An efficient synthesis of ,β,γ-disubstituted α-diethoxyphosphoryl- γ-lactones: A convenient approach to α-methylene-γ-lactones

Article abstract of DOI:10.1080/10426500902719313

A synthesis of β, γ-disubstituted-diethoxyphosphoryl--lactones from easily available dicyclohexylammonium 3-aryl-2-diethoxyphosphoryl-4- oxopentanoates is reported. The phosphonolactones were transformed into the corresponding α-methylene-γ-lactones by means of the Horner-Wadsworth-Emmons reaction with formaldehyde.

Full text of DOI:10.1080/10426500902719313

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Phosphorus, Sulfur, and Silicon
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An Efficient Synthesis
of β,γ -Disubstituted α -
Diethoxyphosphoryl-γ -
lactones: A Convenient
Approach to α -Methylene-γ -
lactones
Henryk Krawczyk a & Łukasz Albrecht a
a Institute of Organic Chemistry, Technical University
(Politechnika) , Łódź, Poland
Published online: 26 Mar 2009.
To cite this article: Henryk Krawczyk & Łukasz Albrecht (2009) An Efficient Synthesis
of β,γ -Disubstituted α -Diethoxyphosphoryl-γ -lactones: A Convenient Approach to
α -Methylene-γ -lactones, Phosphorus, Sulfur, and Silicon and the Related Elements,
184:4, 963-978, DOI: 10.1080/10426500902719313
To link to this article: http://dx.doi.org/10.1080/10426500902719313
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Phosphorus, Sulfur, and Silicon, 184:963–978, 2009
Copyright © Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500902719313
An Efficient Synthesis of β,γ-Disubstituted
α-Diethoxyphosphoryl-γ-lactones: A Convenient
Approach to α-Methylene-γ-lactones
Henryk Krawczyk and Łukasz Albrecht
Institute of Organic Chemistry, Technical University (Politechnika),
Lꢀ o´dz´, Poland
A synthesis of β,γ-disubstituted α-diethoxyphosphoryl-γ-lactones from easily avail-
able dicyclohexylammonium 3-aryl-2-diethoxyphosphoryl-4-oxopentanoates is re-
ported. The phosphonolactones were transformed into the corresponding α-
methylene-γ-lactones by means of the Horner–Wadsworth–Emmons reaction with
formaldehyde.
Keywords
α-Alkylidene-γ-lactones;
α-diethoxyphosphoryl-γ-lactones;
Horner–
Wadsworth–Emmons reaction
INTRODUCTION
The α-alkylidene-γ-lactone system is widely distributed in nature, and
some derivatives have been shown to exhibit biological and pharmaco-
logical activity.1−8 The α-alkylidene-γ-lactones are also very attractive
precursors for a wide variety of compounds, since they can readily un-
dergo reduction,9−11 oxidation,12 aziridination,13 1,3-dipolar14,15 and
Diels–Alder cycloadditions,16−18 nucleophilic conjugate additions,16−18
cross-metathesis reactions,19,20 and intramolecular Stetter reactions.21
Therefore a significant effort has been devoted towards development of
methods for their simple and efficient preparation. Over the years, sev-
eral approaches for the synthesis of α-alkylidene-γ-lactones have been
reported.22−37
Received 20 December 2007; accepted 29 January 2008.
Dedicated to Professor Marian Mikolꢀajczyk from the CBMiM PAN in Lꢀ o´dz´, Poland,
on the occasion of his 70th birthday.
This work was financed by the Ministry of Education and Science (Project No. 3 T09A
075 28).
Address correspondence to Henryk Krawczyk, Institute of Organic Chemistry,
˙
Technical University (Politechnika), Zeromskiego 116, 90-924 Lꢀ o´dz´, Poland. E-mail:
henkrawc@p.lodz.pl
963

964
H. Krawczyk and Ł. Albrecht
Recently, we have been involved in the chemistry of α-
diethoxyphosphoryl-γ-38−40 and δ-lactones.41−46 In our previous work
we have reported the synthesis of β- and γ-monosubstituted α-
diethoxyphosphoryl-γ-lactones.38−40 We have also demonstrated that
the Horner—Wadsworth–Emmons reaction of the corresponding α-
diethoxyphosphoryl-γ-lactones with formaldehyde constitutes a use-
ful method for the preparation of α-methylene-γ-lactones.38 More-
over, we have discovered that α-diethoxyphosphoryl-γ-lactones can be
successfully used as starting materials for the preparation of ethyl
cyclopropanecarboxylates.39−40 We have come to the conclusion that
both of these methodologies would significantly benefit from the avail-
ability of functionalized α-diethoxyphosphoryl-γ-lactones.
In the course of our earlier studies, we reported the synthe-
sis of 3-aryl-2-diethoxyphosphoryl-4-nitroalkanoic acids 1 as well as
their conversion into the corresponding 3-aryl-2-diethoxyphosphoryl-
4-oxopentanoic acids 3 by means of a spontaneous Nef reaction.47 The
resulting acids were isolated as dicyclohexylammonium salts 2. It be-
came clear that alkanoates of this type are particularly well suited for
the preparation of β,γ-disubstituted α-diethoxyphosphoryl-γ-lactones.
This article reports on an effective and original synthesis of a series
of β,γ-disubstituted α-diethoxyphosphoryl-γ-lactones 7 from the salts
2. Transformation of α-diethoxyphosphoryl-γ-lactones 7 into the corre-
sponding α-methylene-γ-lactones 8 is also described.
RESULTS AND DISCUSSION
Scheme 1 outlines the transformation of dicyclohexylammonium 3-
aryl-2-diethoxyphosphoryl-4-oxopentanoates 2 into the corresponding
α-methylene-γ-lactones 8. The salts 2 were subjected to ion-exchange
chromatography. It was found that the pure acids 3 could not be ob-
tained by this method, most likely due to equilibrium with the cor-
responding γ-hydroxylactones 4. Therefore, we decided to convert the
mixtures of the products obtained directly to the esters 5. The esterifi-
cation was performed using methyl iodide in the presence of potassium
carbonate and provided the corresponding esters 5 in high yields, each
as a mixture of diasteroisomers in a ratio shown in Table I.
With the suitable substrates in hand, we turned our attention
to their effective conversion into substituted α-methylene-γ-lactones
8. The chemoselective reduction of the carbonyl group in the γ-
oxoalkanoates 5 with potassium borohydride afforded the correspond-
ing γ-hydroxyalkanoates 6, which spontaneously lactonized to the cor-
responding α-diethoxyphosphoryl-γ-lactones 7. The 31P NMR spectra

β, γ-Disubstituted α-Diethoxyphosphoryl-γ-lactones
965
SCHEME 1 Reagents and conditions: (a) H2O, reflux; (b) cHex2NH (1.1 equiv),
CH2Cl2, rt; (c) Dowex 50W, acetone/water, (d) K2CO3 (2.1 equiv), CH3I (4 equiv),
acetone, rt, 4 days; (e) KBH4 (1.5 equiv), MeOH, O◦C, 65 minutes; (f) t-BuOK
(1.2 equiv), THF, rt, 0.5 h.; then (HCHO)n (5 equiv), THF, rt, 1 h.
TABLE I Methyl 4-Aryl-2-diethoxyphosphoryl-4-oxopentanoates
5a–e, 4-Aryl-3-diethoxyphosphoryl-5-methyldihydrofuran-2(3H)-ones
7a–e, and 4-Aryl-5-methyl-3-methylenedihydrofuran-2(3H)-ones 8a–e
Prepared
α-Diethoxyphosphoryl- α-Methylene-
4-Oxopentanoates 5
γ-lactones 7
γ-lactones 8
Yield
[%]
Yield
[%]
Yield
[%] (cis:trans)
dr
Ar
dr
dr
a
b
c
d
e
4-NO2-C6H4-
4-Br-C6H4-
4-CH3-C6H4-
4-CH3O-C6H4-
90
92
81
87
1:0.09
1:0.14
1:0.52
1:0.40
1:0.42
76
88
85
77
78
0.51:1
0.68:1
0.87:1
0.94:1
0.95:1
72
76
61
71
66
0.51:1
0.68:1
0.87:1
0.94:1
0.95:1
3,4-(OCH2O)C6H3- 92

966
H. Krawczyk and Ł. Albrecht
of these compounds revealed the presence of two signals in a ra-
tio shown in Table I. The mixtures of diastereomeric lactones could
1
not be separated by column chromatography. The H NMR data indi-
cated that diastereomeric lactones 7 differed in relative configuration
at the stereogenic centers C-4 and C-5. Unfortunately, the spectral
data were insufficient to assign unequivocally the relative configura-
tion of the stereogenic centers C-3 and C-4. The relative stereochem-
istry was assigned to be trans by analogy with the results of our earlier
work.40
Then we focused our attention on the Horner—Wadsworth–Emmons
olefination of formaldehyde with α-diethoxyphosphoryl-γ-lactones 7.
The reaction was performed in diethyl ether in the presence of
potassium tert-butoxide as a base following our previously described
procedure42 and provided α-methylene-γ-lactones 8, each as a mixture
of two diastereoisomers. The mixtures of diastereomeric lactones were
separated by column chromatography. The assignment of relative con-
figuration to particular diastereoisomers was based on the analysis of
1
the H NMR spectra, by taking into account the shielding effect ex-
erted by the aryl group and methyl group on the substituents at C-4
and C-5 located in the cis position. In general, the signals from the
substituents (methyl group, C-4 and C-5 protons) cis-oriented to aryl
or methyl group appeared at higher field with respect to those of trans-
oriented substituents. It is worth noting that the ratios of diastere-
omeric α-methylene-γ-lactones 8 reflect the degree of diastereoselection
which is attained in the reduction of oxoesters 5.
In conclusion, we have succeeded in developing the simple
and efficient synthesis of β,γ-disubstituted α-diethoxyphosphoryl-
γ-lactones from easily available dicyclohexylammonium 3-aryl-2-
diethoxyphosphoryl-4-oxopentanoates. Moreover, we have shown that
the corresponding α-phosphono-γ-lactones can be utilized for the syn-
thesis of biologically important α-methylene-γ-lactones. The protocol
benefits from easily available starting materials, experimental sim-
plicity, and high efficiency.
EXPERIMENTAL
NMR spectra were recorded with a Bruker DPX 250 instrument at
250.13 MHz for 1H, 62.9 MHz for 13C, and 101.3 MHz for 31P, us-
ing tetramethylsilane as an internal and 85% H3PO4 as an exter-
nal standard. The number of protons at the carbon atoms was deter-
mined by DEPT experiments. IR spectra were measured with a Specord
M80 (Zeiss) instrument. Elemental analyses were performed with a

β, γ-Disubstituted α-Diethoxyphosphoryl-γ-lactones
967
Perkin-Elmer PE 2400 analyzer. Melting points were determined in
open capillaries and are uncorrected. Dicyclohexylammonium 3-aryl-
2-diethoxyphosphoryl-4-oxopentanoates 2a–e were prepared according
to the previously described procedure.47
Methyl 3-Aryl-2-(diethoxyphosphoryl)-4-oxopentanoates 5a–e:
General Procedure
Ion-exchange chromatography of the salts 2 was performed on a glass
column packed with Dowex 50W using H2O/acetone (1:1) as eluent. The
eluent was evaporated under reduced pressure, affording the crude
acids 3 as viscous oils, which were subjected to the next step with-
out any further purification. To a solution of a corresponding acid 3
(3 mmol) in acetone (15 mL), K2CO3 (869 mg, 6.3 mmol) and methyl
iodide (1.704 g, 12 mmol) were added, and the resulting mixture was
stoppered tightly and stirred at room temperature for 4 days. The re-
action progress was occasionally monitored by 31P NMR spectroscopy.
After the acid 3 was completely reacted, the acetone was removed under
reduced pressure, and water was added (10 mL). The water layer was
extracted with CH2Cl2 (2 × 15 mL). The combined organic layers were
dried over MgSO4. Evaporation of the solvent under reduced pressure
afforded a crude product, which was purified by column chromatog-
raphy (eluent:ethyl acetate/hexane 2:1) or crystallized from diethyl
ether.
Methyl 2-(Diethoxyphosphoryl)-3-(4-nitrophenyl)-4-
oxopentanoate (5a)
(1.046 g, 90%), white solid. IR (CCl4): ν = 1728, 1528, 1344, 1288,
1152, 1016 cm−1
.
31P NMR (CDCl3): δ = 20.0, 20.4 (1 : 0.09); (2R∗,3S∗)-
5a: 31P NMR (CDCl3): δ = 20.0. 1H NMR (CDCl3): δ = 1.08 (t, 3JHH = 7.1
3
Hz, 3H, CH3CH2OP), 1.16 (t, JHH = 7.1 Hz, 3H, CH3CH2OP), 2.09 (s,
5
3H, CH3CO), 3.68–4.03 (m, 3H, CH3CH2OP, CHP), 3.79 (d, JPH = 0.6
Hz, 3H, CH3OC, major), 4.05–4.25 (d, 2H, CH3CH2OP), 4.68 (dd, 3JHH
=
3
3
11.7 Hz, JPH = 7.7 Hz, 1H, CHAr), 7.50 (d, JHH = 8.8 Hz, 2H, arom-
3
H), 8.22 (d, JHH = 8.8 Hz, 2H, arom-H). 13C NMR (CDCl3): δ = 15.7
(d, 3JPC = 4.1 Hz,CH3CH2OP), 15.8 (d, 3JPC = 5.4 Hz,CH3CH2OP), 28.6
(CH3CO), 47.9 (d, 1JPC = 131.5 Hz, PCH), 52.6 (ArCH), 57.0 (COOCH3),
62.4 (d, 2JPC = 6.5 Hz, CH3CH2OP), 62.6 (d, 2JPC = 6.8 Hz, CH3CH2OP),
2
123.7 (CHAr), 130.2 (CHAr), 141.7 (CAr), 147.5 (CAr), 168.6 (d, JPC
=
3
5.1 Hz, COOCH3), 204.3 (d, JPC = 16.2 Hz, CH3CO). Anal. Calcd for
C16H22NO8P: C, 49.62; H, 5.73; N, 3.62. Found: C, 49.54; H, 5.67; N,
3.52%.

968
H. Krawczyk and Ł. Albrecht
Methyl 3-(4-Bromophenyl)-2-(diethoxyphosphoryl)-4-
oxopentanoate (5b)
(1.162 g, 92%), white solid. IR (CCl4): ν = 1720, 1488, 1348,
1292, 1256, 1156, 1024 cm−1
.
31P NMR (CDCl3): δ = 20.9, 21.3 (1:
3
4
0.14). 1H NMR (CDCl3): δ = 1.08 (dt, JHH = 7.1 Hz, JHP = 0.5
3
4
Hz, 3H, CH3CH2OP, major), 1.15 (dt, JHH = 7.1 Hz, JHP = 0.6 Hz,
3
4
3H, CH3CH2OP, major), 1.30 (dt, JHH = 7.1 Hz, JHP = 0.6 Hz, 3H,
3
4
CH3CH2OP, minor), 1.38 (dt, JHH = 7.1 Hz, JHP = 0.6 Hz, 3H,
CH3CH2OP, minor), 2.05 (s, 3H, CH3CO, major), 2.19 (s, 3H, CH3CO,
5
minor), 3.47 (d, JPH = 0.6 Hz, 3H, CH3OC, minor), 3.63–4.01 (m, 3H,
5
CH3CH2OP, CHP), 3.77 (d, JPH = 0.7 Hz, 3H, CH3OC, major), 4.03–
4.24 (d, 2H, CH3CH2OP), 4.43 (dd, 3JHH = 11.7 Hz, 3JPH = 10.1 Hz, 1H,
CHAr, minor), 4.52 (dd, 3JHH = 11.8 Hz, 3JPH = 7.9 Hz, 1H, CHAr, ma-
jor), 7.15 (d, 3JHH = 8.6 Hz, 2H, arom-H, minor), 7.18 (d, 3JHH = 8.5 Hz,
3
2H, arom-H, major), 7.43 (d, JHH = 8.6 Hz, 2H, arom-H, minor), 7.48
3
(d, JHH = 8.5 Hz, 2H, arom-H, major). 13C NMR (CDCl3): δ = 15.5 (d,
3JPC = 6.0 Hz,CH3CH2OP, major), 15.6 (d, JPC = 6.1 Hz,CH3CH2OP,
3
3
major), 15.8 (d, JPC = 5.3 Hz,CH3CH2OP, minor), 28.0 (CH3CO, ma-
jor), 28.9 (CH3CO, minor), 47.7 (d, 1JPC = 131.7 Hz, PCH, major), 47.8
1
(d, JPC = 127.0 Hz, PCH, minor), 51.8 (ArCH, minor), 52.2 (ArCH,
4
major), 55.5 (d, JPC = 2.3 Hz, COOCH3, minor), 56.6 (COOCH3, ma-
jor), 62.0 (d, 2JPC = 6.7 Hz, CH3CH2OP, major), 62.2 (d, 2JPC = 6.8 Hz,
2
CH3CH2OP, major), 62.6 (d, JPC = 6.7 Hz, CH3CH2OP, minor), 62.7
2
(d, JPC = 6.7 Hz, CH3CH2OP, minor), 121.7 (CAr, minor), 121.8 (CAr,
major), 129.9 (CHAr, minor), 130.7 (CHAr, major), 131.6 (CHAr), 133.2
(CAr, major), 133.9 (d, 3JPC = 16.2 Hz, CAr, minor), 167.0 (d, 2JPC = 5.3
Hz, COOCH3, minor), 168.6 (d, 2JPC = 4.9 Hz, COOCH3, major), 203.9
(CH3CO, minor), 204.8 (d, 3JPC = 16.6 Hz, CH3CO, major). Anal. Calcd.
for C16H22BrO6P: C, 45.62; H, 5.26. Found: C, 45.70; H, 5.33%.
Methyl 2-(Diethoxyphosphoryl)-3-(4-methylphenyl)-4-
oxopentanoate (5c)
(866 mg, 81%), yellow oil. IR (CCl4): ν = 1724, 1436, 1352, 1264, 1156,
1048 cm−1
.
31P NMR (CDCl3): δ = 21.0, 21.5 (1 : 0.52). 1H NMR (CDCl3):
δ = 1.05 (dt, 3JHH = 7.0 Hz, 4JHP = 0.5 Hz, 3H, CH3CH2OP, major), 1.13
3
4
(dt, JHH = 7.0 Hz, JHP = 0.8 Hz, 3H, CH3CH2OP, major), 1.30 (dt,
3JHH = 7.0 Hz, 4JHP = 0.8 Hz, 3H, CH3CH2OP, minor), 1.38 (dt, 3JHH
=
7.0 Hz, 4JHP = 0.5 Hz, 3H, CH3CH2OP, minor), 2.04 (s, 3H, CH3CO, ma-
jor), 2.17 (s, 3H, CH3CO, minor), 2.30 (s, 3H, CH3Ar, minor), 2.33 (s, 3H,
5
CH3Ar, major), 3.44 (d, JPH = 0.5 Hz, 3H, CH3OC, minor), 3.58–3.98
(m, 3H, CH3CH2OP, CHP), 3.77 (d, 5JPH = 0.5 Hz, 3H, CH3OC, major),
4.06–4.22 (d, 2H, CH3CH2OP), 4.43 (dd, 3JHH = 11.8 Hz, 3JPH = 10.2 Hz,

β, γ-Disubstituted α-Diethoxyphosphoryl-γ-lactones
969
1H, CHAr, minor), 4.51 (dd, 3JHH = 12.0 Hz, 3JPH = 8.2 Hz, 1H, CHAr,
major), 7.10–7.13 (m, 4H, arom-H, minor), 7.15–7.16 (m, 4H, arom-
3
H, major). 13C NMR (CDCl3): δ = 15.5 (d, JPC = 6.1 Hz,CH3CH2OP,
3
3
major), 15.6 (d, JPC = 6.4 Hz,CH3CH2OP, major), 15.8 (d, JPC = 5.7
Hz,CH3CH2OP, minor), 15.9 (d, 3JPC = 5.5 Hz,CH3CH2OP, minor), 20.6
1
(CH3Ar), 27.8 (CH3CO, major), 28.7 (CH3CO, minor), 47.8 (d, JPC
=
1
131.2 Hz, PCH, minor), 47.9 (d, JPC = 132.1 Hz, PCH, major), 51.6
4
(ArCH, minor), 52.1 (ArCH, major), 55.9 (d, JPC = 2.7 Hz, COOCH3,
minor), 56.9 (COOCH3, major), 61.9 (d, 2JPC = 7.0 Hz, CH3CH2OP, ma-
jor), 62.0 (d, 2JPC = 7.2 Hz, CH3CH2OP, major), 62.4 (d, 2JPC = 6.6 Hz,
2
CH3CH2OP, minor), 62.6 (d, JCP = 6.5 Hz, CH3CH2OP, minor), 128.1
(CHAr, minor), 128.8 (CHAr, major), 129.2 (CHAr), 131.1 (CAr, major),
3
131.7 (d, JPC = 16.0 Hz, CAr, minor), 137.3 (CAr, minor), 137.5 (CAr,
2
2
major), 167.3 (d, JPC = 5.2 Hz, COOCH3, minor), 169.0 (d, JPC = 4.8
Hz, COOCH3, major), 204.4 (CH3CO, minor), 205.4 (d, 3JPC = 16.8 Hz,
CH3CO, major). Anal. Calcd. for C17H25O6P: C, 57.30; H, 7.07. Found:
C, 57.42; H, 7.12%.
Methyl 2-(Diethoxyphosphoryl)-3-(4-methoxyphenyl)-4-
oxopentanoate (5d)
(972 mg, 87%), yellow oil. 31P NMR (CDCl3): δ = 21.4, 21.8 (1
3
4
: 0.40). 1H NMR (CDCl3): δ = 1.06 (dt, JHH = 7.1 Hz, JHP = 0.5
3
4
Hz, 3H, CH3CH2OP, major), 1.14 (dt, JHH = 7.1 Hz, JHP = 0.6 Hz,
3
4
3H, CH3CH2OP, major), 1.30 (dt, JHH = 7.1 Hz, JHP = 0.5 Hz, 3H,
3
4
CH3CH2OP, minor), 1.38 (dt, JHH = 7.1 Hz, JHP = 0.6 Hz, 3H,
CH3CH2OP, minor), 2.04 (s, 3H, CH3CO, major), 2.17 (s, 3H, CH3CO,
5
minor), 3.45 (d, JPH = 0.6 Hz, 3H, CH3OC, minor), 3.60–4.00 (m, 3H,
CH3CH2OP, CHP), 3.77 (d, 5JPH = 0.7 Hz, 3H, CH3OC, major), 3.79 (s,
3H, CH3OAr), 4.03–4.22 (d, 2H, CH3CH2OP), 4.41 (dd, 3JHH = 10.3 Hz,
3JPH = 10.1 Hz, 1H, CHAr, minor), 4.50 (dd, JHH = 11.7 Hz, JPH
=
3
3
8.1 Hz, 1H, CHAr, major), 6.82 (d, 3JHH = 8.9 Hz, 2H, arom-H, minor),
6.87 (d, 3JHH = 8.8 Hz, 2H, arom-H, major), 7.17 (d, 3JHH = 8.9 Hz, 2H,
arom-H, minor), 7.20 (d, 3JHH = 8.8 Hz, 2H, arom-H, major). 13C NMR
(CDCl3): δ = 15.7 (d, 3JPC = 6.2 Hz,CH3CH2OP, major), 16.0 (d, 3JPC
=
5.6 Hz,CH3CH2OP, minor), 27.9 (CH3CO, major), 28.8 (CH3CO, minor),
47.9 (d, 1JPC = 125.9 Hz, PCH, minor), 48.0 (d, JPC = 132.2 Hz, PCH,
1
major), 51.8 (ArCH, minor), 52.2 (ArCH, major), 54.8 (CH3OAr, minor),
4
54.9 (CH3OAr, major), 55.5 (d, JPC = 2.7 Hz, COOCH3, minor), 56.5
2
(COOCH3, major), 62.0 (d, JPC = 7.2 Hz, CH3CH2OP, major), 62.1 (d,
2JPC = 7.4 Hz, CH3CH2OP, major), 62.5 (d, 2JPC = 6.6 Hz, CH3CH2OP,
minor), 62.7 (d, 2JPC = 6.5 Hz, CH3CH2OP, minor), 113.9 (CHAr, minor),
3
114.0 (CHAr, major), 126.0 (CAr, major), 126.6 (d, JPC = 16.2 Hz, CAr,

970
H. Krawczyk and Ł. Albrecht
minor), 129.4 (CHAr, minor), 130.1 (CHAr, major), 159.0 (CAr, minor),
2
159.2 (CAr, major), 167.4 (d, JPC = 5.1 Hz, COOCH3, minor), 169.1
2
(d, JPC = 4.9 Hz, COOCH3, major), 204.5 (CH3CO, minor), 205.6 (d,
3JPC = 16.8 Hz, CH3CO, major). Anal. Calcd. for C17H25O7P: C, 54.84;
H, 6.77. Found: C, 54.71; H, 6.63%.
Methyl 2-(Diethoxyphosphoryl)-3-(3,4-
methylenedioxyphenyl)-4-oxopentanoate (5e)
(1.066 g, 92%), yellow oil. IR (CCl4): ν = 1736, 1488, 1440, 1352, 1248,
1
1160, 1040 cm−1
.
31P NMR (CDCl3): δ = 20.9, 21.3 (1 : 0.42). H NMR
3
4
(CDCl3): δ = 1.12 (dt, JHH = 7.1 Hz, JHP = 0.5 Hz, 3H, CH3CH2OP,
major), 1.18 (dt, 3JHH = 7.1 Hz, 4JHP = 0.6 Hz, 3H, CH3CH2OP, major),
3
4
1.30 (dt, JHH = 7.1 Hz, JHP = 0.6 Hz, 3H, CH3CH2OP, minor), 1.38
(dt, 3JHH = 7.1 Hz, 4JHP = 0.6 Hz, 3H, CH3CH2OP, minor), 2.06 (s, 3H,
CH3CO, major), 2.19 (s, 3H, CH3CO, minor), 3.50 (d, 5JPH = 0.6 Hz, 3H,
5
CH3OC, minor), 3.65–4.03 (m, 3H, CH3CH2OP, CHP), 3.77 (d, JPH
=
0.7 Hz, 3H, CH3OC, major), 4.06–4.23 (d, 2H, CH3CH2OP), 4.37 (dd,
3JHH = 11.8 Hz, 3JPH = 10.2 Hz, 1H, CHAr, minor), 4.46 (dd, 3JHH = 11.7
Hz, 3JPH = 8.1 Hz, 1H, CHAr, major), 5.94 (s, 2H, CH2O2Ar, minor), 5.95
(s, 2H, CH2O2Ar, major), 6.72–6.75 (m, 2H, arom-H), 6.77–6.79 (m, 1H,
CHAr). 13C NMR (CDCl3): δ = 15.7 (d, 3JPC = 6.4 Hz,CH3CH2OP, major),
3
15.9 (d, JPC = 5.3 Hz,CH3CH2OP, minor), 27.8 (CH3CO, major), 28.7
1
(CH3CO, minor), 47.9 (d, JPC = 131.2 Hz, PCH), 51.8 (ArCH, minor),
52.3 (ArCH, major), 55.8 (COOCH3, minor), 56.8 (COOCH3, major),
2
2
62.1 (d, JPC = 7.3 Hz, CH3CH2OP, major), 62.2 (d, JPC = 8.2 Hz,
2
CH3CH2OP, major), 62.6 (d, JPC = 6.6 Hz, CH3CH2OP, minor), 62.8
2
(d, JPC = 6.6 Hz, CH3CH2OP, minor), 100.9 (CH2O2Ar), 108.2 (CHAr,
minor), 108.2 (CHAr), 108.9 (CHAr, major), 122.0 (CHAr, minor), 122.7
(CHAr, major), 127.6 (CAr, major), 128.2 (d, 3JPC = 16.5 Hz, CAr, minor),
2
147.1 (CAr, minor), 147.2 (CAr, major), 147.7 (CAr), 167.3 (d, JPC = 5.1
Hz, COOCH3, minor), 169.0 (d, 2JPC = 4.7 Hz, COOCH3, major), 204.4
(CH3CO, minor), 205.4 (d, 3JPC = 16.8 Hz, CH3CO, major). Anal. Calcd.
for C17H23O8P: C, 52.85; H, 6.00. Found: C, 52.92; H, 6.07%.
4-Aryl-3-diethoxyphosphoryl-5-methyldihydrofuran-2(3H)-
ones (7a–e): General Procedure
To a stirred solution of 4-oxopentanoate 5 (2 mmol) in methanol (10
mL), potassium borohydride (168 mg, 3 mmol) was added in portions
at 0◦C. Stirring was continued for 65 min, and the reaction mixture
was acidified to pH 1.5 with concentrated HCl. Next, water (10 mL)
was added, and methanol was evaporated under reduced pressure. The

β, γ-Disubstituted α-Diethoxyphosphoryl-γ-lactones
971
residue was extracted with CH2Cl2 (2 × 15 mL). The combined organic
layers were dried over MgSO4, and the solvent was evaporated un-
der reduced pressure to afford a crude product, which was purified by
column chromatography (eluent:CHCl3/acetone 98:2).
3-Diethoxyphosphoryl-5-methyl-4-(4-
nitrophenyl)dihydrofuran-2(3H)-one (7a)
(543 mg, 76%), pale yellow oil. IR (CCl4): ν = 1778, 1382, 1262, 1024
cm−1
.
31P NMR (CDCl3): δ = 18.7, 19.1 (0.51 : 1). 1H NMR (CDCl3): δ =
1.02 (d, 3JHH = 6.6 Hz, 3H, CH3CH, minor), 1.13 (t, 3JHH = 7.1 Hz, 3H,
CH3CH2OP, major), 1.28 (t, 3JHH = 7.0 Hz, 3H, CH3CH2OP, major), 1.31
3
3
(t, JHH = 7.1 Hz, 3H, minor), 1.37 (t, JHH = 7.1 Hz, 3H, CH3CH2OP,
minor), 1.47 (d, 3JHH = 6.1 Hz, 3H, CH3CH, major), 3.31 (dd, 3JHH = 3.6
Hz, 3JPH = 24.6 Hz, 1H, CHP, minor), 3.36 (dd, 3JHH = 10.8 Hz, 3JPH
=
23.3 Hz, 1H, CHP, major), 3.48–3.76 (m, 1H, CHAr), 3.87–4.39 (m, 4H,
CH3CH2OP), 4.54 (dq, 3JHH = 8.4 Hz, 3JHH = 6.1 Hz, 1H, OCH, major),
5.18 (dq, 3JHH = 6.6 Hz, 3JHH = 6.6 Hz, 1H, OCH, minor), 7.47–7.59 (m,
2H, arom-H), 8.16–8.27 (m, 2H, arom-H). 13C NMR (CDCl3): δ = 15.7 (d,
3JPC = 6.4 Hz,CH3CH2OP, minor), 15.8 (d, JPC = 6.0 Hz,CH3CH2OP,
3
1
major), 16.3 (CH3CH, minor), 18.4 (CH3CH, major), 46.5 (d, JPC
=
1
138.1 Hz, PCH, minor), 47.0 (ArCH, minor), 47.3 (d, JPC = 150.7 Hz,
2
2
PCH, major), 51.5 (d, JPC = 1.4 Hz, ArCH, major), 62.3 (d, JPC
=
2
6.8 Hz, CH3CH2OP, major), 62.9 (d, JPC = 6.6 Hz, CH3CH2OP, mi-
nor), 63.4 (d, 2JPC = 6.5 Hz, CH3CH2OP, major), 63.7 (d, 2JPC = 6.8 Hz,
CH3CH2OP, minor), 78.4 (d, 3JPC = 4.6 Hz, OCH, minor), 81.5 (d, 3JPC
=
12.9 Hz, OCH, major), 123.6 (CHAr, minor), 123.7 (CHAr, major), 128.7
(CHAr, major), 128.8 (CHAr, minor), 144.4 (CAr, minor), 144.6 (CAr, ma-
jor), 146.7 (CAr, minor), 147.2 (CAr, major), 169.7 (COO, major), 170.6
(d, 2JPC = 3.2 Hz, COO, minor). Anal. Calcd. for C15H20NO7P: C, 50.42;
H, 5.64; N, 3.92. Found: C, 50.33; H, 5.71; N, 3.99%.
4-(4-Bromophenyl)-3-diethoxyphosphoryl-5-
methyldihydrofuran-2(3H)-one (7b)
(688 mg, 88%), colorless oil. IR (CCl4): ν = 1770, 1508, 1168, 1024
cm−1
.
31P NMR (CDCl3): δ = 19.2, 19.5 (0.68 : 1). 1H NMR (CDCl3): δ =
1.01 (d, 3JHH = 6.6 Hz, 3H, CH3CH, minor), 1.13 (t, 3JHH = 7.1 Hz, 3H,
CH3CH2OP, major), 1.27 (t, 3JHH = 7.1 Hz, 3H, CH3CH2OP, major), 1.31
3
3
(t, JHH = 7.0 Hz, 3H, minor), 1.36 (t, JHH = 7.0 Hz, 3H, CH3CH2OP,
minor), 1.43 (d, 3JHH = 6.1 Hz, 3H, CH3CH, major), 3.25 (dd, 3JHH = 3.4
Hz, 3JPH = 24.5 Hz, 1H, CHP, minor), 3.28 (dd, 3JHH = 10.8 Hz, 3JPH
=
23.2 Hz, 1H, CHP, major), 3.44–3.59 (m, 1H, CHAr), 3.87–4.31 (m, 4H,
CH3CH2OP), 4.46 (dq, 3JHH = 8.3 Hz, 3JHH = 6.1 Hz, 1H, OCH, major),

972
H. Krawczyk and Ł. Albrecht
3
3
5.13 (dq, JHH = 6.6 Hz, JHH = 6.6 Hz, 1H, OCH, minor), 7.00 (d,
3JHH = 8.4 Hz, 2H, arom-H, minor), 7.14 (d, JHH = 8.5 Hz, 2H, arom-
3
H, major), 7.48 (d, 3JHH = 8.4 Hz, 2H, arom-H, minor), 7.51 (d, 3JHH
=
8.5 Hz, 2H, arom-H, major). 13C NMR (CDCl3): δ = 15.8 (d, JPC = 6.3
Hz,CH3CH2OP, minor), 16.0 (d, 3JPC = 5.7 Hz,CH3CH2OP, major), 16.5
(CH3CH, minor), 18.6 (CH3CH, major), 47.1 (ArCH, minor), 47.5 (d,
3
1JPC = 149.6 Hz, PCH, major), 47.5 (d, JPC = 136.0 Hz, PCH, minor),
1
51.3 (d, 2JPC = 1.0 Hz, ArCH, major), 61.3 (d, 2JPC = 6.7 Hz, CH3CH2OP,
2
2
major), 62.9 (d, JPC = 6.8 Hz, CH3CH2OP, minor), 63.4 (d, JPC = 6.1
Hz, CH3CH2OP, major), 63.7 (d, 2JPC = 6.8 Hz, CH3CH2OP, minor), 79.0
3
3
(d, JPC = 3.5 Hz, OCH, minor), 82.2 (d, JPC = 12.9 Hz, OCH, major),
121.6 (CAr, major), 121.7 (CAr, minor), 129.2 (CHAr, major), 129.3 (CHAr,
minor), 131.8 (CHAr, minor), 131.9 (CHAr, major), 136.5 (CAr, major),
2
136.6 (CAr, minor), 170.1 (d, JPC = 4.0 Hz, COO, major), 171.2 (d,
2JPC = 3.6 Hz, COO, minor). Anal. Calcd. for C15H20BrO5P: C, 46.05;
H, 5.15. Found: C, 46.14; H, 5.22%.
3-Diethoxyphosphoryl-5-methyl-4-(4-
methylphenyl)dihydrofuran-2(3H)-one (7c)
(554 mg, 85%), colorless oil. IR (CCl4): ν = 1772, 1388, 1256, 1028
cm−1
.
31P NMR (CDCl3): δ = 19.7, 19.9 (0.87 : 1). 1H NMR (CDCl3): δ =
1.00 (d, 3JHH = 6.5 Hz, 3H, CH3CH, minor), 1.11 (t, 3JHH = 7.1 Hz, 3H,
CH3CH2OP, major), 1.24 (t, 3JHH = 7.0 Hz, 3H, CH3CH2OP, major), 1.31
3
3
(t, JHH = 7.0 Hz, 3H, minor), 1.36 (t, JHH = 7.0 Hz, 3H, CH3CH2OP,
minor), 1.43 (d, 3JHH = 6.1 Hz, 3H, CH3CH, major), 2.34 (s, 3H, CH3Ar)
3
3
3.29 (dd, JHH = 3.0 Hz, JPH = 24.6 Hz, 1H, CHP, minor), 3.32 (dd,
3JHH = 10.8 Hz, JPH = 22.9 Hz, 1H, CHP, major), 3.43–3.63 (m, 1H,
3
CHAr), 3.68–4.30 (m, 4H, CH3CH2OP), 4.48 (dq, 3JHH = 8.1 Hz, 3JHH
=
3
3
6.3 Hz, 1H, OCH, major), 5.13 (dq, JHH = 6.5 Hz, JHH = 6.5 Hz, 1H,
OCH, minor), 6.98–7.16 (m, 4H, arom-H). 13C NMR (CDCl3): δ = 15.6 (d,
3JPC = 6.4 Hz,CH3CH2OP, minor), 15.8 (d, JPC = 6.4 Hz,CH3CH2OP,
3
major), 16.3 (CH3CH, minor), 18.4 (CH3CH, major), 20.6 (CH3Ar), 47.0
1
1
(ArCH, minor), 47.4 (d, JPC = 149.2 Hz, PCH, major), 47.7 (d, JPC
=
2
135.3 Hz, PCH, minor), 51.3 (d, JPC = 1.1 Hz, ArCH, major), 62.0 (d,
2JPC = 6.8 Hz, CH3CH2OP, major), 62.6 (d, 2JPC = 6.8 Hz, CH3CH2OP,
2
2
minor), 63.1 (d, JPC = 6.2 Hz, CH3CH2OP, major), 63.3 (d, JPC = 6.7
3
Hz, CH3CH2OP, minor), 79.3 (d, JPC = 3.6 Hz, OCH, minor), 82.2 (d,
3JPC = 13.2 Hz, OCH, major), 127.2 (CHAr, major), 127.3 (CHAr, minor),
129.1 (CHAr, major), 129.2 (CHAr, minor), 134.1 (CAr, major), 134.4 (CAr,
minor), 137.0 (CAr, minor), 137.2 (CAr, major), 170.2 (COO, major), 171.4
2
(d, JPC = 3.7 Hz, COO, minor). Anal. Calcd. for C16H23O5P: C, 58.89;
H, 7.10. Found: C, 58.76; H, 7.08%.

β, γ-Disubstituted α-Diethoxyphosphoryl-γ-lactones
973
3-Diethoxyphosphoryl-4-(4-methoxyphenyl)-5-
methyldihydrofuran-2(3H)-one (7d)
(527 mg, 77%), colorless oil. IR (CCl4): ν = 1768, 1380, 1260, 1028
cm−1
.
31P NMR (CDCl3): δ = 19.7, 19.9 (0.86 : 1). 1H NMR (CDCl3): δ =
3
3
1.00 (d, JHH = 6.5 Hz, 3H, CH3CH, minor), 1.11 (dt, JHH = 7.1 Hz,
4JHH = 0.5 Hz, 3H, CH3CH2OP, major), 1.25 (dt, 3JHH = 7.1 Hz, 4JHH
=
0.5 Hz, 3H, CH3CH2OP, major), 1.31 (dt, 3JHH = 7.0 Hz, 4JHH = 0.5 Hz,
3
4
3H, minor), 1.36 (dt, JHH = 7.0 Hz, JHH = 0.5 Hz, 3H, CH3CH2OP,
3
3
minor), 1.42 (d, JHH = 6.1 Hz, 3H, CH3CH, major), 3.27 (dd, JHH
=
3
3
3.2 Hz, JPH = 24.5 Hz, 1H, CHP, minor), 3.27 (dd, JHH = 10.9 Hz,
3JPH = 23.1 Hz, 1H, CHP, major), 3.42–3.58 (m, 1H, CHAr), 3.75–4.30
(m, 4H, CH3CH2OP), 3.80 (s, 3H, CH3OAr, minor), 3.81 (s, 3H, CH3OAr,
major), 4.46 (dq, 3JHH = 8.3 Hz, 3JHH = 6.1 Hz, 1H, OCH, major), 5.12
3
3
3
(dq, JHH = 6.5 Hz, JHH = 6.5 Hz, 1H, OCH, minor), 6.87 (d, JHH
=
3
8.7 Hz, arom-H, 2H, minor), 6.89 (d, JHH = 8.7 Hz, 2H, arom-H, ma-
3
3
jor), 7.03 (d, JHH = 8.7 Hz, arom-H, 2H, minor), 7.18 (d, JHH = 8.7
Hz, 2H, arom-H, major). 13C NMR (CDCl3): δ = 15.7 (d, JPC = 6.4
3
Hz,CH3CH2OP, minor), 15.9 (d, 3JPC = 5.9 Hz,CH3CH2OP, major), 16.4
(CH3CH, minor), 18.4 (CH3CH, major), 46.7 (ArCH, minor), 47.5 (d,
1JPC = 149.6 Hz, PCH, major), 47.8 (d, JPC = 136.0 Hz, PCH, mi-
1
nor), 51.0 (d, 2JPC = 2.0 Hz, ArCH, major), 54.9 (CH3OAr, minor), 54.8
2
(CH3OAr, major), 62.1 (d, JPC = 6.7 Hz, CH3CH2OP, major), 62.7 (d,
2JPC = 6.8 Hz, CH3CH2OP, minor), 63.1 (d, 2JPC = 6.4 Hz, CH3CH2OP,
2
3
major), 63.4 (d, JPC = 6.7 Hz, CH3CH2OP, minor), 79.5 (d, JPC = 3.8
3
Hz, OCH, minor), 82.3 (d, JPC = 13.4 Hz, OCH, major), 113.9 (CHAr,
major), 114.0 (CHAr, minor), 128.4 (CHAr, major), 128.5 (CHAr, minor),
129.0 (CAr, major), 129.4 (CAr, minor), 159.0 (CAr, major), 158.9 (CAr,
minor), 170.3 (COO, major), 171.5 (d, 2JPC = 4.0 Hz, COO, minor). Anal.
Calcd. for C16H23O6P: C, 56.14; H, 6.77. Found: C, 56.27; H, 6.85%.
3-Diethoxyphosphoryl-5-methyl-4-(3,4-
methylenedioxyphenyl)dihydrofuran-2(3H)-one (7e)
(1.21 g, 56%), pale-yellow oil. IR (CCl4): ν = 1772, 1512, 1376, 1258,
1020 cm−1
.
31P NMR (CDCl3): δ = 19.5, 19.8 (0.95 : 1). 1H NMR (CDCl3):
δ = 1.05 (d, 3JHH = 6.5 Hz, 3H, CH3CH, minor), 1.16 (t, 3JHH = 7.1 Hz,
3
3H, CH3CH2OP, major), 1.27 (t, JHH = 7.1 Hz, 3H, CH3CH2OP, ma-
3
3
jor), 1.32 (t, JHH = 7.0 Hz, 3H, minor), 1.36 (t, JHH = 7.0 Hz, 3H,
3
CH3CH2OP, minor), 1.43 (d, JHH = 6.1 Hz, 3H, CH3CH, major), 3.25
(dd, 3JHH = 2.9 Hz, 3JPH = 24.5 Hz, 1H, CHP, minor), 3.27 (dd, 3JHH
=
3
10.7 Hz, JPH = 8.2 Hz, 1H, CHP, major), 3.39–3.61 (m, 1H, CHAr),
3.76–4.32 (m, 4H, CH3CH2OP), 4.45 (dq, 3JHH = 8.2 Hz, 3JHH = 6.1 Hz,
3
3
1H, OCH, major), 5.10 (dq, JHH = 6.5 Hz, JHH = 6.5 Hz, 1H, OCH,

974
H. Krawczyk and Ł. Albrecht
minor), 5.97 (s, 2H, CH2O2Ar), 6.56–6.60 (m, 1H, CHAr), 6.74–6.81 (m,
2H, arom-H). 13C NMR (CDCl3): δ = 15.9 (d, 3JPC = 6.4 Hz,CH3CH2OP,
3
minor), 16.1 (d, JPC = 6.1 Hz,CH3CH2OP, major), 16.5 (CH3CH, mi-
2
nor), 18.8 (CH3CH, major), 47.4 (d, JPC = 1.4 Hz, ArCH, minor), 47.8
1
1
(d, JPC = 149.2 Hz, PCH, major), 48.2 (d, JPC = 134.9 Hz, PCH, mi-
2
2
nor), 51.5 (d, JPC = 2.0 Hz, ArCH, major), 62.4 (d, JPC = 6.7 Hz,
CH3CH2OP, major), 62.9 (d, 2JPC = 6.8 Hz, CH3CH2OP, minor), 63.5 (d,
2JPC = 6.3 Hz, CH3CH2OP, major), 63.7 (d, 2JPC = 6.7 Hz, CH3CH2OP,
3
3
minor), 79.6 (d, JPC = 3.3 Hz, OCH, minor), 82.5 (d, JPC = 13.1 Hz,
OCH, major), 101.2 (CH2O2Ar), 107.4 (CHAr, major), 107.9 (CHAr, mi-
nor), 108.3 (CHAr, minor), 108.4 (CHAr, major), 121.0 (CHAr, minor),
121.1 (CHAr, major), 131.3 (CAr, major), 131.4 (CAr, minor), 147.1 (CAr,
minor), 147.2 (CAr, major), 148.0 (CAr, minor), 148.1 (CAr, major), 170.3
2
(COO, major), 171.6 (d, JPC = 4.2 Hz, COO, minor). Anal. Calcd. for
C16H21O7P: C, 53.93; H, 5.94. Found: C, 53.99; H, 6.01%.
4-Aryl-5-methyl-3-methylenedihydrofuran-2(3H)-ones (8a–e):
General Procedure
To a stirred solution of the corresponding 4-aryl-3-diethoxyphosphoryl-
5-methyl-dihydrofuran-2(3H)-one 7 (1 mmol) in diethyl ether (10 mL),
potassium tert-butoxide (134 mg, 1.2 mmol) was added, and the re-
sulting mixture was stirred at room temperature for 30 min. Then
paraformaldehyde (150 mg, 5 mmol) was added in one portion. After
1 h, the reaction mixture was quenched with brine (10 mL), and the
water layer was extracted with CH2Cl2 (2 × 10 mL). The combined or-
ganic layers were dried over MgSO4 and evaporated. The crude product
was purified by column chromatography (eluent:ethyl acetate/hexane
4:1). Separation of diastereoisomers was accomplished by column chro-
matography using ethyl acetate:hexane 1:4 as eluent.
5-Methyl-3-methylene-4-(4-nitrophenyl)dihydrofuran-2(3H)-
one (8a)
(168 mg, 72%), (4R∗, 5S∗)-8a: yellow oil. IR (film): ν = 1778, 1258,
1
3
1160, 1020 cm−1. H NMR (CDCl3): δ = 1.51 (d, JHH = 6.2 Hz, 3H,
3
4
4
CH3), 3.88 (ddd, JHH = 7.5 Hz, JHH = 3.3 Hz, JHH = 2.9 Hz, 1H,
3
3
CH−4), 4.50 (dq, JHH = 7.5 Hz, JHH = 6.2 Hz, 1H, CH−5), 5.42 (d,
4JHH = 2.9 Hz, 1H, H2C C), 6.43 (d, JHH = 3.3 Hz, 1H, H2C C), 7.43
4
3
3
(d, JHH = 8.6 Hz, 2H, arom-H), 8.26 (d, JHH = 8.6 Hz, 2H, arom-H).
13C NMR (CDCl3): 19.9 (CH3), 53.7 (C4), 80.9 (C5), 124.2 (CHAr), 124.1
(H2C C), 129.2 (CHAr), 139.2 (CAr), 145.8 (CAr), 147.4 (CH2 = C), 168.7
(C2). Anal. Calcd. for C12H11NO4: C, 61.80; H, 4.75. Found: C, 61.72;

β, γ-Disubstituted α-Diethoxyphosphoryl-γ-lactones
975
H, 4.65%. (4R∗,5R∗)-8a: yellow oil. IR (film): ν = 1774, 1254, 1164,
1
3
1028 cm−1. H NMR (CDCl3): δ = 1.02 (d, JHH = 6.6 Hz, 3H, CH3),
3
4
4
4.50 (ddd, JHH = 8.1 Hz, JHH = 2.7 Hz, JHH = 2.5 Hz, 1H, CH−4),
3
3
4
4.98 (dq, JHH = 8.1 Hz, JHH = 6.6 Hz, 1H, CH−5), 5.65 (d, JHH
=
4
2.5 Hz, 1H, H2C=C), 6.55 (d, JHH = 2.7 Hz, 1H, H2C=C), 7.36 (d,
3JHH = 8.9 Hz, 2H, arom-H), 8.24 (d, JHH = 8.9 Hz, 2H, arom-H). 13C
3
NMR (CDCl3): δ = 17.9 (CH3), 49.0 (C4), 76.8 (C5), 123.8 (CHAr), 123.0
(H2C =C), 129.9 (CHAr), 137.8 (CAr), 144.9 (CAr), 147.3 (CH2 = C), 169.3
(C2). Anal. Calcd. for C12H11NO4: C, 61.80; H, 4.75. Found: C, 61.95; H,
4.83%.
4-(4-Bromophenyl)-5-methyl-3-methylenedihydrofuran-2(3H)-
one (8b)
(203 mg, 76%). (4R∗, 5S∗)-8b: pale-yellow oil. IR (film): ν = 1780,
1
3
1250, 1160, 1024 cm−1. H NMR (CDCl3): δ = 1.47 (d, JHH = 6.2 Hz,
3H, CH3), 3.68 (ddd, 3JHH = 7.8 Hz, 4JHH = 3.3 Hz, 4JHH = 3.0 Hz, 1H,
3
3
CH−4), 4.43 (dq, JHH = 7.8 Hz, JHH = 6.2 Hz, 1H, CH−5), 5.38 (d,
4JHH = 3.0 Hz, 1H, H2C=C), 6.36 (d, 4JHH = 3.3 Hz, 1H, H2C=C), 7.10
(d, 3JHH = 8.3 Hz, 2H, arom-H), 7.52 (d, 3JHH = 8.3 Hz, 2H, arom-H). 13
C
NMR (CDCl3): δ = 19.7 (CH3), 53.8 (C4), 81.4 (C5), 121.9 (CAr), 123.5
(H2C =C), 130.0 (CHAr), 132.3 (CHAr), 139.9 (CAr), 137.3 (CH2 = C),
169.2 (C2). Anal. Calcd. for C12H11BrO2: C, 53.96; H, 4.15. Found: C,
53.83; H, 4.07%. (4R*,5R*)-8b: colorless oil. IR (film): ν = 1776, 1256,
1164, 1020 cm−1. H NMR (CDCl3): δ = 1.00 (d, JHH = 6.8 Hz, 3H,
1
3
3
4
4
CH3), 4.35 (ddd, JHH = 8.0 Hz, JHH = 2.2 Hz, JHH = 2.5 Hz, 1H,
3
3
CH−4), 4.92 (dq, JHH = 8.0 Hz, JHH = 6.8 Hz, 1H, CH−5), 5.61 (d,
4JHH = 2.2 Hz, 1H, H2C=C), 6.48 (d, 4JHH = 2.5 Hz, 1H, H2C=C), 7.04
(d, 3JHH = 8.2 Hz, 2H, arom-H), 7.50 (d, 3JHH = 8.2 Hz, 2H, arom-H). 13
C
NMR (CDCl3): δ = 18.1 (CH3), 49.0 (C4), 77.3 (C5), 121.7 (CAr), 124.7
(H2C =C), 130.6 (CHAr), 131.9 (CHAr), 136.3 (CAr), 138.4 (CH2 = C),
169.9 (C2). Anal. Calcd. for C12H11BrO2: C, 53.96; H, 4.15. Found: C,
53.80; H, 4.04.
5-Methyl-3-methylene-4-(4-methylphenyl)dihydrofuran-2(3H)-
one (8c)
(123 mg, 61%). (4R∗, 5S∗)-8c: colorless oil. IR (film): ν = 1764, 1280,
1
3
1224, 1160 cm−1. H NMR (CDCl3): δ = 1.46 (d, JHH = 6.2 Hz, 3H,
3
4
CH3), 2.36 (s, 3H, CH3Ar), 3.68 (ddd, JHH = 7.8 Hz, JHH = 3.5 Hz,
4JHH = 3.0 Hz, 1H, CH-4), 4.45 (dq, 3JHH = 7.8 Hz, 3JHH = 6.2 Hz, 1H,
4
4
CH−5), 5.38 (d, JHH = 3.0 Hz, 1H, H2C=C), 6.33 (d, JHH = 3.5 Hz,
3
3
1H, H2C=C), 7.10 (d, JHH = 8.2 Hz, 2H, arom-H), 7.19 (d, JHH = 8.2
Hz, 2H, arom-H). 13C NMR (CDCl3): δ = 19.7 (CH3), 21.0 (CH3Ar), 54.0

976
H. Krawczyk and Ł. Albrecht
(C4), 81.8 (C5), 123.2 (H2C C), 128.1 (CHAr), 129.7 (CHAr), 135.2 (CAr),
137.6 (CAr), 140.5 (CH2 = C), 169.7 (C2). Anal. Calcd. for C13H14O2: C,
77.20; H, 6.98. Found: C, 77.13; H, 6.85%. (4R∗, 5R∗)-8c: pale yellow
oil. IR (film): ν = 1768, 1384, 1224, 1160, 1064 cm−1. 1H NMR (CDCl3):
3
δ = 0.99 (d, JHH = 6.5 Hz, 3H, CH3), 2.35 (s, 3H, CH3Ar), 4.34 (ddd,
4
4
3JHH = 8.0 Hz, JHH = 3.0 Hz, JHH = 2.5 Hz, 1H, CH-4), 4.90 (dq,
3
4
3JHH = 8.0 Hz, JHH = 6.5 Hz, 1H, CH-5), 5.61 (d, JHH = 2.5 Hz, 1H,
4
3
H2C C), 6.46 (d, JHH = 3.0 Hz, 1H, H2C=C), 7.03 (d, JHH = 8.2 Hz,
2H, arom-H), 7.16 (d, JHH = 8.2 Hz, 2H, arom-H). 13C NMR (CDCl3):
3
δ = 18.1 (CH3), 21.0 (CH3Ar), 49.2 (C4), 77.9 (C5), 124.3 (H2C C), 128.9
(CHAr), 129.4 (CHAr), 129.9 (CAr), 134.1 (CAr), 138.8 (CH2 = C), 170.4
(C2). Anal. Calcd. for C13H14O2: C, 77.20; H, 6.98. Found: C, 77.33; H,
7.09%.
4-(4-Methoxyphenyl)-5-methyl-3-methylenedihydrofuran-
2(3H)-one (8d)
(155 mg, 71%). (4R∗, 5S∗)-8d: colorless oil. IR (film): ν = 1768, 1512,
1252 cm−1. 1H NMR (CDCl3): δ = 1.46 (d, 3JHH = 6.2 Hz, 3H, CH3), 3.66
(ddd, 3JHH = 8.0 Hz, 4JHH = 3.4 Hz, 4JHH = 3.0 Hz, 1H, CH-4), 3.82 (s,
3H, CH3OAr), 4.43 (dq, 3JHH = 8.0 Hz, 3JHH = 6.2 Hz, 1H, CH5), 5.38 (d,
4JHH = 3.0 Hz, 1H, H2C=C), 6.33 (d, 4JHH = 3.4 Hz, 1H, H2C=C), 6.91
3
3
(d, JHH = 8.8 Hz, 2H, arom-H), 7.13 (d, JHH = 8.8 Hz, 2H, arom-H).
13C NMR (CDCl3): δ = 19.6 (CH3), 53.8 (CH3OAr), 55.2 (C4), 81.2 (C5),
114.5 (CHAr), 123.0 (H2C =C), 129.4 (CHAr), 130.1 (CAr), 140.7 (CAr),
159.2 (CH2 = C), 169.7 (C2). Anal. Calcd. for C13H14O3: C, 71.54; H,
6.47. Found: C, 71.39; H, 6.32%. (4R*,5R*)-8d: colorless oil. IR (film):
1
3
ν = 1764, 1512, 1256 cm−1. H NMR (CDCl3): δ = 0.99 (d, JHH = 6.5
3
4
Hz, 3H, CH3), 3.82 (s, 3H, CH3OAr), 4.33 (ddd, JHH = 8.0 Hz, JHH
=
3.0 Hz, 4JHH = 2.8 Hz, 1H, CH−4), 4.89 (dq, 3JHH = 8.0 Hz, 3JHH = 6.5
Hz, 1H, CH−5), 5.60 (d, 4JHH = 2.8 Hz, 1H, H2C=C), 6.46 (d, 4JHH = 3.0
Hz, 1H, H2C=C), 6.89 (d, 3JHH = 8.8 Hz, 2H, arom-H), 7.07 (d, 3JHH
=
8.8 Hz, 2H, arom-H). 13C NMR (CDCl3): δ = 18.1 (CH3), 48.9 (C4),
55.2 (CH3OAr), 78.0 (C5), 114.1 (CHAr), 124.2 (H2C =C), 129.1 (CAr),
130.1 (CHAr), 138.9 (CAr), 159.0 (CH2 = C), 170.4 (C2). Anal. Calcd. for
C13H14O3: C, 71.54; H, 6.47. Found: C, 71.45; H, 6.38%.
5-Methyl-3-methylene-4-(3,4-methylenedioxyphenyl)
dihydrofuran-2(3H)-one (8e)
(153 mg, 66%). (4R∗, 5S∗)-8e: pale yellow oil. IR (film): ν = 1772,
1
3
1516, 1278, 1250 cm−1. H NMR (CDCl3): δ = 1.46 (d, JHH = 6.0 Hz,
3
4
4
3H, CH3), 3.63 (ddd, JHH = 7.8 Hz, JHH = 3.2 Hz, JHH = 2.8 Hz,
3
3
1H, CH-4), 4.40 (dq, JHH = 7.8 Hz, JHH = 6.0 Hz, 1H, CH-5), 5.42

β, γ-Disubstituted α-Diethoxyphosphoryl-γ-lactones
977
(d, 4JHH = 2.8 Hz, 1H, H2C C), 5.98 (s, 2H, CH2O2), 6.35 (d, 4JHH = 3.2
Hz, 1H, H2C=C), 6.67 (s, 1H, CHAr), 6.68 (d, 3JHH = 7.8 Hz, 1H, CHAr),
3
6.80 (d, JHH = 7.8 Hz, 1H, CHAr). 13C NMR (CDCl3): δ = 19.6 (CH3),
53.8 (C4), 81.7 (C5), 101.2 (CH2O2), 108.3 (CHAr), 108.5 (CHAr), 121.9
(CHAr), 123.2 (H2C =C), 137.8 (CAr), 140.3 (CAr), 147.2 (CH2 = C), 148.2
(CAr), 169.5 (C2). Anal. Calcd. for C13H12O4: C, 67.23; H, 5.21. Found: C,
67.12; H, 5.10%. (4R∗, 5R∗)-8e: pale yellow oil. IR (film): ν = 1768, 1510,
2180, 1254 cm−1. 1H NMR (CDCl3): δ 1.03 (d, 3JHH = 6.8 Hz, 3H, CH3),
4.31 (ddd, 3JHH = 7.8 Hz, 4JHH = 2.5 Hz, 4JHH = 2.2 Hz, 1H, CH-4), 4.88
3
3
4
(dq, JHH = 7.8 Hz, JHH = 6.8 Hz, 1H, CH-5), 5.63 (d, JHH = 2.2 Hz,
1H, H2C C), 5.98 (s, 2H, CH2O2), 6.47 (d, 4JHH = 2.5 Hz, 1H, H2C C),
3
3
6.62 (s, 1H, CHAr), 6.63 (d, JHH = 8.2 Hz, 1H, CHAr), 6.79 (d, JHH
=
8.2 Hz, 1H, CHAr). 13C NMR (CDCl3): δ = 18.0 (CH3), 49.2 (C4), 77.9
(C5), 101.2 (CH2O2), 108.4 (CHAr), 109.0 (CHAr), 122.1 (CHAr), 124.5
(H2C C), 130.8 (CAr), 138.7 (CAr), 147.1 (CH2 = C), 147.9 (CAr), 170.2
(C2). Anal. Calcd. for C13H12O4: C, 67.23; H, 5.21. Found: C, 67.37; H,
5.31%.
REFERENCES
[1] H. M. R. Hoffmann and J. Rabe, Angew. Chem. Int. Ed. Engl., 24, 94 (1985).
[2] M. De Bernardi, L. Garlaschelli, L. Toma, G. Vidari, and P. Vita-Finzi, Tetrahedron,
47, 7109 (1991).
[3] G. Vidari, G. Lanfranchi, N. Pazzi, and S. Serra, Tetrahedron Lett., 40, 3063 (1999).
[4] M. Jung, S. Lee, and B. Yoon, Tetrahedron Lett., 38, 2871 (1997).
[5] S. Tesaki, H. Kikuzaki, S. Yonemori, and N. Nakatani, J. Nat. Prod., 64, 515 (2001).
[6] S. Oh, I. H. Jeong, W.-S. Shin, Q. Wang, and S. Lee, Bioorg. Med. Chem. Lett., 16,
1656 (2006).
[7] T. Janecki, E. Blꢀaszczyk, K. Studzian, A. Janecka, U. Krajewska, and M. Ro´z˙alski,
J. Med. Chem., 48, 3516 (2005).
[8] T. Janecki, A. Albrecht, E. Warzycha, K. Studzian, A. Janecka, U. Krajewska, and
M. Ro´z˙alski, Chem.Biodiv., 2, 1256 (2005).
[9] D. De, M. Seth, and A. P. Bhaduri, Synthesis, 956 (1990).
[10] T. Ohta, T. Miyake, N. Seido, H. Kumobayashi, and H. Takaya, J. Org. Chem., 60,
357 (1995).
[11] A. Arcadi, M. Chiarini, F. Marinelli, Z. Berente, and L. Kolla`r, Org. Lett., 2, 69
(2000).
[12] A. Otto and J. Liebscher, Synthesis, 1209 (2003).
[13] T. Gasperi, M. A. Loreto, P. A. Tardella, and E. Veri, Tetrahedron Lett., 44, 4953
(2003).
ˇ
[14] J. Castul´ık, J. Marek, and C. Mazal, Tetrahedron, 57, 8339 (2001).
[15] A. Otto, B. Ziemer, and J. Liebscher, Synthesis, 965 (1999).
[16] A. Otto, B. Ziemer, and J. Liebscher, Eur. J. Org. Chem., 2667 (1998).
[17] A. Otto, B. Abegaz, B. Ziemer, and J. Liebscher, Tetrahedron: Asymmetry, 10, 3381
(1999).
[18] K. Nishimura and K. Tomioka, J. Org. Chem., 67, 431 (2002).

978
H. Krawczyk and Ł. Albrecht
[19] J. Mo¨ıse, S. Arseniyadis, and J. Cossy, Org. Lett., 9, 1695 (2007).
[20] R. Raju, L. J. Allen, T. Le, C. D. Taylor, and A. R. Howell, Org. Lett., 9, 1699 (2007).
[21] J. Read de Alaniz and T. Rovis, J. Am. Chem. Soc., 127, 6284 (2005).
[22] J. Villie´ras and M. Rambaud, Synthesis, 406 (1984).
[23] T. Minami, K. Hirakawa, S. Koyanagi, S. Nakamura, and M. Yamaguchi, J. Chem.
Soc., Perkin Trans 1, 2385 (1990).
[24] K. Lee, J. A. Jackson, and D. F. Wiemer, J. Org. Chem., 58, 5967 (1993).
[25] M. S. Sawant, R. Katoch, G. K. Trivedi, and U. R. Desai, J. Chem. Soc., Perkin Trans.
1, 843 (1998).
[26] R. Ballini, E. Marcantoni, and S. Perella, J. Org. Chem., 64, 2954 (1999).
[27] S. V. Gagnier and R. C. Larock, J. Org. Chem., 65, 1525 (2000).
[28] T. Janecki and E. Blꢀaszczyk, Synthesis, 403 (2001).
[29] R. Ballini, C. Bosica, and D. A. Livi, Synthesis, 1519 (2001).
[30] T. Janecki and E. Blꢀaszczyk, Tetrahedron Lett., 42, 2919 (2001).
[31] A. S.-Y. Lee, Y.-T. Chang, S.-H. Wang, and S.-F. Chu, Tetrahedron Lett., 43, 8489
(2002).
[32] J. W. Kennedy and D. G. Hall, J. Am. Chem. Soc., 124, 898 (2002).
[33] P. Veeraraghavan Ramachandran, D. Pratihar, D. Biswas, A. Srivastava, and M.
Venkat Ram Reddy, Org. Lett., 6, 481 (2004).
[34] P. Veeraraghavan Ramachandran and D. Pratihar, Org. Lett., 9, 2087 (2007).
[35] M. Paira, B. Banerjee, S. Jana, S. K. Mandal, and S. C. Roy, Tetrahedron Lett., 48,
3205 (2007).
[36] D. Blanc, J. Madec, F. Popowyck, T. Ayad, P. Phansavath, V. Ratovelomanana-Vidal,
and J.-P. Geneˆt, Adv. Synth. Catal., 349, 943 (2007).
[37] P. Veeraraghavan Ramachandran, G. Garner, and D. Pratihar, Org. Lett., 9, 4753
(2007).
[38] E. Blꢀaszczyk, H. Krawczyk, and T. Janecki, Synlett, 2685 (2004).
[39] H. Krawczyk, K. Wasek, and J. Kedzia, Synlett, 2648 (2005).
ꢀ
ꢀ
ꢀ
[40] H. Krawczyk, K. Wasek, J. Kedzia, J. Wojciechowski, and W. M. Wolf, Org. Biomol.
ꢀ
Chem., 6, 308 (2008).
´
[41] H. Krawczyk and M. Sliwin´ski, Tetrahedron, 59, 9199 (2003).
[42] H. Krawczyk, M. Sliwin´ski, W. M. Wolf, and R. Bodalski, Synlett, 1995 (2004).
[43] H. Krawczyk, M. Sliwin´ski, J. Kedzia, J. Wojciechowski, and W. M. Wolf, Tetrahedron
Asymmetry, 17, 908 (2006).
[44] H. Krawczyk, M. Sliwin´ski, and J. Kedzia, Tetrahedron Asymmetry, 17, 2817 (2006).
[45] H. Krawczyk, M. Sliwin´ski, J.Kedzia, J. Wojciechowski, and W. M. Wolf, Tetrahedron
´
´
ꢀ
´
´
ꢀ
ꢀ
Asymmetry, 18, 2712 (2007).
[46] H. Krawczyk, Ł. Albrecht, J. Wojciechowski, and W. M. Wolf, Tetrahedron, 63, 12583
(2007).
[47] H. Krawczyk, Ł. Albrecht, J. Wojciechowski, and W. M. Wolf, Tetrahedron, 62, 9135
(2006).