A novel and convenient synthesis of cyclopent-1-enecarboxylates by an intramolecular Horner-Wadsworth-Emmons reaction

Article abstract of DOI:10.1055/s-0028-1083242

A general and efficient method for the preparation of 2-diethoxyphosphoryl- 6-oxohexanoates is presented. This approach is based on the Michael addition of [2-(1,3-dioxolan-2-yl)ethyl]magnesium bromide to various 3-substituted tert-butyl (E)-2-(diethoxyphosphoryl)alk-2-enoates as a key step. Application of the 2-diethoxyphosphoryl-6-oxohexanoates obtained in the intramolecular Horner-Wadsworth-Emmons reaction for the preparation of 5-substituted tert-butyl cyclopent-1-enecarboxylates is also reported. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0028-1083242

PAPER
3951
A Novel and Convenient Synthesis of Cyclopent-1-enecarboxylates by an
Intramolecular Horner–Wadsworth–Emmons Reaction
S
ynthesis of Cyclo
e
pent-1-ene
c
n
arboxylatesryk Krawczyk,* Łukasz Albrecht
Institute of Organic Chemistry, Technical University (Politechnika), Żeromskiego 116, 90-924 Łódź, Poland
Fax +48(42)6365530; E-mail: henkrawc@p.lodz.pl
Received 21 August 2008; revised 6 September 2008
tention.6 Hitherto no general preparative method existed
for this class of phosphonates.
Abstract: A general and efficient method for the preparation of 2-
diethoxyphosphoryl-6-oxohexanoates is presented. This approach
is based on the Michael addition of [2-(1,3-dioxolan-2-yl)eth-
yl]magnesium bromide to various 3-substituted tert-butyl (E)-2-(di-
ethoxyphosphoryl)alk-2-enoates as a key step. Application of the 2-
diethoxyphosphoryl-6-oxohexanoates obtained in the intramolecu-
lar Horner–Wadsworth–Emmons reaction for the preparation of 5-
substituted tert-butyl cyclopent-1-enecarboxylates is also reported.
In anticipation that 2-diethoxyphosphoryl-6-oxohex-
anoates 3 could serve as useful building blocks, we exam-
ined the reaction sequence depicted in Scheme 1
involving Michael addition of [2-(1,3-dioxolan-2-yl)eth-
yl]magnesium bromide to the acceptors 1 followed by
deprotection of an aldehyde moiety as a general method
for their preparation. Moreover, we report that an intramo-
lecular Horner–Wadsworth–Emmons reaction of com-
pounds 3 constitutes a facile approach to 5-substituted
tert-butyl cyclopent-1-enecarboxylates 4. Decisive to this
synthetic methodology was the convenient access to tert-
butyl (E)-2-(diethoxyphosphoryl)alk-2-enoates 1 from di-
ethoxyphosphorylacetic acid through our previously es-
tablished protocol.7,8
Key words: Michael reaction, intramolecular Horner–Wadsworth–
Emmons reaction, cyclopent-1-enecarboxylates, phosphonates, 6-
oxoalkanoates
The cyclopent-1-enecarboxylate motif constitutes a key
structural feature in numerous naturally occurring com-
pounds.1 Moreover, during the past several years the util-
ity of substituted cyclopent-1-enecarboxylates as versatile
building blocks for further elaboration to complex com-
pounds of biological interest has grown in importance.2
Despite the relevance of the cyclopent-1-enecarboxylates
in synthetic organic chemistry and natural product chem-
istry the range of available methods for their preparation
is limited.2,3 Surprisingly, only one method specifically
describing the preparation of 5-substituted cyclopent-1-
enecarboxylates 4 has been reported.2c,e,3b,c This method
relies on the SN2¢ substitution reaction of 5-acetoxycyclo-
pent-1-enecarboxylate with carbon nucleophiles.
We began our investigations with the goal of finding ap-
propriate conditions for the Michael addition of [2-(1,3-
dioxolan-2-yl)ethyl]magnesium bromide to the acceptors
1. After preliminary experiments, it became evident that
the use of excess Grignard reagent (5 equiv) in THF in the
presence of catalytic copper(I) iodide was necessary to
obtain high conversion of the starting materials. Indeed
under these conditions the reactions proceeded smoothly
giving access to a variety of alkanoates 2 bearing a pro-
tected aldehyde functionality in high yields. All the phos-
phonates 2 were formed as inseparable mixtures of
diastereoisomers. In a next step, deprotection of aldehyde
moiety was performed. The deprotection carried out in 3
N HCl–THF solution at 0 °C for 24 hours proved fully
chemoselective affording the corresponding 2-diethoxy-
phosphoryl-6-oxohexanoates 3 again as mixtures of two
An intramolecular Horner–Wadsworth–Emmons (HWE)
reaction provides a means for the preparation of cyclic
alkenes.4 This cyclization has been accomplished with a
number of 2-diethoxyphosphoryl-7-oxoalkanoates.5 In
contrast, the related intramolecular HWE reaction em-
ploying 2-diethoxyphosphoryl-6-oxoalkanoates to give
cyclopent-1-enecarboxylates has attracted only little at-
O
O
(EtO)2P
COOt-Bu
R
(EtO)2P
COOt-Bu
R
O
COOt-Bu
R
c
a
b
(EtO)2P
COOt-Bu
R
H
O
O
1
2
3
4
O
Scheme 1 Reagents and conditions: (a) [2-(1,3-dioxolan-2-yl)ethyl]magnesium bromide (5 equiv), CuI (0.2 equiv), THF, –40 °C to r.t., over-
night; (b) 3 N HCl–THF (0.8:1), 0 °C, 24 h; (c) t-BuOK (1.2 equiv), Et2O, r.t., 90 min.
SYNTHESIS 2008, No. 24, pp 3951–3956
x
x.
x
x
.
2
0
0
8
Advanced online publication: 01.12.2008
DOI: 10.1055/s-0028-1083242; Art ID: Z19308SS
© Georg Thieme Verlag Stuttgart · New York

3952
H. Krawczyk, Ł. Albrecht
PAPER
tert-Butyl 3-(4-Bromophenyl)-2-(diethoxyphosphoryl)-5-(1,3-
dioxolan-2-yl)pentanoate (2a)
Table 1 Compounds 2–4 Prepared
Yield: 1.248 g (80%); pale yellow oil.
Entry
R
2
3
4
IR (film): 1728, 1484, 1408, 1392, 1368, 1252, 1144, 1024 cm–1.
Yield dr
(%)
Yield dr
(%)
Yield
(%)
1H NMR (CDCl3): d = 1.10 (dt, 3JH,H = 7.3 Hz, 4JH,P = 0.3 Hz, 3 H,
CH3CH2OP, minor), 1.12 [s, 9 H, (CH3)3C], 1.14 (dt, 3JH,H = 7.3 Hz,
4JH,P = 0.3 Hz, 3 H, CH3CH2OP, minor), 1.28–1.52 (m, 1 H, CH2),
a
b
c
4-BrC6H4
80
85
94
1:0.8 87
1:0.7 62
3
4
1.35 (dt, JH,H = 7.1 Hz, JH,P = 0.3 Hz, 3 H, CH3CH2OP, major),
4-MeC6H4
4-MeOC6H4
1:0.35 82
1:0.8 84
1:0.8 89
1:0.8 74
1:0.4 66
1:0.7 65
1:0.4 59
1:0.5 49
3
4
1.36 (dt, JH,H = 7.0 Hz, JH,P = 0.3 Hz, 3 H, CH3CH2OP, major),
1.56–1.88 (m, 2 H, CH2), 1.88–2.00 (m, 1 H, CH2, minor), 2.24–
2.37 (m, 1 H, CH2, major), 3.04–3.36 (m, 2 H, CHP, CHAr), 3.59–
3.97 (m, 6 H, 2 × CH2O, CH3CH2OP), 4.12–4.27 (m, 2 H,
d
e
3,4-(OCH2O)C6H3 86
i-Pr 88
3
CH3CH2OP), 4.75 (t, JH,H = 4.5 Hz, 1 H, CHO2, minor), 4.77 (t,
3JH,H = 4.5 Hz, 1 H, CHO2, major), 7.05–7.14 (m, 2 H, 2 × CHAr),
7.38–7.43 (m, 2 H, 2 × CHAr).
13C NMR (CDCl3): d = 15.96 (d, JC,P = 6.2 Hz, CH3CH2OP, mi-
3
diastereoisomers. Under these conditions no cleavage of
the tert-butyl ester moiety was observed.
3
nor), 16.03 (d, JC,P = 5.5 Hz, CH3CH2OP, minor), 16.23 (d,
3JC,P = 6.1 Hz, CH3CH2OP, major), 16.27 (d, JC,P = 5.5 Hz,
3
CH3CH2OP, major), 27.29 [(CH3)3C, major], 27.75 [(CH3)3C, mi-
2-Diethoxyphosphoryl-6-oxohexanoates 3 were then uti-
lized in the intramolecular Horner–Wadsworth–Emmons
reaction. Thus, treatment of compounds 3 with potassium
tert-butoxide (1.2 equiv) in diethyl ether for 90 minutes
gave the expected 5-substituted tert-butyl cyclopent-1-
enecarboxylates 4 in satisfactory overall yields (Table 1).
3
nor], 28.42 (CH2, major), 28.61 (d, JC,P = 16.8 Hz, CH2, minor),
2
31.13 (CH2, minor), 31.28 (CH2, major), 43.90 (d, JC,P = 3.8 Hz,
2
CHAr, major), 44.31 (d, JC,P = 3.1 Hz, CHAr, minor), 53.20 (d,
1JC,P = 130.4 Hz, CHP, major), 53.68 (d, 1JC,P = 133.3 Hz, CHP, mi-
2
nor), 61.91 (d, JC,P = 7.3 Hz, CH3CH2OP, minor), 62.06 (d,
2
2JC,P = 6.7 Hz, CH3CH2OP, minor), 62.42 (d, JC,P = 6.6 Hz,
2
CH3CH2OP, major), 62.61 (d, JC,P = 7.1 Hz, CH3CH2OP, major),
In conclusion, we have developed a novel and efficient
method for the preparation of 2-diethoxyphosphoryl-6-
oxohexanoates 3. Our methodology utilizes Michael addi-
tion of [2-(1,3-dioxolan-2-yl)ethyl]magnesium bromide
to various 3-substituted tert-butyl (E)-2-(diethoxyphos-
phoryl)alk-2-enoates 1 as a key step. Moreover, we have
shown that an intramolecular Horner–Wadsworth–
Emmons reaction of 2-diethoxyphosphoryl-6-oxohex-
anoates 3 constitutes an efficient and reliable method for
the preparation of 5-substituted tert-butyl cyclopent-1-
enecarboxylates 4.
64.62 (2 × CH2O, minor), 64.69 (2 × CH2O, major), 81.44 [(CH3)3C,
major], 82.10 [(CH3)3C, minor], 103.75 (CHO2, minor), 103.93
(CHO2, major), 120.45 (CAr, minor), 120.51 (CAr, major), 130.11 (2
× CHAr, major), 130.38 (2 × CHAr, minor), 131.16 (2 × CHAr),
3
3
139.73 (d, JC,P = 2.9 Hz, CAr, minor), 140.33 (d, JC,P = 17.7 Hz,
2
CAr, major), 166.82 (d, JC,P = 4.7 Hz, C=O, major), 167.47 (d,
2JC,P = 4.1 Hz, C=O, minor).
31P NMR (CDCl3): d = 21.78 (45%), 22.56 (55%).
Anal. Calcd for C22H34BrO7P: C, 50.68; H, 6.57. Found: C, 50.74;
H, 6.41.
tert-Butyl 2-(Diethoxyphosphoryl)-5-(1,3-dioxolan-2-yl)-3-(4-
methylphenyl)pentanoate (2b)
NMR spectra were recorded on a Bruker DPX 250 instrument at
250.13 MHz for 1H, 62.9 MHz for 13C and 101.3 MHz for 31P NMR
respectively, using TMS as internal and 85% H3PO4 as external
standards. The multiplicities of carbons were determined by DEPT
experiments. IR spectra were measured on a Specord M80 (Zeiss)
instrument. Elemental analyses were performed on a PerkinElmer
PE 2400 analyzer. Melting points were determined in open capillar-
ies and are uncorrected. tert-Butyl 2-(diethoxyphosphoryl)alk-2-
enoates 1a–e were prepared according to the literature proce-
dures.7,8
Yield: 1.163 g (85%); pale yellow oil.
IR (film): 1728, 1480, 1452, 1392, 1368, 1248, 1144, 1032 cm–1.
1H NMR (CDCl3): d = 1.08 (t, 3JH,H = 7.1 Hz, 3 H, CH3CH2OP, mi-
nor), 1.10 [s, 9 H, (CH3)3C], 1.14 (t, JH,H = 7.0 Hz, 3 H,
3
CH3CH2OP, minor), 1.35 (t, 3JH,H = 7.1 Hz, 3 H, CH3CH2OP, ma-
jor), 1.37 (t, 3JH,H = 7.0 Hz, 3 H, CH3CH2OP, major), 1.41–1.49 (m,
1 H, CH2), 1.58–1.78 (m, 2 H, CH2), 1.92–1.99 (m, 1 H, CH2, mi-
nor), 2.22–2.35 (m, 1 H, CH2, major), 2.28 (s, 3 H, CH3, major),
2.30 (s, 3 H, CH3, minor), 3.12–3.32 (m, 2 H, CHP, CHAr), 3.49–
3.89 (m, 6 H, 2 × CH2O, CH3CH2OP), 4.14–4.26 (m, 2 H,
3
tert-Butyl 2-(Diethoxyphosphoryl)-5-(1,3-dioxolan-2-yl)pen-
tanoates 2a–e; General Procedure
CH3CH2OP), 4.75 (t, JH,H = 5.6 Hz, 1 H, CHO2, minor), 4.77 (t,
3JH,H = 5.6 Hz, 1 H, CHO2, major), 7.05 (s, 4 H, 4 × CHAr, major),
7.09–7.10 (m, 4 H, 4 × CHAr, minor).
To Mg turnings (720 mg, 30 mmol) in THF (20 mL) under argon
was added a crystal of I2 and 1,2-dibromoethane (1 drop). Then, a
solution of 2-(2-bromoethyl)-1,3-dioxolane (2.70 g, 15 mmol) in
THF (10 mL) was added dropwise over a period of 10 min maintain-
ing the temperature at 40–45 °C. After stirring for 30 min, the mix-
ture was cooled to –40 °C, CuI (114 mg, 0.6 mmol) was added all
at once, and a solution of a corresponding tert-butyl 2-(diethoxy-
phosphoryl)alk-2-enoate 1 (3 mmol) in THF (10 mL) was added
dropwise. The resulting mixture was warmed to r.t. and left over-
night at this temperature. It was then quenched with sat. aq NH4Cl
(30 mL), THF was removed under reduced pressure, and the residue
was extracted with CH2Cl2 (3 ´ 20 mL), dried (MgSO4), and con-
centrated. The crude product was purified by column chromatogra-
phy using CHCl3–acetone 98:2 as eluent affording pure 2.
3
13C NMR (CDCl3): d = 15.79 (d, JC,P = 6.2 Hz, CH3CH2OP, mi-
3
nor), 15.85 (d, JC,P = 6.1 Hz, CH3CH2OP, minor), 16.07 (d,
3JC,P = 6.0 Hz, CH3CH2OP, major), 16.11 (d, JC,P = 5.7 Hz,
3
CH3CH2OP, major), 20.68 (CH3), 27.08 [(CH3)3C, major], 27.59
[(CH3)3C, minor], 28.48 (CH2, major), 28.62 (d, JC,P = 18.3 Hz,
3
CH2, minor), 31.09 (CH2, minor), 31.23 (CH2, major), 43.79 (d,
2JC,P = 3.7 Hz, CHAr, minor), 44.31 (d, JC,P = 3.1 Hz, CHAr, ma-
2
jor), 53.33 (d, 1JC,P = 129.3 Hz, CHP, major), 53.78 (d, 1JC,P = 133.2
2
Hz, CHP, minor), 61.52 (d, JC,P = 6.9 Hz, CH3CH2OP, minor),
2
2
61.76 (d, JC,P = 6.6 Hz, CH3CH2OP, minor), 62.13 (d, JC,P = 6.5
Hz, CH3CH2OP, major), 62.31 (d, 2JC,P = 7.1 Hz, CH3CH2OP, ma-
jor), 64.43 (2 × CH2O, minor), 64.49 (2 × CH2O, major), 80.87
Synthesis 2008, No. 24, 3951–3956 © Thieme Stuttgart · New York

PAPER
Synthesis of Cyclopent-1-enecarboxylates
3953
[(CH3)3C, major], 81.60 [(CH3)3C, minor], 103.78 (CHO2, minor),
103.97 (CHO2, major), 128.03 (2 × CHAr, major), 128.25 (2 × CHAr,
minor), 128.52 (2 × CHAr, major), 128.59 (2 × CHAr, minor), 135.92
(CAr), 137.34 (d, 3JC,P = 2.9 Hz, CAr, minor), 137.87 (d, 3JC,P = 17.3
Hz, CAr, major), 166.82 (d, 2JC,P = 4.4 Hz, C=O, major), 167.61 (d,
2JC,P = 4.3 Hz, C=O, minor).
CH3CH2OP, major), 27.28 [(CH3)3C, major], 27.65 [(CH3)3C, mi-
3
nor], 28.57 (CH2, major), 28.73 (d, JC,P = 17.4 Hz, CH2, minor),
2
31.13 (CH2, minor), 31.29 (CH2, major), 44.01 (d, JC,P = 3.9 Hz,
2
CHAr, minor), 44.52 (d, JC,P = 3.0 Hz, CHAr, major), 53.55 (d,
1JC,P = 129.4 Hz, CHP, major), 53.90 (d, 1JC,P = 133.2 Hz, CHP, mi-
2
nor), 61.68 (d, JC,P = 7.0 Hz, CH3CH2OP, minor), 61.89 (d,
2
2JC,P = 6.6 Hz, CH3CH2OP, minor), 62.22 (d, JC,P = 6.5 Hz,
31P NMR (CDCl3): d = 22.23 (26%), 23.21 (74%).
2
CH3CH2OP, major), 62.40 (d, JC,P = 7.2 Hz, CH3CH2OP, major),
Anal. Calcd for C23H37O7P: C, 60.51; H, 8.17. Found: C, 60.61; H,
8.02.
64.51 (2 × CH2O, minor), 64.58 (2 × CH2O, major), 81.05 [(CH3)3C,
major], 81.77 [(CH3)3C, minor], 100.60 (OCH2O), 103.81 (CHO2,
minor), 103.99 (CHO2, major), 107.66 (CHAr, major), 107.71
(CHAr, minor), 108.29 (CHAr, major), 108.39 (CHAr, minor), 121.65
(CHAr, major), 121.96 (CHAr, minor), 134.33 (d, 3JC,P = 3.0 Hz, CAr,
minor), 134.89 (d, 3JC,P = 17.7 Hz, CAr, major), 146.07 (CAr, major),
146.13 (CAr, minor), 147.28 (CAr), 166.82 (d, 2JC,P = 4.4 Hz, C=O,
major), 167.55 (d, 2JC,P = 4.3 Hz, C=O, minor).
tert-Butyl 2-(Diethoxyphosphoryl)-5-(1,3-dioxolan-2-yl)-3-(4-
methoxyphenyl)pentanoate (2c)
Yield: 1.343 g (94%); pale yellow oil.
IR (film): 1724, 1456, 1392, 1368, 1252, 1148, 1040 cm–1.
1H NMR (CDCl3): d = 1.09 (t, 3JH,H = 7.1 Hz, 3 H, CH3CH2OP, mi-
31P NMR (CDCl3): d = 22.40 (45%), 23.24 (55%).
3
nor), 1.11 [s, 9 H, (CH3)3C], 1.15 (t, JH,H = 7.1 Hz, 3 H,
CH3CH2OP, minor), 1.35 (t, 3JH,H = 7.0 Hz, 3 H, CH3CH2OP, ma-
jor), 1.36 (t, 3JH,H = 7.1 Hz, 3 H, CH3CH2OP, major), 1.38–1.47 (m,
1 H, CH2), 1.58–1.75 (m, 2 H, CH2), 1.82–1.89 (m, 1 H, CH2, mi-
nor), 2.21–2.34 (m, 1 H, CH2, major), 3.06–3.36 (m, 2 H, CHP,
CHAr), 3.76–4.02 (m, 12 H, 2 × CH2O, CH3CH2OP, 2 × CH3O),
4.14–4.26 (m, 2 H, CH3CH2OP), 4.75 (t, 3JH,H = 4.5 Hz, 1 H, CHO2,
minor), 4.77 (t, 3JH,H = 4.8 Hz, 1 H, CHO2, major), 6.78–6.84 (m, 2
H, 2 × CHAr), 7.07–7.17 (m, 2 H, 2 × CHAr).
Anal. Calcd for C23H35O9P: C, 56.78; H, 7.25. Found: C, 57.01; H,
7.36.
tert-Butyl 2-(Diethoxyphosphoryl)-5-(1,3-dioxolan-2-yl)-3-(iso-
propyl)pentanoate (2e)
Yield: 1.078 mg (88%); pale yellow oil.
IR (film): 1724, 1476, 1392, 1368, 1252, 1140, 1048 cm–1.
1H NMR (CDCl3): d = 0.85 (d, 3JH,H = 6.9 Hz, 3 H, CH3CH, minor),
0.91 (d, 3JH,H = 6.7 Hz, 3 H, CH3CH, major), 0.92 (d, 3JH,H = 6.8 Hz,
3 H, CH3CH, major), 0.96 (d, 3JH,H = 6.9 Hz, 3 H, CH3CH, minor),
1.32 (t, 3JH,H = 7.1 Hz, 3 H, CH3CH2OP, major), 1.33 (t, 3JH,H = 7.1
13C NMR (CDCl3): d = 15.74 (d, JC,P = 5.9 Hz, CH3CH2OP, mi-
3
3
nor), 15.82 (d, JC,P = 6.0 Hz, CH3CH2OP, minor), 15.98 (d,
3
3JC,P = 6.0 Hz, CH3CH2OP, major), 16.02 (d, JC,P = 5.8 Hz,
CH3CH2OP, major), 27.05 [(CH3)3C, major], 27.49 [(CH3)3C, mi-
3
Hz, 3 H, CH3CH2OP, major), 1.33 (t, JH,H = 7.1 Hz, 3 H,
3
nor], 28.48 (CH2, major), 28.65 (d, JC,P = 17.4 Hz, CH2, minor),
3
CH3CH2OP, minor), 1.33 (t, JH,H = 7.2 Hz, 3 H, CH3CH2OP, mi-
2
31.15 (CH2, major), 31.98 (CH2, minor), 43.34 (d, JC,P = 3.8 Hz,
nor), 1.38–1.78 [m, 3 H, CH2, (CH3)2CH], 1.46 [s, 9 H, (CH3)3C,
minor], 1.47 [s, 9 H, (CH3)3C, major], 1.85–2.09 (m, 3 H, CH2, CH–
2
CHAr, minor), 43.85 (d, JC,P = 3.2 Hz, CHAr, major), 53.37 (d,
1JC,P = 129.4 Hz, CHP, major), 53.78 (d, 1JC,P = 130.1 Hz, CHP, mi-
3
2
i-Pr), 2.92 (dd, JH,H = 9.7 Hz, JH,P = 20.7 Hz, 1 H, CHP, minor),
2
nor), 54.83 (CH3O), 61.45 (d, JC,P = 7.0 Hz, CH3CH2OP, minor),
2.99 (dd, 3JH,H = 6.4 Hz, JH,P = 22.3 Hz, 1 H, CHP, major), 3.78–
2
2
2
61.65 (d, JC,P = 6.6 Hz, CH3CH2OP, minor), 62.03 (d, JC,P = 6.5
Hz, CH3CH2OP, major), 62.21 (d, 2JC,P = 7.2 Hz, CH3CH2OP, ma-
jor), 64.33 (2 × CH2O, minor), 64.40 (2 × CH2O, major), 80.77
[(CH3)3C, major], 81.49 [(CH3)3C, minor], 103.70 (CHO2, minor),
103.86 (CHO2, major), 113.23 (2 × CHAr, major), 113.43 (2 × CHAr,
major), 129.03 (2 × CHAr, minor), 129.26 (2 × CHAr, minor), 132.34
(d, 3JC,P = 3.0 Hz, CAr, minor), 132.96 (d, 3JC,P = 17.6 Hz, CAr, ma-
4.02 (m, 4 H, 2 × CH2O), 4.08–4.22 (m, 4 H, 2 × CH3CH2OP), 4.81
3
(t, 3JH,H = 4.5 Hz, 1 H, CHO2, minor), 4.83 (t, JH,H = 4.5 Hz, 1 H,
CHO2, major).
13C NMR (CDCl3): d = 15.91 (d, 3JC,P = 6.1 Hz, CH3CH2OP), 16.27
(CH3CH, minor), 18.24 (CH3CH, major), 19.35 (CH3CH, major),
3
20.91 (CH3CH, minor), 21.24 (d, JC,P = 4.1 Hz, CH3CH, minor),
2
jor), 158.14 (CAr), 166.76 (d, JC,P = 4.3 Hz, C=O, major), 167.50
22.56 (d, 3JC,P = 9.2 Hz, CH3CH, major), 27.41 [(CH3)3C], 29.36 (d,
3JC,P = 13.3 Hz, CH2, minor), 29.65 (d, 3JC,P = 8.8 Hz, CH2, major),
(d, 2JC,P = 4.3 Hz, C=O, minor).
2
33.18 (CH2, minor), 35.53 (CH2, major), 42.43 (d, JC,P = 4.4 Hz,
31P NMR (CDCl3): d = 22.63 (45%), 23.49 (55%).
2
CH–i-Pr, minor), 42.57 (d, JC,P = 3.9 Hz, CH–i-Pr, major), 48.12
(d, 1JC,P = 132.8 Hz, CHP, major), 51.23 (d, 1JC,P = 133.0 Hz, CHP,
Anal. Calcd for C23H37O8P: C, 58.46; H, 7.89. Found: C, 58.63; H,
8.01.
2
minor), 61.85 (d, JC,P = 6.7 Hz, CH3CH2OP, major), 61.88 (d,
2
2JC,P = 6.1 Hz, CH3CH2OP, major), 61.92 (d, JC,P = 5.5 Hz,
2
tert-Butyl 3-(Benzo[d][1,3]dioxol-5-yl)-2-(diethoxyphosphoryl)-
5-(1,3-dioxolan-2-yl)pentanoate (2d)
Yield: 1.254 g (86%); pale yellow oil.
IR (film): 1724, 1488, 1440, 1392, 1368, 1244, 1144, 1048 cm–1.
CH3CH2OP, minor), 61.95 (d, JC,P = 6.1 Hz, CH3CH2OP, minor),
64.34 (2 × CH2O), 81.10 [(CH3)3C, minor], 81.14 [(CH3)3C, major],
104.08 (CHO2, major), 104.18 (CHO2, minor), 167.62 (d, 2JC,P = 3.8
Hz, C=O), major), 168.02 (d, 2JC,P = 4.3 Hz, C=O, minor).
31P NMR (CDCl3): d = 24.87 (55%), 24.90 (45%).
1H NMR (CDCl3): d = 1.13 (t, 3JH,H = 7.5 Hz, 3 H, CH3CH2OP, mi-
3
nor), 1.16 [s, 9 H, (CH3)3C], 1.17 (t, JH,H = 7.0 Hz, 3 H,
Anal. Calcd for C19H37O7P: C, 55.87; H, 9.13. Found: C, 55.51; H,
9.10.
CH3CH2OP, minor), 1.35 (t, 3JH,H = 7.1 Hz, 3 H, CH3CH2OP, ma-
jor), 1.36 (t, 3JH,H = 7.1 Hz, 3 H, CH3CH2OP, major), 1.39–1.48 (m,
1 H, CH2), 1.62–1.71 (m, 2 H, CH2), 1.79–1.99 (m, 1 H, CH2, mi-
nor), 2.18–2.34 (m, 1 H, CH2, major), 3.02–3.29 (m, 2 H, CHP,
CHAr), 3.64–3.95 (m, 6 H, 2 × CH2O, CH3CH2OP), 4.12–4.25 (m,
2 H, CH3CH2OP), 4.76 (t, 3JH,H = 4.3 Hz, CHO2, 1 H, minor), 4.78
(t, 3JH,H = 5.2 Hz, 1 H, CHO2, major), 5.90 (s, 2 H, OCH2O, major),
5.91 (s, 2H, OCH2O, minor), 6.59–6.88 (m, 3 H, 3 × CHAr).
tert-Butyl 2-(Diethoxyphosphoryl)-6-oxohexanoates 3a–e;
General Procedure
To a stirred solution of a corresponding tert-butyl 2-(diethoxyphos-
phoryl)-5-(1,3-dioxolan-2-yl)pentanoate 2 (2 mmol) in THF (20
mL) at 0 °C was added dropwise aq 3 N HCl (16 mL). The resultant
mixture was left overnight at 0 °C. THF was removed under re-
duced pressure and the residue extracted with CH2Cl2 (3 × 10 mL).
The combined organic layers were washed with H2O (10 mL),
dried, and concentrated. The crude product was used in the next step
without any further purification.
3
13C NMR (CDCl3): d = 15.91 (d, JC,P = 6.0 Hz, CH3CH2OP, mi-
3
nor), 15.99 (d, JC,P = 6.1 Hz, CH3CH2OP, minor), 16.13 (d,
3
3JC,P = 6.1 Hz, CH3CH2OP, major), 16.17 (d, JC,P = 5.6 Hz,
Synthesis 2008, No. 24, 3951–3956 © Thieme Stuttgart · New York

3954
H. Krawczyk, Ł. Albrecht
PAPER
tert-Butyl 3-(4-Bromophenyl)-2-(diethoxyphosphoryl)-6-oxo-
hexanoate (3a)
Yield: 828 mg (87%); pale yellow oil.
IR (film): 1728, 1484, 1452, 1392, 1368, 1252, 1160, 1028 cm–1.
31P NMR (CDCl3): d = 21.81 (30%), 22.78 (70%).
tert-Butyl 2-(Diethoxyphosphoryl)-3-(4-methoxyphenyl)-6-oxo-
hexanoate (3c)
Yield: 719 mg (84%); pale yellow oil.
IR (film): 1732, 1512, 1452, 1392, 1368, 1256, 1148, 1040 cm–1.
1H NMR (CDCl3): d = 1.12 (dt, 3JH,H = 8.1 Hz, 4JH,P = 0.4 Hz, 3 H,
CH3CH2OP, minor), 1.13 [s, 9 H, (CH3)3C], 1.15 (dt, 3JH,H = 7.0 Hz,
3
4JH,P = 0.4 Hz, 3 H, CH3CH2OP, minor), 1.37 (dt, JH,H = 7.1 Hz,
1H NMR (CDCl3): d = 1.12 [s, 9 H, (CH3)3C], 1.13 (t, 3JH,H = 6.5 Hz,
3
4JH,P = 0.4 Hz, 3 H, CH3CH2OP, major), 1.38 (dt, JH,H = 7.1 Hz,
3 H, CH3CH2OP, minor), 1.16 (t, 3JH,H = 7.0 Hz, 3 H, CH3CH2OP,
4JH,P = 0.4 Hz, 3 H, CH3CH2OP, major), 1.67–1.93 (m, 2 H, CH2),
2.03–2.15 (m, 1 H, CH2, minor), 2.18–2.24 (m, 1 H, CH2, major),
2.48–2.64 (m, 1 H, CH2), 3.11–3.30 (m, 2 H, CHP, CHAr), 3.63–
3.93 (m, 2 H, CH3CH2OP), 4.14–4.27 (m, 2 H, CH3CH2OP), 7.03–
7.13 (m, 2 H, 2 × CHAr), 7.39–7.45 (m, 2 H, 2 × CHAr), 9.64 (t,
3JH,H = 1.1 Hz, 1 H, HCO, minor), 9.64 (t, 3JH,H = 1.4 Hz, 1 H, HCO,
major).
minor), 1.37 (dt, JH,H = 7.1 Hz, JH,P = 0.4 Hz, 3 H, CH3CH2OP,
3
4
3
4
major), 1.38 (dt, JH,H = 7.1 Hz, JH,P = 0.4 Hz, 3 H, CH3CH2OP,
major), 1.77–1.94 (m, 2 H, CH2), 2.03–2.31 (m, 1 H, CH2), 2.43–
2.59 (m, 1 H, CH2), 3.08–3.30 (m, 2 H, CHP, CHAr), 3.60–3.96 (m,
2 H, CH3CH2OP), 3.77 (s, 3 H, CH3O, major), 3.78 (s, 3 H, CH3O,
minor), 4.16–4.28 (m, 2 H, CH3CH2OP), 6.79–6.86 (m, 2 H, 2 ×
CHAr), 7.05–7.16 (m, 2 H, 2 × CHAr), 9.58 (t, 3JH,H = 0.9 Hz, 1 H,
HCO, major), 9.59 (t, 3JH,H = 1.5 Hz, 1 H, HCO, minor)
3
13C NMR (CDCl3): d = 15.86 (d, JC,P = 5.5 Hz, CH3CH2OP, mi-
3
3
nor), 15.94 (d, JC,P = 5.0 Hz, CH3CH2OP, minor), 16.13 (d,
13C NMR (CDCl3): d = 15.71 (d, JC,P = 5.1 Hz, CH3CH2OP, mi-
3
3
3JC,P = 5.9 Hz, CH3CH2OP, major), 16.17 (d, JC,P = 5.5 Hz,
nor), 15.78 (d, JC,P = 5.3 Hz, CH3CH2OP, minor), 15.89 (d,
CH3CH2OP, major), 26.50 (d, 3JC,P = 7.7 Hz, CH2, major), 26.63 (d,
3JC,P = 8.7 Hz, CH2, minor), 27.17 [(CH3)3C, major], 27.66
[(CH3)3C, minor], 41.17 (CH2), 43.29 (d, 2JC,P = 3.6 Hz, CHAr, ma-
jor), 43.58 (d, 2JC,P = 2.8 Hz, CHAr, minor), 52.94 (d, 1JC,P = 129.9
Hz, CHP, major), 53.33 (d, 1JC,P = 133.4 Hz, CHP, minor), 61.90 (d,
3JC,P = 8.4 Hz, CH3CH2OP, major), 15.95 (d, JC,P = 8.7 Hz,
3
3
CH3CH2OP, major), 26.67 (d, JC,P = 11.3 Hz, CH2, minor), 26.79
3
(d, JC,P = 4.2 Hz, CH2, major), 27.00 [(CH3)3C, major], 27.47
[(CH3)3C, minor], 41.17 (CH2), 42.85 (d, 2JC,P = 2.7 Hz, CHAr, mi-
nor), 43.24 (d, 2JC,P = 2.3 Hz, CHAr, major), 53.15 (d, 1JC,P = 129.1
Hz, CHP, major), 53.49 (d, 1JC,P = 133.3 Hz, CHP, minor), 61.49 (d,
2
2JC,P = 7.2 Hz, CH3CH2OP, minor), 62.06 (d, JC,P = 7.3 Hz,
2
2
CH3CH2OP, minor), 62.44 (d, JC,P = 6.4 Hz, CH3CH2OP, major),
2JC,P = 6.9 Hz, CH3CH2OP, minor), 61.69 (d, JC,P = 6.6 Hz,
62.64 (d, 2JC,P = 7.1 Hz, CH3CH2OP, major), 81.47 [(CH3)3C, ma-
jor], 82.23 [(CH3)3C, minor], 120.74 (CAr, major), 120.78 (CAr, mi-
nor), 129.90 (2 × CHAr, major), 130.21 (2 × CHAr, minor), 131.28 (2
CH3CH2OP, minor), 62.09 (d, JC,P = 6.3 Hz, CH3CH2OP, major),
2
62.29 (d, 2JC,P = 7.2 Hz, CH3CH2OP, major), 80.88 [(CH3)3C, ma-
jor], 81.68 [(CH3)3C, minor], 113.39 (2 × CHAr), 128.96 (2 × CHAr,
major), 129.22 (2 × CHAr, minor), 131.52 (d, 3JC,P = 2.3 Hz, CAr, mi-
3
× CHAr), 138.94 (d, JC,P = 3.4 Hz, CAr, minor), 139.49 (d,
3JC,P = 17.4 Hz, CAr, major), 166.45 (d, 2JC,P = 4.7 Hz, C=O, major),
nor), 132.07 (d, JC,P = 17.6 Hz, CAr, major), 158.36 (CAr), 166.46
3
2
167.22 (d, JC,P = 4.5 Hz, C=O, minor), 200.63 (HC=O, minor),
(d, 2JC,P = 3.8 Hz, C=O, major), 167.33 (d, 2JC,P = 3.5 Hz, C=O, mi-
200.93 (HC=O, major).
nor), 200.82 (HCO, minor), 201.12 (HCO, major).
31P NMR (CDCl3): d = 21.68 (40%), 22.46 (60%).
31P NMR (CDCl3): d = 22.19 (40%), 23.05 (60%).
tert-Butyl 2-(Diethoxyphosphoryl)-3-(4-methylphenyl)-6-oxo-
hexanoate (3b)
Yield: 676 mg (82%); pale yellow oil.
tert-Butyl 3-(Benzo[d][1,3]dioxol-5-yl)-2-(diethoxyphosphoryl)-
6-oxohexanoate (3d)
Yield: 787 mg (89%); pale yellow oil.
IR (film): 1724, 1452, 1392, 1368, 1252, 1144, 1024 cm–1.
IR (film): 1724, 1488, 1440, 1392, 1368, 1244, 1144, 1032 cm–1.
1H NMR (CDCl3): d = 1.09 (dt, 3JH,H = 8.5 Hz, 4JH,P = 0.4 Hz, 3 H,
1H NMR (CDCl3): d = 1.14 (dt, 3JH,H = 7.1 Hz, 4JH,P = 0.4 Hz, 3 H,
CH3CH2OP, minor), 1.10 [s, 9 H, (CH3)3C], 1.14 (dt, 3JH,H = 6.6 Hz,
CH3CH2OP, minor), 1.17 [s, 9 H, (CH3)3C], 1.18 (dt, 3JH,H = 6.6 Hz,
3
3
4JH,P = 0.4 Hz, 3 H, CH3CH2OP, minor), 1.36 (dt, JH,H = 7.1 Hz,
4JH,P = 0.4 Hz, 3 H, CH3CH2OP, minor), 1.36 (dt, JH,H = 7.1 Hz,
3
3
4JH,P = 0.4 Hz, 3 H, CH3CH2OP, major), 1.37 (dt, JH,H = 7.1 Hz,
4JH,P = 0.4 Hz, 3 H, CH3CH2OP, major), 1.37 (dt, JH,H = 7.1 Hz,
4JH,P = 0.4 Hz, 3 H, CH3CH2OP, major), 1.64–1.96 (m, 2 H, CH2),
2.06–2.24 (m, 1 H, CH2), 2.29 (s, 3 H, CH3, major), 2.31 (s, 3 H,
CH3, minor), 2.46–2.59 (m, 1 H, CH2), 3.10–3.31 (m, 2 H, CHP,
CHAr), 3.54–3.94 (m, 2 H, CH3CH2OP), 4.13–4.29 (m, 2 H,
CH3CH2OP), 7.01–7.10 (m, 4 H, 4 × CHAr), 9.58 (t, 3JH,H = 1.2 Hz,
1 H, HCO, minor), 9.58 (t, 3JH,H = 1.5 Hz, 1 H, HCO, major).
4JH,P = 0.4 Hz, 3 H, CH3CH2OP, major), 1.82–1.91 (m, 2 H, CH2),
2.00–2.12 (m, 1 H, CH2, minor), 2.17–2.29 (m, 1 H, CH2, major),
2.45–2.59 (m, 1 H, CH2), 3.05–3.31 (m, 2 H, CHP, CHAr), 3.67–
3.97 (m, 2 H, CH3CH2OP), 4.08–4.27 (m, 2 H, CH3CH2OP), 5.92
(s, 2 H, OCH2O, major), 5.93 (s, 2 H, OCH2O, minor), 6.59–6.76
(m, 3 H, 3 × CHAr), 9.61 (t, 3JH,H = 1.5 Hz, 1 H, HCO).
3
3
13C NMR (CDCl3): d = 15.79 (d, JC,P = 5.8 Hz, CH3CH2OP, mi-
13C NMR (CDCl3): d = 15.83 (d, JC,P = 5.3 Hz, CH3CH2OP, mi-
3
3
nor), 15.88 (d, JC,P = 4.5 Hz, CH3CH2OP, minor), 16.07 (d,
nor), 15.92 (d, JC,P = 6.0 Hz, CH3CH2OP, minor), 16.05 (d,
3
3
3JC,P = 6.7 Hz, CH3CH2OP, major), 16.13 (d, JC,P = 5.6 Hz,
3JC,P = 6.1 Hz, CH3CH2OP, major), 16.10 (d, JC,P = 5.7 Hz,
CH3CH2OP, major), 26.71 (d, 3JC,P = 12.0 Hz, CH2, minor), 26.84
CH3CH2OP, major), 26.68 (d, JC,P = 11.4 Hz, CH2, minor), 26.81
3
3
3
(d, JC,P = 4.2 Hz, CH2, major), 27.08 [(CH3)3C, major], 27.62
(d, JC,P = 4.6 Hz, CH2, major), 27.19 [(CH3)3C, major], 27.59
[(CH3)3C, minor], 41.31 (CH2), 43.33 (d, 2JC,P = 3.4 Hz, CHAr, mi-
nor), 43.73 (d, 2JC,P = 2.8 Hz, CHAr, major), 53.14 (d, 1JC,P = 129.4
Hz, CHP, major), 53.49 (d, 1JC,P = 133.5 Hz, CHP, minor), 61.66 (d,
[(CH3)3C, minor], 41.25 (CH2), 43.46 (d, 2JC,P = 3.8 Hz, CHAr, mi-
nor), 43.85 (d, 2JC,P = 3.1 Hz, CHAr, major), 53.29 (d, 1JC,P = 129.2
Hz, CHP, major), 53.54 (d, 1JC,P = 133.2 Hz, CHP, minor), 61.72 (d,
2
2
2JC,P = 7.2 Hz, CH3CH2OP, minor), 61.91 (d, JC,P = 6.7 Hz,
2JC,P = 7.0 Hz, CH3CH2OP, minor), 61.93 (d, JC,P = 6.6 Hz,
2
2
CH3CH2OP, minor), 62.29 (d, JC,P = 6.6 Hz, CH3CH2OP, major),
CH3CH2OP, minor), 62.28 (d, JC,P = 6.5 Hz, CH3CH2OP, major),
62.49 (d, 2JC,P = 7.1 Hz, CH3CH2OP, major), 81.08 [(CH3)3C, ma-
jor], 81.91 [(CH3)3C, minor], 127.99 (2 × CHAr, major), 128.23 (2 ×
CHAr, minor), 128.76 (2 × CHAr, major), 128.82 (2 × CHAr, minor),
62.47 (d, 2JC,P = 7.1 Hz, CH3CH2OP, major), 81.13 [(CH3)3C, ma-
jor], 81.95 [(CH3)3C, minor], 100.51 (OCH2O, minor), 100.67
(OCH2O, major), 107.74 (CHAr, major), 107.79 (CHAr, minor),
108.01 (CHAr, major), 108.16 (CHAr, minor), 121.57 (CHAr, major),
121.87 (CHAr, minor), 133.49 (d, 3JC,P = 3.4 Hz, CAr, minor), 133.99
3
136.46 (CAr), 136.63 (d, JCP = 3.0 Hz, CAr, minor), 137.11 (d,
3JC,P = 17.5 Hz, CAr, major), 166.60 (d, 2JC,P = 4.6 Hz, C=O, major),
2
3
167.52 (d, JC,P = 4.4 Hz, C=O, minor), 201.07 (HCO, minor),
(d, JC,P = 17.7 Hz, CAr, major), 146.32 (CAr, major), 146.37 (CAr,
2
201.38 (HCO, major).
minor), 147.45 (CAr), 166.47 (d, JC,P = 4.6 Hz, C=O, major),
Synthesis 2008, No. 24, 3951–3956 © Thieme Stuttgart · New York

PAPER
Synthesis of Cyclopent-1-enecarboxylates
3955
2
167.33 (d, JC,P = 4.6 Hz, C=O, minor), 200.89 (HCO, minor),
tert-Butyl 5-(4-Methylphenyl)cyclopent-1-enecarboxylate (4b)
201.18 (HCO, major).
Yield: 170 mg; (66%); pale yellow oil.
31P NMR (CDCl3): 21.67 (30%), 22.51 (70%);
IR (film): 1708, 1512, 1368, 1288, 1164, 1092 cm–1.
1H NMR (CDCl3): d = 1.28 [s, 9 H, (CH3)3C], 1.81–1.91 (m, 1 H,
tert-Butyl 2-(Diethoxyphosphoryl)-3-isopropyl-6-oxohexanoate
(3e)
Yield: 539 mg (74%); pale yellow oil.
IR (film): 1728, 1464, 1392, 1368, 1256, 1112, 1052 cm–1.
1H NMR (CDCl3): d = 0.86 (d, 3JH,H = 6.9 Hz, 3 H, CH3CH, minor),
0.92 (d, 3JH,H = 6.7 Hz, 3 H, CH3CH, major), 0.93 (d, 3JH,H = 6.6 Hz,
3 H, CH3CH, major), 0.96 (d, 3JH,H = 6.9 Hz, 3 H, CH3CH, minor),
CH2), 2.30 (s, 3 H, CH3), 2.43–2.66 (m, 3 H, CH2), 3.97–4.07 (m, 1
3
4
H, CHAr), 6.47 (dt, JH,H = 2.3 Hz, JH,H = 1.9 Hz, 1 H, CH=C),
7.03–7.09 (m, 4 H, 4 × CHAr).
13C NMR (CDCl3): d = 20.91 (CH3), 27.83 [(CH3)3C], 31.87 (CH2),
34.28 (CH2), 49.89 (CHAr), 79.82 [(CH3)3C], 126.83 (2 × CHAr),
128.81 (2 × CHAr), 135.20 (CAr), 141.17 (CAr), 142.51 (CH=C),
143.25 (CH=C), 164.22 (C=O).
3
4
1.32 (dt, JH,H = 7.1 Hz, JH,P = 0.4 Hz, 3 H, CH3CH2OP, minor),
Anal. Calcd for C17H22O2: C, 79.03; H, 8.58. Found: C, 79.17; H,
8.43.
3
4
1.33 (dt, JH,H = 7.1 Hz, JH,P = 0.5 Hz, 3 H, CH3CH2OP, major),
1.47 [s, 9 H, (CH3)3C], 1.69–1.88 (m, 2 H, CH2), 1.90–2.12 [m, 2 H,
CH2, (CH3)2CH, CH-i-Pr], 2.48–2.60 (m, 1 H, CH2), 2.92 (dd,
tert-Butyl 5-(4-Methoxyphenyl)cyclopent-1-enecarboxylate (4c)
Yield: 178 mg (65%); pale yellow oil.
IR (film): 1708, 1512, 1460, 1368, 1248, 1164, 1096 cm–1.
3JH,H = 9.9 Hz, JH,P = 20.7 Hz, 1 H, CHP, minor), 3.01 (dd,
2
3JH,H = 5.0 Hz, 2JH,P = 23.1 Hz, 1 H, CHP, major), 3.72–3.96 (m, 2
H, CH3CH2OP), 4.07–4.23 (m, 2 H, CH3CH2OP), 9.75 (t,
3JH,H = 1.6 Hz, 1 H, HCO, major), 9.76 (t, 1 H, 3JH,H = 1.2 Hz, HCO,
minor).
1H NMR (CDCl3): d = 1.28 [s, 9 H, (CH3)3C], 1.79–1.90 (m, 1 H,
CH2), 2.39–2.67 (m, 3 H, CH2), 3.70 (s, 3 H, CH3O), 3.98–4.06 (m,
3
13C NMR (CDCl3): d = 16.12 (d, 3JC,P = 6.0 Hz, CH3CH2OP), 16.36
(CH3CH, minor), 18.82 (CH3CH, major), 19.26 (CH3CH, major),
1 H, CHAr), 6.81 (d, JH,H = 8.8 Hz, 2 H, 2 × CHAr) 6.87 (dt,
3JH,H = 2.3 Hz, 4JH,H = 1.9 Hz, 1 H, CH=C), 7.07 (d, 3JH,H = 8.8 Hz,
2 H, 2 × CHAr).
3
19.45 (d, JC,P = 5.8 Hz, CH3CH, minor), 20.97 (CH3CH, minor),
21.03 (d, 3JC,P = 7.9 Hz, CH3CH, major), 27.62 [(CH3)3C], 29.77 (d,
3JC,P = 13.7 Hz, CH2, minor), 30.47 (d, 3JC,P = 10.0 Hz, CH2, major),
42.22 (d, 2JC,P = 4.2 Hz, CH–i-Pr, minor), 42.39 (d, 2JC,P = 3.8 Hz,
CH–i-Pr, major), 43.55 (CH2, minor), 43.69 (CH2, major), 47.64 (d,
1JC,P = 133.8 Hz, CHP, major), 50.39 (d, 1JC,P = 132.7 Hz, CHP, mi-
13C NMR (CDCl3): d = 27.69 [(CH3)3C], 31.67 (CH2), 34.10 (CH2),
49.37 (CHAr), 54.87 (CH3O), 79.61 [(CH3)3C], 113.40 (2 × CHAr),
127.73 (2 × CHAr), 137.58 (CAr), 141.17 (CH=C), 142.87 (CH=C),
157.71 (CAr), 164.02 (C=O).
Anal. Calcd for C17H22O3: C, 74.42; H, 8.08. Found: C, 74.31; H,
7.97.
2
nor), 62.19 (d, JC,P = 6.1 Hz, CH3CH2OP, minor), 62.29 (d,
2JC,P = 6.2 Hz, CH3CH2OP, major), 81.61 [(CH3)3C, minor], 81.68
[(CH3)3C, major], 167.68 (d, 2JC,P = 3.4 Hz, C=O, major), 168.02 (d,
2JC,P = 4.2 Hz, C=O, minor), 202.01 (HCO).
tert-Butyl 5-(Benzo[d][1,3]dioxol-5-yl)cyclopent-1-enecarboxy-
late (4d)
Yield: 170 mg (59%); pale yellow oil.
31P NMR (CDCl3): 24.18 (35%), 24.38 (65%);
IR (film): 1708, 1480, 1368, 1248, 1164, 1092 cm–1.
1H NMR (CDCl3): d = 1.32 [s, 9 H, (CH3)3C], 1.77–1.88 (m, 1 H,
CH2), 2.38–2.71 (m, 3 H, CH2), 3.96–4.04 (m, 1 H, CHAr), 5.91 (s,
tert-Butyl Cyclopent-1-enecarboxylates 4a–e; General Proce-
dure
To a stirred solution of a corresponding tert-butyl 2-(diethoxyphos-
phoryl)-6-oxohexanoate 3 (1 mmol) in Et2O (10 mL) was added t-
BuOK (134 mg, 1.2 mmol) and the resulting mixture was stirred at
25 °C for 90 min. After that time, the mixture was quenched with
brine (10 mL) and the aqueous layer was extracted with CH2Cl2
(3 × 10 mL). The combined organic layers were dried (MgSO4) and
evaporated. The crude product was purified by column chromatog-
raphy (eluent: CHCl3–acetone, 98:2).
3
2 H, OCH2O), 6.60–6.73 (m, 3 H, 3 × CHAr), 6.87 (dt, JH,H = 2.4
Hz, 4JH,H = 1.8 Hz, 1 H, CH=C).
13C NMR (CDCl3): d = 27.91 [(CH3)3C], 31.79 (CH2), 34.19 (CH2),
50.05 (CHAr), 79.96 [(CH3)3C], 100.62 (OCH2O), 107.37 (CHAr),
107.91 (CHAr), 119.89 (CHAr), 139.63 (CAr), 141.03 (CAr), 143.40
(CH=C), 145.61 (CH=C), 147.49 (CAr), 164.13 (C=O).
Anal. Calcd for C17H20O4: C, 70.81; H, 6.99. Found: C, 70.99; H,
6.13.
tert-Butyl 5-(4-Bromophenyl)cyclopent-1-enecarboxylate (4a)
Yield: 200 mg (62%); pale yellow oil.
IR (film): 1708, 1484, 1368, 1296, 1164, 1096 cm–1.
tert-Butyl 5-(Isopropyl)cyclopent-1-enecarboxylate (4e)
Yield: 103 mg (49%); pale yellow oil.
IR (film): 1708, 1464, 1368, 1292, 1164, 1092 cm–1.
1H NMR (CDCl3): d = 1.29 [s, 9 H, (CH3)3C], 1.77–1.88 (m, 1 H,
CH2), 2.41–2.64 (m, 3 H, CH2), 3.99–4.07 (m, 1 H, CHAr), 6.91 (dt,
3JH,H = 2.4 Hz, 4JH,H = 1.9 Hz, 1 H, CH=C), 7.03 (d, 3JH,H = 8.3 Hz,
2 H, 2 × CHAr), 7.38 (d, 3JH,H = 8.3 Hz, 2 H, 2 × CHAr).
13C NMR (CDCl3): d = 27.85 [(CH3)3C], 31.87 (CH2), 34.04 (CH2),
49.77 (CHAr), 80.10 [(CH3)3C], 119.54 (CAr), 128.74 (2 × CHAr),
131.19 (2 × CHAr), 140.56 (CAr), 143.94 (CH=C), 144.69 (CH=C),
163.86 (C=O).
1H NMR (CDCl3): d = 0.72 (d, 3JH,H = 6.9 Hz, 3 H, CH3CH), 0.91
(d, 3JH,H = 6.9 Hz, 3 H, CH3CH), 1.48 [s, 9 H, (CH3)3C], 1.73–1.98
(m, 1 H, CH2), 2.11–2.22 [m, 1 H, (CH3)2CH], 2.29–2.40 (m, 3 H,
3
CH2), 2.87–2.95 (m, 1 H, CH–i-Pr), 6.68 (dt, JH,H = 2.6 Hz,
4JH,H = 1.6 Hz, 1 H, CH=C).
13C NMR (CDCl3): d = 16.23 (CH3CH), 20.97 (CH3CH), 23.93
[(CH3)2CH], 27.85 [(CH3)3C], 28.97 (CH2), 31.83 (CH2), 49.76
(CH–i-Pr), 79.43 [(CH3)3C], 140.32 (CH=C), 142.53 (CH=C),
164.66 (C=O).
Anal. Calcd for C16H19BrO2: C, 59.45; H, 5.92. Found: C, 59.24; H,
6.11.
Anal. Calcd for C13H22O2: C, 74.24; H, 10.54. Found: C, 74.01; H,
10.27.
Synthesis 2008, No. 24, 3951–3956 © Thieme Stuttgart · New York

3956
H. Krawczyk, Ł. Albrecht
PAPER
(3) (a) Hudlicky, T.; Price, J. D. Chem. Rev. 1989, 89, 1467.
References
(b) Amri, H.; Villiéras, J. Tetrahedron Lett. 1987, 28, 5521.
(c) Amri, H.; Rambaud, M.; Villiéras, J. Tetrahedron 1990,
46, 3335. (d) Palaty, J.; Abbott, F. S. J. Med. Chem. 1995,
38, 3398. (e) Dambrin, V.; Villiéras, M.; Janvier, P.; Toupet,
L.; Amri, H.; Lebreton, J.; Villiéras, J. Tetrahedron 2001,
57, 2155.
(1) (a) Cane, D. E.; Rossi, T. Tetrahedron Lett. 1979, 2973.
(b) Cane, D. E.; Sohng, J.-K.; Williard, P. G. J. Org. Chem.
1992, 57, 844. (c) Katsushima, T.; Nieves, L.; Wells, J. N.
J. Med. Chem. 1990, 33, 1906. (d) Giannetti, B. M.; Steffan,
B.; Steglich, W.; Kupka, J.; Anke, T. Tetrahedron 1986, 42,
3587. (e) Subrahmanyam, C.; Kumar, S. R.; Reddy, G. D.
Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem.
2005, 44, 2186. (f) Song, W.-Y.; Ma, Y.-B.; Bai, X.; Zhang,
X.-M.; Gu, Q.; Zheng, Y.-T.; Zhou, J.; Chen, J.-J. Planta
Med. 2007, 73, 372.
(2) (a) Bunnage, M. E.; Davies, S. G.; Parkin, R. M.; Roberts, P.
M.; Smith, A. D.; Withey, J. M. Org. Biomol. Chem. 2004,
2, 3337. (b) Davies, S. G.; Garner, A. C.; Long, M. J. C.;
Smith, A. D.; Sweet, M. J.; Withey, J. M. Org. Biomol.
Chem. 2004, 2, 3355. (c) Davies, S. G.; Garner, A. C.; Long,
M. J. C.; Morrison, R. M.; Roberts, P. M.; Savory, E. D.;
Smith, A. D.; Sweet, M. J.; Withey, J. M. Org. Biomol.
Chem. 2005, 3, 2762. (d) Tanaka, A.; Hattori, K.;
(4) (a) Minami, T.; Motoyoshiya, J. Synthesis 1992, 333.
(b) Iorga, B.; Eymery, F.; Mouriès, V.; Savignac, P.
Tetrahedron 1998, 54, 14637.
(5) (a) Snider, B. B.; Phillips, G. B. J. Org. Chem. 1983, 48,
3685. (b) Taguchi, T.; Hosoda, A.; Kobayashi, Y.
Tetrahedron Lett. 1985, 26, 6209. (c) Kraus, G. A.; Jones,
C. Synlett 2001, 793. (d) Kraus, G. A.; Goronga, T.
Synthesis 2007, 1765. (e) Shie, J.-J.; Fang, J.-M.; Wang, S.-
Y.; Tsai, K.-C.; Cheng, Y.-S. E.; Yang, A.-S.; Hsiao, S.-C.;
Su, C.-Y.; Wong, C.-H. J. Am. Chem. Soc. 2007, 129, 11892.
(6) (a) Bestmann, H.-J.; Lehnen, H. Tetrahedron Lett. 1991, 32,
4279. (b) Kraus, G. A.; Choudhury, P. K. Org. Lett. 2002, 4,
2033. (c) Kraus, G. A.; Choudhury, P. K. Chem. Eur. J.
2004, 2193.
Taniguchi, K.; Okitsu, O.; Tabuchi, S.; Nishio, M.;
Nagakura, Y.; Maeda, N.; Murai, H.; Seki, J. Bioorg. Med.
Chem. Lett. 2006, 16, 4861. (e) Le Diguarher, T.; Chollet,
A.-M.; Bertrand, M.; Hennig, P.; Raimbaud, E.; Sabatini,
M.; Guilbaud, N.; Pierré, A.; Tucker, G. C.; Casara, P.
J. Med. Chem. 2003, 46, 3840.
(7) Krawczyk, H.; Albrecht, Synthesis 2005, 2887.
(8) Krawczyk, H.; Albrecht, ; Wojciechowski, J.; Wolf, W. M.
Tetrahedron 2006, 62, 9135.
Synthesis 2008, No. 24, 3951–3956 © Thieme Stuttgart · New York