Synthesis of 4-alkoxycarbonyl-butenolides by uncatalyzed one-pot cyclization of 1,3-bis(silyloxy)alk-1-enes with oxalyl chloride

Article abstract of DOI:10.1016/j.tet.2007.10.025

3-Hydroxy-4-alkoxycarbonyl-butenolides were prepared by one-pot cyclizations of 1,3-bis(silyloxy)alk-1-enes with oxalyl chloride.

Full text of DOI:10.1016/j.tet.2007.10.025

Tetrahedron 63 (2007) 12547–12561
Synthesis of 4-alkoxycarbonyl-butenolides by uncatalyzed one-pot
cyclization of 1,3-bis(silyloxy)alk-1-enes with oxalyl chloride
a
Rudiger Dede, Lars Michaelis, Dilver Fuentes, Mirza Arfan Yawer, Ibrar Hussain,
a
a
a
a
€
Christine Fischerb and Peter Langera,b,
*
aInstitut fu€r Chemie, Universita€t Rostock, Albert-Einstein-Strasse 3a, 18059 Rostock, Germany
bLeibniz-Institut fu€r Katalyse e. V. an der Universita€t Rostock, Albert-Einstein-Strasse 29a, 18059 Rostock, Germany
Received 23 August 2007; revised 1 October 2007; accepted 4 October 2007
Available online 7 October 2007
Abstract—3-Hydroxy-4-alkoxycarbonyl-butenolides were prepared by one-pot cyclizations of 1,3-bis(silyloxy)alk-1-enes with oxalyl
chloride.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
6-thiosialic and neuraminic acids,18–21 nactins,22 and eryth-
ronolide A.23
4-Carboxy-, 4-alkoxycarbonyl-, and 4-acyl-butenolides are
of considerable pharmacological relevance and occur in a
variety of natural products.1 This includes, for example,
(+)- and (ꢀ)-lichesterolic acid,2 neuropogolic acid,3 isomur-
onic acid (Scheme 1),3a (+)-praesorediosic acid,4 dihydro-
constiputic acid,5 paniculid C,6 and medium-sized bicycles
such as 8,14-dioxo-7,11-dehydro-11,13-dihydroacantho-
spermolide,7 cyclospinosolide,8 pachyclavulariolide P,9 and
phlogacanthoside B.10 4-Alkoxycarbonyl-butenolides are
also important synthetic building blocks. For example, (+)-
nephrosteranic acid and related g-lactones were prepared
by diastereoselective hydrogenation of 5-alkyl-3-mesyloxy-
4-ethoxycarbonyl-butenolides.11 Isotetronic acid derivatives,
containing a hydroxy group at carbon atom C-3 of the
butenolide moiety, are also occurring in many natural
products. This includes (+)-leptosphaerin12 and compound
WF-3681,13 distomadine B,14 various ascorbic acid deriva-
tives,15 and many other pharmacologically relevant natural
products.16 Isotetronic acids have been used also as synthetic
building blocks during the synthesis of (ꢀ)-tetrodotoxin,17
3-Hydroxy-4-alkoxycarbonyl-butenolides and related struc-
tures have been previously prepared mainly by base-medi-
ated cyclization reactions. This includes the reaction of
pyruvates with aldehydes,24 of benzaldehyde with dimethyl
methoxyfumarate,25 of acetophenones with formaldehyde
and diethyl oxalate,26 and by DABCO mediated dimeriza-
tion of methyl 2,4-dioxopentanoate.27 A different approach
relies on the PPh3 mediated reaction of ketones with methyl
acetoxypropynoate.28 Nair et al. reported the synthesis of
spirocycles based on PPh3 mediated reactions of 1,2-qui-
nones.29 Saalfrank and co-workers reported the synthesis
of 5-alkylidene-3-hydroxy-4-alkoxycarbonyl-butenolides
by cyclization of 1,3-dicarbonyl compounds with oxalyl
chloride.30 Sonoda and co-workers reported the synthesis
of 2,3-dioxo-2,3-dihydrofurans by cyclization of acetophe-
none derived silyl enol ethers with oxalyl chloride.31
We developed an efficient approach to 3-hydroxy-5-alkyl-
idenebutenolides by cyclization of 1,3-bis(silyloxy)buta-
1,3-dienes32 with oxalyl chloride.33 Recently, we reported34
a convenient one-pot synthesis of 3-hydroxy-4-alkoxycarb-
onyl-butenolides by cyclization of oxalyl chloride with
1-alkoxy-1,3-bis(silyloxy)alk-1-enes,35 which can be regarded
as bis-silylated 3-hydroxyesters. Herein, we report full de-
tails of these studies. With regard to our preliminary commu-
nication, we significantly extended the preparative scope. In
addition, we report the application of our methodology to the
synthesis of an enantiomerically pure butenolide and the
functionalization of the products by Suzuki reactions. The
reactions reported herein proceed under mild conditions;
and the starting materials are readily available.
Me
CO2H
O
R
O
R = H: (+)-Lichesterolic acid
R = CH(OH)Me: Neuropogolic acid
R = COMe: Isomuronic acid
Scheme 1. Naturally occurring 4-carboxy-butenolides.
* Corresponding author. Tel.: +49 381 4986410; fax: +49 381 4986412;
e-mail: peter.langer@uni-rostock.de
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.10.025

12548
R. Dede et al. / Tetrahedron 63 (2007) 12547–12561
Table 2. Optimization of the synthesis of 3a
2. Results and discussion
Entry Lewis acid
(equiv)
(COCl)2 c (2a) t [h], T [ꢁC]
(equiv) [M]
%
(3a)a
1,3-Bis(silyloxy)alk-1-enes 2a–t were prepared by the reac-
tion of dilithiated 3-hydroxyesters 1a–t (available by aldol
reaction) with trimethylchlorosilane (Scheme 2, Tables 1
and 2). The cyclization of 2a–t with oxalyl chloride afforded
the 3-hydroxy-4-alkoxycarbonyl-butenolides 3a–t. The best
yields were obtained when the reactions were carried out
without the presence of a Lewis acid (Table 2). Noteworthy,
the reaction of 1,3-bis(silyl enol ethers) with simple acid
chlorides36 and the condensation of silyl ketene acetals
with oxalyl chloride37 were reported to be best carried out
in the absence of Lewis acid. In contrast, the cyclization
reactions of 1,3-bis(silyl enol ethers)33 and 1,1-bis(silyloxy)-
ketene acetals38 with oxalyl chloride were reported to
require the use of catalytic amounts of Me3SiOTf.
1
2
3
4
5
Me3SiOTf (0.5) 2.0
0.12 0.5 h, ꢀ78 ꢁC, 96 h, 20 ꢁC 51
Me3SiOTf (0.5) 2.5
Me3SiOTf (0.5) 1.3
Me3SiOTf (1.0) 1.3
Me3SiOTf (4.0) 4.3
Me3SiOTf (4.0) 4.3
0.075 0.5 h, ꢀ78 ꢁC, 2 h, 50 ꢁC 14
0.15 18 h, 20 ꢁC
50
0.12 0.5 h, ꢀ78 ꢁC, 96 h, 20 ꢁC 53
0.03 72 h, ꢀ78/20 ꢁC
0.03 72 h, 0/20 ꢁC
0.10 18 h, ꢀ78/20 ꢁC
0.12 72 h, ꢀ78/20 ꢁC
0.12 72 h, ꢀ78/20 ꢁC
30
23
54
6
7
8
none
BF3$OEt2 (2.0) 1.3
1.0
0.12 0.5 h, ꢀ78 ꢁC, 96 h, 20 ꢁC 40
9
10
TiCl4 (2.0)
TiCl4 (2.0)
1.3
1.3
0b
0b
a
Isolated yields.
Complex mixture.
b
acetate, gave the 5,5-dimethyl-butenolide 3u in low yield,
presumably due to the steric hindrance (Scheme 3).
R1
O
R1
O
i
O
Me Me
HO
O
+
OR2
Me
Me
HO
i
OR2
O
+
OEt
1a-t
OEt
O
1u (77%)
ii
ii
R1
Cl
O
Cl
O
Me Me
O
OR2
O
OEt
R1 OSiMe3
OR2
OSiMe3
OEt
Me Me
Me3SiO
O
O
Cl
O
Cl
O
iii
iii
Me3SiO
O
OH
O
OH
3a-t
2a-t
2u (35%)
3u (21%)
Scheme 2. Synthesis of 4-alkoxycarbonyl-butenolides 3a–t. Conditions: (i)
LDA, THF, 5 min, ꢀ78 ꢁC; (ii) (1) LDA (2.2 equiv), THF, 1 h, ꢀ78 ꢁC, (2)
Me3SiCl (2.5 equiv), ꢀ78/20 ꢁC, 24 h; (iii) ꢀ78/20 ꢁC, 18 h.
Scheme 3. Synthesis of 5,5-dimethyl-butenolide 3u. Conditions: (i) LDA,
THF, 5 min, ꢀ78 ꢁC; (ii) (1) LDA (2.2 equiv), THF, 1 h, ꢀ78 ꢁC, (2)
Me3SiCl (2.5 equiv), ꢀ78/20 ꢁC, 24 h; (iii) ꢀ78/20 ꢁC, 18 h.
Most butenolides 3a–t were isolated in moderate to good
yields. The relatively low yields of 3j, 3l, and 3d,h can be
explained by steric hindrance of the tert-butyl group, the
unstable nature of the vinyl group, and the cleavage of the
tert-butyl ester (by HCl formed during the cyclization),
respectively. The cyclization of oxalyl chloride with 1,3-
bis(silyloxy)alk-1-ene 2u, prepared from acetone and ethyl
Butenolides 3a–t were prepared in racemic form (as racemic
3-hydroxyesters 1 were employed). Starting with (R)-1a, the
optically pure butenolide (R)-3a could be successfully
prepared (Scheme 4, Fig. 1). This experiment shows that
no racemization occurred during the formation of 1,3-bis-
(trimethylsilyloxy)alk-1-ene (R)-2a and the subsequent
cyclization.
Me
O
OSiMe3
OMe
Me
Table 1. Synthesis of 4-(alkoxycarbonyl)-butenolides 3a–t
i
R1
R2
% (1)a
% (2)a
% (3)a
HO
OMe
SiO
Me3
1–3
(R)-2a
(R)-1a
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
s
Me
Me
Et
Et
n-Pr
i-Pr
n-Bu
n-Bu
i-Bu
t-Bu
n-Hex
CH2]CH
CH2]CH(CH2)8
PhCH2
Ph
4-MeC6H4
4-(MeO)C6H4
2-(Me)C6H4
2-(MeO)C6H4
4-ClC6H4
Me
Et
Et
t-Bu
Et
Et
Et
t-Bu
Et
Me
Me
Et
Et
Me
Et
Et
Et
Me
Et
Et
54
73
75
99
97
79
86
100
76
75
73
91
52
93
87
92
95
91
74
88
95
52
54
77
32
71
65
75
21
63
35
61
34
83
38
62
67
32
50
60
43
b
ii
Me
83
89
71
78
83
92
62
60
65
70
65
77
78
73
83
69
37
76
Cl
O
OMe
O
O
O
Cl
O
OH
(R)-3a (98% ee)
Scheme 4. Synthesis of optically pure butenolide (R)-3a. Conditions: (i)
LDA, THF, 5 min, ꢀ78 ꢁC; (ii) (1) LDA (2.2 equiv), THF, 1 h, ꢀ78 ꢁC,
(2) Me3SiCl (2.5 equiv), ꢀ78/20 ꢁC, 24 h; (iii) ꢀ78/20 ꢁC, 18 h.
The hydroxy group of the isotetronic acid was successfully
functionalized by transition metal catalyzed cross-coupling
reactions (Scheme 5, Table 3). The products were isolated
in moderate to good yields, except for 5d prepared from
2-(methoxyphenyl)boronic acid.
t
a
In conclusion, a variety of 3-hydroxy-4-alkoxycarbonyl-
butenolides were prepared by one-pot cyclizations of
Isolated yields.
Commercially available.
b

R. Dede et al. / Tetrahedron 63 (2007) 12547–12561
12549
and 13C NMR spectra the deuterated solvents indicated
were used. Mass spectrometric data (MS) were obtained
by electron ionization (EI, 70 eV), chemical ionization
(CI, H2O), or electrospray ionization (ESI). For preparative
scale chromatography, silica gel (60–200 mesh) was used.
Melting points are uncorrected.
120
100
80
60
40
20
0
Resolution of Enantiomers by Chiral HPLC
Racemate
Optically pure, R
3.2. General procedure for the preparation of 4-alkoxy-
carbonyl-butenolides 3a–u
To a CH2Cl2 solution of 2a–u was added a CH2Cl2 solution
of oxalyl chloride at ꢀ78 ꢁC. The reaction mixture was
allowed to warm to 20 ꢁC within 15–24 h. Ether (60 mL)
and brine (20 mL) were added, the organic and the aqueous
layer were separated, and the latter was extracted with ether
(3ꢂ30 mL). The combined organic layers were washed with
water (10 mL), dried (Na2SO4), and filtered. The filtrate was
concentrated in vacuo. The residue was purified by column
chromatography (silica gel) or recrystallized (CH2Cl2/
n-hexane) to give 4-alkoxycarbonyl-butenolides 3a–u.
19
20
21
22
Time [min]
23
24
25
Figure 1. Determination of the enantiomeric excess of butenolide (R)-3a:
chiral HPLC on a CHIRALCEL OD-H column. Conditions: hexane/
ethanol¼95:5+0.1% CF3COOH (0.5 mL/min). Maxima after 20.61/22.50/
22.74 min.
R1
R1
OR2
O
OR2
O
3.2.1. Methyl 4-hydroxy-2-methyl-5-oxo-2,5-dihydro-
furan-3-carboxylate (3a). Starting with 2a (261 mg,
0.99 mmol), CH2Cl2 (10 mL), and oxalyl chloride (2.0 M
in CH2Cl2, 0.50 mL, 1.00 mmol), 3a was isolated by column
chromatography (n-hexane/Et2O¼1:1) as a slightly yellow
solid (89 mg, 52%). Mp 48–49 ꢁC; Rf 0.25 (tailing; Et2O).
O
O
i
O
OTf
O
OH
3
4a-f
ii
R1
R3B(OH)2
OR2
O
1
Reaction time: 17 h. H NMR (250 MHz, CDCl3): d¼1.55
O
3
(d, J¼6.4 Hz, 3H, CHCH3), 3.91 (s, 3H, OCH3), 5.16 (q,
O
R3
3J¼6.4 Hz, 1H, CHCH3), 8.4 (br, 1H, OH). 13C NMR
(75 MHz, CDCl3): d¼19.4 (CHCH3), 52.5 (OCH3), 74.8
(OCH), 119.8 (CCH), 151.6 (COH), 164.6, 165.7 (CO). IR
(KBr, cmꢀ1): ~n¼3395 (br, s), 3344 (s), 2958 (w), 1781 (s),
1717 (s), 1456 (m), 1336 (m), 1229 (s), 1139 (s), 1053
(m), 772 (m). MS (EI, 70 eV): m/z (%)¼172 (M+, 15), 127
(27), 112 (18), 100 (37), 85 (56), 70 (100), 53 (20), 39
(40), 29 (21). Anal. Calcd for C7H8O5 (172.14): C, 48.84;
H, 4.68. Found: C, 49.01; H, 4.81.
5a-k
Scheme 5. Synthesis of butenolides 5a–k. Conditions: (i) Tf2O, pyridine,
ꢀ78 to ꢀ10 ꢁC; (ii) Pd(PPh3)4 (3 mol %), K3PO4 (1.5 equiv), dioxane, reflux.
Table 3. Synthesis of butenolides 5a–k
3
4
5
R1
R2
R3
% (4)a % (5)a
f
a
b
b
b
b
b
b
c
a
b
c
d
e
f
g
h
i
i-Pr
Et
Et
Et
Et
Et
Et
Et
Et
Ph
Ph
91
84
84
84
84
63
76
45
24
56
64
66
57
86
61
45
g
g
g
g
g
g
i
j
k
o
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
n-Bu
i-Bu
t-Bu
4-MeC6H4
2-MeOC6H4
3,4-(MeO)2C6H3
3,4,5-(MeO)3C6H2 84
Thien-2-yl
4-MeOC6H4
3.2.2. Ethyl 2,5-dihydro-4-hydroxy-2-methyl-5-oxofuran-
3-carboxylate (3b). Starting with 2b (0.41 g, 1.50 mmol),
CH2Cl2 (15 mL), and oxalyl chloride (2.0 M in CH2Cl2,
0.75 mL, 1.50 mmol), 3b was isolated by column chro-
matography (n-hexane/Et2O¼1:1) as a slightly yellow oil
(0.151 g, 54%). Reaction time: 17 h. 1H NMR (CDCl3,
300 MHz): d¼1.34 (t, 3H, 3J¼7.1 Hz, OCH2CH3), 1.57 (d,
84
86
51
77
53
d
e
f
Me Ph
j
k
n-Hex Me Ph
Ph Et Ph
3
3H, J¼6.5 Hz, CH3), 4.33–4.44 (m, 2H, CH2), 5.10 (q,
a
1H, 3J¼6.5 Hz, CH), 8.75 (br s, 1H, OH). 13C NMR
(CDCl3, 75 MHz): d¼14.2 (OCH2CH3), 19.6 (CH3), 62.0
(CH2), 74.79 (CH), 120.14 (C), 152.19 (COH), 164.64
(CO), 165.55 (CO2CH2CH3). IR (KBr, cmꢀ1): ~n¼3328
(w), 2985 (m), 2938 (w), 2876 (w), 1781 (s), 1709 (s),
1443 (m), 1332 (m), 1225 (s), 1184 (s), 1102 (m), 1052
(m), 923 (w), 769 (w). UV–vis (MeCN, nm): l (log 3)¼
205.51 (3.49), 251.03 (4.04). MS (EI, 70 eV): m/z
(%)¼186 ([M]+, 1.5), 187 (1.5), 141 (85), 130 (15), 112
(78), 99 (48), 86 (50), 70 (100), 53 (12), 43 (66), 29 (57).
Anal. Calcd for C8H10O5: C, 51.61; H, 5.41. Found: C,
51.2; H, 5.82.
Isolated yields.
1,3-bis(silyloxy)alk-1-enes with oxalyl chloride. The
method is applicable to the synthesis of enantiomerically
pure butenolides. This is useful, since there exist many
methods for the enantioselective synthesis of 3-hydroxyest-
ers. The oxalyl derived hydroxy group can be functionalized
by Suzuki cross-coupling reactions of the enol triflate.
3. Experimental section
3.1. General comments
3.2.3. Ethyl 2-ethyl-4-hydroxy-5-oxo-2,5-dihydrofuran-
3-carboxylate (3c). Starting with 2c (322 mg, 1.11 mmol),
CH2Cl2 (10 mL), and oxalyl chloride (2.0 M in CH2Cl2,
All solvents were dried by standard methods and all reac-
tions were carried out under an inert atmosphere. For H
1

12550
R. Dede et al. / Tetrahedron 63 (2007) 12547–12561
0.55 mL, 1.10 mmol), 3c was isolated by column chromato-
graphy (n-hexane/Et2O¼1:1) as a slightly brown oil
(170 mg, 77%); Rf 0.50 (tailing; Et2O). Reaction time:
solid (109 mg, 54%). Mp 52–54 ꢁC; Rf 0.38 (tailing;
Et2O). Reaction time: 16 h. H NMR (300 MHz, CDCl3):
1
3
3
d¼0.72 (d, J¼6.9 Hz, 3H, CHCH3), 1.18 (d, J¼7.0 Hz,
3H, CHCH3), 1.38 (t, 3J¼7.1 Hz, 3H, OCH2CH3), 2.39
(m, 1H, CH(CH3)2), 4.38 (m, 2H, OCH2), 5.06 (d,
3J¼2.5 Hz, 1H, OCH), 8.2 (br, 1H, OH). 13C NMR
(75 MHz, CDCl3): d¼13.7, 14.0 (OCH2CH3, CHCH3),
19.4 (CHCH3), 30.0 (CH(CH3)2), 61.9 (OCH2), 82.2
(OCH), 117.8 (CCH), 152.4 (COH), 164.6, 166.1 (CO). IR
(KBr, cmꢀ1): ~n¼3332 (m), 2976 (m), 1786 (s), 1693 (s),
1440 (m), 1377 (m), 1303 (m), 1222 (s), 1185 (m), 1123
(m), 1000 (m). MS (EI, 70 eV): m/z (%)¼214 (M+, 18),
172 (100), 144 (36), 126 (49), 114 (28), 70 (32), 43 (38).
Anal. Calcd for C10H14O5 (214.22): C, 56.07; H, 6.59.
Found: C, 56.25; H, 6.75.
1
3
17 h. H NMR (300 MHz, CDCl3): d¼0.97 (t, J¼7.3 Hz,
3H, CHCH2CH3), 1.38 (t, 3J¼7.1 Hz, 3H, OCH2CH3),
1.62–1.76 (m, 1H, CHCHAHB), 2.10–2.23 (m, 1H,
3
CHCHAHB), 4.39 (m, 2H, OCH2), 5.09 (dd, J1¼7.3 Hz,
3J2¼3.2 Hz, 1H, CH), 8.78 (br, 1H, OH). 13C NMR
(150 MHz, CDCl3): d¼8.2, 14.0 (CH3), 26.0 (CHCH2),
61.9 (OCH2), 79.1 (CH), 118.4 (CCH), 152.1 (COH),
164.4, 165.9 (CO). IR (neat, cmꢀ1): ~n¼3326 (br, s), 2980
(s), 2939 (m), 1781 (s), 1703 (s), 1447 (s), 1379 (m), 1303
(s), 1224 (s), 1184 (s), 1137 (s), 1083 (m), 771 (m). MS
(EI, 70 eV): m/z (%)¼200 (M+, 33), 155 (47), 143 (72),
114 (100), 70 (85), 29 (99). HRMS (EI, 70 eV): calcd for
C9H12O5 (M+) 200.06792; found 200.06746.
3.2.7. Ethyl 2-butyl-4-hydroxy-5-oxo-2,5-dihydrofuran-
3-carboxylate (3g). Starting with 2g (322 mg, 1.01 mmol),
CH2Cl2 (10 mL), and oxalyl chloride (2.0 M in CH2Cl2,
0.50 mL, 1.00 mmol), 3g was isolated by column chromato-
graphy (n-hexane/Et2O¼1:1) as a slightly orange solid
(173 mg, 75%). Mp¼40 ꢁC; Rf 0.45 (tailing; Et2O). Reaction
3.2.4. tert-Butyl 2,5-dihydro-4-hydroxy-2-ethyl-5-oxo-
furan-3-carboxylate (3d). Starting with 2d (0.52 g,
1.50 mol), CH2Cl2 (10 mL), and oxalyl chloride (2.0 M in
CH2Cl2, 0.55 mL, 1.10 mmol), 3d was isolated by column
chromatography (n-hexane/Et2O¼1:1) as a slightly brown
oil (0.110 g, 32%); Rf 0.50 (tailing; Et2O). Reaction time:
17 h. 1H NMR (CDCl3, 300 MHz): d¼0.94 (t, 3H,
3J¼7.4 Hz, CH2CH3), 1.57 (s, 9H, CH3), 1.60–1.80 (m, 1H,
(dd, 1H, 3J¼3.2, 7.1 Hz, CH). 13C NMR (CDCl3,
75 MHz): d¼8.2 (CH2CH3), 25.9 (CH2CH3), 28.0 (CH3),
79.1 (CH), 84.2 (C(CH3)3), 119.7 (C), 152.1 (COH), 164.1
(CO), 166.0 (CO2-t-Bu). IR (KBr, cmꢀ1): ~n¼3404 (w),
2978 (w), 1782 (m), 1688 (m), 1440 (w), 1372 (w), 1239
(w), 1149 (m), 1081 (w). MS (EI, 70 eV): m/z (%)¼228
([M]+, 1), 184 (1), 155 (7), 142 (1), 127 (5), 108 (1), 77
(1), 59 (2), 57 (22), 28 (100). A correct elemental analysis
or HRMS data could not be obtained, due to decomposition.
1
3
time: 17 h. H NMR (300 MHz, CDCl3): d¼0.91 (t, J¼
7.1 Hz, 3H, CH2CH2CH3), 1.25–1.45 (m, 7H, OCH2CH3,
CH2CH2CH3), 1.50–1.70 (m, 1H, CHCHAHB), 2.00–2.20
(m, 1H, CHCHAHB), 4.39 (m, 2H, OCH2), 5.11 (dd,
3
CHAHB), 2.14 (sextd, 1H, J¼7.4, 3.2 Hz, CHAHB), 5.05
3
3J1¼7.9 Hz, J2¼2.9 Hz, 1H, CH), 8.1 (br, 1H, OH). 13C
NMR (75 MHz, CDCl3): d¼13.7, 14.1 (CH3), 22.2, 26.3,
32.7 (CH2), 61.9 (OCH2), 78.3 (CH), 118.7 (CCH), 152.1
(COH), 164.5, 165.9 (CO). IR (KBr, cmꢀ1): ~n¼3330 (br,
w), 2960 (m), 2935 (m), 2870 (w), 1780 (s), 1708 (s),
1662 (m), 1443 (m), 1378 (w), 1336 (m), 1301 (m), 1226
(m), 1183 (m), 1138 (m), 1103 (m), 1018 (w), 770 (w).
MS (EI, 70 eV): m/z (%)¼228 (M+, 3), 183 (43), 172 (25),
143 (100), 126 (33), 114 (92), 113 (89), 97 (46), 86 (52),
70 (71), 41 (60), 29.0 (90), 28 (47), 27 (47). Anal. Calcd
for C11H16O5 (228.24): C, 57.88; H, 7.07. Found: C,
57.52; H, 7.12.
3.2.5. Ethyl 2,5-dihydro-4-hydroxy-2-propyl-5-oxofuran-
3-carboxylate (3e). Starting with 2e (0.442 g, 1.5 mmol),
CH2Cl2 (15 mL), and oxalyl chloride (2.0 M in CH2Cl2,
0.75 mL, 1.5 mmol), 3e was isolated by column chromato-
graphy (n-hexane/Et2O¼1:1) as a slightly brown oil
(0.227 g, 71%); Rf 0.50 (tailing; Et2O). Reaction time:
17 h. 1H NMR (CDCl3, 300 MHz): d¼0.96 (t, 3H, 3J¼
7.3 Hz, CH3), 1.38 (t, 3H, 3J¼7.1 Hz, OCH2CH3), 1.43–1.49
(m, 2H, CH2CH3), 1.53–1.63 (m, 1H, CHAHBCH2CH3),
2.04–2.15 (m, 1H, CHACHBCH2CH3), 4.30–4.45 (m, 2H,
3.2.8. tert-Butyl 2-butyl-4-hydroxy-5-oxo-2,5-dihydro-
furan-3-carboxylate (3h). Starting with 2h (674 mg,
1.94 mmol), CH2Cl2 (20 mL), and oxalyl chloride (2.0 M
in CH2Cl2, 0.97 mL, 1.94 mmol), 3h was isolated by column
chromatography (n-hexane/Et2O¼4:1) as a slightly brown
oil (104 mg, 21%); Rf 0.59–0.77 (tailing; Et2O). Reaction
1
time: 22 h. H NMR (300 MHz, CDCl3): d¼0.91 (m, 3H,
3
OCH2CH3), 5.11 (dd, 1H, J¼3, 8.1 Hz, CH), 8.78 (br s,
CH2CH3), 1.25–1.50 (m, 4H, CH2CH2CH3), 1.57 (s, 9H,
C(CH3)3), 1.59–1.70 (m, 1H, CHCHAHB), 2.03–2.15 (m,
1H, OH). 13C NMR (CDCl3, 75 MHz): d¼13.7 (CH3),
14.1 (OCH2CH3), 17.8 (CH2CH3), 35.2 (CH2CH2CH3),
61.9 (OCH2CH3), 78.1 (CH), 118.2 (C), 152.2 (COH),
164.6 (CO), 165.7 (CO2CH2CH3). IR (KBr, cmꢀ1):
~n¼2977 (m), 2934 (m), 2865 (m), 1781 (w), 1742 (w),
1710 (w), 1447 (m), 1383 (m), 1238 (w), 1126 (s), 1044
(w), 795 (w). MS (EI, 70 eV): m/z (%)¼215 ([M+1+], 2),
214 ([M]+, 8), 169 (28), 143 (48), 123 (11), 113 (48), 86
(20), 70 (41), 43 (43), 28 (100). Anal. Calcd for C10H14O5:
C, 56.07; H, 6.59. Found: C, 56.34; H, 7.13.
3
3
1H, CHCHAHB), 5.06 (dd, J1¼7.7 Hz, J2¼2.9 Hz, 1H,
CH), 8.7 (br, 1H, OH). 13C NMR (62 MHz, CDCl3):
d¼13.7 (CH2CH3), 22.1, 26.1 (CH2), 28.0 (C(CH3)3), 32.4
(CH2), 78.3 (OCH), 84.1 (C(CH3)3), 120.1 (CCH), 151.9
(COH), 164.1, 165.9 (CO). IR (neat, cmꢀ1): ~n¼3327 (br,
s), 2960 (s), 2933 (s), 2874 (s), 1786 (s), 1685 (s), 1458
(m), 1371 (s), 1237 (s), 1151 (s), 771 (m). MS (CI, isobu-
tane): m/z (%)¼257 ([M+1]+, 19), 202 (21), 201 (100),
157 (11).
3.2.6. Ethyl 4-hydroxy-2-isopropyl-5-oxo-2,5-dihydro-
furan-3-carboxylate (3f). Starting with 2f (287 mg,
0.94 mmol), CH2Cl2 (10 mL), and oxalyl chloride (2.0 M
in CH2Cl2, 0.47 mL, 0.94 mmol), 3f was isolated by column
chromatography (n-hexane/Et2O¼1:1) as a slightly yellow
3.2.9. Ethyl 4-hydroxy-2-isobutyl-5-oxo-2,5-dihydro-
furan-3-carboxylate (3i). Starting with 2i (306 mg,
0.96 mmol), CH2Cl2 (10 mL), and oxalyl chloride (2.0 M
in CH2Cl2, 0.48 mL, 0.96 mmol), 3i was isolated by column
chromatography (n-hexane/Et2O¼1:1) as a colorless solid

R. Dede et al. / Tetrahedron 63 (2007) 12547–12561
12551
4
3
(138 mg, 63%). Mp 99–100 ꢁC; Rf 0.38 (tailing; Et2O). Re-
action time: 16 h. 1H NMR (300 MHz, CDCl3): d¼0.97 (d,
3J¼6.4 Hz, 3H, CHCH3), 1.01 (d, 3J¼6.2 Hz, 3H,
CHCH3), 1.38 (t, 3J¼7.1 Hz, 3H, OCH2CH3), 1.46 (m,
1H, CHAHBCH), 1.85–2.00 (m, 2H, CHAHBCH(CH3)2),
4.39 (m, 2H, OCH2CH3), 5.13 (dd, 3J1¼9.9 Hz,
3J2¼2.0 Hz, 1H, CH), 8.7 (br, 1H, OH). 13C NMR
(75 MHz, CDCl3): d¼14.0 (OCH2CH3), 21.6, 23.4, 24.8
(CH(CH3)2), 42.5 (CHCH2), 61.8 (OCH2), 77.0 (OCH),
119.3 (CCH), 151.8 (COH), 164.5, 165.8 (CO). IR (KBr,
cmꢀ1): ~n¼3276 (br, w), 2958 (m), 1747 (s), 1710 (s), 1676
(w), 1464 (w), 1344 (w), 1299 (m), 1218 (m), 1190 (m),
1144 (w). MS (EI, 70 eV): m/z (%)¼228 (M+, 2), 184
(40), 172 (72), 143 (100), 126 (50), 114 (93), 86 (42), 70
(68), 41 (81), 29 (77). Anal. Calcd for C11H16O5 (228.24):
C, 57.88; H, 7.07. Found: C, 58.16; H, 7.43.
1H, J¼1.0 Hz, J¼17.0 Hz, CHCHCHAcisHBtrans), 5.778
(m, 1H, CHCHCH2), 8.78 (br s, 1H, OH). 13C NMR
(CDCl3, 75 MHz): d¼14.2 (CH3), 62.0 (CH2), 78.1
(CHCHCH2), 118.0 (C), 120.3 (CHCHCH2), 131.6
(CHCHCH2), 152.0 (COH), 164.5 (CO), 165.4 (CO2Et).
IR (KBr, cmꢀ1): ~n¼2984 (w), 1782 (s), 1708 (s), 1665
(m), 1442 (w), 1379 (w), 1307 (m), 1224 (m), 1126 (m),
1011 (w), 941 (w). MS (EI, 70 eV): m/z (%)¼198 ([M]+,
7), 170 (12), 152 (34), 142 (16), 125 (63), 107 (79), 97
(42), 80 (44), 55 (25), 43 (14), 28 (100).
3.2.13. Ethyl 2-(9-decenyl)-4-hydroxy-5-oxo-2,5-dihy-
drofuran-3-carboxylate (3m). Starting with 2m (374 mg,
0.93 mmol), CH2Cl2 (10 mL), and oxalyl chloride (2.0 M
in CH2Cl2, 0.42 mL, 0.84 mmol), 3m was isolated by
column chromatography (n-hexane/Et2O¼1:1) as a slightly
yellow oil (216 mg, 83%). Reaction time: 24 h. 1H
NMR (250 MHz, CDCl3): d¼1.23–1.45 (m, 15H,
OCHCH2(CH2)6, CH3), 1.52–1.67 (m, 1H, OCHCHAHB),
1.97–2.16 (m, 3H, H2C]CHCH2, OCHCHAHB), 4.37 (m,
2H, OCH2), 4.89–5.02 (m, 2H, H2C]CH), 5.09 (dd,
3J1¼7.8 Hz, 3J2¼2.9 Hz, 1H, OCH), 5.80 (ddt, 3J1¼
3.2.10. Methyl 2-tert-butyl-4-hydroxy-5-oxo-2,5-dihydro-
furan-3-carboxylate (3j). Starting with 2j (4.07 g,
13.4 mmol), CH2Cl2 (100 mL), and oxalyl chloride (2.0 M
in CH2Cl2, 6.68 mL, 13.4 mmol), 3j was isolated by column
chromatography (n-hexane/Et2O¼2:1/1:1) as an orange
oil (1.01 g, 35%); Rf 0.18–0.37 (tailing; Et2O). Reaction
3
3
17.0 Hz, J2¼10.3 Hz, J3¼6.7 Hz, 1H, H2C]CH), 8.70
(br, 1H, OH). 13C NMR (75 MHz, CDCl3): d¼14.1 (CH3),
24.3, 28.8, 29.0, 29.1, 29.2, 29.3, 33.0, 33.7 (OCH(CH2)8),
61.9 (OCH2), 78.3 (OCH), 114.1 (H2C]CH), 118.9
(CCH), 139.1 (H2C]CH), 152.2 (COH), 164.6, 165.7
(CO). IR (KBr, cmꢀ1): ~n¼3393 (br, s), 2980 (m), 2924 (s),
2854 (s), 1784 (s), 1748 (s), 1710 (s), 1669 (m), 1467 (m),
1300 (m), 1218 (s), 1190 (s), 776 (m). MS (CI, isobutane):
m/z (%)¼311 ([M+1]+, 100), 265 (49). Anal. Calcd for
C17H26O5 (310.39): C, 65.78; H, 8.44. Found: C, 65.82;
H, 8.65.
1
time: 15 h. H NMR (300 MHz, CDCl3): d¼0.99 (s, 9H,
C(CH3)3), 3.90 (s, 3H, OCH3), 4.93 (s, 1H, CH), 7.3 (br,
1H, OH). 13C NMR (75 MHz, CDCl3): d¼25.8 (C(CH3)3),
36.5 (C(CH3)3), 52.4 (OCH3), 85.5 (OCH), 117.6
(C]COH), 153.2 (COH), 165.5, 165.6 (CO). IR (neat,
cmꢀ1): ~n¼3348 (br, w), 2966 (m), 1776 (s), 1724 (s), 1654
(m), 1456 (m), 1324 (m), 1231 (s), 1180 (m), 1128 (m),
1019 (w), 979 (w), 773 (w). MS (EI, 70 eV): m/z (%)¼214
(M+, 0.53), 158 (100), 126 (22), 70 (33), 57 (98), 29 (27).
3.2.11. Methyl 2-hexyl-4-hydroxy-5-oxo-2,5-dihydro-
furan-3-carboxylate (3k). Starting with 2k (377 mg,
1.13 mmol), CH2Cl2 (10 mL), and oxalyl chloride (2.0 M
in CH2Cl2, 0.57 mL, 1.14 mmol), 3k was isolated by column
chromatography (n-hexane/Et2O¼1:1) as a slightly yellow
solid (168 mg, 61%). Mp 73–74 ꢁC; Rf 0.42 (tailing;
3.2.14. Methyl 2-benzyl-2,5-dihydro-4-hydroxy-5-oxo-
furan-3-carboxylate (3n). Starting with 2n (0.49 g,
1.50 mmol), CH2Cl2 (10 mL), and oxalyl chloride (2.0 M
in CH2Cl2, 0.75 mL, 1.5 mmol), 3n was isolated by column
chromatography (n-hexane/Et2O¼1:1) as a slightly yellow
1
1
Et2O). Reaction time: 15 h. H NMR (300 MHz, CDCl3):
d¼0.88 (t, J¼6.6 Hz, 3H, CH2CH3), 1.18–1.49 (m, 8H,
oil (0.148 g, 38%). Reaction time: 24 h. H NMR (CDCl3,
3
300 MHz): d¼3.02 (dd, 1H, 3J¼6.2 Hz, 2J¼14.5 Hz,
(CH2)4CH3), 1.52–1.67 (m, 1H, CHCHAHB), 2.05–2.18
(m, 1H, CHCHAHB), 3.92 (s, 3H, OCH3), 5.11 (dd,
CHACHB), 3.42 (dd, 1H, 3J¼3.3 Hz, 2J¼14.5 Hz, CHACHB),
3
3.96 (s, 1H, OCH3), 5.34 (dd, 1H, J¼6.23, 3.38 Hz, CH),
3
3J1¼8.1 Hz, J2¼2.8 Hz, 1H, CH), 8.38 (br, 1H, OH). 13C
7.95–7.15 (m, 2H, Ar), 7.19–7.31 (m, 3H, Ar). 13C NMR
(CDCl3, 75 MHz): d¼38.7 (CH2), 52.6 (OCH3), 77.9
(CH), 117.5 (C), 127.2 (Ar), 128.5 (Ar), 129.5 (Ar), 134.2
(Ar), 152.3 (COH), 164.5 (CO), 165.4 (CO2Me). IR (KBr,
cmꢀ1): ~n¼3400 (m), 2979 (w), 1777 (s), 1713 (s), 1660
(m), 1515 (w), 1455 (m), 1341 (w), 1224 (m), 1172 (m),
1123 (m), 1044 (w), 771 (w). MS (EI, 70 eV): m/z
(%)¼248 ([M]+, 11), 278 (2), 223 (1), 205 (1), 177 (2),
160 (3), 114 (6), 91 (100), 66 (8).
NMR (75 MHz, CDCl3): d¼13.8 (CH2CH3), 22.3, 24.2,
28.7, 31.4, 33.0 (CH2), 52.4 (OCH3), 78.4 (OCH), 118.3
(CCH), 151.6 (COH), 164.6, 166.1 (CO). IR (KBr, cmꢀ1):
~n¼3321 (s), 2925 (s), 2857 (m), 1788 (s), 1699 (s), 1456
(m), 1343 (m), 1309 (m), 1220 (s), 1115 (m), 994 (w), 772
(w). MS (EI, 70 eV): m/z (%)¼242 (M+, 2), 186 (37), 158
(82), 129 (100), 100 (72), 70 (28). Anal. Calcd for
C12H18O5 (242.27): C, 59.49; H, 7.49. Found: C, 59.68; H,
7.66.
3.2.15. Ethyl 4-hydroxy-5-oxo-2-phenyl-2,5-dihydro-
furan-3-carboxylate (3o). Starting with 2o (314 mg,
0.93 mmol), CH2Cl2 (10 mL), and oxalyl chloride (2.0 M
in CH2Cl2, 0.46 mL, 0.92 mmol), 3o was isolated by column
chromatography (n-hexane/Et2O¼1:1) as a slightly yellow
solid (143 mg, 62%). Mp 105 ꢁC; Rf 0.25 (tailing; Et2O). Re-
3.2.12. Ethyl 2,5-dihydro-4-hydroxy-5-oxo-2-vinylfuran-
3-carboxylate (3l). Starting with 2l (0.432 g, 1.5 mmol),
CH2Cl2 (15 mL), and oxalyl chloride (2.0 M in CH2Cl2,
0.75 mL, 1.5 mmol), 3l was isolated by column chromato-
graphy (n-hexane/Et2O¼1:1) as a slightly yellow oil
(0.100 g, 34%). Reaction time: 15 h. 1H NMR (CDCl3,
300 MHz): d¼1.35 (t, 3H, 3J¼7.1 Hz, –CH3), 4.35 (m, 2H,
1
action time: 17 h. H NMR (300 MHz, CDCl3): d¼1.16 (t,
3J¼7.1 Hz, 3H, CH3), 4.21 (q, 3J¼7.1 Hz, 2H, OCH2),
6.00 (s, 1H, OCH), 7.26–7.31 (m, 2H, Ph), 7.35–7.40 (m,
3H, Ph), 8.87 (br, 1H, OH). 13C NMR (75 MHz, CDCl3):
4
3
CH2), 5.39 (dt, 1H, J¼1.0 Hz, J¼10.2 Hz, CH), 5.47 (dt,
4
3
1H, J¼1.0 Hz, J¼6.5 Hz, CHCHCHAcisHBtrans), 5.53 (dt,

12552
R. Dede et al. / Tetrahedron 63 (2007) 12547–12561
d¼13.8 (CH3), 61.8 (OCH2), 79.4 (OCH), 118.9 (C]COH),
127.2, 128.7, 129.6 (CHAr), 134.2 (CAr), 152.0 (COH),
164.3, 165.7 (CO). IR (KBr, cmꢀ1): ~n¼3300 (br, m), 2992
(w), 1749 (s), 1715 (s), 1674 (m), 1456 (w), 1319 (m),
1207 (s), 1179 (s), 1127 (m), 998 (m). MS (EI, 70 eV):
m/z (%)¼248 (M+, 33), 203 (21), 175 (16), 158 (41), 130
(59), 105 (39), 77 (47), 28 (100). Anal. Calcd for
C13H12O5 (248.23): C, 62.90; H, 4.87. Found: C, 62.82;
H, 4.93.
(Ar), 152.4 (COH), 164.7 (CO), 165.8 (CO2Me). IR (KBr,
cmꢀ1): ~n¼3366 (w), 1776 (s), 1727 (s), 1666 (w), 1460
(w), 1315 (m), 1208 (s), 1172 (m), 1129 (m), 1006 (w),
772 (w). MS (EI, 70 eV): m/z (%)¼248 ([M]+, 23), 216
(5), 203 (39), 171 (52), 144 (34), 115 (78), 114 (100), 91
(78), 66 (20), 28 (15). Anal. Calcd for C13H12O5: C, 62.9;
H, 4.87. Found: C, 62.82; H, 4.98.
3.2.19. Ethyl 4-hydroxy-2-(2-methoxyphenyl)-5-oxo-2,5-
dihydrofuran-3-carboxylate (3s). Starting with 2s
(317 mg, 0.86 mmol), CH2Cl2 (10 mL), and oxalyl chloride
(2.0 M in CH2Cl2, 0.41 mL, 0.82 mmol), and recrystalliza-
tion from a mixture of CH2Cl2 (2.5 mL) and n-hexane
(25 mL) at ꢀ24 ꢁC yielded 2s as a slightly brown solid
3.2.16. Ethyl 4-hydroxy-2-(4-methylphenyl)-5-oxo-2,5-
dihydrofuran-3-carboxylate (3p). Starting with 2p
(337 mg, 0.96 mmol), CH2Cl2 (10 mL), and oxalyl chloride
(2.0 M in CH2Cl2, 0.45 mL, 0.90 mmol), and recrystalliza-
tion from a mixture of CH2Cl2 (3 mL) and n-hexane
(25 mL) at ꢀ24 ꢁC yielded 3p as a slightly brown solid
1
(137 mg, 60%); mp 111–112 ꢁC. Reaction time: 24 h. H
NMR (250 MHz, CDCl3): d¼1.13 (t, 3J¼7.1 Hz, 3H,
1
3
(159 mg, 67%); mp 113–114 ꢁC. Reaction time: 24 h. H
CH2CH3), 3.83 (s, 3H, OCH3), 4.19 (q, J¼7.1 Hz, 2H,
NMR (250 MHz, CDCl3): d¼1.18 (t, 3J¼7.1 Hz, 3H,
CH2CH3), 2.36 (s, 3H, ArCH3), 4.21 (m, 2H, OCH2), 5.98
(s, 1H, OCH), 7.17 (s, 4H, Ar), 8.8 (br, 1H, OH). 13C
NMR (75 MHz, CDCl3): d¼13.8 (CH2CH3), 21.2
(ArCH3), 61.9 (OCH2), 79.3 (OCH), 118.9 (C]COH),
127.2, 129.4 (CHAr), 131.2, 139.6 (CAr), 152.0 (COH),
164.4, 165.8 (CO). IR (KBr, cmꢀ1): ~n¼3316 (br, m), 2997
(m), 1753 (s), 1744 (s), 1716 (s), 1671 (s), 1460 (m), 1318
(s), 1201 (s), 1174 (s), 992 (s), 775 (m). MS (EI, 70 eV):
m/z (%)¼262 (M+, 49), 217 (28), 189 (25), 145 (58), 144
(100), 121 (56), 119 (80), 117 (54), 116 (36), 115 (71), 91
(66), 44 (70). Anal. Calcd for C14H14O5 (262.26): C,
64.12; H, 5.38. Found: C, 63.97; H, 5.22.
OCH2), 6.36 (s, 1H, OCH), 6.89–6.96 (m, 2H, Ar), 7.06–
7.10 (m, 1H, Ar), 7.31–7.38 (m, 1H, Ar), 8.9 (br, 1H, OH).
13C NMR (75 MHz, CDCl3): d¼13.8 (CH2CH3), 55.7
(OCH3), 61.6 (OCH2), 75.3 (OCH), 111.3 (CHAr), 118.2
(C), 120.5 (CHAr), 122.0 (C), 128.7, 131.0 (CHAr), 152.6,
158.1, 164.7, 166.1 (C). IR (KBr, cmꢀ1): ~n¼3272 (s), 2979
(m), 2939 (w), 1787 (s), 1749 (s), 1704 (s), 1690 (s), 1602
(m), 1496 (m), 1234 (s), 1186 (s), 761 (m). MS (EI,
70 eV): m/z (%)¼278 (M+, 100), 233 (68), 188 (37), 161
(59), 135 (63), 131 (85), 44 (66). Anal. Calcd for
C14H14O6 (278.26): C, 60.43; H, 5.07. Found: C, 60.73;
H, 5.29.
3.2.20. Ethyl 2-(4-chlorophenyl)-4-hydroxy-5-oxo-2,5-di-
hydrofuran-3-carboxylate (3t). Starting with 2t (336 mg,
0.90 mmol), CH2Cl2 (10 mL), and oxalyl chloride (2.0 M
in CH2Cl2, 0.41 mL, 0.82 mmol), and recrystallization
from a mixture of CH2Cl2 (5 mL) and n-hexane (20 mL) at
ꢀ24 ꢁC yielded 3t as a slightly brown solid (99 mg, 43%);
CDCl3): d¼1.19 (t, 3J¼7.1 Hz, 3H, CH3), 4.22 (q,
3J¼7.1 Hz, 2H, OCH2), 5.97 (s, 1H, OCH), 7.18–7.27 (m,
2H, Ar), 7.32–7.39 (m, 2H, Ar), 8.90 (br, 1H, OH). 13C
NMR (62 MHz, CDCl3): d¼13.8 (CH3), 61.9 (OCH2),
78.6 (OCH), 118.4 (C]COH), 128.6, 128.9 (CHAr),
132.9, 135.5 (CAr), 152.0 (COH), 164.0, 165.8 (CO). IR
(KBr, cmꢀ1): ~n¼3363 (br, s), 2999 (m), 1749 (s), 1713 (s),
1672 (s), 1496 (m), 1318 (s), 1202 (s), 1178 (s), 997 (s),
835 (m). Anal. Calcd for C13H11ClO5 (282.68): C, 55.24;
H, 3.92. Found: C, 55.28; H, 4.30.
3.2.17. Ethyl 2,5-dihydro-4-hydroxy-2-(40-methoxy-
phenyl)-5-oxofuran-3-carboxylate (3q). Starting with 2q
(0.55 g, 1.50 mmol), CH2Cl2 (15 mL), and oxalyl chloride
(2.0 M in CH2Cl2, 0.75 mL, 1.5 mmol), 3q was isolated by
column chromatography (n-hexane/Et2O¼1:1) as a slightly
1
1
yellow solid (0.134 g, 32%); mp 97.6–100.3 ꢁC. H NMR
mp 115–116 ꢁC. Reaction time: 24 h. H NMR (250 MHz,
3
(CDCl3, 300 MHz): d¼1.18 (t, 3H, J¼7.1 Hz, CH3), 3.82
(s, 3H, OCH3), 4.21 (q, 2H, CH2), 5.97 (s, 1H, CH), 6.89
(dd, 2H, 3J¼6.8 Hz, 4J¼1.9 Hz, Ar), 7.20 (dd, 2H,
4
3J¼6.7 Hz, J¼2 Hz, Ar), 8.78 (br s, 1H, OH). 13C NMR
(CDCl3, 75 MHz): d¼13.9 (CH3), 55.3 (OCH3), 61.8
(CH2), 79.2 (CH), 114.1 (C), 118.8 (Ar), 126.1 (Ar), 128.7
(Ar), 152.1 (COH), 160.6 (Ar), 164.5 (CO), 165.7
(CO2Et). IR (KBr, cmꢀ1): ~n¼3299 (w), 1742 (s), 1676
(m), 1612 (w), 1515 (w), 1460 (w), 1315 (s), 1256 (m),
1174 (s), 1126 (w), 1024 (w), 992 (m), 838 (w). MS (EI,
70 eV): m/z (%)¼278 ([M]+, 45), 279 (3), 233 (19), 205
(14), 178 (11), 160 (100), 117 (21), 89 (36), 77 (25), 28
(63). Anal. Calcd for C14H14O6: C, 60.43; H, 5.07. Found:
C, 60.05; H, 5.10.
3.2.21. Ethyl 4-hydroxy-2,2-dimethyl-5-oxo-2,5-dihydro-
furan-3-carboxylate (3u). Starting with 2u (291 mg,
1.00 mmol), CH2Cl2 (10 mL), and oxalyl chloride (2.0 M
in CH2Cl2, 0.50 mL, 1.00 mmol), 3u was isolated by column
chromatography (n-heptane/Et2O¼1:1) as a slightly yellow
solid (43 mg, 21%). Mp 61–62 ꢁC; Rf 0.22 (tailing; Et2O).
3.2.18. Methyl 2,5-dihydro-4-hydroxy-5-oxo-2-ortho-tol-
ylfuran-3-carboxylate (3r). Starting with 2q (0.49 g,
1.50 mmol), CH2Cl2 (15 mL), and oxalyl chloride (2.0 M
in CH2Cl2, 0.75 mL, 1.5 mmol), 3r was isolated by column
chromatography (n-hexane/Et2O¼1:1) as a slightly yellow
1
Reaction time: 22 h. H NMR (250 MHz, CDCl3): d¼1.38
3
(t, J¼7.1 Hz, 3H, CH2CH3), 1.59 (s, 6H, C(CH3)2), 4.38
(q, 3J¼7.1 Hz, 2H, CH2), 7.0 (br, 1H, OH). 13C NMR
(62 MHz, CDCl3): d¼14.1 (CH2CH3), 25.9 (C(CH3)2),
61.9 (OCH2), 83.4 (OC(CH3)2), 123.3 (C]COH), 151.7
(COH), 164.6, 165.0 (CO). IR (KBr, cmꢀ1): ~n¼3314 (br,
s), 2981 (m), 1747 (s), 1707 (s), 1664 (s), 1448 (m), 1368
(m), 1315 (s), 1249 (s), 1182 (s), 1128 (s), 1065 (s), 986
(m), 772 (m). MS (EI, 70 eV): m/z (%)¼200 (M+, 24), 185
1
oil (0.172 g, 49%). H NMR (CDCl3, 300 MHz): d¼2.50
(s, 3H, ArCH3), 3.75 (s, 3H, OCH3), 6.32 (s, 1H, Ar), 6.97
3
4
(dd, 1H, J¼8.3 Hz, J¼0.6 Hz, Ar), 6.98–7.29 (m, 3H,
Ar), 8.77 (br s, 1H, OH). 13C NMR (CDCl3, 75 MHz):
d¼19.0 (CH3), 52.5 (OCH3), 76.2 (CH), 118.1 (C), 126.3
(Ar), 126.3 (Ar), 129.6 (Ar), 131.0 (Ar), 132.1 (Ar), 137.5

R. Dede et al. / Tetrahedron 63 (2007) 12547–12561
12553
(20), 157 (31), 155 (42), 129 (28), 100 (33), 86 (60), 84
(100), 69 (30), 49 (62). HRMS (EI, 70 eV): calcd for
C9H12O5 (M+) 200.06792; found 200.06864.
found 361.05555. Anal. Calcd for C12H15F3O7S (360.30):
C, 40.00; H, 4.20. Found: C, 40.34; H, 4.09.
3.3.3. Ethyl 2-isobutyl-5-oxo-4-trifluoromethanesulfonyl-
oxy-2,5-dihydrofuran-3-carboxylate (4c). Starting with 3i
(106 mg, 0.46 mmol), CH2Cl2 (10 mL), pyridine (95 mg,
1.2 mmol), and Tf2O (205 mg, 0.73 mmol), 4c was isolated
as a yellow oil (144 mg, 86%); Rf 0.79 (CH2Cl2). After stir-
ring for 90 min, the reaction mixture (temperature: 12 ꢁC)
was purified by column chromatography (CH2Cl2). 1H
NMR (300 MHz, CDCl3): d¼0.99 (d, 3J¼6.4 Hz, 3H,
3.2.22. Determination of the enantiomeric excess of (R)-
3a. The enantiomeric excess (ee) was determined by
HPLC on an analytical column (CHIRALCEL OD-H). Con-
ditions: hexane/ethanol¼95:5+0.1% CF3COOH (0.5 mL/
min). Maxima after 20.61/22.50/22.74 min.
3.3. General procedure for the preparation of triflates
4a–f
3
3
CHCH3), 1.03 (d, J¼6.3 Hz, 3H, CHCH3), 1.41 (t, J¼
7.2 Hz, 3H, OCH2CH3), 1.55 (m, 1H, CHCHAHB), 1.88–
2.04 (m, 2H, CHAHBCH(CH3)2), 4.42 (m, 2H, OCH2),
To a CH2Cl2 solution of the appropriate isotetronic acids
3f,g,i–o was added pyridine. After stirring for 15 min the
solution was cooled to ꢀ78 ꢁC and Tf2O was added. The
reaction mixture was allowed to warm to 0 ꢁC within 90–
120 min and the reaction mixture was directly purified
(without aqueous work-up) by column chromatography (sil-
ica gel) to give the triflates 4a–f.
3
3
5.31 (dd, J1¼9.9 Hz, J2¼2.2 Hz, 1H, OCH). 13C NMR
(75 MHz, CDCl3): d¼13.8 (OCH2CH3), 21.4, 23.3, 24.9
(CH(CH3)2), 41.7 (CHCH2), 63.2 (OCH2), 78.2 (OCH),
1
118.3 (q, JCF¼321 Hz, CF3), 137.6, 142.4 (C]C), 158.7,
163.2 (CO). IR (neat, cmꢀ1): ~n¼2964 (m), 2876 (w), 1796
(s), 1735 (s), 1438 (s), 1254 (s), 1221 (s), 1134 (s), 1100
(m), 819 (m), 608 (m). MS (CI, isobutane): m/z (%)¼361
([M+1]+, 35).
3.3.1. Ethyl 2,5-dihydro-2-isopropyl-4-trifluormethane-
sulfonyloxy-5-oxofuran-3-carboxylate (4a). Starting with
3f (0.161 g, 0.752 mmol), CH2Cl2 (100 mL), pyridine
(0.118 g, 1.53 mmol), and Tf2O (0.318 g, 1.127 mmol), 4a
was isolated as a yellow liquid (0.237 g, 91%); Rf 0.78
(CH2Cl2). After stirring for 120 min, the reaction mixture
(temperature: ꢀ5 ꢁC) was purified by column chromato-
graphy (CH2Cl2). 1H NMR (CDCl3, 300 MHz): d¼0.76 (d,
3.3.4. Methyl 2-tert-butyl-5-oxo-4-trifluoromethanesulfo-
nyloxy-2,5-dihydrofuran-3-carboxylate (4d). Starting
with 3j (900 mg, 4.20 mmol), CH2Cl2 (100 mL), pyridine
(831 mg, 10.5 mmol), and Tf2O (1.42 g, 5.04 mmol), 4d
was isolated as an orange oil (736 mg, 51%); Rf 0.76
(CH2Cl2). After stirring for 100 min, the reaction mixture
(temperature: 0 ꢁC) was purified by column chromatography
(CH2Cl2). 1H NMR (300 MHz, CDCl3): d¼1.02 (s, 9H,
C(CH3)3), 3.95 (s, 3H, OCH3), 5.12 (s, 1H, OCH). 13C
NMR (75 MHz, CDCl3): d¼25.6 (C(CH3)3), 36.7
(C(CH3)3), 53.4 (OCH3), 86.0 (OCH), 118.3 (q, 1JCF¼321 Hz,
CF3), 137.3, 142.4 (C]C), 159.9, 162.8 (CO). IR (neat,
cmꢀ1): ~n¼2971 (m), 2878 (w), 1798 (s), 1744 (s), 1438 (s),
1255 (s), 1225 (s), 1134 (s), 1107 (s), 609 (m). MS (EI,
70 eV): m/z (%)¼347 ([M+1]+, 0.2). HRMS (EI, 70 eV): calcd
for C11H14F3O7S ([M+1]+) 347.04068; found 347.04000.
Anal. Calcd for C11H13F3O7S (346.28): C, 38.15; H, 3.78.
Found: C, 38.39; H, 3.78.
3
3
3H, J¼6.9 Hz, CH3), 1.21 (d, 3H, J¼7.0 Hz, CH3), 1.40
(t, 3H, 3J¼7.1 Hz, CH2CH3), 2.54 (septd, 1H, 3J¼7.0,
2.6 Hz, CH(CH3)2), 4.41 (q, 2H, 3J¼7.1 Hz, CH2CH3),
5.22 (d, 1H, 3J¼2.6 Hz, CH). 13C NMR (CDCl3, 75 MHz):
d¼13.8 (CH3), 13.8 (CH2CH3), 19.4 (CH3), 30.4
(CH(CH3)2), 63.2 (CH2CH3), 83.2 (CH), 118.3 (q,
1JC–F¼321 Hz, CF3), 137.8 (C), 141.43 (COS), 158.74
(CO), 163.4 (CO2Et). IR (KBr, cmꢀ1): ~n¼3438 (m), 2977
(w), 1796 (s), 1735 (s), 1676 (w), 1439 (s), 1385 (w), 1218
(s), 1131 (s), 1011 (w), 753.86 (w), 609 (m). MS (EI,
70 eV): m/z (%)¼304 ([M+, C3H3], 6), 222 (5), 171 (19),
143 (100), 114 (59), 70 (50), 43 (56), 29 (35). Anal. Calcd
for C11H13F3O7S: C, 38.15; H, 3.78. Found: C, 38.37;
H, 3.60.
3.3.5. Methyl 2-hexyl-5-oxo-4-trifluoromethanesulfonyl-
oxy-2,5-dihydrofuran-3-carboxylate (4e). Starting with
3j (1.52 g, 6.27 mmol), CH2Cl2 (100 mL), pyridine
(1.24 g, 15.7 mmol), and Tf2O (2.12 g, 7.52 mmol), 4e was
isolated as an orange liquid (1.81 g, 77%); Rf 0.80
(CH2Cl2). After stirring for 100 min, the reaction mixture
(temperature: 0 ꢁC) was purified by column chromatography
(CH2Cl2). 1H NMR (300 MHz, CDCl3): d¼0.88 (t,
3J¼6.8 Hz, 3H, CH2CH3), 1.20–1.48 (m, 8H, (CH2)4CH3),
1.77 (m, 1H, CHCHAHB), 2.12–2.27 (m, 1H, CHCHAHB),
3.96 (s, 3H, OCH3), 5.31 (dd, 3J1¼7.7 Hz, 3J2¼3.2 Hz,
1H, OCH). 13C NMR (75 MHz, CDCl3): d¼13.9 (CH2CH3),
22.4, 23.9, 28.6, 31.4, 32.3 (CH2), 53.2 (OCH3), 79.2
3.3.2. Ethyl 2-butyl-5-oxo-4-trifluoromethanesulfonyl-
oxy-2,5-dihydrofuran-3-carboxylate (4b). Starting with
3g (1.16 g, 5.10 mmol), CH2Cl2 (100 mL), pyridine
(1.03 g, 13.0 mmol), and Tf2O (1.93 g, 6.84 mmol), 4b
was isolated as a yellow liquid (1.54 g, 84%); Rf 0.78
(CH2Cl2). After stirring for 120 min, the reaction mixture
(temperature: ꢀ5 ꢁC) was purified by column chromato-
graphy (CH2Cl2). 1H NMR (300 MHz, CDCl3): d¼0.92
(m, 3H, CH2CH2CH3), 1.25–1.50 (m, 7H, OCH2CH3,
CH2CH2CH3), 1.70–1.85 (m, 1H, CHCHAHB), 2.15–2.28
(m, 1H, CHCHAHB), 4.42 (m, 2H, OCH2), 5.30 (dd,
3
1
3J1¼7.6 Hz, J2¼3.2 Hz, 1H, OCH). 13C NMR (75 MHz,
(OCH), 118.3 (q, JCF¼321 Hz, CF3), 138.1, 141.2
CDCl3): d¼13.6, 13.7 (CH3), 22.1, 26.0, 32.0 ((CH2)3),
(C]C), 159.0, 163.1 (CO). IR (neat, cmꢀ1): ~n¼2960 (m),
2932 (m), 2861 (m), 1797 (s), 1740 (s), 1440 (s), 1255 (s),
1221 (s), 1134 (s), 608 (m). MS (EI, 70 eV): m/z (%)¼375
([M+1]+, 0.2). HRMS (EI, 70 eV): calcd for C13H18F3O7S
([M+1]+) 375.07198; found 375.07116. Anal. Calcd for
C13H17F3O7S (374.33): C, 41.71; H, 4.58. Found: C,
42.15; H, 4.68.
1
63.2 (OCH2), 79.3 (OCH), 118.3 (q, JCF¼321 Hz, CF3),
137.7, 141.8 (C]C), 158.6, 163.2 (CO). IR (neat, cmꢀ1):
~n¼2964 (m), 2936 (m), 2877 (w), 1796 (s), 1735 (s), 1438
(s), 1254 (s), 1220 (s), 1135 (s), 608 (m). MS (EI, 70 eV):
m/z (%)¼361 ([M+1]+, 0.4), 304 (5), 143 (100). HRMS
(EI, 70 eV): calcd for C12H16F3O7S ([M+1]+) 361.05633;

12554
R. Dede et al. / Tetrahedron 63 (2007) 12547–12561
3.3.6. Ethyl 5-oxo-2-phenyl-4-trifluoromethanesulfonyl-
oxy-2,5-dihydrofuran-3-carboxylate (4f). Starting with
3o (62 mg, 0.25 mmol), CH2Cl2 (5 mL), pyridine (50 mg,
0.63 mmol), and Tf2O (92 mg, 0.33 mmol), 4f was isolated
as an orange solid (50 mg, 53%); Rf 0.74 (CH2Cl2). After
stirring for 110 min, the reaction mixture (temperature:
5 ꢁC) was purified by column chromatography (CH2Cl2).
(m, 1H, CHCHAHB), 2.05–2.17 (m, 1H, CHCHAHB), 4.26
(m, 2H, OCH2CH3), 5.27 (dd, 3J1¼7.8 Hz, 3J2¼3.3 Hz,
1H, OCH), 7.38–7.44 (m, 3H, Ph), 7.52–7.59 (m, 2H, Ph).
13C NMR (75 MHz, CDCl3): d¼13.7 (2ꢂCH3), 22.2, 26.6,
32.3 ((CH2)3), 61.7 (OCH2), 80.8 (OCH), 127.8 (CHAr),
128.4 (C), 129.4, 129.7 (CHAr), 135.4, 148.9 (C), 162.2,
171.1 (CO). IR (neat, cmꢀ1): ~n¼2959 (m), 2932 (m), 2873
(w), 1766 (s), 1721 (s), 1377 (w), 1224 (m), 1177 (m),
1015 (m), 696 (m). MS (EI, 70 eV): m/z (%)¼288 (M+,
32), 243 (16), 204 (99), 203 (100), 175 (97), 147 (39), 129
(31), 77 (8), 57 (17). HRMS (EI, 70 eV): calcd for
C17H20O4 (M+) 288.13561; found 288.13484.
3
1H NMR (300 MHz, CDCl3): d¼1.27 (t, J¼7.2 Hz, 3H,
CH3), 4.28 (m, 2H, OCH2), 6.20 (s, 1H, OCH), 7.28–7.34
(m, 2H, Ph), 7.39–7.47 (m, 3H, Ph). 13C NMR (75 MHz,
CDCl3): d¼13.6 (CH3), 63.2 (OCH2), 80.3 (OCH), 118.4
1
(q, JCF¼321 Hz, CF3), 127.4, 129.2, 130.4 (CHAr), 131.6,
137.7, 141.2 (C), 158.2, 163.3 (CO). IR (Nujol, cmꢀ1):
~n¼1785 (s), 1726 (s), 1258 (s), 1224 (s), 1153 (s), 1117
(s), 1005 (m), 813 (m), 761 (m), 608 (m). MS (EI, 70 eV):
m/z (%)¼380 (M+, 11), 105 (100), 77 (34), 69 (27). HRMS
(EI, 70 eV): calcd for C14H11F3O7S (M+) 380.01721; found
380.01671. Anal. Calcd for C14H11F3O7S (380.29): C,
44.22; H, 2.92. Found: C, 44.53; H, 2.83.
3.4.3. Ethyl 2-butyl-5-oxo-4-(4-tolyl)-2,5-dihydrofuran-
3-carboxylate (5c). Starting with 4b (220 mg, 0.61 mmol),
K3PO4 (194 mg, 0.91 mmol), 4-tolylboronic acid (108 mg,
0.79 mmol), Pd(PPh3)4 (21 mg, 0.018 mmol), and1,4-dioxane
(3.0 mL), 5c was isolated by column chromatography (silica
gel; n-hexane/EtOAc¼100:1/20:1) as a colorless oil
(84 mg, 45%); Rf 0.24 (n-hexane/EtOAc¼10:1). Reaction
time: 6 h. 1H NMR (300 MHz, CDCl3): d¼0.92 (t,
3J¼7.2 Hz, 3H, CH2CH2CH3), 1.25 (t, 3J¼7.1 Hz, 3H,
OCH2CH3), 1.29–1.52 (m, 4H, CH2CH2CH3), 1.64–1.76
(m, 1H, CHCHAHB), 2.04–2.17 (m, 1H, CHCHAHB), 2.38
(s, 3H, ArCH3), 4.27 (m, 2H, OCH2CH3), 5.25 (dd,
3.4. General procedure for the synthesis of aryl-
substituted isotetronic acids 5a–k
A mixture of triflates 4a–f, K3PO4, arylboronic acids,
Pd(PPh3)4, and 1,4-dioxane was heated at 90–95 ꢁC for 4–
8 h. To the solution was added ether, the mixture was filtered,
and the filtrate was concentrated in vacuo. The coupling
products 5a–k were isolated by column chromatography
(silica gel).
3
3
3J1¼7.8 Hz, J2¼3.3 Hz, 1H, OCH), 7.22 (d, J¼8.2 Hz,
2H, Ar), 7.48 (m, 2H, Ar). 13C NMR (75 MHz, CDCl3):
d¼13.8, 13.9 (CH2CH3), 21.5 (ArCH3), 22.3, 26.7, 32.5
((CH2)3), 61.8 (OCH2CH3), 80.9 (OCH), 125.5 (C), 128.7,
129.5 (CHAr), 135.5, 140.2, 148.1 (C), 162.5, 171.4 (CO).
IR (neat, cmꢀ1): ~n¼2959 (m), 2932 (m), 2873 (w), 1765
(s), 1729 (s), 1718 (s), 1376 (w), 1225 (m), 1177 (m), 1015
(m). MS (EI, 70 eV): m/z (%)¼302 (M+, 69), 257 (23), 229
(25), 218 (99), 217 (99), 189 (100), 161 (76), 143 (37), 115
(30), 91 (11), 57 (21). Anal. Calcd for C18H22O4 (302.36):
C, 71.50; H, 7.33. Found: C, 71.34; H, 7.41.
3.4.1. Ethyl 2,5-dihydro-2-isopropyl-5-oxo-phenylfuran-3-
carboxylate (5a). Starting with 4a (89.00 mg, 0.25 mmol),
K3PO4 (85 mg, 0.4 mmol), phenylboronic acid (40 mg,
0.325 mmol), Pd(PPh3)4 (9 mg, 0.007 mmol), and 1,4-dioxane
(4.0 mL), 5a was isolated by column chromatography (silica
gel; n-hexane/EtOAc¼20:1) as a slightly yellow oil (41 mg,
63%); Rf 0.20 (n-hexane/EtOAc¼10:1). Reaction time: 4 h.
3
1H NMR (CDCl3, 300 MHz): d¼0.84 (d, 3H, J¼6.9 Hz,
3.4.4. Ethyl 2-butyl-4-(2-methoxyphenyl)-5-oxo-2,5-di-
hydrofuran-3-carboxylate (5d). Starting with 4b (211 mg,
0.59 mmol), K3PO4 (186 mg, 0.88 mmol), 2-methoxy-
phenylboronic acid (116 mg, 0.76 mmol), Pd(PPh3)4
(20 mg, 0.017 mmol), and 1,4-dioxane (3.0 mL), 5d was iso-
lated by column chromatography (silica gel; n-hexane/
EtOAc¼1:0/15:1) as a slightly yellow solid (44 mg,
24%). Mp 71–72 ꢁC; Rf 0.13 (n-hexane/EtOAc¼10:1). Reac-
3
3
CH3), 1.21 (d, J¼7.3 Hz, CH3), 1.24 (t, 3H, J¼7.2 Hz,
CH2CH3), 2.38 (septd, 3H, 3J¼2.9, 6.9 Hz, CH(CH3)2),
4.14–4.35 (m, 2H, CH2CH3), 5.21 (d, 1H, 3J¼2.9 Hz, CH),
7.38–7.45 (m, 3H, Ar), 7.52–7.6 (m, 2H, Ar). 13C NMR
(CDCl3, 75 MHz): d¼13.8 (CH3), 14.5 (CH2CH3), 19.5
(CH3), 30.7 (CH(CH3)2), 61.9 (CH2CH3), 84.9 (CH),
128.0 (Ar), 128.5 (Ar), 129.4 (Ar), 129.8 (Ar), 135.3 (C),
148.7 (CAr), 162.7 (CO2Et), 171.3 (CO). IR (KBr, cmꢀ1):
~n¼3405 (w), 3061 (w), 2968 (m), 2361 (w), 1765 (s), 1725
(s), 1494 (w), 1465 (m), 1374 (m), 1396 (m), 1294 (m),
1222 (s), 1176 (s), 1111 (w), 1011 (m), 957 (w), 783 (w),
696 (m). MS (EI, 70 eV): m/z (%)¼274 ([M]+, 10), 232
(10), 229 (1), 186 (28), 175 (9), 146 (7.67), 129 (12), 103
(5), 77 (5), 57 (1), 28 (100).
1
tion time: 6 h. H NMR (300 MHz, CDCl3): d¼0.92 (t,
3J¼7.1 Hz, 3H, CH2CH2CH3), 1.14 (t, 3J¼7.1 Hz, 3H,
OCH2CH3), 1.30–1.50 (m, 4H, CH2CH2CH3), 1.63–1.80
(m, 1H, CHCHAHB), 2.03–2.17 (m, 1H, CHCHAHB), 3.76
(m, 3H, OCH3), 4.19 (m, 2H, OCH2), 5.30 (dd,
3
3
3J1¼7.7 Hz, J2¼3.3 Hz, 1H, OCH), 6.89 (d, J¼8.0 Hz,
3
4
1H, Ar), 7.03 (dt, J¼7.5 Hz, J¼1.0 Hz, 1H, Ar), 7.35–
7.44 (m, 2H, Ar). 13C NMR (75 MHz, CDCl3): d¼13.75,
13.83 (CH2CH3), 22.3, 26.6, 32.3 ((CH2)3), 55.3 (OCH3),
61.3 (OCH2), 81.0 (OCH), 110.6 (CHAr), 118.2 (C), 120.3,
130.4, 130.9 (CHAr), 132.1, 151.0, 156.9 (C), 162.5, 171.5
(CO). IR (KBr, cmꢀ1): ~n¼2958 (m), 2936 (m), 2873 (w),
1762 (s), 1723 (s), 1494 (m), 1467 (m), 1381 (m), 1253
(m), 1240 (m), 1172 (m), 1016 (m), 763 (m). MS (EI,
70 eV): m/z (%)¼318 (M+, 81), 272 (53), 257 (22), 234
(64), 233 (100), 205 (92), 177 (13), 159 (33), 57 (15).
HRMS (EI, 70 eV): calcd for C18H22O5 (M+) 318.14618;
found 318.14636.
3.4.2. Ethyl 2-butyl-5-oxo-4-phenyl-2,5-dihydrofuran-3-
carboxylate (5b). Starting with 4b (215 mg, 0.60 mmol),
K3PO4 (190 mg, 0.90 mmol), phenylboronic acid (100 mg,
0.82 mmol), Pd(PPh3)4 (21 mg, 0.018 mmol), and 1,4-diox-
ane (3.0 mL), 5b was isolated by column chromatography
(silica gel; n-hexane/EtOAc¼20:1) as a slightly yellow oil
(130 mg, 76%); Rf 0.20 (n-hexane/EtOAc¼10:1). Reaction
time: 4 h. 1H NMR (300 MHz, CDCl3): d¼0.92 (t,
3J¼7.1 Hz, 3H, CH2CH2CH3), 1.22 (t, 3J¼7.1 Hz, 3H,
OCH2CH3), 1.32–1.53 (m, 4H, CH2CH2CH3), 1.65–1.78

R. Dede et al. / Tetrahedron 63 (2007) 12547–12561
12555
3.4.5. Ethyl 2-butyl-4-(3,4-dimethoxyphenyl)-5-oxo-2,5-
dihydrofuran-3-carboxylate (5e). Starting with 4b (195 mg,
0.54 mmol), K3PO4 (172 mg, 0.81 mmol), 3,4-dimethoxy-
phenylboronic acid (128 mg, 0.70 mmol), Pd(PPh3)4 (19 mg,
0.016 mmol), and 1,4-dioxane (3.0 mL), 5e was isolated
by column chromatography (silica gel; n-hexane/EtOAc¼
5:1) as a slightly turbid yellow oil (105 mg, 56%); Rf 0.31
(n-hexane/EtOAc¼3:1). Reaction time: 6 h. 1H NMR
(dd, 3J1¼7.7 Hz, 3J2¼3.2 Hz, 1H, OCH), 7.14 (dd,
3
3
3J1¼5.1 Hz, J2¼3.9 Hz, 1H, Ar), 7.58 (dd, J1¼5.1 Hz,
3
3
3J2¼1.0 Hz, 1H, Ar), 8.31 (dd, J1¼3.9 Hz, J2¼1.0 Hz,
1H, Ar). 13C NMR (75 MHz, CDCl3): d¼13.7, 14.0 (CH3),
22.2, 26.6, 32.6 ((CH2)3), 61.9 (OCH2), 80.9 (OCH), 127.1
(CHAr), 128.1, 129.5 (C), 131.1, 132.9 (CHAr), 142.5 (C),
162.3, 170.5 (CO). IR (neat, cmꢀ1): ~n¼2959 (m), 2932
(m), 2872 (w), 1764 (s), 1721 (s), 1306 (m), 1237 (s),
1204 (s), 1136 (m), 1016 (m). MS (EI, 70 eV): m/z
(%)¼294 (M+, 65), 237 (26), 210 (88), 209 (99), 181
(100), 153 (44), 135 (21), 57 (23). HRMS (EI, 70 eV): calcd
for C15H18O4S (M+) 294.09203; found 294.09169.
3
(300 MHz, CDCl3): d¼0.93 (t, J¼7.1 Hz, 3H, CH2CH2-
3
CH3), 1.29 (t, J¼7.2 Hz, 3H, OCH2CH3), 1.32–1.53 (m,
4H, CH2CH2CH3), 1.62–1.76 (m, 1H, CHCHAHB), 2.03–
2.14 (m, 1H, CHCHAHB), 3.91 (s, 3H, OCH3), 3.92 (s, 3H,
OCH3), 4.30 (m, 2H, OCH2), 5.25 (dd, 3J1¼7.9 Hz,
3
3J2¼3.3 Hz, 1H, OCH), 6.91 (d, J¼8.2 Hz, 1H, Ar), 7.23
3.4.8. Ethyl 2-isobutyl-4-(4-methoxyphenyl)-5-oxo-2,5-
dihydrofuran-3-carboxylate (5h). Starting with 4c
(40 mg, 0.11 mmol), K3PO4 (35 mg, 0.16 mmol), 4-methoxy-
phenylboronic acid (22 mg, 0.14 mmol), Pd(PPh3)4 (6 mg,
0.005 mmol), and 1,4-dioxane (1.5 mL), 5h was isolated
by column chromatography (silica gel; n-heptane/EtOAc¼
20:1) as a colorless solid (20 mg, 57%). Mp 56–58 ꢁC; Rf
0.13 (n-heptane/EtOAc¼10:1). Reaction time: 8 h. 1H
NMR (250 MHz, CDCl3): d¼0.99 (d, 3J¼6.4 Hz, 3H,
CHCH3), 1.04 (d, 3J¼6.4 Hz, 3H, CHCH3), 1.27 (t,
3J¼7.0 Hz, 3H, OCH2CH3), 1.52 (ddd, 2J¼14.0 Hz,
3J1¼9.8 Hz, 3J2¼4.3 Hz, 1H, CHCHAHB), 1.84 (ddd,
2J¼14.0 Hz, 3J1¼9.2 Hz, 3J2¼2.7 Hz, 1H, CHCHAHB),
1.92–2.05 (m, 1H, CH(CH3)2), 3.84 (s, 3H, OCH3), 4.28
(m, 2H, OCH2), 5.27 (dd, 3J1¼9.8 Hz, 3J2¼2.7 Hz, 1H,
OCH), 6.94 (m, 2H, Ar), 7.58 (m, 2H, Ar). 13C NMR
(75 MHz, CDCl3): d¼13.9 (OCH2CH3), 21.6, 23.5, 25.3
(CH(CH3)2), 42.3 (CHCH2), 55.3 (OCH3), 61.8 (OCH2),
79.7 (OCH), 113.5 (CHAr), 120.8 (C), 131.4 (CHAr),
134.8, 147.5 (C), 161.0, 162.5 (C, CO), 171.6 (CO). IR
(KBr, cmꢀ1): ~n¼2950 (s), 2867 (m), 1747 (s), 1712 (s),
1607 (s), 1514 (s), 1300 (s), 1261 (s), 1247 (s), 1190 (s),
1184 (s), 1018 (s), 1001 (s), 769 (m). MS (EI, 70 eV): m/z
(%)¼318 (M+, 59), 272 (25), 234 (57), 233 (100), 205
(91), 177 (68), 57 (15). HRMS (EI, 70 eV): calcd for
C18H22O5 (M+) 318.14618; found 318.14633.
4
3
4
(d, J¼2.0 Hz, 1H, Ar), 7.25 (dd, J¼8.2 Hz, J¼2.0 Hz,
1H, Ar). 13C NMR (75 MHz, CDCl3): d¼13.7, 13.9
(CH2CH3), 22.2, 26.6, 32.4 ((CH2)3), 55.76, 55.80 (OCH3),
61.7 (OCH2), 80.7 (OCH), 110.3, 112.6 (CHAr), 120.8 (C),
123.0 (CHAr), 134.6, 147.2, 148.2, 150.4 (C), 162.5, 171.3
(CO). IR (KBr, cmꢀ1): ~n¼3007 (m), 2957 (s), 2935 (m),
2869 (m), 1763 (s), 1728 (s), 1603 (m), 1515 (s), 1466 (m),
1327 (m), 1262 (s), 1208 (s), 1143 (s), 1024 (s), 760 (m). MS
(EI, 70 eV): m/z (%)¼348 (M+, 100), 302 (28), 275 (32),
264 (49), 263 (94), 236 (33), 235 (90), 207 (72), 189 (17),
57 (13). Anal. Calcd for C19H24O6 (348.39): C, 65.50; H,
6.94. Found: C, 65.73; H, 7.08.
3.4.6. Ethyl 2-butyl-5-oxo-4-(3,4,5-trimethoxyphenyl)-
2,5-dihydrofuran-3-carboxylate (5f). Starting with 4b
(154 mg, 0.43 mmol), K3PO4 (136 mg, 0.64 mmol), 3,4,5-
trimethoxyphenylboronic acid (118 mg, 0.56 mmol),
Pd(PPh3)4 (15 mg, 0.013 mmol), and 1,4-dioxane (2.5 mL),
5f was isolated by column chromatography (silica gel;
n-hexane/EtOAc¼10:1/5:1) as a yellow oil (104 mg,
64%); Rf 0.25 (n-hexane/EtOAc¼3:1). Reaction time: 6 h.
3
1H NMR (300 MHz, CDCl3): d¼0.93 (t, J¼7.2 Hz, 3H,
3
CH2CH2CH3), 1.28 (t, J¼7.1 Hz, 3H, OCH2CH3), 1.32–
1.54 (m, 4H, CH2CH2CH3), 1.64–1.80 (m, 1H, CHCHAHB),
2.03–2.14 (m, 1H, CHCHAHB), 3.88 (s, 6H, OCH3), 3.89 (s,
3
3H, OCH3), 4.30 (m, 2H, OCH2), 5.26 (dd, J1¼7.9 Hz,
3J2¼3.3 Hz, 1H, OCH), 6.89 (s, 2H, Ar). 13C NMR
(75 MHz, CDCl3): d¼13.7, 13.9 (CH2CH3), 22.2, 26.6,
32.4 ((CH2)3), 56.1, 60.7 (OCH3), 61.8 (OCH2), 80.7
(OCH), 106.9 (CHAr), 123.5, 134.5, 139.4, 148.6, 152.7
(C), 162.4, 171.0 (CO). IR (neat, cmꢀ1): ~n¼2959 (m),
2938 (m), 2873 (w), 1764 (s), 1726 (m), 1582 (m), 1507
(m), 1461 (m), 1418 (m), 1294 (m), 1246 (m), 1211 (m),
1129 (s), 1010 (m). MS (EI, 70 eV): m/z (%)¼378 (M+,
100), 332 (19), 305 (26), 293 (84), 265 (77), 237 (39), 57
(16). Anal. Calcd for C20H26O7 (378.42): C, 63.48; H,
6.93. Found: C, 63.46; H, 7.08.
3.4.9. Methyl 2-tert-butyl-5-oxo-4-phenyl-2,5-dihydro-
furan-3-carboxylate (5i). Starting with 4d (295 mg,
0.85 mmol), K3PO4 (271 mg, 1.28 mmol), phenylboronic
acid (135 mg, 1.11 mmol), Pd(PPh3)4 (30 mg, 0.026 mmol),
and 1,4-dioxane (4.0 mL), 5i was isolated by column chroma-
tography (silica gel; n-heptane/EtOAc¼20:1/10:1) as a col-
orless oil (201 mg, 86%); Rf 0.17 (n-heptane/EtOAc¼10:1).
1
Reaction time: 8 h. H NMR (250 MHz, CDCl3): d¼1.03
(s, 9H, C(CH3)3), 3.79 (s, 3H, OCH3), 5.05 (s, 1H, OCH),
7.38–7.45 (m, 3H, Ph), 7.53–7.62 (m, 2H, Ph). 13C NMR
(75 MHz, CDCl3): d¼25.5 (C(CH3)3), 36.3 (C(CH3)3), 52.7
(OCH3), 88.0 (OCH), 128.29 (C), 128.34, 129.0, 129.9
(CHAr), 133.7, 149.3 (C), 164.7, 170.7 (CO). IR (neat,
cmꢀ1): ~n¼2967 (m), 2911 (w), 2874 (w), 1767 (s), 1735 (s),
1437 (m), 1369 (m), 1319 (m), 1232 (s), 1166 (s), 1117
(m), 1043 (m), 977 (m), 696 (m). MS (EI, 70 eV): m/z
(%)¼274 (M+, 2), 218 (100), 186 (99), 129 (50), 57 (86).
HRMS (EI, 70 eV): calcd for C16H18O4 (M+) 274.11996;
found 274.11928.
3.4.7. Ethyl 2-butyl-5-oxo-4-(thien-2-yl)-2,5-dihydro-
furan-3-carboxylate (5g). Starting with 4b (188 mg,
0.52 mmol), K3PO4 (166 mg, 0.78 mmol), (thien-2-yl)boronic
acid (87 mg, 0.68 mmol), Pd(PPh3)4 (18 mg, 0.016 mmol),
and 1,4-dioxane (3.0 mL), 5g was isolated by column chro-
matography (silica gel; n-hexane/EtOAc¼20:1) as a yellow
oil (101 mg, 66%); Rf 0.32 (n-hexane/EtOAc¼10:1).
1
Reaction time: 4 h. H NMR (300 MHz, CDCl3): d¼0.91
(t, 3J¼7.1 Hz, 3H, CH2CH2CH3), 1.25–1.50 (m, 7H,
OCH2CH3, CH2CH2CH3), 1.60–1.75 (m, 1H, CHCHAHB),
2.01–2.13 (m, 1H, CHCHAHB), 4.40 (m, 2H, OCH2), 5.27
3.4.10. Methyl 2-hexyl-5-oxo-4-phenyl-2,5-dihydro-
furan-3-carboxylate (5j). Starting with 4e (208 mg,
0.56 mmol), K3PO4 (177 mg, 0.83 mmol), phenylboronic

12556
R. Dede et al. / Tetrahedron 63 (2007) 12547–12561
acid (88 mg, 0.72 mmol), Pd(PPh3)4 (19 mg, 0.016 mmol),
and 1,4-dioxane (3.0 mL), 5j was isolated by column chro-
matography (silica gel; n-hexane/EtOAc¼1:0/50:1) as
a slightly yellow oil (103 mg, 61%); Rf 0.30 (n-hexane/
EtOAc¼10:1). Reaction time: 4 h. 1H NMR (300 MHz,
3.5.1. Methyl 3-hydroxybutyrate (1a). Starting with diiso-
propylamine (10.12 g, 100 mmol), THF (100 mL), n-BuLi
(2.5 M in hexanes, 41 mL, 103 mmol), methyl acetate
(7.41 g, 100 mmol), acetaldehyde (5.29 g, 120 mmol), and
hydrochloric acid (2.0 M, 50 mL), 1a was isolated by destil-
lation as a clear colorless liquid (6.43 g, 54%); bp 34 ꢁC
3
CDCl3): d¼0.89 (t, J¼6.8 Hz, 3H, CH2CH3), 1.20–1.42
1
(m, 6H, CH2), 1.48 (m, 2H, CH2), 1.63–1.76 (m, 1H,
CHCHAHB), 2.03–2.15 (m, 1H, CHCHAHB), 3.78 (s, 3H,
OCH3), 5.26 (dd, 3J1¼7.9 Hz, 3J2¼3.3 Hz, 1H, OCH),
7.38–7.46 (m, 3H, Ph), 7.51–7.58 (m, 2H, Ph). 13C NMR
(75 MHz, CDCl3): d¼13.9 (CH2CH3), 22.4, 24.5, 28.8,
31.4, 32.7 (CH2), 52.4 (OCH3), 80.8 (OCH), 128.0 (CHAr),
128.3 (C), 129.4, 129.8 (CHAr), 135.6, 148.4 (C), 162.7,
171.0 (CO). IR (neat, cmꢀ1): ~n¼2955 (s), 2929 (s), 2858
(m), 1766 (s), 1733 (s), 1437 (m), 1225 (s), 1170 (s), 982
(m), 695 (m). MS (EI, 70 eV): m/z (%)¼302 (M+, 36), 273
(26), 190 (99), 189 (100), 186 (34), 172 (12), 161 (66),
129 (49), 113 (67), 85 (16), 57 (8). Anal. Calcd for
C18H22O4 (302.36): C, 71.50; H, 7.33. Found: C, 71.48; H,
7.45.
(0.1 mbar). Reaction time: 3.5 min. H NMR (300 MHz,
CDCl3): d¼1.24 (d, 3J¼6.3 Hz, 3H, CHCH3), 2.43 (dd,
2J¼16.5 Hz, 3J¼7.4 Hz, 1H, CHAHB), 2.51 (dd,
3
2J¼16.5 Hz, J¼3.8 Hz, 1H, CHAHB), 2.8 (br, 1H, OH),
3.72 (s, 3H, OCH3), 4.21 (m, 1H, CHOH). 13C NMR
(75 MHz, CDCl3): d¼22.3 (CHCH3), 42.6 (CH2), 51.4
(OCH3), 64.0 (CH), 172.9 (CO). IR (neat, cmꢀ1): ~n¼3431
(br, s), 2974 (m), 2935 (w), 1737 (s), 1439 (m), 1377 (m),
1297 (m), 1196 (m), 1176 (m), 1126 (m), 1089 (m), 946
(w). MS (GC–EI, 70 eV): m/z (%)¼117 ([Mꢀ1]+, 2), 103
(38), 100 (6), 87 (29), 74 (83), 71 (45), 59 (18), 45 (57),
43 (100).
3.5.2. Ethyl 3-hydroxyvalerate (1c). Starting with diisopro-
pylamine (10.12 g, 100 mmol), THF (100 mL), n-BuLi
(2.5 M in hexanes, 41 mL, 103 mmol), ethyl acetate
(8.81 g, 100 mmol), propionaldehyde (6.97 g, 120 mmol),
and hydrochloric acid (2.0 M, 50 mL), 1c was isolated by
destillation as a clear colorless liquid (12.09 g, 83%); bp
100 ꢁC (5 mbar). Reaction time: 3.5 min. 1H NMR
3.4.11. Ethyl 5-oxo-2,4-diphenyl-2,5-dihydrofuran-3-
carboxylate (5k). Starting with 4f (190 mg, 0.50 mmol),
K3PO4 (159 mg, 0.75 mmol), phenylboronic acid (79 mg,
0.65 mmol), Pd(PPh3)4 (17 mg, 0.015 mmol), and 1,4-diox-
ane (2.5 mL), 5k was isolated by column chromatography
(silica gel; n-hexane/EtOAc¼1:0/20:1) as a slightly yel-
low solid (70 mg, 45%). Mp 110–112 ꢁC; Rf 0.13 (n-hex-
ane/EtOAc¼10:1). Reaction time: 4 h. 1H NMR
3
(300 MHz, CDCl3): d¼0.97 (t, J¼7.4 Hz, 3H, CH3CH2-
CH), 1.28 (t, 3J¼7.1 Hz, 3H, OCH2CH3), 1.52 (m,
2
3
2H, CH3CH2CH), 2.40 (dd, J¼16.4 Hz, J¼8.9 Hz, 1H,
CHAHBCO), 2.51 (dd, 2J¼16.4 Hz, 3J¼3.3 Hz, 1H,
3
(300 MHz, CDCl3): d¼1.06 (t, J¼7.1 Hz, 3H, CH3), 4.11
3
(m, 2H, OCH2), 6.20 (s, 1H, OCH), 7.30–7.42 (m, 5H,
Ph), 7.42–7.48 (m, 3H, Ph), 7.63–7.71 (m, 2H, Ph). 13C
NMR (150 MHz, CDCl3): d¼13.6 (CH3), 61.8 (OCH2),
82.2 (OCH), 127.3, 128.05 (CHAr), 128.12 (C), 128.9,
129.6, 129.7, 130.1 (CHAr), 133.8, 134.8, 148.4 (C),
161.8, 171.2 (CO). IR (KBr, cmꢀ1): ~n¼2981 (m), 1758 (s),
1729 (m), 1651 (m), 1494 (m), 1446 (m), 1369 (m), 1288
(m), 1220 (s), 1117 (m), 1014 (s), 792 (m), 692 (m). MS
(EI, 70 eV): m/z (%)¼308 (M+, 23), 279 (22), 235
(34), 203 (22), 175 (21), 105 (100), 77 (18). HRMS (EI,
70 eV): calcd for C19H16O4 (M+) 308.10431; found
308.10351.
CHAHBCO), 2.85 (br, 1H, OH), 3.94 (dddd, J1¼8.9 Hz,
3J2¼7.0 Hz, 3J3¼5.5 Hz, 3J4¼3.3 Hz, 1H, CHOH), 4.18
3
(q, J¼7.1 Hz, 2H, OCH2). 13C NMR (75 MHz, CDCl3):
d¼9.7 (CH3CH2CH), 14.0 (OCH2CH3), 29.3 (CH3CH2CH),
40.9 (CH2CO), 60.5 (OCH2), 69.2 (CHOH), 172.9 (CO). IR
(neat, cmꢀ1): ~n¼3447 (br, m), 2968 (m), 2936 (m), 2880 (w),
1735 (s), 1465 (w), 1374 (m), 1282 (m), 1250 (m), 1179 (s),
1112 (m), 1034 (m), 983 (m). MS (GC–EI, 70 eV): m/z
(%)¼145 ([Mꢀ1]+, 1), 128 (3), 117 (100), 101 (29), 89
(48), 71 (93), 59 (40), 43 (49). HRMS (EI, 70 eV): calcd
for C7H13O3 ([Mꢀ1]+) 145.08592; found 145.08556.
3.5.3. Ethyl 3-hydroxyheptanoate (1g). Starting with diiso-
propylamine (10.12 g, 100 mmol), THF (100 mL), n-BuLi
(2.5 M in hexanes, 41 mL, 103 mmol), ethyl acetate
(8.81 g, 100 mmol), valeraldehyde (10.34 g, 120 mmol),
and hydrochloric acid (2.0 M, 50 mL), 1g was isolated by
destillation as a clear colorless liquid (14.52 g, 83%);
bp 70 ꢁC (0.1 mbar). Reaction time: 3.5 min. 1H NMR
3.5. General procedure for the preparation of
3-hydroxyesters 1a–u
An LDA solution was prepared by the addition of n-BuLi to
a THF solution of diisopropylamine at 0 ꢁC. After stirring
for 1 h, the solution was cooled to ꢀ78 ꢁC and the respective
ester or ketone was dropwise added. After stirring for 1 h at
ꢀ78 ꢁC, the appropriate electrophile was added within 30 s.
After stirring for 3–5 min, hydrochloric acid was added. The
organic and the aqueous layer were separated and the sol-
vents were removed under reduced pressure. The aqueous
layer was extracted with ethyl acetate (2ꢂ150 mL). The
combined organic layers were washed with a saturated aque-
ous solution of NaHCO3 (2ꢂ50 mL), dried (Na2SO4), and
filtered. The filtrate was concentrated in vacuo. The residue
was purified by vacuum destillation or by column chromato-
graphy (silica gel) to give 3-hydroxyesters 1a–u. The syn-
thesis of 1a,39 1b,40 1c,41 1d,42 1e,43 1f,43 1g,44 1h,45 1i,46
1j,47 1k,48 1l,49 1n,47 1o,50 1p,51 1q,51 1r,52 1s,53 and 1t53
was previously reported.
3
(300 MHz, CDCl3): d¼0.91 (t, J¼7.1 Hz, 3H, CH3CH2-
3
CH2), 1.28 (t, J¼7.1 Hz, 3H, OCH2CH3), 1.30–1.60 (m,
6H, (CH2)3), 2.40 (dd, 2J¼16.4 Hz, 3J¼8.8 Hz, 1H,
2
3
CHAHBCO), 2.51 (dd, J¼16.4 Hz, J¼3.3 Hz, 1H, CHA-
HBCO), 2.89 (br, 1H, OH), 4.00 (m, 1H, CHOH), 4.17 (q,
3J¼7.1 Hz, 2H, OCH2). 13C NMR (75 MHz, CDCl3):
d¼13.9, 14.1 (CH3), 22.5, 27.5, 36.2 ((CH2)3), 41.3
(CH2CO), 60.5 (OCH2), 67.9 (CHOH), 173.0 (CO). IR
(neat, cmꢀ1): ~n¼3447 (br, m), 2959 (s), 2933 (s), 2873
(m), 2862 (m), 1735 (s), 1374 (m), 1300 (m), 1249 (m),
1176 (m), 1028 (m). MS (GC–EI, 70 eV): m/z (%)¼173
([Mꢀ1]+, 0.5), 156 (2), 117 (100), 89 (33), 88 (31), 71
(59), 43 (30). HRMS (EI, 70 eV): calcd for C9H17O3
([Mꢀ1]+) 173.11722; found 173.11724.

R. Dede et al. / Tetrahedron 63 (2007) 12547–12561
12557
3.5.4. tert-Butyl 3-hydroxyheptanoate (1h). Starting with
diisopropylamine (10.12 g, 100 mmol), THF (100 mL), n-
BuLi (2.5 M in hexanes, 41 mL, 103 mmol), tert-butyl acetate
(11.62 g, 100 mmol), valeraldehyde (10.34 g, 120 mmol),
and hydrochloric acid (2.0 M, 50 mL), 1h was isolated by
destillation as a clear colorless liquid (18.55 g, 92%); bp
78 ꢁC (0.1 mbar). Reaction time: 3.5 min. 1H NMR
n-BuLi (2.5 M in hexanes, 41 mL, 103 mmol), ethyl acetate
(8.81 g, 100 mmol), 10-undecenal (13.46 g, 80 mmol), and
hydrochloric acid (2.0 M, 50 mL), 1m was isolated by
column chromatography (silica gel; n-heptane/ethyl
acetate¼7:1/5:1) as a clear slightly yellow oil (13.23 g,
65%); Rf 0.33 (n-heptane/ethyl acetate¼5:1). Reaction
1
time: 4.5 min. H NMR (250 MHz, CDCl3): d¼1.23–1.55
3
(300 MHz, CDCl3): d¼0.91 (t, J¼7.1 Hz, 3H, CH3CH2),
(m, 17H, CHOH(CH2)7, CH3), 2.03 (m, 2H, H2C]CHCH2),
2.38 (dd, J¼16.4 Hz, J¼8.7 Hz, 1H, CHAHBCO), 2.50
2
3
1.25–1.55 (m, 6H, (CH2)3), 1.47 (s, 9H, C(CH3)3), 2.31
(dd, 2J¼16.3 Hz, 3J¼8.8 Hz, 1H, CHAHBCO), 2.43
(dd, 2J¼16.3 Hz, 3J¼3.3 Hz, 1H, CHAHBCO), 2.94 (br,
1H, OH), 3.96 (m, 1H, CHOH). 13C NMR (75 MHz,
CDCl3): d¼13.9 (CH3CH2), 22.6, 27.6 (CH2), 28.1
(C(CH3)3), 36.1 (CH2), 42.3 (CH2CO), 68.1 (CHOH), 81.1
(C(CH3)3), 172.5 (CO). IR (neat, cmꢀ1): ~n¼3443 (br, m),
2959 (s), 2933 (s), 2873 (m), 2862 (m), 1730 (s), 1458
(m), 1393 (m), 1368 (s), 1298 (m), 1255 (m), 1156 (s),
1039 (w). MS (CI, isobutane): m/z (%)¼203 ([M+1]+, 1),
147 (100).
(dd, 2J¼16.4 Hz, 3J¼3.4 Hz, 1H, CHAHBCO), 2.66 (br,
3
1H, OH), 3.99 (m, 1H, CHOH), 4.16 (q, J¼7.1 Hz, 2H,
OCH2), 4.88–5.03 (m, 2H, H2C]CH), 5.80 (ddt,
3J1¼17.0 Hz, 3J2¼10.3 Hz, 3J3¼6.7 Hz, 1H, H2C]CH).
13C NMR (75 MHz, CDCl3): d¼14.2 (CH3), 25.5, 28.9,
29.1, 29.4, 29.5, 29.5, 33.8, 36.5, 41.3 ((CH2)8, CH2CO),
60.7 (OCH2), 68.0 (CHOH), 114.1 (H2C]CH), 139.2
(H2C]CH), 173.1 (CO). IR (neat, cmꢀ1): ~n¼3454 (br, w),
2979 (m), 2927 (s), 2855 (m), 1736 (s), 1641 (w), 1465 (m),
1373 (m), 1301 (m), 1182 (m), 1030 (m), 910 (m). MS (CI,
isobutane): m/z (%)¼257 ([M+1]+, 100), 239 (20). Anal.
Calcd for C15H28O3 (256.38): C, 70.27; H, 11.01. Found: C,
70.10; H, 11.20.
3.5.5. Methyl 3-hydroxy-4,4-dimethylvalerate (1j). Start-
ing with diisopropylamine (7.08 g, 70 mmol), THF
(70 mL), n-BuLi (2.5 M in hexanes, 29 mL, 72 mmol),
methyl acetate (5.19 g, 70 mmol), pivalaldehyde (7.24 g,
84 mmol), and hydrochloric acid (2.0 M, 35 mL), 1j was iso-
lated by destillation as a clear colorless liquid (6.76 g, 60%);
bp 69 ꢁC (0.1 mbar). Reaction time: 4 min. 1H NMR
(300 MHz, CDCl3): d¼0.92 (s, 9H, C(CH3)3), 2.36 (dd,
2J¼16.1 Hz, 3J¼10.5 Hz, 1H, CHAHBCO), 2.54 (dd,
2J¼16.1 Hz, 3J¼2.3 Hz, 1H, CHAHBCO), 2.85 (br, 1H,
OH), 3.71 (dd, 3J1¼10.5 Hz, 3J2¼2.3 Hz, 1H, CHOH),
3.72 (s, 3H, OCH3). 13C NMR (75 MHz, CDCl3): d¼25.5
(C(CH3)3), 34.3 (CCH), 36.4 (CH2), 51.8 (OCH3), 75.4
(CHOH), 174.2 (CO). IR (neat, cmꢀ1): ~n¼3515 (br, m),
2957 (s), 2909 (m), 2873 (m), 1731 (s), 1439 (m), 1366
(m), 1304 (m), 1166 (m), 1015 (m). MS (GC–EI, 70 eV):
m/z (%)¼159 ([Mꢀ1]+, 0.1), 103 (100), 87 (14), 71 (65),
57 (35), 43 (41). HRMS (EI, 70 eV): calcd for C8H15O3
([Mꢀ1]+) 159.10157; found 159.10226.
3.5.8. Ethyl 3-hydroxy-3-phenylpropionate (1o). Starting
with diisopropylamine (6.07 g, 60 mmol), THF (70 mL),
n-BuLi (2.5 M in hexanes, 25 mL, 63 mmol), ethyl acetate
(4.85 g, 55 mmol), benzaldehyde (5.31 g, 50 mmol), and hy-
drochloric acid (2.0 M, 28 mL), 1o was isolated by destilla-
tion as a clear slightly yellow liquid (7.58 g, 78%); bp
110 ꢁC (0.1 mbar). Reaction time: 4 min. 1H NMR
3
(300 MHz, CDCl3): d¼1.25 (t, J¼7.1 Hz, 3H, CH3), 2.68
2
3
(dd, J¼16.3 Hz, J¼4.4 Hz, 1H, CHAHBCO), 2.75 (dd,
2J¼16.3 Hz, 3J¼8.4 Hz, 1H, CHAHBCO), 3.34 (d,
3J¼3.5 Hz, 1H, OH), 4.17 (q, 3J¼7.1 Hz, 2H, OCH2), 5.12
(m, 1H, CHOH), 7.24–7.39 (m, 5H, Ph). 13C NMR
(75 MHz, CDCl3): d¼14.0 (CH3), 43.3 (CH2CO), 60.7
(OCH2), 70.2 (CHOH), 125.6, 127.6, 128.4 (CHAr), 142.5
(CAr), 172.2 (CO). IR (neat, cmꢀ1): ~n¼3458 (br, m), 2982
(w), 1732 (s), 1454 (w), 1372 (m), 1298 (m), 1268 (m),
1196 (m), 1162 (m), 1038 (m), 701 (m). MS (EI, 70 eV):
m/z (%)¼194 (M+, 39), 147 (10), 120 (19), 107 (100), 106
(25), 105 (75), 88 (19), 79 (65), 77 (53). HRMS (EI,
70 eV): calcd for C11H14O3 (M+) 194.09375; found
194.09339.
3.5.6. Methyl 3-hydroxynonanoate (1k). Starting with di-
isopropylamine (8.91 g, 88 mmol), THF (80 mL), n-BuLi
(2.5 M in hexanes, 36 mL, 90 mmol), methyl acetate
(5.93 g, 80 mmol), heptanal (9.14 g, 80 mmol), and hydro-
chloric acid (2.0 M, 44 mL), 1k was isolated by destillation
as a clear colorless liquid (9.83 g, 65%); bp 77 ꢁC
(0.1 mbar). Reaction time: 4 min. 1H NMR (300 MHz,
3.5.9. Ethyl 3-hydroxy-3-(4-methylphenyl)-propionate
(1p). Starting with diisopropylamine (10.12 g, 100 mmol),
THF (100 mL), n-BuLi (2.5 M in hexanes, 42 mL,
105 mmol), ethyl acetate (8.81 g, 100 mmol), 4-methylbenz-
aldehyde (9.57 g, 80 mmol), and hydrochloric acid (2.0 M,
50 mL), 1p was isolated by column chromatography (silica
gel; n-heptane/ethyl acetate¼5:1) as a clear yellow oil
(12.17 g, 73%); Rf 0.22 (n-heptane/ethyl acetate¼5:1). Re-
3
CDCl3): d¼0.88 (t, J¼6.8 Hz, 3H, CH3CH2), 1.15–1.60
2
3
(m, 10H, (CH2)5), 2.41 (dd, J¼16.4 Hz, J¼8.8 Hz, 1H,
CHAHBCO), 2.52 (dd, 2J¼16.4 Hz, 3J¼3.4 Hz, 1H,
CHAHBCO), 2.94 (br, 1H, OH), 3.71 (s, 3H, OCH3), 4.00
(m, 1H, CHOH). 13C NMR (75 MHz, CDCl3): d¼13.9
(CH3CH2), 22.5, 25.3, 29.1, 31.7, 36.5 ((CH2)5), 41.1
(CH2CO), 51.6 (OCH3), 67.9 (CHOH), 173.3 (CO). IR
(neat, cmꢀ1): ~n¼3457 (br, m), 2955 (s), 2930 (s), 2858
(m), 1740 (s), 1438 (m), 1290 (m), 1197 (m), 1167 (m),
1056 (w). MS (GC–EI, 70 eV): m/z (%)¼187 ([Mꢀ1]+,
0.5), 170 (0.6), 103 (100), 74 (33), 71 (35), 55 (19), 43
(34). HRMS (EI, 70 eV): calcd for C10H19O3 ([Mꢀ1]+)
187.13287; found 187.13289.
1
action time: 5 min. H NMR (250 MHz, CDCl3): d¼1.26
3
(t, J¼7.1 Hz, 3H, CH2CH3), 2.34 (s, 3H, ArCH3), 2.67
2
3
(dd, J¼16.1 Hz, J¼4.3 Hz, 1H, CHAHBCO), 2.76 (dd,
2J¼16.1 Hz, 3J¼8.4 Hz, 1H, CHAHBCO), 3.21 (br, 1H,
OH), 4.18 (q, 3J¼7.1 Hz, 2H, OCH2), 5.10 (dd,
3
3J1¼8.6 Hz, J2¼4.3 Hz, 1H, CHOH), 7.14–7.28 (m, 4H,
Ar). 13C NMR (62 MHz, CDCl3): d¼14.1 (CH2CH3), 21.1
(ArCH3), 43.3 (CH2CO), 60.8 (OCH2), 70.1 (CHOH),
125.6, 129.2 (CHAr), 137.5, 139.5 (CAr), 172.4 (CO). IR
(neat, cmꢀ1): ~n¼3459 (br, s), 2982 (m), 2925 (m), 1734
3.5.7. Ethyl 3-hydroxy-12-tridecenoate (1m). Starting
with diisopropylamine (10.12 g, 100 mmol), THF (100 mL),

12558
R. Dede et al. / Tetrahedron 63 (2007) 12547–12561
(s), 1515 (m), 1372 (m), 1195 (m), 1160 (m), 1038 (m), 819
(m). MS (EI, 70 eV): m/z (%)¼208 (M+, 12), 190 (13), 145
(29), 121 (67), 120 (64), 119 (100), 93 (21), 91 (90), 65 (20).
Anal. Calcd for C12H16O3 (208.25): C, 69.21; H, 7.74.
Found: C, 69.09; H, 7.85.
isolated by destillation as a clear colorless liquid (11.33 g,
77%); bp 48 ꢁC (0.1 mbar). Reaction time: 10 min
1
(ꢀ60 ꢁC). H NMR (250 MHz, CDCl3): d¼1.25 (m, 9H,
CH2CH3, C(CH3)2), 2.45 (s, 2H, CH2CO), 3.59 (s, 1H,
3
OH), 4.15 (q, J¼7.1 Hz, 2H, OCH2). 13C NMR (75 MHz,
CDCl3): d¼14.1 (CH2CH3), 29.1 (C(CH3)2), 46.3
(CH2CO), 60.5 (OCH2), 68.9 (COH), 172.9 (CO).
3.5.10. Ethyl 3-hydroxy-3-(2-methoxyphenyl)-propio-
nate (1s). Starting with diisopropylamine (20.24 g,
200 mmol), THF (180 mL), n-BuLi (2.5 M in hexanes,
82 mL, 205 mmol), ethyl acetate (17.62 g, 200 mmol),
2-methoxybenzaldehyde (21.78 g, 160 mmol), dissolved in
THF (20 mL), and hydrochloric acid (2.0 M, 100 mL), 1s
was isolated by column chromatography (silica gel;
n-heptane/ethyl acetate¼3:1) as a clear slightly yellow oil
(16.41 g, 37%*); Rf 0.27 (n-heptane/ethyl acetate¼3:1). Re-
action time: 4.5 min. *Only 55% of the raw product was
used for column chromatography. 1H NMR (250 MHz,
3.6. General procedure for the preparation of
1,3-bis(trimethylsilyloxy)alk-1-enes 2a–u
An LDA solution was prepared by the addition of n-BuLi to
a THF solution of diisopropylamine at 0 ꢁC. After stirring
for 1 h, the solution was cooled to ꢀ78 ꢁC and the respective
3-hydroxyesters (1a–u) were added. After stirring for 1 h at
ꢀ78 ꢁC, TMSCl was added and the solution was allowed to
warm to 20 ꢁC within 14–24 h. The solvent and volatile
compounds were removed in vacuo. The residue was dis-
solved in n-hexane and the suspension was filtered under in-
ert atmosphere. The filtrate was concentrated in vacuo to
give 1,3-bis(trimethylsilyloxy)alk-1-enes 2a–u, which
were used without further purification. Due to their low sta-
bility, products 2a–u could be only characterized by NMR.
3
CDCl3): d¼1.26 (t, J¼7.1 Hz, 3H, CH2CH3), 2.69 (dd,
2J¼16.1 Hz, 3J¼9.0 Hz, 1H, CHAHBCO), 2.83 (dd,
2J¼16.1 Hz, 3J¼4.0 Hz, 1H, CHAHBCO), 3.2 (br, 1H,
OH), 3.85 (s, 3H, OCH3), 4.17 (q, 7.1 Hz, 2H, OCH2),
3
3
5.36 (dd, J1¼8.9 Hz, J2¼3.7 Hz, 1H, CHOH), 6.87 (dd,
4
3J¼8.2 Hz, J¼0.9 Hz, 1H, Ar), 6.97 (m, 1H, Ar), 7.26
(m, 1H, Ar), 7.43 (dd, 3J¼7.6 Hz, 4J¼1.5 Hz, 1H, Ar). 13
C
NMR (62 MHz, CDCl3): d¼14.0 (CH2CH3), 41.6
(CH2CO), 55.1 (OCH3), 60.5 (OCH2), 66.3 (CHOH),
110.1, 120.6, 126.4, 128.4 (CHAr), 130.5 (CArCHOH),
155.9 (CArOCH3), 172.5 (CO). IR (neat, cmꢀ1): ~n¼3497
(br, s), 2981 (m), 2939 (m), 1733 (s), 1602 (m), 1492 (s),
1465 (s), 1286 (s), 1243 (s), 1190 (s), 1159 (s), 1029 (s),
756 (s). MS (EI, 70 eV): m/z (%)¼224 (M+, 14), 206 (8),
175 (9), 161 (14), 150 (28), 137 (100), 135 (44), 107 (44),
77 (22). Anal. Calcd for C12H16O4 (224.25): C, 64.27; H,
7.19. Found: C, 64.25; H, 7.26.
3.6.1. 1-Methoxy-1,3-bis(trimethylsilyloxy)but-1-ene
(2a). Starting with 1a (2.66 g, 22.5 mmol) and TMSCl
(6.11 g, 56.3 mmol), 2a was obtained as a slightly yellow
liquid (4.34 g, 73%). Reaction time: 18 h. 1H NMR
(300 MHz, CDCl3): d¼0.08 (s, 9H, Si(CH3)3), 0.18 (s, 9H,
3
Si(CH3)3), 1.20 (d, J¼6.3 Hz, 3H, CHCH3), 3.46 (s, 3H,
OCH3), 3.59 (d, 3J¼8.8 Hz, 1H, CCH), 4.60 (dq,
3
3J1¼8.8 Hz, J2¼6.3 Hz, 1H, OCH). 13C NMR (75 MHz,
CDCl3): d¼0.2, 0.3 (Si(CH3)3), 25.9 (CHCH3), 54.3
(OCH3), 64.6, 81.9 (CH), 156.5 (C).
3.5.11. Ethyl 3-(4-chlorophenyl)-3-hydroxypropionate
(1t). Starting with diisopropylamine (10.12 g, 100 mmol),
THF (90 mL), n-BuLi (2.5 M in hexanes, 41 mL,
103 mmol), ethyl acetate (8.81 g, 100 mmol), 4-chlorobenz-
aldehyde (11.25 g, 80 mmol), dissolved in THF (10 mL),
and hydrochloric acid (2.0 M, 50 mL), 1t was isolated by
column chromatography (silica gel; n-heptane/ethyl
acetate¼3:1) as a clear slightly yellow oil (13.91 g, 76%);
Rf 0.30 (n-heptane/ethyl acetate¼3:1). Reaction time:
4.5 min. 1H NMR (250 MHz, CDCl3): d¼1.26 (t, 3J¼
7.1 Hz, 3H, CH3), 2.68 (s, 1H, CHAHBCO), 2.70 (d,
3J¼2.1 Hz, 1H, CHAHBCO), 3.2 (br, 1H, OH), 4.18 (q,
3.6.2. 1,3-Bis(trimethylsilyloxy)-1-ethoxy-but-1-ene (2b).
Starting with 1b (2.64 g, 20.00 mmol) and TMSCl (6.11 g,
56.3 mmol), 2b was obtained as a slightly yellow liquid
(4.143 g, 75%). Reaction time: 18 h. 1H NMR (CDCl3,
300 MHz): d¼0.06 (s, 9H, Si(CH3)3), 0.17 (s, 9H, COSi(CH3)3-
3
3
OEt), 1.18 (d, 3H, J¼6.3 Hz, CH3), 1.22 (t, 3H, J¼7.0 Hz,
3
CH2CH3), 3.54 (d, 1H, J¼8.8 Hz, C]CH), 3.66 (dq, 2H,
2
3J¼7.0 Hz, J¼1.7 Hz, CH2), 4.52–4.64 (m, 1H, CH). 13C
NMR (CDCl3, 75 MHz): d¼0.3 (Si(CH3)3), 0.5 (Si(CH3)3),
14.3 (CH2CH3), 26.0 (CH3), 62.8 (CH2), 64.7 (CCH3), 82.3
(CH), 155.5 (COEt).
3
3
3J¼7.1 Hz, 2H, OCH2), 5.10 (dd, J1¼7.3 Hz, J2¼5.5 Hz,
1H, CHOH), 7.31 (s, 4H, Ar). 13C NMR (75 MHz,
CDCl3): d¼14.1 (CH3), 43.2 (CH2CO), 61.0 (OCH2), 69.6
(CHOH), 127.1, 128.7 (CHAr), 133.5, 141.0 (CAr), 172.3
(CO). IR (neat, cmꢀ1): ~n¼3457 (br, s), 2983 (m), 1732 (s),
1493 (m), 1373 (m), 1194 (s), 1162 (m), 1091 (m), 1014
(s), 831 (m). MS (EI, 70 eV): m/z (%)¼230 (M+, 37Cl, 4),
228 (M+, 35Cl, 9), 165 (25), 141 (77), 140 (52), 139 (100),
111 (34), 88 (20), 77 (36). Anal. Calcd for C11H13ClO3
(228.67): C, 57.78; H, 5.73. Found: C, 57.66; H, 5.78.
3.6.3. 1-Ethoxy-1,3-bis(trimethylsilyloxy)pent-1-ene (2c).
Starting with 1c (6.58 g, 45.0 mmol) and TMSCl (12.22 g,
112 mmol), 2c was obtained as a clear yellow liquid
1
(12.92 g, 99%). Reaction time: 19 h. H NMR (300 MHz,
CDCl3): d¼0.09 (s, 9H, Si(CH3)3), 0.21 (s, 9H, Si(CH3)3),
0.85 (t, 3J¼7.4 Hz, 3H, CHCHAHBCH3), 1.28 (t,
3J¼7.1 Hz, 3H, OCH2CH3), 1.33–1.65 (m, 2H, CHCHAHB),
3
3
3.51 (d, J¼8.9 Hz, 1H, CCH), 3.72 (q, J¼7.1 Hz, 2H,
OCH2), 4.33 (dt, J1¼8.9 Hz, J2¼6.6 Hz, 1H, OCH). 13C
NMR (75 MHz, CDCl3): d¼0.3, 0.4 (Si(CH3)3), 10.3, 14.3
(CH3), 32.3 (CHCH2), 62.8 (OCH2), 70.0, 80.7 (CH),
156.1 (C). MS (EI, 70 eV): m/z (%)¼292 ([M+2]+, 2), 261
(16), 143 (29), 131 (33), 75 (50), 74 (100), 28 (75).
3
3
3.5.12. Ethyl 3-hydroxy-3-methylbutyrate (1u). Starting
with diisopropylamine (10.12 g, 100 mmol), THF
(100 mL), n-BuLi (2.5 M in hexanes, 41 mL, 103 mmol),
ethyl acetate (8.81 g, 100 mmol), acetone (6.97 g,
120 mmol), and hydrochloric acid (2.0 M, 50 mL), 1u was
3.6.4. 1-tert-Butoxy-1,3-bis(trimethylsilyloxy)-pent-1-ene
(2d). Starting with 1d (3.48 g, 20.00 mmol) and TMSCl

R. Dede et al. / Tetrahedron 63 (2007) 12547–12561
12559
(12.22 g, 112 mmol), 2d was obtained as a clear yellow
liquid (6.178 g, 97%). Reaction time: 19 h. 1H NMR
(CDCl3, 300 MHz): d¼0.11 (s, 9H, Si(CH3)3), 0.22 (s, 9H,
COSi(CH3)3O-t-Bu), 0.87 (t, >3H, CH3), 1.34 (s, 9H,
C(CH3)3), 1.45 (m, >2H, CH2), 3.94 (d, 1H, 3J¼9 Hz,
C]CH), 4.28 (m, 1H, CH). 13C NMR (CDCl3, 75 MHz):
d¼0.3 (Si(CH3)3), 0.6 (COSi(CH3)3O-t-Bu), 10.4 (CH2CH3),
28.4 (C(CH3)3), 32.0 (CH2CH3), 70.3 (C]CH), 78.8
(C(CH3)3), 93.7 (CH), 151.6 (CO2-t-Bu).
3.6.9. 1,3-Bis(trimethylsilyloxy)-1-ethoxy-5-methyl-hex-
1-ene (2i). Starting with 1i (3.48 g, 20.00 mmol) and TMSCl
(3.447 g, 32 mmol), 2i was obtained as a clear yellow
liquid (4.754 g, 75%). Reaction time: 22 h. 1H NMR
(CDCl3, 300 MHz): d¼0.10 (s, 9H, Si(CH3)3), 0.20 (s, 9H,
COSi(CH3)3OEt), 0.87 (d, 6H, 3J¼6.3 Hz, CH3), 1.20–
1.30 (m, 4H, CHAHB, CH3), 1.36–1.48 (m, 1H, CHAHB),
1.55–1.65 (m, 1H, CH(CH3)2), 3.47 (d, 1H, 3J¼9 Hz,
C]CH), 3.70 (q, 2H, 3J¼6.9 Hz, CH2CH3), 4.46–4.56 (m,
1H, CH). 13C NMR (CDCl3, 75 MHz): d¼0.3 (Si(CH3)3),
0.5 (COSi(CH3)3OEt), 14.3 (CH2CH3), 23.7 (CH(CH3)2),
24.8 (CH3), 48.9 (CH2), 62.8 (CH2CH3), 67.0 (C]CH),
81.1 (CH), 155.9 (COEt).
3.6.5. 1,3-Bis(trimethylsilyloxy)-1-ethoxy-hex-1-ene (2e).
Starting with 1e (3.2 g, 20.0 mmol) and TMSCl (3.447 g,
32 mmol), 2e was obtained as a clear yellow liquid
(4.811 g, 79%) Reaction time: 19 h. 1H NMR (CDCl3,
300 MHz): d¼0.06 (s, 9H, Si(CH3)3), 0.17 (s, 9H, COSi-
3.6.10. 1-Methoxy-4,4-dimethyl-1,3-bis(trimethylsilyloxy)-
pent-1-ene (2j). Starting with 1j (3.58 g, 22.3 mmol) and
TMSCl (6.11 g, 56.3 mmol), 2j was obtained as a clear yel-
3
(CH3)3OEt), 0.91 (t, 3H, CH3), 1.23 (t, 3H, J¼6.9 Hz,
OCH2CH3), 1.18–1.50 (signal overlap, 4H, CH2CH2CH3),
3.49 (d, 1H, 3J¼8.9 Hz, C]CH), 3.71 (q, 3J¼7.0 Hz,
2H, OCH2CH3), 4.46–4.39 (m, 1H, CH). 13C NMR
(CDCl3, 75 MHz): d¼0.3 (Si(CH3)3), 0.4 (COSi(CH3)3OEt),
13.9 (CH3), 14.3 (OCH2CH3), 19.1 (CH2CH2CH3), 41.8
(CH2CH2CH3), 62.8 (OCH2CH3), 68.3 (C]CH), 80.9 (CH),
156.0 (COEt).
1
low liquid (4.97 g, 73%). Reaction time: 19 h. H NMR
(300 MHz, CDCl3): d¼0.07 (s, 9H, Si(CH3)3), 0.20 (s, 9H,
Si(CH3)3), 0.84 (s, 9H, C(CH3)3), 3.51 (s, 3H, OCH3),
3.54 (d, 3J¼9.3 Hz, 1H, OCHCH), 4.07 (d, 3J¼9.3 Hz,
1H, OCH). 13C NMR (75 MHz, CDCl3): d¼0.3, 0.5
(Si(CH3)3), 25.8 (C(CH3)3), 35.9 (C(CH3)3), 54.4 (OCH3),
75.9, 77.1 (CH), 157.2 (C]CH).
3.6.6. 1,3-Bis(trimethylsilyloxy)-1-ethoxy-4-methyl-pent-
1-ene (2f). Starting with 1f (3.2 g, 20.0 mmol) and TMSCl
(3.447 g, 32 mmol), 2f was obtained as a clear yellow liquid
(5.221 g, 86%). Reaction time: 19 h. 1H NMR (CDCl3,
300 MHz): d¼0.09 (s, 9H, Si(CH3)3), 0.20 (s, 9H, COSi-
3.6.11. 1-Methoxy-1,3-bis(trimethylsilyloxy)non-1-ene
(2k). Starting with 1k (4.23 g, 22.5 mmol) and TMSCl
(6.11 g, 56.3 mmol), 2k was obtained as a clear yellow
liquid (6.81 g, 91%). Reaction time: 17 h. 1H NMR
(300 MHz, CDCl3): d¼0.09 (s, 9H, Si(CH3)3), 0.20 (s, 9H,
Si(CH3)3), 0.88 (m, 3H, CH2CH3), 1.15–1.60 (m, 10H,
(CH2)5), 3.49 (s, 3H, OCH3), 3.54 (d, 3J¼8.9 Hz, 1H,
CCH), 4.40 (m, 1H, OCH). 13C NMR (75 MHz, CDCl3):
d¼0.27, 0.34 (Si(CH3)3), 14.0 (CH2CH3), 22.6, 25.8, 29.1,
31.9, 39.5 (CH2), 54.4 (OCH3), 68.5, 80.7 (CH), 157.0 (C).
3
(CH3)3OEt), 0.82 (d, 3H, J¼6.7 Hz, CH3), 0.87 (d, 3H,
3
3J¼6.7 Hz, CH3), 1.28 (t, 3H, J¼7.0 Hz, CH2CH3), 1.6
3
(m, 1H, CH(CH3)2), 3.5 (d, 1H, J¼9 Hz, C]CH), 3.72
3
(q, 2H, J¼7.0 Hz, CH2), 4.08–4.21 (m, >1H, CH). 13C
NMR (CDCl3, 75 MHz): d¼0.3 (Si(CH3)3), 0.5 (COSi-
(CH3)3OEt), 14.4 (CH2CH3), 18.3 (CH3), 18.9 (CH3), 35.6
(CH(CH3)2), 62.8 (CH2), 73.7 (C]CH), 87.7 (CH), 156.3
(COEt).
3.6.12. 1,3-Bis(trimethylsilyloxy)-1-ethoxy-3-vinylprop-
1-ene (2l). Starting with 1l (2.88 g, 20.00 mmol) and TMSCl
(3.447 g, 32 mmol), 2l was obtained as a clear yellow
liquid (3.024 g, 52%). Reaction time: 22 h. 1H NMR
(CDCl3, 300 MHz): d¼0.13 (s, 9H, Si(CH3)3), 0.23 (s, 9H,
COSi(CH3)3OEt), 1.25–1.32 (m, overlap, 3H, CH3), 3.58
(d, 1H, 3J¼9.1 Hz, C]CH), 3.74 (qd, 2H, 2J¼1.4 Hz,
3J¼7.0 Hz, CH2), 4.06–4.26 (m, 1H, CH), 4.90–4.98 (m,
2H, CHCH2), 5.79–5.94 (m, 1H, CHCH2). 13C NMR
(CDCl3, 75 MHz): d¼0.3 (Si(CH3)3), 0.4 (COSi(CH3)3OEt),
14.3 (CH3), 62.9 (CH2), 69.4 (C]CH), 79.3 (CH), 111.8
(CHCH2), 142.1 (CHCH2), 156.5 (COEt).
3.6.7. 1-Ethoxy-1,3-bis(trimethylsilyloxy)hept-1-ene (2g).
Starting with 1g (3.92 g, 22.5 mmol) and TMSCl (6.11 g,
56.3 mmol), 2g was obtained as a clear yellow liquid
1
(7.17 g, 100%). Reaction time: 24 h. H NMR (300 MHz,
CDCl3): d¼0.10 (s, 9H, Si(CH3)3), 0.21 (s, 9H, Si(CH3)3),
0.86–0.94 (m, 3H, CH2CH2CH3), 1.20–1.60 (m, 9H,
(CH2)3, OCH2CH3), 3.51 (d, J¼8.9 Hz, 1H, CCH), 3.72
3
3
(q, J¼7.1 Hz, 2H, OCH2), 4.41 (m, 1H, OCH). 13C NMR
(75 MHz, CDCl3): d¼0.3, 0.5 (Si(CH3)3), 14.1, 14.3
(CH3), 22.6, 28.1, 39.3 (CH2), 62.8 (OCH2), 68.6, 81.0
(CH), 156.0 (C). MS (EI, 70 eV): m/z (%)¼318 (M+, 0.2),
261 (42), 231 (11), 189 (13), 159 (12), 146 (25), 143
(100), 110 (19), 28 (20).
3.6.13. 1-Ethoxy-1,3-bis(trimethylsilyloxy)trideca-1,12-
diene (2m). Starting with 1m (5.86 g, 22.9 mmol) and
TMSCl (6.23 g, 57.3 mmol), 2m was obtained as a clear yel-
1
3.6.8. 1-(tert-Butoxy)-1,3-bis(trimethylsilyloxy)hept-1-
ene (2h). Starting with 1h (4.56 g, 22.5 mmol) and TMSCl
(6.11 g, 56.3 mmol), 2h was obtained as a clear yellow liq-
uid (5.95 g, 76%). Reaction time: 22 h. 1H NMR
(300 MHz, CDCl3): d¼0.08 (s, 9H, Si(CH3)3), 0.18 (s, 9H,
Si(CH3)3), 0.86 (m, 3H, CH2CH3), 1.13–1.52 (m, 15H,
low liquid (8.51 g, 93%). Reaction time: 20 h. H NMR
(250 MHz, CDCl3): d¼0.09 (s, 9H, Si(CH3)3), 0.20 (s, 9H,
Si(CH3)3), 1.20–1.60 (m, 17H, OCH(CH2)7, CH3), 2.03
3
(m, 2H, H2C]CHCH2), 3.49 (d, J¼8.9 Hz, 1H, CCH),
3.71 (q, 3J¼7.0 Hz, 2H, OCH2), 4.40 (dt, 3J1¼8.9 Hz,
3J2¼6.4 Hz, 1H, OCH), 4.87–5.03 (m, 2H, H2C]CH),
5.80 (ddt, 3J1¼17.0 Hz, 3J2¼10.3 Hz, 3J3¼6.7 Hz, 1H,
H2C]CH). 13C NMR (75 MHz, CDCl3): d¼0.3, 0.5
(Si(CH3)3), 14.3 (CH3), 25.9, 28.9, 29.1, 29.5, 29.5, 29.6,
33.8, 39.5 ((CH2)8), 62.8 (OCH2), 68.6, 81.0 (CH), 114.0
(CH2CHCH2CH2), 139.1 (CH2CHCH2), 156.0 (C).
3
(CH2)3), C(CH3)3), 3.90 (d, J¼8.9 Hz, 1H, CCH), 4.33
(ddd, 3J1¼8.9 Hz, 3J2¼7.2 Hz, 3J3¼5.6 Hz, 1H, OCH).
13C NMR (75 MHz, CDCl3): d¼0.3, 0.5 (Si(CH3)3), 14.1
(CH2CH3), 22.5, 28.1 (CH2), 28.4 (C(CH3)3), 38.9 (CH2),
68.8 (CH), 78.6 (OC(CH3)3), 93.8 (CH), 151.4 (CCH).

12560
R. Dede et al. / Tetrahedron 63 (2007) 12547–12561
3.6.14. 1,3-Bis(trimethylsilyloxy)-1-methoxy-4-phenyl-
but-1-ene (2n). Starting with 1n (3.88 g, 20.00 mmol) and
TMSCl (3.447 g, 32 mmol), 2n was obtained as a clear yel-
3.6.19. 3-1-Ethoxy-3-(2-methoxyphenyl)-1,3-bis(trime-
thylsilyloxy)prop-1-ene (2s). Starting with 1s (5.05 g,
22.5 mmol) and TMSCl (6.11 g, 56.3 mmol), 2s was ob-
tained as a clear yellow-orange liquid (7.28 g, 88%). Reac-
1
low liquid (5.877 g, 87%). Reaction time: 22 h. H NMR
1
(CDCl3, 300 MHz): d¼0.05 (s, 9H, Si(CH3)3), 0.19 (s, 9H,
COSi(CH3)3OEt), 2.81 (qd, 3J¼7.4, 5.7 Hz, 2J¼13 Hz,
2H, CH2), 3.51 (s, 3H, OMe), 3.70 (d, 1H, 3J¼8.9 Hz,
ꢀC]CH), 4.60–4.68 (m, 1H, CH), 7.10–7.45 (m, 5H, Ar).
13C NMR (CDCl3, 75 MHz): d¼0.01 (Si(CH3)3), 0.3
(COSi(CH3)3OEt), 46.0 (CH2), 54.5 (OMe), 69.9
(C]CH), 80.1 (CH), 125.7 (Ar), 127.8 (Ar), 129.8 (Ar),
139.6 (Ar), 157.1 (COMe).
tion time: 17 h. H NMR (250 MHz, CDCl3): d¼0.11 (s,
3
9H, Si(CH3)3), 0.28 (s, 9H, Si(CH3)3), 1.27 (t, J¼7.0 Hz,
3
3H, CH2CH3), 3.73 (q, J¼7.0 Hz, 2H, OCH2), 3.80 (d,
3J¼9.2 Hz, 1H, OCHCH), 3.84 (s, 3H, OCH3), 5.95 (d,
3J¼9.2 Hz, 1H, OCH), 6.82–7.03 (m, 2H, Ar), 7.17–7.29
(m, 1H, Ar), 7.50–7.57 (m, 1H, Ar). 13C NMR (75 MHz,
CDCl3): d¼0.2, 0.4 (Si(CH3)3), 14.3 (CH2CH3), 55.3
(OCH3), 62.8 (CH2), 64.7, 80.9 (CH), 110.5, 120.5, 126.9,
127.3 (CHAr), 135.0, 155.6, 156.4 (C).
3.6.15. 1-Ethoxy-3-phenyl-1,3-bis(trimethylsilyloxy)-
prop-1-ene (2o). Starting with 1o (4.35 g, 22.4 mmol) and
TMSCl (6.11 g, 56.3 mmol), 2o was obtained as a clear
yellow-orange liquid (7.01 g, 92%). Reaction time: 17 h. 1H
NMR (300 MHz, CDCl3): d¼0.25 (s, 9H, Si(CH3)3, major),
0.27 (s, 9H, Si(CH3)3, minor), 0.34 (s, 9H, Si(CH3)3, minor),
0.37 (s, 9H, Si(CH3)3, major), 1.37 (t, 3J¼7.0 Hz, 3H, CH3,
major), 1.38 (t, 3J¼7.0 Hz, 3H, CH3, minor), 3.78–3.89 (m,
3H, OCH2, OCHCH, major), 4.00–4.07 (m, 3H, OCH2,
OCHCH, minor), 5.72 (m, 1H, OCH, both), 7.30 (m, 1H,
3.6.20. (4-Chlorophenyl)-1-ethoxy-1,3-bis(trimethylsilyl-
oxy)prop-1-ene (2t). Starting with 1t (5.11 g, 22.3 mmol)
and TMSCl (6.19 g, 57.0 mmol), 2t was obtained as a clear
1
orange-red liquid (7.92 g, 95%). Reaction time: 17 h. H
NMR (250 MHz, CDCl3): d¼0.14 (s, 9H, Si(CH3)3, major),
0.16 (s, 9H, Si(CH3)3, minor), 0.23 (s, 9H, Si(CH3)3, mi-
nor), 0.27 (s, 9H, Si(CH3)3, major), 1.28 (t, J¼7.0 Hz,
3
3
3H, CH3, both), 3.67 (d, J¼8.9 Hz, 1H, OCHCH, major),
3.73 (m, 2H, OCH2, major), 3.85 (d, 3J¼8.9 Hz, 1H,
OCHCH, minor), 3.93 (m, 2H, OCH2, minor), 5.56 (d,
3J¼8.9 Hz, 1H, OCH, major), 5.59 (d, 3J¼8.9 Hz, 1H,
OCH, minor), 7.23–7.34 (m, 4H, Ar, both). 13C NMR
(75 MHz, CDCl3): d¼0.3, 0.6 (Si(CH3)3), 14.3 (CH3),
63.0 (CH2), 69.6, 81.2 (CH), 127.0, 128.0 (CHAr), 131.8,
145.3, 156.6 (C).
3
Ph, both), 7.39 (m, 2H, Ph, both), 7.49 (d, J¼7.3 Hz, 2H,
Ph, both). 13C NMR (75 MHz, CDCl3): d¼0.3, 0.6
(Si(CH3)3), 14.3 (CH3), 62.9 (OCH2), 70.1, 81.6 (CH),
125.6, 126.2, 127.9 (CHAr), 146.7, 156.5 (C).
3.6.16. 1-Ethoxy-3-(4-tolyl)-1,3-bis(trimethylsilyloxy)-
prop-1-ene (2p). Starting with 1p (4.34 g, 20.8 mmol) and
TMSCl (6.11 g, 56.3 mmol), 2p was obtained as a clear or-
3.6.21. 1-Ethoxy-3-methyl-1,3-bis(trimethylsilyloxy)but-
1-ene (2u). Starting with 1u (3.29 g, 22.5 mmol) and TMSCl
(6.11 g, 56.3 mmol), 2u was obtained as a clear yellow liq-
uid (2.32 g, 35%). Reaction time: 14 h. 1H NMR
(250 MHz, CDCl3): d¼0.10 (s, 9H, Si(CH3)3, major), 0.11
(s, 9H, Si(CH3)3, minor), 0.15 (s, 9H, Si(CH3)3, major),
0.21 (s, 9H, Si(CH3)3, minor), 1.26 (t, 3J¼7.2 Hz,
1
ange liquid (6.97 g, 95%). Reaction time: 19 h. H NMR
(250 MHz, CDCl3): d¼0.13 (s, 9H, Si(CH3)3, major), 0.16
(s, 9H, Si(CH3)3, minor), 0.24 (s, 9H, Si(CH3)3, minor),
0.26 (s, 9H, Si(CH3)3, major), 1.27 (t, J¼7.0 Hz, 3H, CH3,
3
3
major), 1.28 (t, J¼7.0 Hz, 3H, CH3, minor), 2.33 (s, 3H,
ArCH3, both), 3.66–3.79 (m, 3H, OCH2, OCHCH, major),
3.88–3.97 (m, 3H, OCH2, OCHCH, minor), 5.58 (m, 1H,
OCH, both), 7.06–7.13 (m, 2H, Ar, both), 7.23–7.30 (m,
2H, Ar, both). 13C NMR (75 MHz, CDCl3): d¼0.3, 0.5
(Si(CH3)3), 14.3 (CH2CH3), 21.0 (ArCH3), 62.9 (CH2),
70.0, 81.8 (CH), 125.5, 128.6 (CHAr), 135.7, 143.7, 156.4 (C).
3
3H, CH2CH3, minor), 1.27 (t, J¼7.0 Hz, 3H, CH2CH3,
major), 1.37 (s, 6H, C(CH3)2, minor), 1.39 (s, 6H, C(CH3)2,
3
major), 3.61 (s, 1H, CH, major), 3.67 (q, J¼7.0 Hz, CH2,
major), 4.07–4.18 (m, 2H, CH2 minor). 13C NMR
(75 MHz, CDCl3): d¼0.5, 0.6 (Si(CH3)3), 14.4 (CH2CH3),
30.2 (C(CH3)2), 62.9 (CH2), 72.7 (CH3C), 85.5 (CH),
156.3 (C]CH).
3.6.17. 1-Ethoxy-3-(4-methoxyphenyl)-1,3-bis(trimethyl-
silyloxy)prop-1-ene (2q). Starting with 1q (4.34 g,
20.8 mmol) and TMSCl (6.11 g, 56.3 mmol), 2q was ob-
tained as a clear orange liquid (6.92 g, 91%). Reaction
time: 19 h. The compound was used directly after its prepa-
ration, due to its unstable nature. Spectroscopic data were
not obtained.
Acknowledgements
Financial support from the Deutsche Forschungsgemein-
schaft, from the DAAD (scholarship for D.F.), and from
the state of Pakistan (HEC scholarship for I.H. and
M.A.Y.) is gratefully acknowledged.
3.6.18. 1-([1,3-Bis(trimethylsilyloxy)]-3-methoxy-2-prop-
enyl)-2-methylbenzene (2r). Starting with 1r (3.88 g,
20.00 mmol) and TMSCl (3.447 g, 32 mmol), 2r was ob-
tained as a clear orange liquid (4.989 g, 74%). Reaction
References and notes
1
time: 19 h. H NMR (CDCl3, 300 MHz): d¼0.16 (s, 9H,
Si(CH3)3), 0.21 (s, 9H, COSi(CH3)3OEt), 2.3 (s, 3H,
ArCH3), 3.49 (s, 3H, OCH3), 5.68 (d, 1H, 3J¼2.7 Hz, CH),
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(COSi(CH3)3OEt), 19.0 (ArCH3), 54.6 (OMe), 67.6
(C]CH), 79.6 (CH), 125.2 (Ar), 125.8 (Ar), 126.1 (Ar),
129.8 (Ar), 133.9 (Ar), 144.7 (Ar), 157.5 (COMe).

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