III on
or may rearrange irreversibly to an acylnitroso intermedi- reaction with the alkene (pathway c).
ate C, which functions as an enophile forming hydroxy-
Synthesis 2010, No. 2, 259–266 © Thieme Stuttgart · New York

262
A. V. Chemagin et al.
PAPER
chromatography on silica gel (50% EtOAc–PE) afforded the pure
nitro(diazo)phosphonate.
diethyl [nitro(diazo)methyl]phosphonate. The new class Yellow solid; yield: 2.36 g (63%), mp 35–36 °C.8
In conclusion, terminal alkenes containing small rings
gave the best results in the cyclopropanation reaction with
1H NMR (CDCl3): d = 1.36 (t, 3JH,H = 7.1 Hz, 3 H, OCH2CH3), 1.37
of polyspirocyclopropane a-nitrophosphonates obtained
is of significant interest for the preparation of the corre-
sponding a-aminophosphonic acids containing a cyclo-
propane moiety.
3
(t, JH,H = 7.1 Hz, 3 H, OCH2CH3), 4.32–4.34 (m, 4 H, 2 ×
OCH2CH3).
31P NMR (CDCl3): d = –1.05.
Anal. Calcd for C5H10N3O5P: C, 26.91; H, 4.52; N, 18.83. Found:
C, 26.99; H, 4.67; N, 18.77.
All reactions were performed in flame-dried glassware under a
slight positive pressure of Ar using freshly distilled anhyd solvents.
Petroleum ether (PE) refers to the fraction boiling in the 40–70 °C
range. Products obtained as mixtures of diastereoisomers were not
separated into single isomers unless otherwise stated. Melting
points were determined using an Electrothermal 9100 capillary ap-
paratus and are uncorrected. IR spectra were recorded using a Carl
Zeiss UR-20 IR spectrometer and a Thermo Nicolet IR200 FT-IR
spectrometer. 1H, 13C and 31P NMR spectra were recorded at r.t. on
a Bruker DPX-400 spectrometer at 400.13, 100.61 and 161.98
MHz, respectively. The 1H and 13C chemical shifts d were measured
in ppm with respect to the solvent CDCl3 (1H: d = 7.27, 13C:
d = 77.13). The 31P chemical shifts are given relative to 85% H3PO4
(as external standard, d = 0). The 1H coupling constants were mea-
sured using selective heteronuclear decoupling 1H–{31P}. Elemen-
tal analyses were recorded using a Karlo Erba 1106 apparatus.
Analytical thin layer chromatography (TLC) was carried out on ‘Si-
lufol’ silica gel plates (supported on aluminum) using UV light (254
nm and 365 nm) for visualization and iodine vapor as the develop-
ing agent. Column chromatography was performed using silica gel
60 (230–400 mesh, Macherey-Nagel GmbH & Co KG). All re-
agents, except commercial products of satisfactory quality, were
purified by literature procedures prior to use.13 Commercial samples
of methylenecyclobutane (2a) and 1,1¢-bi(cyclobutylidene) (2h)
were used. Diethyl (2-oxopropyl)phosphonate,14 methylenecyclo-
propane (2b),15 1-methylenespiro[2.2]pentane (2c),16 methyl
2-methylenecyclopropanecarboxylate (2d),17 methyl 3-methyl-
enecyclobutanecarboxylate (2e),18 4-methylenespiro[2.3]hexane
(2i),19 phenyl vinyl ether (2k)20 and triflic azide10 were synthesized
via known procedures. CAUTION: Although we did not experi-
ence any problems in handling diethyl [nitro(diazo)methyl]phos-
phonate, full safety precautions should be taken due to its potential
explosive nature.
Reaction of Diethyl [Nitro(diazo)methyl]phosphonate with Alk-
enes; General Procedure
To a stirred mixture of alkene (10 mmol) and Rh2(OAc)4 (11 mg,
0.025 mmol, 5 mol%) in CH2Cl2 (1 mL) at reflux was added a soln
of diethyl [nitro(diazo)methyl]phosphonate (223 mg, 1 mmol) in
CH2Cl2 (1 mL) over 1 h. The reaction mixture was heated at reflux
for an additional 1 h and then the solvent was removed under re-
duced pressure. The crude mixture was submitted to column chro-
matography (50% EtOAc–PE) to isolate pure products.
Diethyl (1-Nitrospiro[2.3]hex-1-yl)phosphonate (3a)
Yellow oil; yield: 171 mg (65%); Rf = 0.35 (50% EtOAc–PE).
IR (thin film): 2985, 2941, 2914, 2871, 1537, 1419, 1348, 1265,
1165, 1099, 1051, 1022, 974, 860, 850, 797, 598, 567 cm–1.
1H NMR (CDCl3): d = 1.27 (t, 3JH,H = 7.1 Hz, 3 H, OCH2CH3), 1.29
3
2
(t, JH,H = 7.1 Hz, 3 H, OCH2CH3), 1.93 (dd, JH,H = 6.1 Hz,
3JH,P = 10.4 Hz, 1 H, c-Pr-CH2), 1.94–2.16 (m, 5 H, c-Bu-H), 2.18
(dd, 2JH,H = 6.1 Hz, 3JH,P = 6.2 Hz, 1 H, c-Pr-CH2), 2.57–2.65 (m, 1
H, c-Bu-H), 4.21–4.30 (m, 4 H, 2 × OCH2CH3).
13C NMR (CDCl3): d = 15.50 (t, 1JC,H = 138 Hz, c-Bu-CH2), 16.29
1
1
(q, JC,H = 128 Hz, OCH2CH3), 16.35 (q, JC,H = 128 Hz,
1
3
OCH2CH3), 28.28 (dt, JC,H = 166 Hz, JC,P = 4 Hz, c-Pr-CH2),
27.98 (t, 1JC,H = 139 Hz, c-Bu-CH2), 28.31 (t, 1JC,H = 139 Hz, c-Bu-
CH2), 39.25 (Cspiro), 63.46 (t, 1JC,H = 149 Hz, OCH2CH3), 63.57 (t,
1JC,H = 149 Hz, OCH2CH3), 67.62 [d, 1JC,P = 213 Hz,
C(NO2)PO(OEt)2].
31P NMR (CDCl3): d = 11.43.
Anal. Calcd for C10H18NO5P: C, 45.63; H, 6.89; N, 5.32. Found: C,
45.34; H, 6.78; N, 5.29.
Diethyl (1-Nitrospiro[2.2]pent-1-yl)phosphonate (3b)
Reaction was carried out at 0 °C due to the low bp of the starting
material 2b.
Diethyl (Nitromethyl)phosphonate (1)
Diethyl (2-oxopropyl)phosphonate (5.00 g, 25.8 mmol) was dis-
solved in Ac2O (2.5 mL, 26.8 mmol) and warmed to 32–35 °C. A
freshly prepared mixture of HNO3 (1.18 mL, 28.4 mmol) and Ac2O
(1.65 mL, 17.5 mmol) was added dropwise with stirring (the tem-
perature should not rise above 35 °C). The mixture was stirred for 1
h during which time it had cooled to r.t., it was then quenched with
H2O (15 mL) and stirred for a further 1 h. The product was extracted
with Et2O (3 × 15 mL), dried over MgSO4, concd and distilled under
reduced pressure to yield nitrophosphonate 1.
Yellow oil; yield 112 mg (45%); Rf = 0.35 (50% EtOAc–PE).
IR (thin film): 2998, 2990, 2950, 2930, 2880, 1550, 1445, 1400,
1375, 1350, 1270, 1170, 1105, 1060, 1038, 990, 940, 800, 760, 675
cm–1.
1H NMR (CDCl3): d = 1.02–1.07 (m, 1 H, c-Pr-H), 1.17–1.27 (m, 2
3
H, c-Pr-H), 1.34 (t, JH,H = 7.1 Hz, 3 H, OCH2CH3), 1.35 (t,
3JH,H = 7.1 Hz, 3 H, OCH2CH3), 1.40–1.44 (m, 1 H, c-Pr-H), 2.22
Pale-yellow liquid; yield: 2.03 g (40%); bp 100 °C (1 Torr).21
2
3
(dd, JH,H = 5.2 Hz, JH,P = 8.6 Hz, 1 H, c-Pr-CH2), 2.50 (dd,
2JH,H = 5.2 Hz, 3JH,P = 3.3 Hz, 1 H, c-Pr-CH2), 4.21–4.31 (m, 4 H, 2
× OCH2CH3).
1H NMR (CDCl3): d = 1.38 (t, 3JH,H = 7.1 Hz, 6 H, 2 × OCH2CH3),
2
4.24–4.30 (m, 4 H, 2 × OCH2CH3), 4.95 (d, JH,P = 15.4 Hz, 2 H,
CH2P).
13C NMR (CDCl3): d = 6.45 (t, 1JC,H = 166 Hz, c-Pr-CH2), 8.86 (dt,
31P NMR (CDCl3): d = 9.62.
3
1
1JC,H = 166 Hz, JC,P = 3 Hz, c-Pr-CH2), 16.35 (q, JC,H = 128 Hz,
1
OCH2CH3), 16.38 (q, JC,H = 128 Hz, OCH2CH3), 23.04 (t,
1JC,H = 168 Hz, c-Pr-CH2), 27.03 (d, JC,P = 4 Hz, Cspiro), 63.61 (t,
2
Diethyl [Nitro(diazo)methyl]phosphonate (NMDP)
1JC,H = 149 Hz, OCH2CH3), 63.65 (t, 1JC,H = 149 Hz, OCH2CH3),
To a stirred soln of diethyl (nitromethyl)phosphonate (3.3 g, 16.8
mmol) in MeCN (10 mL) under Ar was added a soln of triflic azide
(0.52 M, 35.6 mL, 18.5 mmol) in hexane at 0 °C. Next, py (2.87 mL,
37.0 mmol) was added dropwise over ca. 10 min. The reaction mix-
ture was warmed to r.t., stirred for 15 h, and then concd under re-
duced pressure. Purification of the crude residue by column
65.35 [d, 1JC,P = 214 Hz, C(NO2)PO(OEt)2].
31P NMR (CDCl3): d = 11.97.
Anal. Calcd for C9H16NO5P: C, 43.38; H, 6.47; N, 5.62. Found: C,
43.35; H, 6.62; N, 5.75.
Synthesis 2010, No. 2, 259–266 © Thieme Stuttgart · New York

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Diethyl [Nitro(diazo)methyl]phosphonate
263
Diethyl (1-Nitrodispiro[2.0.2.1]hept-1-yl)phosphonate (3c)
Yellow oil; yield: 149 mg (54%); mixture of 2 diastereoisomers
(A/B = 73:27); Rf (isomer A) = 0.30, Rf (isomer B) = 0.39 (50%
EtOAc–PE).
13C NMR (CDCl3): d = 14.01 (c-Pr-CH2, isomers A/B), 15.95
(OCH2CH3, isomer B), 15.98 (OCH2CH3, isomer B), 16.25 (d,
3
3JC,P = 6 Hz, OCH2CH3, isomer A), 16.38 (d, JC,P = 6 Hz,
OCH2CH3, isomer A), 20.46 (c-Pr-CH2, isomer A), 22.02 (c-Pr-
CH2, isomer B), 22.32 (c-Pr-CH, isomer A), 22.39 (c-Pr-CH, iso-
mer B), 32.38 (Cspiro, isomers A/B), 52.13 (COOCH3, isomer A),
52.33 (COOCH3, isomer B), 63.82 (d, 3JC,P = 7 Hz, OCH2CH3, iso-
IR (thin film): 2998, 2955, 2920, 2880, 1540, 1400, 1350, 1270,
1170, 1105, 1070, 1032, 990, 950, 895, 805, 780, 750 cm–1.
1H NMR (CDCl3): d (diastereoisomer A) = 0.73–0.77 (m, 1 H, c-Pr-
H), 0.79–0.89 (m, 2 H, c-Pr-H), 0.92–0.96 (m, 1 H, c-Pr-H), 1.30
3
mer B), 63.86 (d, JC,P = 7 Hz, OCH2CH3, isomer A), 63.96 (d,
3
3JC,P = 7 Hz, OCH2CH3, isomer A), 64.07 (d, JC,P = 7 Hz,
3
4
1
(dt, JH,H = 7.1 Hz, JH,P = 0.8 Hz, 3 H, OCH2CH3), 1.31 (dt,
OCH2CH3, isomer B), 64.91 [d, JC,P = 214 Hz, C(NO2)PO(OEt)2,
3JH,H = 7.1 Hz, JH,P = 0.8 Hz, 3 H, OCH2CH3), 1.44 (A of AB,
4
1
isomer A], 64.96 [d, JC,P = 212 Hz, C(NO2)PO(OEt)2, isomer B],
2JH,H = 5.1 Hz, 1 H, c-Pr-CH2), 1.64 (B of AB, 2JH,H = 5.1 Hz, 1 H,
c-Pr-CH2), 2.21 (dd, 1 H, 2JH,H = 5.3 Hz, 3JH,P = 8.4 Hz, 1 H, c-Pr-
CH2), 2.31 (dd, 1 H, 2JH,H = 5.3 Hz, 3JH,P = 3.1 Hz, 1 H, c-Pr-CH2),
4.19–4.29 (m, 4 H, 2 × OCH2CH3).
171.12 (COOCH3, isomer A), 171.52 (COOCH3, isomer B).
31P NMR (CDCl3): d = 10.38 (isomer B), 10.41 (isomer A).
Anal. Calcd for C11H18NO7P: C, 43.00; H, 5.91; N, 4.56. Found: C,
43.07; H, 5.83; N, 4.68.
13C NMR (CDCl3): d (diastereoisomer A) = 2.46 (c-Pr-CH2), 5.70
(c-Pr-CH2), 12.92 (d, 3JC,P = 4 Hz, c-Pr-CH2), 14.92 (Cspiro), 16.33
(OCH2CH3), 16.39 (OCH2CH3), 22.52 (c-Pr-CH2), 30.60 (d,
2JC,P = 4 Hz, Cspiro), 63.56 (OCH2CH3), 63.62 (OCH2CH3), 65.17 [d,
1JC,P = 214 Hz, C(NO2)PO(OEt)2].
Methyl 1-(Diethoxyphosphoryl)-1-nitrospriro[2.3]hexane-5-
carboxylate (3e)
Yellow oil; yield: 161 mg (50%); mixture of 2 diastereoisomers
(A/B = 60:40); Rf = 0.3 (50% EtOAc–PE).
31P NMR (CDCl3): d (diastereoisomer A) = 11.51.
1H NMR (CDCl3): d (diastereoisomer B) = 0.83 (ddd, JH,H = 5.8
IR (thin film): 2987, 2914, 2872, 1736, 1539, 1439, 1348, 1263,
1205, 1165, 1020, 976, 868, 796, 578 cm–1.
2
3
3
Hz, JH,H = 9.6 Hz, JH,H = 4.4 Hz, 1 H, c-Pr-H), 0.92 (ddd,
1H NMR (CDCl3): d = 1.30–1.36 (m, 6 H + 6 H, 4 × OCH2CH3, iso-
mers A/B), 1.90–1.98 (m, 1 H + 1 H, c-Pr-CH2, isomers A/B), 2.19–
2.23 (m, 1 H + 1 H, c-Pr-CH2, isomers A/B), 2.33–2.60 (m, 3 H + 3
H, c-Bu-H, isomers A/B), 2.84–2.92 (m, 1 H + 1 H, c-Bu-H, iso-
mers A/B), 3.15–3.25 (m, 1 H + 1 H, c-Bu-H, isomers A/B), 3.63 (s,
3 H, COOCH3, isomer B), 3.66 (s, 3 H, COOCH3, isomer A), 4.18–
4.29 (m, 4 H + 4 H, 4 × OCH2CH3, isomers A/B).
2JH,H = 5.6 Hz, JH,H = 9.1 Hz, JH,H = 4.4 Hz, 1 H, c-Pr-H), 1.04
3
3
2
3
3
(ddd, JH,H = 5.8 Hz, JH,H = 9.1 Hz, JH,H = 4.3 Hz, 1 H, c-Pr-H),
1.20 (ddd, 2JH,H = 5.6 Hz, 3JH,H = 9.6 Hz, 3JH,H = 4.3 Hz, 1 H, c-Pr-
3
4
H), 1.31 (dt, JH,H = 7.1 Hz, JH,P = 0.8 Hz, 3 H, OCH2CH3), 1.32
3
4
(dt, JH,H = 7.1 Hz, JH,P = 0.6 Hz, 3 H, OCH2CH3), 1.42 (d,
2JH,H = 5.1 Hz, 1 H, c-Pr-CH2), 1.61 (dd, 2JH,H = 5.2 Hz, 3JH,P = 3.2
Hz, 1 H, c-Pr-CH2), 2.07 (dd, 2JH,H = 5.2 Hz, 3JH,P = 8.8 Hz, 1 H, c-
Pr-CH2), 2.50 (dd, 2JH,H = 5.2 Hz, JH,P = 3.1 Hz, 1 H, c-Pr-CH2),
13C NMR (CDCl3): d = 16.29 (q, JC,H = 128 Hz, OCH2CH3, iso-
3
1
1
4.17–4.26 (m, 4 H, 2 × OCH2CH3).
mers A/B), 16.24 (q, JC,H = 128 Hz, OCH2CH3, isomers A/B),
27.82 (t, 1JC,H = 167 Hz, c-Pr-CH2, isomer A), 27.90 (t, 1JC,H = 167
13C NMR (CDCl3): d (diastereoisomer B) = 5.81 (c-Pr-CH2), 6.11
1
Hz, c-Pr-CH2, isomer B), 30.82 (t, JC,H = 138 Hz, c-Bu-CH2, iso-
3
(c-Pr-CH2), 12.60 (c-Pr-CH2), 16.28 (d, JC,P = 7 Hz, OCH2CH3),
1
3
mer A), 31.30 (dt, JC,H = 140 Hz, JC,P = 4 Hz, c-Bu-CH2, isomer
3
3
16.34 (d, JC,P = 7 Hz, OCH2CH3), 17.23 (d, JC,P = 4 Hz, Cspiro),
1
A), 31.39 (t, JC,H = 138 Hz, c-Bu-CH2, isomer B), 31.83 (d,
22.88 (c-Pr-CH2), 32.55 (d, 2JC,P = 2 Hz, Cspiro), 63.37 (d, JC,P = 7
2
1JC,H = 142 Hz, c-Bu-CH, isomer B), 32.16 (dt, JC,H = 140 Hz,
1
2
Hz, OCH2CH3), 63.55 (d, JC,P = 7 Hz, OCH2CH3), 64.79 [d,
3JC,P = 3 Hz, c-Bu-CH2, isomer B), 32.30 (d, 1JC,H = 142 Hz, c-Bu-
CH, isomer A), 35.31 (s, Cspiro, isomer B), 36.39 (s, Cspiro, isomer B),
51.95 (q, 1JC,H = 147 Hz, COOCH3, isomer B), 52.03 (q, 1JC,H = 147
1JC,P = 215 Hz, C(NO2)PO(OEt)2].
31P NMR (CDCl3): d (diastereoisomer A) = 12.05.
1
3
Hz, COOCH3, isomer A), 63.58 (dt, JC,H = 149 Hz, JC,P = 5 Hz,
Anal. Calcd for C11H18NO5P: C, 48.00; H, 6.59; N, 5.09. Found: C,
48.05; H, 6.81; N, 5.14.
1
3
OCH2CH3, isomers A/B), 63.71 (dt, JC,H = 149 Hz, JC,P = 7 Hz,
OCH2CH3, isomers A/B), 66.63 [d, 1JC,P = 211 Hz,
1
C(NO2)PO(OEt)2, isomer B], 67.50 [d, JC,P = 212 Hz,
Methyl 4-(Diethoxyphosphoryl)-4-nitrospriro[2.2]pentane-1-
carboxylate (3d)
Yellow oil; yield: 77 mg (25%); mixture of 2 diastereoisomers
(A/B = 56:44); Rf = 0.35 (50% EtOAc–PE).
C(NO2)PO(OEt)2, isomer A], 174.08 (s, COOCH3, isomer B),
174.86 (s, COOCH3, isomer A).
31P NMR (CDCl3): d = 10.71 (isomer B), 10.77 (isomer A).
IR (thin film): 3000, 2978, 2942, 2928, 2880, 1735, 1550, 1435,
1400, 1350, 1280, 1210, 1185, 1060, 1050, 990, 900, 810 cm–1.
Anal. Calcd for C12H20NO7P: C, 44.86; H, 6.27; N, 4.36. Found: C,
44.93; H, 6.32; N, 4.33.
1H NMR (CDCl3): d = 1.35 (m, 6 H, 2 × OCH2CH3, isomer A), 1.36
(t, 3JH,H = 7.1 Hz, 3 H, OCH2CH3, isomer B), 1.37 (t, 3JH,H = 7.1 Hz,
3 H, OCH2CH3, isomer B), 1.61 (dd, 2JH,H = 5.6 Hz, 3JH,H = 8.7 Hz,
1 H, c-Pr-CH2, isomer A), 1.81 (dd, 2JH,H = 5.4 Hz, 3JH,H = 5.5 Hz,
1 H, c-Pr-CH2, isomer B), 1.88 (dd, 2JH,H = 5.4 Hz, 3JH,H = 8.8 Hz,
1 H, c-Pr-CH2, isomer B), 1.90 (ddd, 2JH,H = 5.6 Hz, 3JH,H = 5.5 Hz,
Diethyl (1-Nitro-2-phenylcyclopropyl)phosphonate (3f)
Yellow oil; yield: 218 mg (73%); mixture of 2 diastereoisomers
(A/B = 59:41); Rf = 0.35 (50% EtOAc–PE).
IR (thin film): 2998, 2940, 2925, 2885, 1545, 1455, 1398, 1350,
1268, 1205, 1170, 1108, 1075, 1065, 1030, 900, 870, 785, 715 cm–1.
2
4JH,P = 2.6 Hz, 1 H, c-Pr-CH2, isomer A), 2.22 (dd, JH,H = 5.9 Hz,
1H NMR (CDCl3): d = 1.11 (dt, 3JH,H = 7.1 Hz, 4JH,P = 0.8 Hz, 3 H,
OCH2CH3, isomer B), 1.13 (dt, 3JH,H = 7.1 Hz, 4JH,P = 0.8 Hz, 3 H,
OCH2CH3, isomer B), 1.40 (dt, 3JH,H = 7.1 Hz, 4JH,P = 0.8 Hz, 3 H,
OCH2CH3, isomer A), 1.45 (dt, 3JH,H = 7.1 Hz, 4JH,P = 0.8 Hz, 3 H,
2
3JH,P = 9.0 Hz, 1 H, c-Pr-CH2, isomer A), 2.23 (dd, JH,H = 5.5 Hz,
2
3JH,P = 8.8 Hz, 1 H, c-Pr-CH, isomer B), 2.35 (dd, JH,H = 6.0 Hz,
3JH,P = 8.7 Hz, 1 H, c-Pr-CH2, isomer B), 2.49 (dd, 2JH,H = 6.0 Hz,
3JH,P = 3.7 Hz, 1 H, c-Pr-CH2, isomer B), 2.53 (dd, 2JH,H = 5.5 Hz,
2
OCH2CH3, isomer A), 2.19 (ddd, JH,H = 6.6 Hz, 3JH,H = 9.8 Hz,
2
3JH,H = 8.7 Hz, 1 H, c-Pr-CH, isomer A), 2.60 (dd, JH,H = 5.9 Hz,
3JH,P = 10.4 Hz, 1 H, c-Pr-CH2, isomer A), 2.38 (ddd, 2JH,H = 6.0 Hz,
3JH,H = 9.4 Hz, 3JH,P = 10.8 Hz, 1 H, c-Pr-CH2, isomer B), 2.54 (ddd,
3JH,P = 3.5 Hz, 1 H, c-Pr-CH2, isomer A), 3.70 (s, 3 H, OCH3, isomer
A), 3.74 (s, 3 H, OCH3, isomer B), 4.26 (m, 4 H + 4 H, 4 ×
OCH2CH3, isomers A/B).
3
2JH,H = 6.0 Hz, 3JH,H = 10.6 Hz, JH,P = 3.9 Hz, 1 H, c-Pr-CH2, iso-
2
3
mer B), 2.69 (ddd, JH,H = 6.6 Hz, 3JH,H = 9.2 Hz, JH,P = 6.3 Hz, 1
H, c-Pr-CH2, isomer A), 3.32 (ddd, JH,H = 9.2 Hz, 3JH,H = 9.8 Hz,
3
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264
A. V. Chemagin et al.
PAPER
3JH,P = 13.4 Hz, 1 H, c-Pr-CH2, isomer A), 3.45 (ddd, 3JH,H = 9.4 Hz,
3JH,H = 10.6 Hz, 3JH,P = 6.3 Hz, 1 H, c-Pr-CH2, isomer B), 3.78 (ddq,
2JH,H = 10.3 Hz, 3JH,H = 7.1 Hz, 3JH,P = 9.2 Hz, 2 H, OCH2CH3, iso-
mer B), 3.89 (dq, 3JH,H = 7.1 Hz, 3JH,P = 8.0 Hz, 2 H, OCH2CH3, iso-
mer A), 4.29–4.42 (m, 2 H + 2 H, OCH2CH3, isomers A/B), 7.24–
7.41 (m, 5 H + 5 H, ArCH, isomers A/B).
A/B), 5.63–5.81 (m, 1 H + 1 H, 2 × =CH, isomers A/B), 10.06 (br
s, 1 H + 1 H, 2 × N–OH, isomers A/B).
13C NMR (CDCl3): d = 13.61 (CH2CH2CH3, isomer A), 13.67
(CH2CH2CH3, isomer B), 16.24 (OCH2CH3, isomers A/B), 16.30
(OCH2CH3, isomers A/B), 22.06 (CH2, isomer A), 22.54 (CH2, iso-
mer B), 30.47 (CH2, isomer B), 34.31 (CH2, isomer A), 50.29 (d,
3JC,P = 5 Hz, CH2N, isomer A), 52.23 (CH2N, isomer B), 64.44
(OCH2CH3, isomers A/B), 64.51 (OCH2CH3, isomers A/B), 121.96
(CH=, isomer B), 122.18 (CH=, isomer A), 135.05 (CH=, isomer
B), 136.11 (CH=, isomer A), 163.80 (d, 1JC,P = 233 Hz, C=O, iso-
mer A), 163.73 (d, 1JC,P = 233 Hz, C=O, isomer B).
13C NMR (CDCl3): d = 16.07 (OCH2CH3, isomer B), 16.13
3
(OCH2CH3, isomer B), 16.35 (d, JC,P = 7 Hz, OCH2CH3, isomer
A), 16.42 (d, 3JC,P = 7 Hz, OCH2CH3, isomer A), 18.64 (c-Pr-CH2,
isomer A), 21.21 (c-Pr-CH2, isomer B), 33.57 (c-Pr-CH, isomer A),
37.17 (c-Pr-CH, isomer B), 63.15 (d, 2JC,P = 7 Hz, OCH2CH3, iso-
2
mer B), 63.64 (d, JC,P = 7 Hz, OCH2CH3, isomer B), 64.15 (d,
31P NMR (CDCl3): d = –1.98 (isomer B), 0.47 (isomer A).
2
2JC,P = 7 Hz, OCH2CH3, isomer A), 64.31 (d, JC,P = 7 Hz,
OCH2CH3, isomer A), 65.95 [d, 1JC,P = 214 Hz, C(NO2)PO(OEt)2,
Anal. Calcd for C11H22NO5P: C, 47.31; H, 7.94; N, 5.02. Found: C,
47.42; H, 8.12; N, 5.08.
1
isomer B], 66.49 [d, JC,P = 207 Hz, C(NO2)PO(OEt)2, isomer A],
128.13 (ArCH, isomer A), 128.16 (ArCH, isomer B), 128.51 (2 ×
ArCH, isomer B), 128.59 (2 × ArCH, isomer A), 128.80 (2 × ArCH,
isomer A), 129.68 (2 × ArCH, isomer B), 131.25 (ArC, isomer A),
132.76 (d, 3JC,P = 4 Hz, ArC, isomer B).
Diethyl {[1,1¢-Bi(cyclobutan)-1¢-en-1-yl(hydroxy)amino]carbo-
nyl}phosphonate (3h)
Red oil; yield: 152 mg (50%); Rf = 0.21 (50% EtOAc–PE).
31P NMR (CDCl3): d = 10.38 (isomer B), 12.52 (isomer A).
IR (thin film): 3400, 3160, 3000, 2950, 2940, 2890, 2860, 1802,
1645, 1572, 1485, 1444, 1395, 1372, 1243, 1200, 1175, 1110, 1070,
1032, 990, 978, 807, 785 cm–1.
1H NMR (CDCl3): d = 1.37 (t, 3JH,H = 7.1 Hz, 6 H, 2 × OCH2CH3),
1.84–1.89 (m, 2 H, c-Bu-CH2), 2.27–2.31 (m, 2 H, c-Bu-CH2),
2.36–2.38 (m, 2 H, c-Bu-CH2), 2.54–2.57 (m, 2 H, c-Bu-CH2),
2.58–2.63 (m, 2 H, c-Bu-CH2), 4.22–4.29 (m, 4 H, 2 × OCH2CH3),
5.90–5.92 (m, 1 H, =CH), 10.05 (br s, 1 H, N–OH).
13C NMR (CDCl3): d = 15.56 (c-Bu-CH2), 16.30 (OCH2CH3), 16.36
(OCH2CH3), 25.52 (c-Bu-CH2), 28.47 (c-Bu-C), 30.04 (2 × c-Bu-
CH2), 64.31 (OCH2CH3), 64.38 (OCH2CH3), 127.81 (=CH), 148.25
(=C), 164.52 (d, 1JC,P = 231 Hz, C=O).
Anal. Calcd for C13H18NO5P: C, 52.18; H, 6.06; N, 4.68. Found: C,
52.38; H, 6.19; N, 4.79.
Diethyl (2-Butyl-1-nitrocyclopropyl)phosphonate (3g)
Yellow oil; yield: 70 mg (25%); mixture of 2 diastereoisomers
(A/B = 73:27); Rf = 0.33 (50% EtOAc–PE).
IR (thin film): 2995, 2970, 2945, 2880, 1540, 1485, 1450, 1395,
1360, 1270, 1175, 1070, 1030, 985, 900, 885, 800, 760 cm–1.
3
1H NMR (CDCl3): d = 0.88 (t, 3 H, JH,H = 7.1 Hz, CH2CH2CH3,
3
isomer A), 0.91 (t, 3 H, JH,H = 7.1 Hz, CH2CH2CH3, isomer B),
1.30–1.39 (m, 3 H + 3 H, CH2, isomers A/B), 1.35 (t, 6 H,
31P NMR (CDCl3): d = –0.21.
3
3JH,H = 7.1 Hz, 2 × OCH2CH3, isomer A), 1.39 (t, 6 H, JH,H = 7.1
Hz, 2 × OCH2CH3, isomer B), 1.47–1.53 (m, 2 H + 2 H, CH2, iso-
mers A/B), 1.64–1.70 (m, 1 H + 1 H, CH2, isomers A/B), 1.78–1.85
(m, 1 H + 1 H, c-Pr-H, isomers A/B), 1.91–2.08 (m, 2 H + 1 H, c-
Pr-H, isomers A/B), 2.19–2.24 (m, 1 H, c-Pr-H, isomer B), 4.17–
4.25 (m, 4 H + 4 H, 4 × OCH2CH3, isomers A/B).
Anal. Calcd for C13H22NO5P: C, 51.48; H, 7.31; N, 4.62. Found: C,
51.29; H, 7.21; N, 4.93.
Diethyl (6-Oxido-5-oxa-6-azadispiro[2.0.4.2]dec-6-en-7-
yl)phosphonate (4i)
13C NMR (CDCl3): d = 13.75 (CH2CH2CH3, isomer A), 13.86
(CH2CH2CH3, isomer B), 16.24 (d, 3JC,P = 5 Hz, OCH2CH3, isomers
A/B), 16.28 (d, 3JC,P = 5 Hz, OCH2CH3, isomers A/B), 20.55 (c-Pr-
CH2, isomer A), 22.09 (CH2, isomer A), 22.16 (CH2, isomer B),
23.59 (c-Pr-CH2, isomer A), 26.34 (CH2, isomer A), 27.53 (CH2,
isomer B), 29.55 (c-Pr-CH, isomer A), 30.42 (CH2, isomer A),
31.00 (CH2, isomer B), 34.84 (c-PrCH, isomer B), 63.58
(OCH2CH3, isomer B), 63.64 (OCH2CH3, isomer B), 63.89 (d,
Yellow oil; yield: 188 mg (65%); Rf = 0.25 (50% EtOAc–PE).
IR (thin film): 3000, 2950, 2880, 1620, 1460, 1400, 1340, 1270,
1200, 1175, 1165, 1100, 1070, 1060, 990, 845, 800, 756 cm–1.
1H NMR (CDCl3): d = 0.50–0.59 (m, 3 H, c-Pr-CH2), 0.98–1.03 (m,
3
1 H, c-Pr-CH2), 1.30 (t, JH,H = 7.1 Hz, 3 H, OCH2CH3), 1.32 (t,
3JH,H = 7.1 Hz, 3 H, OCH2CH3), 1.84–1.98 (m, 2 H, c-Bu-CH2),
2.26–2.33 (m, 1 H, c-Bu-CH2), 2.60–2.67 (m, 1 H, c-Bu-CH2),
3.27–3.29 (m, 2 H, CH2), 4.12–4.21 (m, 4 H, 2 × OCH2CH3).
2
2JC,P = 6 Hz, OCH2CH3, isomer A), 64.02 (d, JC,P = 6 Hz,
13C NMR (CDCl3): d = 8.92 (t, 1JC,H = 161 Hz, c-Pr-CH2), 10.35 (t,
OCH2CH3, isomer A), 64.23 [d, 1JC,P = 212 Hz, C(NO2)PO(OEt)2,
1
1JC,H = 163 Hz, c-Pr-CH2), 16.19 (q, JC,H = 128 Hz, OCH2CH3),
isomer B], 64.99 [d, 1JC,P = 213 Hz, C(NO2)PO(OEt)2, isomer A].
16.25 (q, 1JC,H = 128 Hz, OCH2CH3), 22.56 (t, 1JC,H = 139 Hz, c-Bu-
CH2), 29.51 (Cspiro), 33.81 (t, 1JC,H = 138 Hz, c-Bu-CH2), 41.95 (dt,
1JC,H = 139 Hz, 2JC,P = 11 Hz, CH2C=N), 63.72 (dt, 1JC,H = 149 Hz,
31P NMR (CDCl3): d = 12.90 (isomer B), 13.65 (isomer A).
Anal. Calcd for C11H22NO5P: C, 47.31; H, 7.94; N, 5.02. Found: C,
47.20; H, 7.95; N, 5.06.
1
2
2JC,P = 5 Hz, OCH2CH3), 63.76 (dt, JC,H = 149 Hz, JC,P = 6 Hz,
OCH2CH3), 85.19 (d, 3JC,P = 8 Hz, Cspiro), 106.31 (d, 1JC,P = 215 Hz,
C=N).
Diethyl {[(2E,Z)-Hex-2-en-1-yl(hydroxy)amino]carbonyl}phos-
phonate (4g)
Red oil; yield: 84 mg (30%); mixture of 2 diastereoisomers (A/B =
31P NMR (CDCl3): d = 3.66.
Anal. Calcd for C12H20NO5P: C, 49.83; H, 6.97; N, 4.84. Found: C,
49.80; H, 7.07; N, 4.90.
82:18); Rf = 0.15 (50% EtOAc–PE).
IR (thin film): 3170, 3000, 2980, 2940, 2880, 1640, 1540, 1470,
1450, 1400, 1240, 1175, 1085, 1070, 985, 900, 815, 780 cm–1.
Diethyl (5-Ethoxy-2-oxido-4,5-dihydroisoxazol-3-yl)phospho-
nate (3j)
Yellow oil; yield: 245 mg (93%); Rf = 0.35 (50% EtOAc–PE).
1H NMR (CDCl3): d = 0.86–0.93 (m, 3 H + 3 H, 2 × CH2CH2CH3,
isomers A/B), 1.34–1.40 (m, 6 H + 6 H + 2 H + 2 H, 4 × OCH2CH3
+ 2 × CH2, isomers A/B), 1.99–2.12 (m, 2 H + 2 H, 2 × CH2, isomers
A/B), 4.17–4.28 (m, 4 H + 4 H + 2 H + 2 H, 4 × OCH2CH3 + 2 ×
CH2, isomers A/B), 5.44–5.55 (m, 1 H + 1 H, 2 × =CH, isomers
IR (thin film): 2995, 2950, 2925, 1628, 1480, 1450, 1400, 1380,
1340, 1275, 1215, 1175, 1105, 1060, 1030, 990, 960, 830, 790, 745
cm–1.
Synthesis 2010, No. 2, 259–266 © Thieme Stuttgart · New York

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Diethyl [Nitro(diazo)methyl]phosphonate
265
1H NMR (CDCl3): d = 1.22 (t, 3JH,H = 7.1 Hz, 3 H, CHOCH2CH3),
1.36 [t, 3JH,H = 7.1 Hz, 3 H, P(O)OCH2CH3], 1.37 [t, 3JH,H = 7.1 Hz,
3 H, P(O)OCH2CH3], 3.12 (ddd, JH,H = 17.9 Hz, JH,H = 1.1 Hz,
3JH,P = 2.8 Hz, 1 H, CH2), 3.52 (ddd, 2JH,H = 17.9 Hz, 3JH,H = 6.3 Hz,
3JH,P = 3.3 Hz, 1 H, CH2), 3.55–3.60 (m, 1 H, CHOCH2CH3), 3.85–
Acknowledgment
2
3
We thank the Russian Academy of Sciences (program ‘Biomolecu-
lar and Medicinal Chemistry’), the President’s grant ‘Support of
Leading Scientific School’, No. 5538.2008.3 (N. S. Z.) and the
Russian Foundation for Basic Research (Project 07-03-00685-a) for
financial support of this work.
3.90 (m,
1 H, CHOCH2CH3), 4.19–4.28 [m, 4 H, 2 ×
3
3
P(O)OCH2CH3], 5.54 (dd, JH,H = 6.3 Hz, JH,H = 1.1 Hz, 1 H,
CHOCH2CH3).
13C NMR (CDCl3): d = 14.73 (CHOCH2CH3), 16.01
References
2
[P(O)OCH2CH3], 16.04 [P(O)OCH2CH3], 39.89 (d, JC,P = 12 Hz,
2
(1) Sheridan, R. P. J. Chem. Inf. Comput. Sci. 2002, 42, 103.
(2) For comprehensive reviews, see: (a) Ordóñez, M.; Rojas-
Cabrera, H.; Cativiela, C. Tetrahedron 2009, 65, 17.
(b) Kafarski, B.; Lejczak, B. Phosphorus, Sulfur Silicon
Relat. Elem. 1991, 63, 193. (c) Wolfenden, R. Annu. Rev.
Biophys. Bioeng. 1976, 5, 271.
CH2C=N), 63.61 [d, JC,P = 6 Hz, P(O)OCH2CH3], 63.75 [d,
2JC,P = 6 Hz, P(O)OCH2CH3], 64.41 (CHOCH2CH3), 98.54 (d,
3JC,P = 10 Hz, CHOCH2CH3), 104.71 (d, 1JC,P = 214 Hz, C=N).
31P NMR (CDCl3): d = 3.21.
Anal. Calcd for C9H18NO6P: C, 40.45; H, 6.79; N, 5.24. Found: C,
40.47; H, 6.95; N, 5.17.
(3) For a recent review, see: Brackmann, F.; de Meijere, A.
Chem. Rev. 2007, 107, 4493.
Diethyl (2-Oxido-5-phenoxy-4,5-dihydroisoxazol-3-yl)phospho-
nate (3k)
Yellow oil; yield: 189 mg (60%); Rf = 0.30 (50% EtOAc–PE).
(4) (a) Erion, M. D.; Walsh, C. T. Biochemistry 1987, 26, 3417.
(b) Groth, U.; Lehmann, L.; Richter, L.; Schöllkopf, U.
Liebigs Ann. Chem. 1993, 427. (c) Yamazaki, S.; Takada,
T.; Moriguchi, Y.; Yamabe, S. J. Org. Chem. 1998, 63,
5919. (d) Fadel, A. J. Org. Chem. 1999, 64, 4953.
(e) Tesson, N.; Dorigneux, B.; Fadel, A. Tetrahedron:
Asymmetry 2002, 13, 2267.
(5) (a) Yashin, N. V.; Averina, E. B.; Gerdov, S. M.;
Kuznetsova, T. S.; Zefirov, N. S. Tetrahedron Lett. 2003, 44,
8241. (b) Yashin, N. V.; Averina, E. B.; Grishin, Yu. K.;
Kuznetsova, T. S.; Zefirov, N. S. Synthesis 2006, 279.
(6) (a) Averina, E. B.; Yashin, N. V.; Kuznetsova, T. S.;
Zefirov, N. S. Vestn. Mosk. Univer., Ser. 2: Khim. 2002, 43,
246; Chem. Abstr. 2002, 138, 254854. (b) Averina, E. B.;
Yashin, N. V.; Shvorina, E. B.; Grishin, Yu. K.; Kuznetsova,
T. S. Vestn. Mosk. Univer., Ser. 2: Khim. 2005, 46, 314;
Chem. Abstr. 2005, 145, 145989. (c) Yashin, N. V.;
Averina, E. B.; Grishin, Yu. K.; Kuznetsova, T. S.; Zefirov,
N. S. Synthesis 2006, 880.
IR (thin film): 2975, 2940, 2870, 1634, 1606, 1500, 1460, 1345,
1270, 1230, 1165, 1050, 1030, 974, 860, 810, 780 cm–1.
1H NMR (CDCl3): d = 1.35 (t, 3JH,H = 7.1 Hz, 3 H, OCH2CH3), 1.37
3
2
(t, JH,H = 7.1 Hz, 3 H, OCH2CH3), 3.42 (ddd, JH,H = 18.2 Hz,
3JH,H = 0.7 Hz, 3JH,P = 2.8 Hz, 1 H, CH2), 3.73 (ddd, 2JH,H = 18.2 Hz,
3JH,H = 6.4 Hz, JH,P = 3.1 Hz, 1 H, CH2), 4.20–4.29 (m, 4 H, 2 ×
3
OCH2CH3), 6.11 (dd, 3JH,H = 6.4 Hz, 3JH,H = 0.7 Hz, 1 H, CHOPh),
6.96–6.99 (m, 2 H, ArCH), 7.04–7.08 (m, 1 H, ArCH), 7.26–7.30
(m, 2 H, ArCH).
13C NMR (CDCl3): d = 16.23 (d, 3JC,P = 6 Hz, OCH2CH3), 16.25 (d,
3JC,P = 6 Hz, OCH2CH3), 40.39 (d, 2JC,P = 12 Hz, CH2C=N), 64.04
2
2
(d, JC,P = 6 Hz, OCH2CH3), 64.20 (d, JC,P = 6 Hz, OCH2CH3),
96.17 (d, 3JC,P = 10 Hz, CHOPh), 103.97 (d, 1JC,P = 214 Hz, C=N),
117.06 (2 × ArCH), 123.49 (ArCH), 129.69 (2 × ArCH), 155.59
(ArC).
(7) (a) Matveeva, E. D.; Podrugina, T. A.; Tishkovskaja, E. V.;
Tomilova, L. G.; Zefirov, N. S. Synlett 2003, 2321.
(b) Zefirov, N. S.; Matveeva, E. D. ARKIVOC 2008, (i), 1.
(c) Yashin, N. V.; Villemson, E. V.; Chemagin, A. V.;
Averina, E. B.; Kabachnik, M. M.; Kuznetsova, T. S.
Synthesis 2008, 464.
31P NMR (CDCl3): d = 2.72.
Anal. Calcd for C13H18NO6P: C, 49.53; H, 5.75; N, 4.44. Found: C,
49.38; H, 5.90; N, 4.46.
Diethyl (2-Oxido-3a,5,6,7a-tetrahydro-4H-pyrano[3,2-d]isox-
azol-3-yl)phosphonate (3l)
Yellow oil; yield: 124 mg (43%); Rf = 0.15 (50% EtOAc–PE).
(8) Regitz, M.; Weber, B.; Eckstein, U. Liebigs Ann. Chem.
1979, 1002.
(9) (a) Sifniades, S. J. Org. Chem. 1975, 40, 3562.
(b) Neimysheva, A. A.; Muratov, S. S.; Smirnov, E. V.;
Solntseva, L. M. Zh. Obshch. Khim. 1976, 46, 940; Chem.
Abstr. 1976, 85, 712. (c) Takeuchi, Y.; Ogura, H.; Kanada,
A.; Koizumi, T. J. Org. Chem. 1992, 57, 2196.
(10) Charette, A. B.; Wurz, R. P.; Ollevier, T. J. Org. Chem.
2000, 65, 9252.
(11) (a) Charette, A. B.; Wurz, R. P. J. Mol. Catal. A: Chem.
2003, 196, 83. (b) Titanyuk, I. D.; Beletskaya, I. P.;
Peregudov, A. S.; Osipov, S. N. J. Fluorine Chem. 2007,
128, 723.
(12) Charette, A. B.; Wurz, R. P.; Ollevier, T. Helv. Chim. Acta
2002, 85, 4468.
(13) Perrin, D. D.; Armarego, W. L. F. Purification of Laboratory
Chemicals; Pergamon: Oxford, 1966, 362.
(14) Calogeropoulou, T.; Hammond, G. B.; Wiemer, D. F. J. Org.
Chem. 1987, 52, 4185.
(15) Binger, P.; Brinkmann, A.; Wedemann, P. Synthesis 2002,
1344.
IR (thin film): 2990, 2955, 2880, 1695, 1620, 1460, 1450, 1400,
1370, 1335, 1270, 1230, 1170, 1120, 1060, 1045, 980, 915, 815,
780, 755 cm–1.
1H NMR (CDCl3): d = 1.33 (t, 3JH,H = 7.1 Hz, 3 H, OCH2CH3), 1.34
(t, 3JH,H = 7.1 Hz, 3 H, OCH2CH3), 1.65–1.75 (m, 3 H, CH2), 1.82–
1.91 (m, 1 H, CH2), 2.20–2.27 (m, 1 H, CH), 3.63–3.69 (m, 1 H,
CH2O), 3.85–3.90 (m, 1 H, CH2O), 4.15–4.25 (m, 4 H, 2 ×
OCH2CH3), 5.77 (d, 3JH,H = 6.3 Hz, 1 H, OCHO).
13C NMR (CDCl3): d = 16.18 (d, 3JC,P = 4 Hz, OCH2CH3), 16.24 (d,
3JC,P = 3 Hz, OCH2CH3), 19.82 (CH2), 20.36 (CH2), 44.05 (d,
2
2JC,P = 12 Hz, CHC=N), 61.32 (CH2O), 63.81 (d, JC,P = 6 Hz,
OCH2CH3), 64.00 (d, 2JC,P = 6 Hz, OCH2CH3), 97.16 (d, 3JC,P = 10
Hz, OCHO), 107.72 (d, 1JC,P = 212 Hz, C=N).
31P NMR (CDCl3): d = 3.09.
Anal. Calcd for C10H18NO6P: C, 43.01; H, 6.50; N, 5.02. Found: C,
42.94; H, 6.69; N, 4.86.
(16) Zefirov, N. S.; Kozhushkov, S. I.; Kuznetsova, T. S.;
Kokoreva, O. V.; Lukin, K. A.; Trach, S. S.; Ugrak, B. I.
J. Am. Chem. Soc. 1990, 112, 7702.
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Synthesis 2010, No. 2, 259–266 © Thieme Stuttgart · New York