Chemo- and regioselective allylic oxidation: Oxo-derivatives of 2-phospholene sugar analogs

Article abstract of DOI:10.1002/hc.10154

A convenient and facile chemo- and regioselective oxidation of the allylic methylene group in a 2-phospholene ring system afforded the novel carbonyl derivatives of 2-phospholenes (2a-i). The method gives high conversion and selectivity in the formation of allylic ketones. The advantages of this oxidation method in such a five-membered pseudo sugar 2-phospholene ring are mentioned, and the oxidation is examined on several substituted 2-phospholenes (1a-i).

Full text of DOI:10.1002/hc.10154

Heteroatom Chemistry
Volume 14, Number 4, 2003
C
hemo- and Regioselective Allylic
Oxidation: Oxo-Derivatives of
2-Phospholene Sugar Analogs
Valluru Krishna Reddy, Lakonda Nagaprasada Rao, Motoki Maeda,
Buchammagari Haritha, and Mitsuji Yamashita
Department of Materials Chemistry, Faculty of Engineering, Shizuoka University,
Hamamatsu 432-8561, Japan
Received 13 March 2002; revised 2 January 2003
INTRODUCTION
ABSTRACT: A convenient and facile chemo- and re-
gioselective oxidation of the allylic methylene group
in a 2-phospholene ring system afforded the novel
carbonyl derivatives of 2-phospholenes (2a–i). The
method gives high conversion and selectivity in the
formation of allylic ketones. The advantages of this ox-
idation method in such a five-membered pseudo sugar
A number of useful carbon–carbon bond forming re-
actions using aldehydes and ketones have been de-
veloped; efficient and reliable methods for preparing
various types of aldehydes and ketones are impor-
tant in organic synthesis. ꢀ,ꢁ-Unsaturated ketones
are extremely versatile reaction intermediates for
the preparation of various pentofuranose analogs of
phospha sugars.
2
-phospholene ring are mentioned, and the oxidation
is examined on several substituted 2-phospholenes
1a–i). ꢀC 2003 Wiley Periodicals, Inc. Heteroatom Chem
4:320–325, 2003; Published online in Wiley InterScience
www.interscience.wiley.com). DOI 10.1002/hc.10154
(
1
(
Replacement of the oxygen atom in the hemi-
acetal ring of normal sugars by a hetero or carbon
atom leads to pseudo sugars (Scheme 1), some of
SCHEME 1
Correspondence to: Mitsuji Yamashita; e-mail: tcmyama@ipc.
shizuoka.ac.jp.
Contract grant sponsor: Shizuoka Prefecture.
Contract grant sponsor: Shizuoka University.
Contract grant sponsor: Ministry of Education, Culture, Sports,
Science, and Technology, Japan.
ꢀ
c 2003 Wiley Periodicals, Inc.
3
20

Chemo- and Regioselective Allylic Oxidation: Oxo-Derivatives of 2-Phospholene Sugar Analogs 321
which have been widely investigated in synthetic, bi-
ological, and medicinal chemistry [1]. In particular,
hetero sugars in which the ring oxygen has been re-
placed by nitrogen, sulfur, or selenium atom have
been extensively studied and widely developed [2].
Phospha sugars belong to a category of pseudo sugar
derivatives having a phosphorus atom instead of the
oxygen atom in the hemiacetal ring [3] of normal
sugars (Scheme 1) and are of interest in synthesis
and structure analysis because of potent bioactivi-
ties in various fields [4]. Despite extensive studies on
the synthesis, spectrum, and bioactivity of carba [5],
aza [6], and thia sugars [7], little research has been
done on phospha sugars since they have not been
found in naturally occurring sources. Synthesis of
phospha sugars is rather difficult because of long
reaction sequences and low yields [8], and prepa-
rations generally use normal sugars as starting ma-
terials [9,10]. Hence, we wished to develop a more
general synthetic route to such phospha sugars and
have reported the successful synthesis of tetrafura-
nose analogs [11] of phospha sugars using phosp-
holenes as starting materials [12]. Our interest to
develop potential inhibitors of HIV led us to synthe-
size pentafuranose analogs of phospha sugars, such
as Ribavarin [13], AZT [14], etc., in a facile synthetic
route using phospholenes as starting materials. Con-
siderable effort has been devoted to the synthesis
of keto-derivatives of 2-phospholenes based on al-
lylic oxidation [15], because these are expected to be
the active and important precursors in the synthe-
sis of pentafuranose skeleton of phospha sugars. The
present paper deals with the improved synthesis and
structure analysis of allylic carbonyl derivatives, and
determination of selectivity using 2-phospholenes as
starting materials.
SCHEME 2 Preparation of 4-oxo-2-phospholene 1-oxides
2a–i.
Many reported reagents failed to oxidize allylic
methylene group of 2-phospholenes. For reasons
explained in our preliminary communication [16],
however, in early stages the conversion was high but
the isolated yields were low. This is mainly due to
solubility of the products (2a–i) in water during iso-
lation. We improved the isolated yields of all prod-
ucts (2a–i) and extended our oxidation method to
several substituted 2-phospholene derivatives by us-
ing less CrO than used previously. Several inter-
3
esting results have been noticed and are reported.
After completion of the oxidation, the reaction mix-
ture was diluted with CHCl
at room temperature (during this time the prod-
uct completely dissolved in CHCl improving the
isolated yield of 2a–i), followed by the slow neu-
tralization with saturated NaHCO solution. Then
the organic layer was extracted with CHCl . The
3
, stirred for 30–40 min
3
3
3
selectivity is outlined in the oxidation of 3-methyl-
substituted 2-phospholenes 1b, 1d, 1e, 1f, and 1h
(Table 1), where hydrogen atoms are abstracted
from the allylic CH
2
group but not from the CH
3
group, and the 4-oxo-2-phospholenes result. This is
an example of highly regio- and chemoselective C H
bond activation. The reaction progress is monitored
by TLC every 30 min; the rate of the reaction and
the product conversion [characterized from gel per-
meation chromatography (GPC) analysis] are fairly
enhanced by the presence of methyl group at C3 po-
sition of 2-phospholenes 1b, 1d, 1e, 1f, and 1h. The
2-phospholenes that are substituted at P atom with
sterically hindering groups 1d, 1e, and 1f (Table 1)
RESULTS AND DISCUSSION
Recently we reported allylic oxidation of 2-
phospholenes using CrO
3
in an AcOH–Ac O mixture.
2
TABLE 1 Allylic Oxidation of 2-Phospholenes 1a–i
Product
[17]
Reac.
Time (h)
Conv. (%)
[18]
Isol.
Yield (%)
Molar Ratio of
CrO3 to Substrate
R1
R2
R3
Ph
OMe
OMe
H
H
H
H
H
H
Me
H
Me
Me
Me
H
2a
2b
2c
2d
2e
2f
2g
2h
2i
4
4
4
5
6
5
5
4
5
85
90
86
80
78
82
70
75
88
62
60
55
60
62
64
55
60
66
2:1
2:1
2:1
3:1
3:1
3:1
2:1
2:1
2:1
3
4
4
-ClC H
-OMe-3,5-(NO ) C H
-OMeC H
6
4
2
2 6 2
H
6
4
Ph
Ph
Ph
Br
Br
OMe
Me
H

3
22 Reddy et al.
also produced allylic carbonyl derivatives, but the
reaction conditions, yields, and molar ratio of CrO
3
slightly differ from those of other substrates given
in Table 1. The experimental results show that there
is no considerable effect of bulky groups at P atom.
But the molecules being substituted with electron-
donating groups at C2 and C3 of 2-phospholene
afforded high conversions while electron-
withdrawing groups lowered the conversion of allylic
oxidation.
A single crystal of 2a was grown from ethyl ac-
etate by slow evaporation. Its X-ray crystallography
[19] revealed the structure depicted in Fig. 1 and
afforded bond lengths, bond and torsion angles as
shown in Table 2. The substitution of O by P in
the hemiacetal ring caused several changes in the
geometry and conformation of the five-membered
FIGURE 1 ORTEP drawing of compound 2a.
◦
ring. The C1 P1 C4 bond angle of 2a (93.1 ) differs
high conversion and selectivity, and in all cases
where comparison could be made, the yields were
improved and there was no over oxidation, and no
by-products. The reaction conditions are mild and
the work-up of the reaction mixture is easy. The
greatest synthetic use for allylic oxidation is realized
for compounds that possess only one allylic methy-
lene group.
◦
considerably from 110 of C1 O C4 in ribofuranose
◦
and 93.5 of C1 S C4 in thio sugars [20]. The bond
◦
angles of C4 P1 C5 and C1 P1 C5 (∼107 ) show
that the phenyl and phospholenone rings of 2a lie in
different planes (Fig. 1).
The P1 C1 bond is shorter than P1 C4 by
˚
˚
0
0
.029 A. Also C3 O2 is shorter than P1 O1 by
.271 A. The positive C1 P1 C4 C3 torsion angle
and the negative P1 C4 C3 C2 torsion angle of 2a
Table 2) show that the molecule is conformation-
EXPERIMENTAL
(
ally of C3-exo and C2-endo type. All other product
structures are assigned by analogy and spectral com-
parison. While the C5 methylene protons of the sub-
strates 1a–i give a complicated multiplet in the H
NMR spectrum (300 MHz), those of the products
All melting points were determined on a Mel-Temp
apparatus (Gallenkamp) and were uncorrected. TLC
was performed by using 0.2-mm-coated silica gel
plates. Column chromatography was performed on
silica gel Waco gel C-200 by using mixture of CHCl3,
EtOAc, and MeOH as the eluents. All IR spectra were
recorded on FT/IR-8000 and A-3 spectrophotometer
1
2
a–i give a clear pair of double doublets (AB part of
2
an ABX spectrum, δ
A
∼ 2.71, δ
B
∼ 2.85, JAB = JHH
∼
2
2
1
13
1
8.1 Hz, JAX = JPH ∼ 15.2 Hz, JBX = JPH ∼ 6.3 Hz).
(Japan Spectroscopic Co. Ltd., JASCO). H and
C
3
1
The P NMR signals of all the products are shifted
upfield 20–30 ppm from those of the substrates be-
cause of the electron-withdrawing nature of carbonyl
group in good agreement with earlier results [21].
In summary, a convenient and facile allylic oxi-
dation of 2-phospholenes has been developed with
NMR spectra were recorded on JNM-EX300 or JNM-
EX90 (90 MHz) spectrometer (Japan Electron Op-
1
tics Laboratory, JEOL) operating at 300.40 MHz ( H)
1
3
and 75.45 MHz ( C) using chloroform-d and TMS as
the solvent and the internal standard, respectively,
3
1
and P NMR was recorded on JEOL JNM-EX90 (at
˚
TABLE 2 Selected Bond Lengths (A) and Bond and Torsion Angles (deg) of 2a
P(1) O(1)
P(1) C(1)
P(1) C(4)
P(1) C(5)
O(2) C(3)
C(1) C(2)
C(2) C(3)
C(3) C(4)
C(5) C(10)
C(10) C(9)
1.477
1.781
1.810
1.799
1.206
1.311
1.481
1.494
1.390
1.381
O(1) P(1) C(1)
O(1) P(1) C(4)
O(1) P(1) C(5)
C(1) P(1) C(4)
C(1) P(1) C(5)
C(4) P(1) C(5)
C(1) C(2) C(3)
C(2) C(3) C(4)
C(6) C(5) C(10)
C(7) C(8) C(9)
117.3
116.9
112.4
93.1
107.3
107.9
114.4
123.6
119.4
120.3
P(1) C(1) C(2) C(3)
P(1) C(4) C(3) O(2)
P(1) C(4) C(3) C(2)
P(1) C(5) C(6) C(7)
P(1) C(5) C(10) C(9)
O(1) P(1) C(1) C(2)
C(1) P(1) C(4) C(3)
C(1) C(2) C(3) C(4)
C(7) C(6) C(5) C(10)
C(7) C(8) C(9) C(10)
−1.5
173.0
−6.6
178.5
−177.9
−124.8
4.9
5.6
−0.9
0.7

Chemo- and Regioselective Allylic Oxidation: Oxo-Derivatives of 2-Phospholene Sugar Analogs 323
3
8
6.18 MHz) spectrometer by using chloroform-d and
5% H PO as the solvent and external standard, re-
˚
˚
˚
ters, a = 6.242(3) A, b = 6.850(3) A, c = 22.536(3) A,
˚
˚
3
3
4
ꢁ
= 96.13(2) A, V = 958.0(5) A ; Z value, 4; Dcalc.
,
spectively. Mass spectra were measured on Hitachi
RMU7M GC-MS and Shimadzu GCMS-AP5050 gas
chromatograph mass spectrometers.
All starting compounds can be prepared by re-
ported methods [22,23].
3
−1
1
.332 g/cm ; F000, 400.00; ꢃ(Cu Kꢀ), 22.54 cm .
˚
Radiation Cu Kꢀ (λ = 1.54178 A); temperature,
◦
◦
2
3.0 C; scan type, ꢄ-2θ; scan rate, 16.0 /min (in ꢄ)-
◦
up to 5 scans; scan width, (1.89 + 0.30 tan θ) ;
◦
2
θ
max, 120.1 ; p-factor, 0.0010; anomalous disper-
sion, all non-hydrogen atoms; no. of observations
I > 3.00σ(I)), 1342; no. of variables, 155; reflec-
tion/parameter ratio, 8.66; residuals: R; Rw, 0.042;
.050.
(
General Procedure for the Preparation
of 4-Oxo-2-phospholene 1-oxides (2a–i)
0
The oxidation reagent was prepared by adding CrO
3
(
3 g, 30 mmol) in small portions to a mixture of
2
1
1
-Methoxy-3-methyl-4-oxo-2-phospholene
-oxide (2b)
Ac O (7.5 ml) and glacial AcOH (15 ml), followed
by dilution with benzene or dichloromethane un-
der ice cooling. To this reagent was added slowly
the 2-phospholene 1a–i (6 mmol) in benzene or
dichloromethane (5 ml), and the reaction mixture
was stirred for 4–5 h at 0–20 C. After complete ox-
idation, the reaction mixture was diluted with 30
ml of CHCl
temperature followed by slow neutralization with
saturated NaHCO solution. Then the organic layer
was extracted with CHCl
(2 × 40 ml) and dried
over anhydrous Na SO . Evaporating the solvent
1
Yield 60% [24], semisolid. H NMR (CDCl ): δ 1.91
(s, 3H, CH ), 2.52 (dd, 2H, H-5,5 , J 17.2 Hz, JPH 6.6
Hz), 3.71 (d, 3H, OCH , J 16.2 Hz), 6.92–7.12 (dd,
1H, H-2, J 15.1 Hz, JHH 1.8 Hz). C NMR (CDCl ):
δ 13.4 (d, J 19.2 Hz, CH ), 32.1 (d, J 102.1 Hz,
C-5), 52.3 (d, J 6.1 Hz, OCH ), 139.1 (d, J 113.1
Hz, C-2), 157.3 (d, J 2.6 Hz, C-3), 194.8 (d, J 27.3
3
ꢁ
3
HH
3
PH
◦
13
PH
3
3
CP
3
CP
3
3
, and stirred for 30–40 min at room
CP
3
CP
2
2
CP
CP
3
1
3
Hz, C O). P NMR (CDCl ): δ 46.1. MS: m/z = 160
3
+
−1
3
(M ). IR (neat): ꢂ (cm ) 1729 (C O), 1655 (C C),
2
4
1261 (P O).
in a vacuum afforded products 2a–i (Scheme 2).
They were purified by flash chromatography us-
ing EtOAc–MeOH (20:1) as eluent and recycled
by GPC.
1
-Methoxy-4-oxo-2-phospholene 1-oxide (2c)
◦
1
Yield 55%, solid, mp 72–75 C. H NMR (CDCl
3
): δ
ꢁ
2
.72 (dd, 1H, H-5,5 , JHH 16.6 Hz, JPH 6.1 Hz), 2.88
ꢁ
(dd, 1H, H-5,5 , JHH 16.6 Hz, JPH 12.6 Hz), 3.75 (d,
1-Phenyl-4-oxo-2-phospholene 1-oxide (2a)
3
H, OCH , JPH 17.4 Hz), 6.99–7.11 (dd, 1H, H-2, JPH
3
◦
1
13
Yield 62%, solid, mp 92–95 C. H NMR (CDCl
3
): δ
12.9 Hz, JHH 1.5 Hz). C NMR (CDCl ): δ 32.4 (d, J
102.2 Hz, C-5), 52.8 (d, J 6.9 Hz, OCH ), 140.6 (d,
JCP 112.9 Hz, C-2), 157.4 (d, J 8.7 Hz, C-3), 195.3
(d, J 27.4 Hz, C O). P NMR (CDCl ): δ 47.7. MS:
3
CP
ꢁ
3
2
.71 (dd, 1H, H-5,5 , JPH 6.3 Hz, JHH 18.1 Hz), 2.85
dd, 1H, H-5,5 , JPH 15.2 Hz, JHH 18.1 Hz), 6.91 (d,
CP
3
ꢁ
2
(
CP
2
31
1
7
H, H-3, JPH 8.3 Hz), 7.17 (d, 1H, H-2, JPH 8.1 Hz),
CP
3
1
3
+
−1
.52–7.65 (m, 5H, Ph). C NMR (CDCl
3
): δ 36.8 (d,
m/z = 146 (M ). IR (neat): ꢂ (cm ) 1712 (C O), 1645
3
JCP 75.4 Hz, C-5), 128.2 (d, JCP 12.1 Hz, m-Ph), 130.1
(C C), 1250 (P O).
2
4
(d, JCP 10.1 Hz, o-Ph), 131.3 (d, JCP 2.6 Hz, p-Ph),
2
1
33.1 (d, JCP 97.5 Hz, x-Ph), 147.2 (d, JCP 8.2 Hz,
2
1-(3-Chlorophenyl)-3-methyl-4-oxo-
2-phospholene 1-oxide (2d)
C-3), 150.3 (d, JCP 76.5 Hz, C-2), 196.5 (d, JCP 21.8
Hz, C O). P NMR (CDCl
3
1
3
): δ 36.9. MS: m/z = 192
+
−1
(M ). IR (KBr): ꢂ (cm ) 1730 (C O), 1640 (C C),
1
Yield 60%, semisolid. H NMR (CDCl
CH
3
): δ 1.97 (s, 3H,
1
4
260 (P O). Anal. Calcd for C10
.72. Found: C, 62.66; H, 4.77.
H
9
PO
2
: C, 62.51; H,
ꢁ
3
), 2.92 (dd, 2H, H-5,5 , JHH 16.1 Hz, JPH 5.5 Hz),
6
.92–7.12 (dd, 1H, H-2, JPH 15.1 Hz, JHH 1.8 Hz), 7.2–
1
3
7
J
.7 (m, 4H of Ph). C NMR (CDCl
3
): δ 13.2 (d, CH
3
,
3
CP 16.1 Hz), 37.1 (d, C-5, JCP 75.1 Hz), 142.1 (d, C-
Crystal Data for 2a
2
2
, JCP 85.1 Hz), 158.3 (d, C-3, JCP 5.1 Hz), 128.47
2
2
Rigaku AFC7R X-ray diffractometer with four-
axis goniometer was used. Empirical formula,
(d, o-Ph, p-Cl, JCP 9.3 Hz), 129.85 (d, o-Ph, o-Cl, JCP
12.7 Hz), 130.24 (d, m-Ph, m-Cl, JCP 11.3 Hz), 131.57
(d, p-Ph, o-Cl, JCP 2.7 Hz), 134.78 (d, x-Cl, JCP 15.3
Hz), 136.51 (d, x-Ph, JCP 92.8 Hz), 195.8 (d, JCP 19.9
Hz, C O). P NMR (CDCl
(M ), 242 (M + 2).
3
4
3
C
10
H
9
PO
2
; formula weight, 192.15; crystal color
2
and habit, colorless and prismatic; crystal dimen-
3
1
sions, 0.50 × 0.50 × 0.70 mm; crystal system, mon-
3
): δ 29.23. MS: m/z = 240
+
+
oclinic; space group, P2
1
/n(#14); lattice parame-

3
24 Reddy et al.
1
3
1
4
-(4-Methoxy-3,5-dinitrophenyl)-3-methyl-
-oxo-2-phospholene 1-oxide (2e)
(m, 5H, Ph). C NMR (CDCl
3
): δ 35.6 (d, JCP 74.8 Hz,
2
C-5), 114.4 (d, JCP 94.2 Hz, C-2), 158.4 (d, JCP 6.0 Hz,
C-3), 128.2 (d, JCP 12.1 Hz, m-Ph), 130.1 (d, JCP 10.1
Hz, o-Ph), 131.3 (d, JCP 2.6 Hz, p-Ph), 133.1 (d, JCP
7.5 Hz, x-Ph), 195.9 (d, JCP 20.0 Hz, C O). P NMR
3
2
1
Yield 62%, semisolid. H NMR (CDCl
3
): δ 1.68 (s, 3H,
4
ꢁ
CH
.12 (s, 3H, OCH
HH 1.4 Hz), 8.92 (s, 2H, Ph). C NMR (CDCl
3
), 2.42 (dd, 2H, H-5,5 , JHH 16.7 Hz, JPH = 6.2 Hz),
2
31
9
4
J
3
), 7.12 (dd, 1H, H-2, JPH 15.8 Hz,
+
+
(
CDCl
3
): δ 29.23. MS: m/z = 284 (M ), 286 (M + 2).
1
3
3
): δ
), 35.6 (d, JCP 75.0 Hz, C-
), 141.1 (d, JCP 84.2 Hz, C-2), 158.5
3
1
5
3.27 (d, JCP 16.2 Hz, CH
), 62.82 (s, OCH
3
1
-Phenyl-2-methoxy-4-oxo-2-phospholene
3
2
3
1-oxide (2i)
(d, JCP 6.0 Hz, C-3), 152.1 (d, JPC 13.6 Hz, m-Ph, o-
2
OMe), 130.28 (d, JPC 11.8 Hz, o-Ph, m-OMe), 132.26
1
Yield 66%, semisolid. H NMR (CDCl
H, H-5,5 , JPH 4.5 Hz, JHH 18.9 Hz), 3.18 (dd, 1H,
H-5,5 , JPH 16.1 Hz, JHH 18.9 Hz), 3.79 (d, 3H, OCH ,
PH 14.6 Hz), 7.11 (d, 1H, H-3, JPH 15.2 Hz), 7.47 (m,
H of Ph). C NMR (CDCl ): δ 35.1 (d, JCP 67.0 Hz,
C-5), 114.1 (d, JCP 88.2 Hz, C-2), 158.5 (d, JCP 6.0
Hz, C-3), 126.2 (d, JCP 11.1 Hz, m-Ph), 128.1 (d, JCP
0.5 Hz, o-Ph), 131.3 (d, JCP 2.6 Hz, p-Ph), 133.1 (d,
3
): δ 2.99 (dd,
4
(d, JPC 92.6 Hz, x-Ph, p-OMe), 149.56 (d, JPC 2.4 Hz,
ꢁ
1
2
31
p-Ph, x-OMe), 195.9 (d, JCP 20.9 Hz, C O). P NMR
ꢁ
3
+
(
(
CDCl
3
): δ 29.22. MS: m/z = 326 (M ). IR (neat): ꢂ
J
5
−1
cm ) 1731 (C O), 1530 and 1350 (NO
P: C, 44.19; H, 3.40; N, 8.59. Found:
C, 44.01; H, 3.38; N, 8.61.
2
). Anal. Calcd
13
3
for C12
H
11
O
7
N
2
2
3
2
4
1
2
31
1
2
-(4-Methoxyphenyl)-3-methyl-4-oxo-
-phospholene 1-oxide (2f)
J
CP 98.5 Hz, x-Ph), 201.1 (d, JCP 21.1 Hz, C O).
P
+
NMR (CDCl
3
): δ 25.9. MS: m/z = 222 (M ). IR (neat):
−
1
ꢂ (cm ) 1732 (C O).
1
Yield 64%, semisolid. H NMR (CDCl
CH
3
): δ 1.99 (s, 3H,
ꢁ
3
), 2.88 (dd, 1H, H-5,5 , JPH 5.2 Hz, JHH 18.7 Hz),
ꢁ
2
(
1
.95 (dd, 1H, H-5,5 , JPH 15.9 Hz, JHH 18.7 Hz), 4.12
s, 3H, OCH ), 7.12 (dd, 1H, H-2, JPH 15.1 Hz, JHH
.8 Hz), 6.92 (dd, 2H of Ph, JHH 6.7 Hz), 7.54 (dd, 1H
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3
[
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H.; Inokawa, S.; Yamashita, M.; Armour, M. A.;
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4] (a) Yamashita, M.; Nakatsukasa, Y.; Yoshikane, M.;
Yoshida, H.; Ogata, T.; Inokawa, S. Carbohydr Res
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Y.; Yoshida, H.; Ogata, T.; Inokawa, S.; Hirotsu,
K.; Clardy, J. Carbohydr Res 1979, 70, 247;
1
3
of Ph, JHH 6.7 Hz, JPH 12.9 Hz). C NMR (CDCl
3
): δ
), 37.6 (d, JCP 75.0 Hz, C-
), 141.8 (d, JCP 88.2 Hz, C-2), 158.7
3
1
5
3.27 (d, JCP 16.8 Hz, CH
), 62.82 (s, OCH
3
3
2
3
(d, JCP 6.0 Hz, C-3), 152.11 (d, JPC 13.6 Hz, m-Ph, o-
2
OMe), 130.28 (d, JPC 11.8 Hz, o-Ph, m-OMe), 132.26
4
(d, JPC 92.6 Hz, x-Ph, p-OMe), 149.56 (d, JPC 2.4 Hz,
[
2
31
p-Ph, x-OMe), 199.9 (d, JCP 20.6 Hz, C O). P NMR
+
(
(
CDCl
cm ) 1729 (C O).
3
): δ 20.01. MS: m/z = 236 (M ). IR (neat): ꢂ
−1
(
c) Yamada, M.; Yamashita, M. Carbohydr Res 1981,
1
1
-Phenyl-2-bromo-4-oxo-2-phospholene
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95, C9; (d) Yamashita, M.; Yamada, M.; Tsunekawa,
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Res 1983, 121, C4; (e) Yamashita, M.; Yamada, M.;
Sugiura, M.; Nomoto, H.; Oshikawa, T. J Chem Soc
Jpn 1987, 1207; (f) Yamamoto, H.; Inokawa, S. Adv
Carbohydr Chem Biochem 1984, 42, 135.
1
Yield 55%, semisolid. H NMR (CDCl
3
): δ 2.93 (dd,
ꢁ
1H, H-5,5 , JPH 4.5 Hz, JHH 18.6 Hz), 3.08 (dd, 1H,
ꢁ
H-5,5 , JPH 16.5 Hz, JHH 18.6 Hz), 7.21 (d, 1H, H-3,
[
5] (a) Madhavan, G. V. B.; Martin, J. C. J Org Chem 1986,
1
3
JPH 14.1 Hz), 7.47 (m, 5H of Ph). C NMR (CDCl
3
):
5
1
1, 1287; (b) Maag, H.; Rydzwski, R. M. J Org Chem
992, 57, 5823; (c) Patil, S. D.; Koga, M.; Schneller, S.
δ 27.3 (d, JCP 65.0 Hz, C-5), 141.1 (d, JCP 84.2 Hz, C-
2
3
2), 158.5 (d, JCP 6.0 Hz, C-3), 127.2 (d, JCP 12.1 Hz,
W.; Snoeck, R.; De Clercq, E. J Med Chem 1992, 35,
2191; (d) Wang, P.; Agrofoglio, L. A.; Newton, M. G.;
Chu, C. K. J Org Chem 1999, 64, 4173; (e) Cowart, M.;
Bennett, M. J.; Kerwin, J. F., Jr. J Org Chem 1999, 64,
2
4
m-Ph), 129.1 (d, JCP 10.1 Hz, o-Ph), 131.3 (d, JCP
.6 Hz, p-Ph), 132.1 (d, JCP 97.5 Hz, x-Ph), 195.9 (d,
2
2
31
J
CP 20.9 Hz, C O). P NMR (CDCl ): δ 35.5. MS:
3
2
240.
6] (a) Legler, G.; Julich, E. Carbohydr Res 1984, 128,
1; (b) Takayama, S.; Martin, R.; Wu, J.; Laslo, K.;
Siuzdak, G.; Wong, C. H. J Am Chem Soc 1997, 119,
146; (c) Momotake, A.; Togo, H.; Yokoyama, M. J
+
+
m/z = 270 (M ), 272 (M + 2).
[
[
6
1
2
-Phenyl-2-bromo-3-methyl-4-oxo-
-phospholene 1-oxide (2h)
8
Chem Soc, Perkin Trans I 1999, 1193.
7] (a) Branalt, J.; Kvarnstrom, I.; Niklasson, G.;
Svensson, S. C. T. J Org Chem 1994, 59, 1783;
1
Yield 60%, semisolid. H NMR (CDCl
CH
3
): δ 1.22 (s, 3H,
ꢁ
3
), 2.33 (dd, 1H, H-5,5 , JHH 18.6 Hz, JPH 4.8 Hz),
(
b) Secrist, J. A., III; Riggs, R.; Tiwari, K. N.;
ꢁ
2.98 (dd, 1H, H-5,5 , JHH 18.6 Hz, JPH 16.5 Hz), 7.47
Montgomery, J. A. J Med Chem 1992, 35, 533;

Chemo- and Regioselective Allylic Oxidation: Oxo-Derivatives of 2-Phospholene Sugar Analogs 325
(
1
c) Dyson, M. R.; Coe, P. L.; Walker, R. T. J Med Chem
991, 34, 2782.
[17] For optical resolution of product 2a, see: Bodalski,
R.; Janacke, T.; Galdecki, Z.; Glowka, M. Phosphorus
Sulfur Silicon 1982, 14, 15.
[18] Percentage of conversion was determined from GPC
analysis. The unreacted starting material was recov-
ered from column chromatography.
[
[
8] Yamamoto, H.; Inokawa, S. Adv Carbohydr Chem
Biochem 1984, 42, 135.
9] Yamashita, M.; Yamada, M.; Sugiura, M.; Nomoto,
H.; Oshikawa, T. Nippon Kagaku Kaishi 1987, 1207.
[
[
10] Yamamoto, H.; Hanaya, T. In Studies in Natural Prod-
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[19] Tables of atomic coordinates, bond lengths, and bond
angles have been deposited (deposition number:
CCDC 195398) with the Cambridge Crystallographic
Data Centre. These tables may be obtained on request
from the Director, Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge CB2IEZ, UK;
e-mail: deposit@ccdc.cam.ac.uk.
[
[
[
12] Yamashita, M.; Uchimura, M.; Iida, A.; Parkanayi, L.;
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8
2, 7096.
[
[
15] Nakayama, M.; Shinke, S.; Matsushita, Y.; Ohira, S.;
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16] Reddy, V. K.; Rao, L. N.; Maeda, M.; Oshikawa, T.;
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[24] 1-Methoxy-2-phospholene derivatives are more
soluble in water than 1-phenyl-2-phospholenes.
3
2, 69.