DBU-mediated Ireland-Claisen rearrangement of allyl alk-3-enoates: an efficient synthesis of 2-ethylidene-γ,δ-unsaturated carboxylic acids

Article abstract of DOI:10.1016/j.tet.2007.07.031

Ireland-Claisen rearrangement, triggered by silyl enolization of allylic but-3-enoates 2, has been developed using DBU as the base in the presence of an excess amount of TMSCl under reflux in acetonitrile for a couple of hours. The procedure allows the synthesis of a range of 2-ethylidene-γ,δ-unsaturated carboxylic acids 5 in moderate to high yields. It is further revealed that the rearrangement proceeds equally well with allylic (E)-hexa-3,5-dienoates 10 derived from sorbic acid under similar conditions to provide 2-allyl substituted hexa-2,4-dienoic acids 13.

Full text of DOI:10.1016/j.tet.2007.07.031

Tetrahedron 63 (2007) 9605–9613
DBU-mediated Ireland–Claisen rearrangement of allyl
alk-3-enoates: an efficient synthesis of 2-ethylidene-
g,d-unsaturated carboxylic acids
c,
Yunxia Li,a Andreas Goeke,b,c Ruiyao Wang,a Quanrui Wanga, and Georg Frater
*
*
ꢀ
aDepartment of Chemistry, Fudan University, 200433 Shanghai, PR China
bShanghai Givaudan Ltd, Fragrances, 201203 Shanghai, PR China
€
Givaudan Schweiz AG, Fragrance Research, Uberlandstrabe 138, 8600 Du€bendorf, Switzerland
c
Received 16 May 2007; revised 12 July 2007; accepted 13 July 2007
Available online 19 July 2007
Abstract—Ireland–Claisen rearrangement, triggered by silyl enolization of allylic but-3-enoates 2, has been developed using DBU as the base
in the presence of an excess amount of TMSCl under reflux in acetonitrile for a couple of hours. The procedure allows the synthesis of a range
of 2-ethylidene-g,d-unsaturated carboxylic acids 5 in moderate to high yields. It is further revealed that the rearrangement proceeds equally
well with allylic (E)-hexa-3,5-dienoates 10 derived from sorbic acid under similar conditions to provide 2-allyl substituted hexa-2,4-dienoic
acids 13.
Ó 2007 Published by Elsevier Ltd.
1. Introduction
ence of an excess of TMSCl and 1,8-diazabicyclo[5.4.0]un-
dec-7-ene (DBU) in refluxing acetonitrile (Scheme 1).4 In
this procedure, the silylketene acetals II were generated by
a Baylis–Hillman-like addition of DABCO to the acrylate
and subsequent silylation of the zwitterionic intermediate. Af-
terrearrangementofthisintermediatefollowedbytheelimina-
tion of DABCO, a-methylene-g,d-unsaturated carboxylic
acids IV were obtained in good yields. However, this pathway
applies only to non-substituted acrylates, as it becomes
increasingly difficult to add Baylis–Hillman bases to b-
substituted and b-disubstituted acrylates. Working along this
line, we surprisingly found that the combination of DBU and
TMSCl5 is reactive enough to promote the silylketene acetal
formation and subsequent Claisen rearrangement/isomeriza-
tion reactions of a range of allylic but-3-enoates or related vi-
nylogous systems. Herein, we present the results of our mild
and effective variant of the Ireland–Claisen rearrangement.
Numerous significant variants of the Claisen [3,3]-sigma-
tropic rearrangement have been developed in the past de-
cades, which have increased its versatility and made it
a powerful tool to synthesize g,d-unsaturated carbonyl com-
pounds.1 Especially in 1972, Ireland and Mueller found that
esters of allylic alcohols can be rearranged to g,d-unsatu-
rated carboxylic acids in the presence of strong bases (like
LDA) and the reaction has been generally referred to as
Ireland–Claisen rearrangement.2,3 This rearrangement usu-
ally occurs below ambient temperatures via the silylketene
acetals prepared by reaction of allylic ester enolates with
a silylating agent such as trimethylsilyl chloride.
We have recently established a DABCO-catalyzed Ireland–
Claisen [3,3]-rearrangement of allylic acrylates I in the pres-
N
OTMS
O
N
OTMS
O
CO2H
O
R1
R2
aq.HCl
DABCO
R1
R1
R2
TMSCl/DBU
75-90%
O
H
R1
R2
R2
I
II
III
IV
Scheme 1. The DABCO promoted Ireland–Claisen rearrangement of allyl acrylates I.4
Keywords: Ireland–Claisen rearrangement; DBU; 2-Ethylidene-g,d-unsaturated carboxylic acids.
* Corresponding authors. E-mail addresses: qrwang@fudan.edu.cn; georg.frater@givaudan.com
0040–4020/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tet.2007.07.031

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Y. Li et al. / Tetrahedron 63 (2007) 9605–9613
2. Results and discussion
the ease of carrying out this protocol, we performed a series
of experiments with different allylic esters of type 2/3 to
probe the scope of the reaction.
The synthetic sequence is illustrated in Scheme 2. First, we
prepared the corresponding allylic esters easily in good
yields by the reaction of crotonoyl chloride with alcohols 1
in the presence of stoichiometric amounts of triethylamine.6
It was found that, in most cases, the b,g-unsaturated esters 2
were formed as the major products along with varying
amounts of crotonates 3. Since both products provided the
same ester enolates during the following step, separation
of 2 and 3 was not necessary.
As shown in Table 1, this reaction tolerates a wide range of
substitution patterns at both the carboxylate as well as the
allylic alcohol moiety to afford the tandem rearranged/iso-
merized products in good yields.12 It was found that for the
(E)-3-monosubstituted allyl but-3-enoates 2b and 2c the reac-
tion furnished the 3-substituted 2-ethylidene-g,d-unsaturated
acids 5b and 5c, respectively, as a mixture of E and Z products
with the former ones predominating (Table 1, entries 2 and 3),
both in high yields. The remote 6(Z)-double bond in 2c did not
isomerize during the reaction. For allyl but-3-enoate 2d bear-
ing a substituent at the 20-position, the reaction proceeded
equally smoothly to provide 5d in 78% yield (Table 1, entry
4). Similar results were observed for the 1,1-dimethyl
substituted ester 2e and the 1-phenyl substituted ester 2f
(Table 1, entries 5 and 6). As a trend, substitution at the 30-po-
sition of the allyl unit renders (E)-configured products 5 less
selectively, due to the increased allylic strain caused by the
bulkier residue at the 2-position of the crotonic acid (Fig. 1).
In preliminary experiments, we investigated the enolization
of 2a/3a (98:2) with Et3N, DBU, DMAP (4-dimethylamino-
pyridine), and N-ethyldiisopropylamine (Hunig’s base) as
€
a base. After exploring a range of reaction conditions, we
were pleased to discover that DBU can serve as an efficient
base in promoting the formation of the ester enolates. Thus,
2a/3a (1.0 equiv) were treated with DBU (2.0 equiv) and
trimethylsilyl chloride (TMSCl, 3.0 equiv) in acetonitrile
under reflux. The [3,3]-rearrangement (via chair-form tran-
sient state A to give 4) and subsequent isomerization reac-
tion proceeded smoothly and were completed after 5 h.
Acidic work-up provided 2-ethylidene-pent-4-enoic acid
5a in 90% isolated yield and 97% (E)-selectivity for the
a-ethylidene double bond.
Worthy of note is that the rearrangement of cinnamyl but-
3-enoate 2g occurred under our conditions without difficulty.
However, the isolated product was proved to be the fully con-
jugated carboxylic acid 6. Apparently, isomerization of the
4-double bond of the initially formed 2-ethylidene-3-phenyl-
pent-4-enoic acid 5g was involved under our conditions
(Table 1, entry 7). A NOE experiment allowed establishment
of the Z configuration of the C-3 double bond for 6. On the
other hand, when the 3,3-disubstituted but-3-enoates 2h
was subjected to the standard reaction conditions, a mixture
comprised of 2-vinyl and 2-ethylidene substituted g,d-unsat-
urated acids 4h/5h (>98:2; de of 4h: 50%) were produced
(Table 1, entry 8). Again, the higher preference for non-con-
jugated isomer 4h can be accounted for by the large allylic
strain of compound 5h.
Ireland–Claisen rearrangements of conjugated silylketene
acetals are scarce but have been described starting from a,
b-unsaturated or b,g-unsaturated allyl esters.7 In the total syn-
theses of (ꢀ)-grandinolide and (ꢀ)-sapranthin by asymmetric
Sharpless dihydroxylation of methyl trans-3-pentenoate,
Rank and her co-workers conducted the Ireland–Claisen rear-
rangement of the b,g-unsaturated allyl ester 2a using LHMDS
asthebaseatꢀ78 ꢁCfortheinitialdeprotonation.Theproduct
was reported to be an 87:13 mixture of the deconjugated acid
4a and the conjugated acid 5a.8
DBU was initially introduced as a reagent for dehydrohalo-
genation in a vitamin A synthesis during 1960s along with
the other bicyclic amidine compound DBN.9 DBU has
been recognized as a strong hindered organic base with
low nucleophilicity and it finds increasing use in the syn-
thetic works.10,11 To the best of our awareness, there are
no literature precedents for using DBU as the base in gener-
ation of silylketene acetals derived from allyl but-3-enoates
or but-2-enoates. The use of DBU is evidently advantageous
over the commonly used strong bases like LDA or LHMDS
with which low temperatures must be employed. Inspired by
In order to further assess the scope of our protocol, the prop-
argyl but-3-enoate 7 was subjected to the rearrangement.
Apparently, the silylketene acetal could be easily generated
with DBU/TMSCl and did undergo the [3,3]-rearrangement
to give, after an isomerization of the initially formed allene 8
(Scheme 3), 2,4-dienoic acid 9 in moderate yield (Table 1,
entry 9). It is important to note that due to the deprotonation
of terminal alkynes, this reaction cannot be performed under
classical Ireland–Claisen conditions. The E configuration at
the C-2 double bond was established by NOE experiment.
O
O
DBU,TMSCl
CH3CN, reflux
5-9 h
crotonoyl chloride, Et3N
CH2Cl2, 0 °C-r.t., 1.5-2 h
OH
R2
O
O
+
R1
R1
2 (major)
R1
3 (minor)
R2
R2
75-90%
1
O
O
OTMS
R1
[3,3]-~
1,3-proton shift
78-90%
OH
R2
OH
R2
R2
O
R1
R1
5
4
A
Scheme 2. Rearrangement of allylic but-3-enoates.

Y. Li et al. / Tetrahedron 63 (2007) 9605–9613
9607
Table 1. Synthesis of 2-ethylidene or 2-vinyl g,d-unsaturated carboxylic acids based on Ireland–Claisen rearrangementa
Entry
Substrate (major isomer)
Product (major isomer)
Time (h)
Yieldb,c (%)
Ratiod (E/Z)
>97:3
O
COOH
1
5
90b
O
5a
2a
COOH
O
2
3
4
5
6
7
8
7.5
7.5
7
82b
84b
78b
80b
78c
78c
78:22
83:17
O
2b
5b
COOH
O
O
2c
5c
COOH
O
>97:3
>96:4
>97:3
>93:7
O
2d
5d
O
COOH
6
O
5e
2e
O
Ph
COOH
8
O
Ph
5f
2f
COOH
O
9
O
Ph
Ph
2g
6
COOH
O
9
8
79e
47c
O
2h
4h
COOH
O
9
O
7
9
a
Reactions were carried out with 2/3 (1.0 equiv) (GC content of 3 ꢂ5%), DBU (2.0 equiv), and TMSCl (3.0 equiv) in CH3CN (10 mL/g of 2/3) under reflux for
the specified period of time.
b
c
d
e
Isolated yield by bulb-to-bulb distillation.
Isolated yield by column chromatography (hexane/acetone¼10:1).
E/Z by GC.
de 50%; amount of 5h <2%.
Finally, to test if the rearrangement occurs when the conju-
gated system is extended by one more double bond, several
allylic (E)-hexa-3,5-dienoates 10 (containing a minor
amount of the regioisomers 11), which were readily attain-
able from sorboyl chloride and allylic alcohols,6a were
subjected to the standard reaction conditions (Scheme 4).
As illustrated in Table 2, all the reaction proceeded
equally well to offer the tandem rearranged/isomerized
hexa-2,4-dienoic acids 13 in high yields, demonstrating
that the principle of vinylogy13 is applicable to our proto-
col. The initially formed products 12 were not isolated
from the mixture. An NOE experiment for 13e indicated
a predominant E configuration at the C-2 and C-4 double
bonds.
O
O
OH
R2
no allylic strain in (Z)-5
OH
R2
allylic strain in (E)-5
R1
R1
Figure 1.

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Y. Li et al. / Tetrahedron 63 (2007) 9605–9613
O
O
COOH
standard condition
1,3-proton shift
OH
O
7
•
8
9
Scheme 3. Rearrangement of 2-methylbut-3-yn-2-yl but-3-enoate 7.
O
O
sorboyl chloride, Et3N
OH
O
+
R2
O
CH2Cl2, 0°C-r.t., 1.5-2 h
R1
R2
77-89%
R1
R1
R2
1
10 (major)
11 (minor)
DBU,TMSCl
CH3CN, reflux
4.5-8.5 h
O
O
OH
R2
1,5-proton shift
75-85%
OH
R2
R1
R1
13
12
Scheme 4. Rearrangement of allylic (E)-hexa-3,5-dienoates 10.
Table 2. Synthesis of 2-allyl substituted hexa-2,4-dienoic acids based on Ireland–Claisen rearrangement of allylic (E)-hexa-3,5-dienoatesa
Entry
Substrate
Product (major isomer)
Time (h)
Yieldb (%)
Ratioc
O
O
COOH
1
4.5
91
>90:10
13a
10a
10b
10c
O
O
COOH
2
3
4
5
8
81
79
80
85
72:28
88:12
13b
COOH
O
8.5
O
13c
COOH
O
7
>97:3
>97:3
O
13d
10d
O
O
COOH
6
O
O
13e
10e
COOH
6
7.5
87
>98:2
13f
10f
a
Reactions were carried out with 10 (1.0 equiv), DBU (2.0 equiv), and TMSCl (3.0 equiv) in CH3CN (10 mL/g of 10) under reflux for the specified period of
time.
b
c
Isolated yield by column chromatography (hexane/acetone¼10:1).
2E,4E/2E,4Z by GC.

Y. Li et al. / Tetrahedron 63 (2007) 9605–9613
9609
In summary, we have disclosed that DBU and TMSCl
system can be used for the Ireland–Claisen rearrangement
for a range of allylic alk-3 (2)-enoates to give 2-ethylene-
g,d-unsaturated acids 5 and 2-butenylidene-g,d-unsaturated
acids 13 in high yields. The superiority of the present proto-
col lies in its easy operation, cheaper reagents, wide sub-
strate scope, and mild conditions while the presence of
carbon–carbon multiple bonds in the acid products enables
further transformations.
J2¼6.9 Hz, 1H), 5.56 (dt, J1¼16.5 Hz, J2¼6.3 Hz, 1H),
5.17 (dd, J1¼17.4 Hz, J2¼1.5 Hz, 1H), 5.16 (dd,
J1¼11.1 Hz, J2¼1.5 Hz, 1H), 4.53 (d, J¼6.3 Hz, 2H), 3.10
(d, J¼7.2 Hz, 2H), 2.03 (dt, J1¼7.2 Hz, J2¼7.2 Hz, 2H),
1.47–1.35 (m, 2H), 0.90 (t, J¼7.5 Hz, 3H). 13C NMR
(75 MHz, CDCl3): d 171.31, 136.53, 130.33, 123.81,
118.48, 65.50, 39.17, 34.30, 22.03, 13.62. HRMS (EI): m/z
calcd for C10H16O2 [M+]: 168.1150; found: 168.1156.
3.2.3. (2E,6Z)-Nona-2,6-dienyl but-3-enoate (2c). Yield:
87%; colorless oil. IR (neat, n/cmꢀ1): 3297, 2990, 2943,
1749, 1129, 973. H NMR (300 MHz, CDCl3): d 5.98–
1
3. Experimental
5.84 (m, 1H), 5.76 (dt, J1¼15.6 Hz, J2¼5.1 Hz, 1H), 5.56
(dt, J1¼15.0 Hz, J2¼6.3 Hz, 1H), 5.37 (dt, J1¼10.5 Hz,
J2¼7.5 Hz, 1H), 5.28 (dt, J1¼10.8 Hz, J2¼6.3 Hz, 1H),
5.16 (dd, J1¼15.6 Hz, J2¼1.5 Hz, 1H), 5.15 (dd,
J1¼10.2 Hz, J2¼1.5 Hz, 1H), 4.52 (d, J¼6.6 Hz, 2H), 3.08
(d, J¼7.2 Hz, 2H), 2.10–2.09 (m, 4H), 2.01 (dq,
J1¼7.2 Hz, J2¼6.9 Hz, 2H), 0.93 (t, J¼7.5 Hz, 3H). 13C
NMR (75 MHz, CDCl3): d 171.20, 135.88, 132.29, 130.31,
127.86, 124.05, 118.43, 85.34, 39.12, 32.31, 26.49, 20.54,
14.26. HRMS (EI): m/z calcd for C13H20O2 [M+]:
208.1463; found: 208.1467.
3.1. General information
Melting points are uncorrected and expressed in degree Cel-
sius. IR spectral data were obtained for liquid film or KBr
discs with a Bruker Tensor 27 spectrophotometer and ab-
sorptions are given in wavenumbers (cmꢀ1). NMR spectra
were recorded in CDCl3 solutions with a Bruker AMX-
300 or Jeol ECA 400 or Bruker Avance DMX 500 spectro-
meter using TMS as an internal reference. Coupling constant
(J) values are given in Hertz. Mass spectra were determined
with Agilent Technologies 5975 inert Mass Selective Detec-
tor. High-resolution mass spectra were determined with
a Varian MAT 44S with EI ionization. Silica gel Merck 60
(200–300 mesh) was used for flash column chromatography
with hexane/acetone mixtures for elution. A Glass Oven
3.2.4. 2-Methyleneheptyl but-3-enoate (2d). Yield: 86%;
colorless oil. IR (neat, n/cmꢀ1): 3083, 2932, 1744, 1650,
1458, 1326.83, 1166, 993, 918. 1H NMR (300 MHz,
CDCl3): d 5.99–5.85 (m, 1H), 5.15 (dd, J1¼15.9 Hz,
J2¼1.5 Hz, 1H), 5.14 (dd, J1¼11.4 Hz, J2¼1.5 Hz, 1H),
4.99 (s, 1H), 4.90 (s, 1H), 4.52 (s, 2H), 3.11 (d, J¼6.9 Hz,
2H), 2.03 (t, J¼7.8 Hz, 2H), 1.48–1.38 (m, 2H), 1.31–1.25
(m, 4H), 0.87 (t, J¼6.9 Hz, 3H). 13C NMR (75 MHz,
CDCl3): d 171.06, 143.97, 130.19, 118.49, 112.01, 69.93,
39.11, 33.17, 31.47, 27.17, 22.46, 13.96. HRMS (EI): m/z
calcd for C12H20O2 [M+]: 196.1463; found: 196.1459.
€
B-585 kugelrohr apparatus was used for bulb-to-bulb distil-
lation.
3.2. General procedure for esterification: synthesis of
the allylic esters 2a–h, 7, and 10a–f
To a stirred 0 ꢁC solution of the appropriate allylic alcohol 1
(100 mmol) in CH2Cl2 (500 mL) was added triethylamine
(17.0 mL, 120 mmol), followed by freshly distilled croto-
noyl chloride (11.6 mL, 120 mmol) or sorboyl chloride
(16.0 mL, 120 mmol). After 30 min the reaction was al-
lowed to warm to room temperature and stirred further for
1–1.5 h. Then, saturated aqueous NaHCO3 (150 mL) was
added to quench the reaction. The organic layer was sepa-
rated and washed sequentially with saturated aqueous
NaHCO3 (150 mL), 5% aqueous HCl (2ꢃ100 mL), and sat-
urated aqueous NaCl (100 mL), and dried over MgSO4. The
solution was filtered and concentrated in vacuo. Purification
by bulb-to-bulb distillation provided the allylic esters as
colorless oil.
3.2.5. 2-Methylbut-3-en-2-yl but-3-enoate (2e). Yield:
77%; colorless oil. IR (neat, n/cmꢀ1): 3088, 2983, 2938,
1736, 1644, 1189, 1128, 920, 842. H NMR (300 MHz,
1
CDCl3): d 6.06 (dd, J1¼18.0 Hz, J2¼10.8 Hz, 1H), 5.96–
5.83 (m, 1H), 5.16 (d, J¼17.4 Hz, 1H), 5.14 (dd,
J1¼17.4 Hz, J2¼1.8 Hz, 1H), 5.13 (dd, J1¼10.5 Hz,
J2¼1.5 Hz, 1H), 5.06 (dd, J1¼11.1 Hz, J2¼0.9 Hz, 1H),
3.02 (d, J¼6.6 Hz, 2H), 1.51 (s, 6H). 13C NMR (75 MHz,
CDCl3): d 170.39, 142.41, 130.69, 118.15, 112.72, 80.97,
40.21, 26.41. HRMS (EI): m/z calcd for C9H14O2 [M+]:
154.0994; found: 154.0987.
3.2.6. 1-Phenylallyl but-3-enoate (2f). Yield: 80%; color-
less oil. IR (neat, n/cmꢀ1): 3087, 1740, 1644, 1165, 987,
924, 700. H NMR (300 MHz, CDCl3): d 7.39–7.33 (m,
3.2.1. Allyl but-3-enoate (2a).6a Yield: 89%; colorless oil.
IR (neat, n/cmꢀ1): 3007, 2963, 1740, 1264, 1173, 1004,
970. H NMR (300 MHz, CDCl3): d 5.99–5.92 (m, 1H),
5.91–5.84 (m, 1H), 5.29 (dd, J1¼17.4 Hz, J2¼1.5 Hz, 1H),
5.23 (dd, J1¼10.5 Hz, J2¼1.5 Hz, 1H), 5.17 (dd,
J1¼16.5 Hz, J2¼1.5 Hz, 1H), 5.16 (dd, J1¼11.1 Hz,
J2¼1.5 Hz, 1H), 4.59 (d, J¼5.7 Hz, 2H), 3.12 (d,
J¼7.2 Hz, 2H). 13C NMR (75 MHz, CDCl3): d 171.13,
132.06, 130.16, 118.62, 118.28, 65.30, 39.08.
1
1
5H), 6.32 (d, J¼6.3 Hz, 1H), 6.09–6.00 (m, 1H), 5.99–
5.90 (m, 1H), 5.33 (dd, J1¼17.1 Hz, J2¼1.2 Hz, 1H), 5.28
(dd, J1¼11.4 Hz, J2¼1.2 Hz, 1H), 5.20 (dd, J1¼16.8 Hz,
J2¼1.8 Hz, 1H), 5.19 (dd, J1¼10.2 Hz, J2¼1.5 Hz, 1H),
3.19 (d, J¼6.9 Hz, 2H). 13C NMR (75 MHz, CDCl3):
d 170.45, 138.82, 136.20, 130.12, 128.59, 128.22, 127.15,
118.75, 117.05, 76.37, 39.56. HRMS (EI): m/z calcd for
C13H14O2 [M+]: 202.0994; found: 202.0991.
3.2.2. (E)-Hex-2-enyl but-3-enoate (2b). Yield: 89%; col-
orless oil. IR (neat, n/cmꢀ1): 3084, 2961, 2875, 1738,
1645, 1458, 1327, 1171, 976. 1H NMR (300 MHz,
CDCl3): d 5.97–5.86 (m, 1H), 5.76 (dt, J1¼15.3 Hz,
3.2.7. Cinnamyl but-3-enoate (2g).14 Yield: 87%; colorless
oil. IR (neat, n/cmꢀ1): 3028, 1739, 1644, 1256, 1170, 968,
924. H NMR (400 MHz, CDCl3): d 7.37–7.21 (m, 5H),
1

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Y. Li et al. / Tetrahedron 63 (2007) 9605–9613
6.63 (d, J¼15.6 Hz, 1H), 6.26 (dt, J1¼15.6 Hz, J2¼6.4 Hz,
1H), 6.01–5.90 (m, 1H), 5.17 (dd, J1¼15.6 Hz, J2¼1.6 Hz,
1H), 5.16 (dd, J1¼11.0 Hz, J2¼1.6 Hz, 1H), 4.74 (d,
J¼6.9 Hz, 2H), 3.12 (d, J¼6.9 Hz, 2H). 13C NMR
(100 MHz, CDCl3): d 171.41, 136.26, 134.44, 130.28,
128.72, 128.21, 126.74, 123.12, 118.81, 65.40, 39.25.
1H), 5.06 (d, J¼10.1 Hz, 1H), 4.53 (d, J¼6.4 Hz, 2H),
3.13 (d, J¼7.4 Hz, 2H), 2.15–2.12 (m, 4H), 2.03 (dq,
J1¼7.3 Hz, J2¼7.3 Hz, 2H), 0.95 (t, J¼7.3 Hz, 3H). 13C
NMR (100 MHz, CDCl3): d 171.27, 136.45, 136.08,
134.44, 132.39, 127.94, 125.69, 124.08, 116.98, 65.53,
38.03, 32.39, 26.55, 20.62, 14.37. HRMS (EI): m/z calcd
for C15H22O2 [M+]: 234.1620; found: 234.1626.
3.2.8. (E)-3,7-Dimethylocta-2,6-dienyl but-3-enoate
(2h).14 Yield: 87%; colorless oil. IR (neat, n/cmꢀ1): 3023,
2919, 1739, 1452, 1251, 1169, 989, 919. 1H NMR
(400 MHz, CDCl3): d 5.99–5.88 (m, 1H), 5.34 (t,
J¼6.9 Hz, 1H), 5.17 (dd, J1¼15.6 Hz, J2¼1.8 Hz, 1H),
5.16 (dd, J1¼11.4 Hz, J2¼1.8 Hz, 1H), 5.07 (t, J¼6.9 Hz,
1H), 4.61 (d, J¼6.9 Hz, 2H), 3.09 (d, J¼6.9 Hz, 2H),
2.09–2.04 (m, 4H), 1.70 (s, 3H), 1.68 (s, 3H), 1.60 (s, 3H).
13C NMR (100 MHz, CDCl3): d 171.63, 142.45, 131.89,
130.48, 123.80, 118.51, 118.25, 61.69, 39.59, 39.25,
26.34, 25.74, 17.75, 16.54.
3.2.13. (E)-2-Methyleneheptyl hexa-3,5-dienoate (10d).
Yield: 80%; colorless oil. IR (neat, n/cmꢀ1): 3023, 2932,
2861, 1740, 1652, 1238, 1173, 1003, 903. 1H NMR
(300 MHz, CDCl3): d 6.32 (ddd, J1¼17.1 Hz, J2¼10.2 Hz,
J3¼10.2 Hz, 1H), 6.14 (dd, J1¼15.9 Hz, J2¼10.8 Hz, 1H),
5.78 (dt, J1¼15.1 Hz, J2¼10.2 Hz, 1H), 5.14 (d,
J¼17.1 Hz, 1H), 5.04 (dd, J1¼10.5 Hz, J2¼1.2 Hz, 1H),
4.99 (s, 1H), 4.92 (s, 1H), 4.53 (s, 2H), 3.14 (d, J¼6.9 Hz,
1H), 2.03 (t, J¼7.8 Hz, 2H), 1.48–1.39 (m, 2H), 1.32–1.23
(m, 4H), 0.88 (t, J¼6.6 Hz, 3H). 13C NMR (75 MHz,
CDCl3): d 171.01, 143.96, 136.33, 134.45, 125.45, 116.89,
112.09, 67.03, 37.92, 33.19, 31.48, 27.19, 22.46, 13.98.
HRMS (EI): m/z calcd for C14H22O2 [M+]: 222.1620; found:
222.1616.
3.2.9. 2-Methylbut-3-yn-2-yl but-3-enoate (7). Yield:
80%; colorless oil. IR (neat, n/cmꢀ1): 3297, 2990, 2943,
1749, 1644, 1182, 1132, 973, 849, 669. 1H NMR
(300 MHz, CDCl3): d 5.96–5.83 (m, 1H), 5.14 (dd,
J1¼15.6 Hz, J2¼1.5 Hz, 1H), 5.13 (dd, J1¼11.4 Hz,
J2¼1.5 Hz, 1H), 3.04 (d, J¼7.2 Hz, 2H), 2.52 (s, 1H), 1.66
(s, 6H). 13C NMR (75 MHz, CDCl3): d 169.74, 130.21,
118.44, 84.57, 72.41, 71.92, 39.73, 28.85. HRMS (EI): m/z
calcd for C9H12O2 [M+]: 152.0837; found: 152.0835.
3.2.14. (E)-2-Methylbut-3-en-2-yl hexa-3,5-dienoate
(10e). Yield: 79%; colorless oil. IR (neat, n/cmꢀ1): 3090,
2981, 2936, 1736, 1647, 1188, 1129, 1004, 921, 847. H
1
NMR (300 MHz, CDCl3): d 6.32 (ddd, J1¼17.1 Hz,
J2¼10.0 Hz, J3¼9.9 Hz, 1H), 6.13 (dd, J1¼15.6 Hz,
J2¼10.5 Hz, 1H), 6.06 (dd, J1¼16.8, J2¼11.1 Hz, 1H),
5.76 (dt, J1¼15.1 Hz, J2¼10.2 Hz, 1H), 5.16 (d, J¼
18.0 Hz, 1H), 5.14 (d, J¼16.5 Hz, 1H), 5.06 (d, J¼11.1 Hz,
1H), 5.03 (d, J¼9.6 Hz, 1H), 3.05 (d, J¼7.2 Hz, 2H), 1.51
(s, 6H). 13C NMR (75 MHz, CDCl3): d 170.31, 142.37,
136.50, 134.10, 126.08, 116.65, 112.77, 81.10, 38.98,
26.41. HRMS (EI): m/z calcd for C11H16O2 [M+]:
180.1150; found: 180.1154.
3.2.10. (E)-Allyl hexa-3,5-dienoate (10a).6b Yield: 89%;
colorless oil. H NMR (400 MHz, CDCl3): d 6.34 (ddd,
1
J1¼16.9 Hz, J2¼10.5 Hz, J3¼10.5 Hz, 1H), 6.16 (dd,
J1¼15.1 Hz, J2¼10.5 Hz, 1H), 5.97–5.87 (m, 1H), 5.80
(dt, J1¼15.1 Hz, J2¼10.2 Hz, 1H), 5.32 (dd, J1¼17.4 Hz,
J2¼1.4 Hz, 1H), 5.24 (dd, J1¼10.5 Hz, J2¼1.4 Hz, 1H),
5.17 (d, J¼16.9 Hz, 1H), 5.07 (d, J¼10.1 Hz, 1H), 4.60 (d,
J¼5.9 Hz, 2H), 3.16 (d, J¼6.9 Hz, 2H).
3.2.15. (E)-1-Vinylcyclohexyl hexa-3,5-dienoate (10f).
Yield: 65%; colorless oil. IR (neat, n/cmꢀ1): 3087, 2936,
2862, 1734, 1651, 1449, 1415, 1182, 1130, 1004, 908. H
3.2.11. (E)-((E)-Hex-2-enyl)hexa-3,5-dienoate (10b).
Yield: 87%; colorless oil. IR (neat, n/cmꢀ1): 3033, 2960,
1738, 1336, 1241, 1174, 1004, 972, 904. 1H NMR
(400 MHz, CDCl3): d 6.33 (ddd, J1¼16.9 Hz, J2¼10.6 Hz,
J3¼10.2 Hz, 1H), 6.14 (dd, J1¼15.1 Hz, J2¼10.1 Hz, 1H),
5.79 (dt, J1¼15.1 Hz, J2¼7.3 Hz, 1H), 5.77 (dt,
J1¼16.5 Hz, J2¼6.9 Hz, 1H), 5.58 (dt, J1¼15.1 Hz,
J2¼10.2 Hz, 1H), 5.16 (d, J¼16.0 Hz, 1H), 5.05 (d,
J¼10.1 Hz, 1H), 4.53 (d, J¼6.4 Hz, 2H), 3.13 (d,
J¼7.3 Hz, 2H), 2.03 (dt, J1¼6.9 Hz, J2¼6.9 Hz, 2H),
1.45–1.36 (m, 2H), 0.90 (t, J¼7.3 Hz, 3H). 13C NMR
(100 MHz, CDCl3): d 171.29, 136.63, 136.43, 134.40,
125.69, 123.85, 116.94, 65.63, 38.01, 34.35, 22.07, 13.68.
HRMS (EI): m/z calcd for C12H18O2 [M+]: 194.1307; found:
194.1307.
1
NMR (400 MHz, CDCl3): d 6.34 (ddd, J1¼16.9 Hz,
J2¼10.9 Hz, J3¼10.1 Hz, 1H), 6.16 (dd, J1¼16.0 Hz,
J2¼10.6 Hz, 1H), 6.09 (dd, J1¼17.8 Hz, J2¼11.0 Hz, 1H),
5.79 (dt, J1¼15.1 Hz, J2¼10.1 Hz, 1H), 5.16 (d,
J¼16.5 Hz, 2H), 5.12 (d, J¼10.6 Hz, 1H), 5.05 (d,
J¼10.1 Hz, 1H), 3.09 (d, J¼7.3 Hz, 2H), 2.21–2.18 (m,
2H), 1.61–1.46 (m, 7H), 1.35–1.25 (m, 1H). 13C NMR
(100 MHz, CDCl3): d 170.15, 141.82, 136.56, 134.22,
126.25, 116.73, 113.81, 82.30, 39.09, 34.88, 25.40, 21.89.
HRMS (EI): m/z calcd for C14H20O2 [M+]: 220.1463; found:
220.1466.
3.3. General procedure for Ireland–Claisen
rearrangement of 2/3
3.2.12. (E)-((2E,6Z)-Nona-2,6-dienyl)hexa-3,5-dienoate
(10c). Yield: 84%; colorless oil. IR (neat, n/cmꢀ1): 3007,
2964, 1740, 1265, 1173, 970, 903. H NMR (400 MHz,
To a solution of allyl but-3-enoate 2 (containing minor
amount of the respective allylic crotonate 3) (8 mmol) in
acetonitrile (10 mL/g of 2/3) were added DBU (2.44 g,
16 mmol) and TMSCl (2.61 g, 24 mmol). The mixture was
heated under reflux and stirred for 4.5–8.5 h (as specified
in Table 1), and then concentrated under reduced pressure.
The residue was dissolved in ether (30 mL) and washed
with 3 M hydrogen chloride (15 mL) and brine, and dried
1
CDCl3):
d
6.34 (ddd, J1¼16.9 Hz, J2¼11.1 Hz,
J3¼10.1 Hz, 1H), 6.14 (dd, J1¼15.1 Hz, J2¼10.6 Hz, 1H),
5.79 (dt, J1¼15.1 Hz, J2¼6.9 Hz, 1H), 5.77 (dt,
J1¼14.2 Hz, J2¼6.9 Hz, 1H), 5.59 (dt, J1¼15.1 Hz,
J2¼10.2 Hz, 1H), 5.39 (dt, J1¼10.5 Hz, J2¼6.9 Hz, 1H),
5.30 (dt, J1¼10.5 Hz, J2¼6.8 Hz, 1H), 5.16 (d, J¼16.9 Hz,

Y. Li et al. / Tetrahedron 63 (2007) 9605–9613
9611
with anhydrous MgSO4. Concentration under reduced pres-
sure and k€ugelrohr distillation or silica gel column chroma-
tography (hexane/acetone¼10:1) afforded 5a–e as colorless
oils and 5f, 6, and 9 as colorless solids.
(75 MHz, CDCl3): d 172.79 (s), 146.53 (s), 141.85 (d),
130.41 (s), 108.86 (t), 36.76 (t), 32.11 (t), 31.60 (t), 27.43
(t), 22.58 (t), 14.70 (q), 14.09 (q). HRMS: m/z calcd for
C12H20O2 [M+]: 196.1463; found: 196.1461.
3.3.1. (E)-2-Ethylidenepent-4-enoic acid (5a).15 Yield:
90%; colorless oil; E/Z>97:3. IR (neat, n/cmꢀ1): w3000,
2983, 1690, 1640, 1421, 1290, 1224, 1154, 915, 685. H
NMR (300 MHz, CDCl3): d 7.12 (q, J¼7.2 Hz, 1H), 5.88–
5.77 (m, 1H), 5.03 (dd, J1¼16.9 Hz, J2¼1.5 Hz, 1H), 5.02
(dd, J1¼10.5 Hz, J2¼1.5 Hz, 1H), 3.09 (d, J¼6.0 Hz, 1H),
1.85 (d, J¼6.9 Hz, 3H). 13C NMR (75 MHz, CDCl3):
d 172.68 (s), 141.57 (d), 134.85 (d), 130.14 (t), 115.14 (s),
30.09 (t), 14.51 (q). HRMS: m/z calcd for C7H10O2 [M+]:
126.0681; found: 126.0679.
3.3.5. (E)-2-Ethylidene-5-methylhex-4-enoic acid (5e).15
Yield: 80%; colorless oil; E/Z>96:4. IR (neat, n/cmꢀ1):
w3000, 2932, 1695, 1418, 1276, 1235, 935. 1H NMR
(300 MHz, CDCl3): d 7.01 (q, J¼7.2 Hz, 1H), 5.05 (t,
J¼5.7 Hz, 1H), 3.02 (d, J¼7.2 Hz, 2H), 1.86 (d, J¼7.5 Hz,
3H), 1.70 (s, 3H), 1.69 (s, 3H). 13C NMR (75 MHz,
CDCl3): d 173.28 (s), 140.02 (d), 132.36 (s), 132.07 (s),
121.32 (d), 25.72 (q), 25.22 (t), 17.87 (q), 14.54 (q).
HRMS: m/z calcd for C9H14O2 [M+]: 154.0994; found:
154.0994.
1
3.3.2. 2-Ethylidene-3-vinylcaproic acid (5b). Yield: 82%;
colorless oil; E/Z¼78:22. IR (neat, n/cmꢀ1): w3000, 2962,
1694, 1634, 1417, 1276, 914. 1H NMR (300 MHz, CDCl3):
d 7.04 (q, J¼7.5 Hz, 1H, E-isomer), 6.11 (q, J¼6.6 Hz, 1H,
Z-isomer), 6.09 (ddd, J1¼17.3 Hz, J2¼10.2 Hz, J3¼7.5 Hz,
1H, E-isomer), 5.81 (ddd, J1¼17.3 Hz, J2¼10.2 Hz,
J3¼7.5 Hz, 1H, Z-isomer), 5.01 (d, J¼17.3 Hz, 1H), 4.99
(d, J¼10.2 Hz, 1H), 3.36 (dt, J1¼7.5 Hz, J2¼7.5 Hz, 1H,
E-isomer), 3.14 (dt, J1¼7.5 Hz, J2¼7.5 Hz, 1H, Z-isomer),
2.04 (d, J¼7.2 Hz, 3H, Z-isomer), 1.88 (d, J¼7.2 Hz, 3H,
E-isomer), 1.70 (dt, J1¼7.5 Hz, J2¼7.5 Hz, 2H), 1.58–1.48
(m, 2H, Z-isomer), 1.37–1.22 (m, 2H, E-isomer), 0.91 (t,
J¼7.5 Hz, 3H). 13C NMR (75 MHz, CDCl3): d 173.04 (s),
140.59 (d), 140.54 (d), 134.64 (s), 114.28 (t), 42.02 (d),
35.11 (t), 20.97 (t), 14.48 (q), 13.99 (q) (E-isomer); 173.91
(s), 140.93 (d), 138.13 (d), 135.14 (s), 114.72 (t), 46.60 (d),
35.99 (t), 20.59 (t), 16.06 (q), 14.03 (q) (Z-isomer). HRMS:
m/z calcd for C10H16O2 [M+]: 168.1150; found: 168.1143.
3.3.6. (2E,4E)-2-Ethylidene-5-phenylpent-4-enoic acid
(5f).15 Yield: 78%; colorless solid; 2E,4E/2Z,4E>97:3; mp
78–80 ꢁC. IR (KBr, n/cmꢀ1): w3000, 1676, 1420, 1287,
1
1203, 961, 742. H NMR (400 MHz, CDCl3): d 12.15 (br,
1H), 7.34–7.16 (m, 5H), 7.14 (q, J¼6.9 Hz, 1H), 6.39 (d,
J¼16.0 Hz, 1H), 6.20 (dt, J1¼16.0 Hz, J2¼6.0 Hz, 1H),
3.23 (d, J¼6.4 Hz, 2H), 1.90 (d, J¼7.2 Hz, 3H). 13C NMR
(125 MHz, CDCl3): d 172.68 (s), 141.58 (d), 137.45 (s),
130.53 (d), 130.51 (s), 128.44 (d), 127.04 (d), 126.82 (d),
126.08 (d), 29.39 (t), 14.59 (q). HRMS: m/z calcd for
C13H14O2 [M+]: 202.0994; found: 202.0994.
3.3.7. (2E,3Z)-2-Ethylidene-3-phenylpent-3-enoic acid
(6). Yield: 78%; colorless solid; 2E,3Z/2Z,3Z>93:7; mp
106–109 ꢁC. IR (KBr, n/cmꢀ1): w3000, 1689, 1427, 1288,
1
959, 765, 700. H NMR (300 MHz, CDCl3): d 7.36 (q,
J¼7.2 Hz, 1H), 7.31–7.20 (m, 5H), 6.28 (q, J¼6.6 Hz,
1H), 1.78 (d, J¼6.9 Hz, 3H), 1.71 (d, J¼6.9 Hz, 3H). 13C
NMR (75 MHz, CDCl3): d 170.68 (s), 143.90 (d), 140.01
(s), 134.73 (s), 131.33 (s), 128.43 (d), 127.01 (d), 126.60
(d), 125.57 (d), 15.52 (t), 15.40 (t). HRMS: m/z calcd for
C13H14O2 [M+]: 202.0994; found: 202.0997.
3.3.3. 2-Ethylidene-3-vinylnon-6-enoic acid (5c). Yield:
84%; colorless oil; E/Z¼83:17. IR (neat, n/cmꢀ1): w3000,
1
2966, 1680, 1634, 1417, 1269, 914. H NMR (300 MHz,
CDCl3): d 7.05 (q, J¼7.2 Hz, 1H, E-isomer), 6.13 (q,
J¼7.5 Hz, 1H, Z-isomer), 6.09 (ddd, J1¼16.5 Hz,
J2¼10.2 Hz, J3¼7.5 Hz, 1H, E-isomer), 5.82 (ddd,
J1¼16.5 Hz, J2¼10.2 Hz, J3¼7.5 Hz, 1H, Z-isomer), 5.38
(dt, J1¼10.8 Hz, J2¼5.4 Hz, 1H), 5.32 (dt, J1¼10.5 Hz,
J2¼5.1 Hz, 1H), 5.01 (dd, J1¼17.4 Hz, J2¼1.5 Hz, 1H),
4.99 (dd, J1¼10.2 Hz, J2¼0.9 Hz, 1H), 3.37 (dt,
J1¼7.5 Hz, J2¼7.5 Hz, 1H, E-isomer), 3.15 (dt, J1¼7.5 Hz,
J2¼7.5 Hz, 1H, Z-isomer), 2.07–1.95 (m, 4H), 1.88 (d,
J¼7.2 Hz, 3H), 1.80–1.72 (m, 2H), 0.96 (d, J¼7.5 Hz, 3H).
13C NMR (75 MHz, CDCl3): d 173.12 (s), 140.82 (d),
140.22 (d), 134.48 (s), 132.12 (d), 128.63 (d), 114.61 (t),
41.74 (d), 32.99 (t), 25.27 (t), 20.58 (t), 14.45 (q), 14.33 (q)
(E-isomer); 173.96 (s), 140.61 (d), 138.44 (d), 134.89 (s),
132.20 (d), 128.51 (d), 115.05 (t), 46.57 (d), 33.77 (t),
25.04 (t), 20.60 (t), 16.09 (q), 14.37 (q) (Z-isomer). HRMS:
m/z calcd for C13H20O2 [M+]: 208.1463; found: 208.1454.
3.3.8. 3,7-Dimethyl-2,3-divinyloct-6-enoic acid (4h).
Yield: 79%; colorless oil; de 50%. IR (neat, n/cmꢀ1):
w3000, 2972, 1701, 1414, 1377, 1259, 918. 1H NMR
(400 MHz, CDCl3): d 5.90 (dd, J1¼17.4 Hz, J2¼11.5 Hz,
1H), 5.88–5.78 (m, 1H), 5.21 (dd, J1¼10.1 Hz, J2¼1.8 Hz,
1H), 5.15 (dd, J1¼16.5 Hz, J2¼1.8 Hz, 1H), 5.11 (dd,
J1¼10.5 Hz, J2¼1.4 Hz, 1H), 5.06 (t, J¼7.3 Hz, 1H), 4.97
(dd, J1¼17.4 Hz, J2¼1.4 Hz, 1H), 2.92 (d, J¼9.6 Hz, 1H),
1.95–1.82 (m, 2H), 1.67 (s, 3H), 1.57 (s, 3H), 1.53–1.44
(m, 1H), 1.38–1.25 (m, 1H), 1.07 (s, 3H). Major isomer:
13C NMR (100 MHz, CDCl3): d 179.19 (s), 143.18 (d),
133.08 (d), 131.57 (s), 124.45 (d), 119.65 (t), 114.18 (t),
60.11 (d), 42.33 (s), 39.18 (t), 25.77 (q), 22.71 (t), 19.03
(q), 17.66 (q). HRMS: m/z calcd for C14H22O2 [M+]:
222.1620; found: 222.1625.
3.3.9. (E)-5-Methyl-2-vinylhexa-2,4-dienoic acid (9).
Yield: 47%; colorless solid; mp 102–104 ꢁC. IR (KBr,
n/cmꢀ1) w3000, 2972, 1675, 1433, 1280, 920, 706. 1H
NMR (300 MHz, CDCl3): d 7.62 (d, J¼12.0 Hz, 1H), 6.59
(dd, J1¼17.7 Hz, J2¼11.7 Hz, 1H), 6.40 (d, J¼12.0 Hz,
1H), 5.69 (dd, J1¼17.7 Hz, J2¼1.8 Hz, 1H), 5.44 (d,
J¼11.7 Hz, 1H), 1.95 (s, 6H). 13C NMR (75 MHz, CDCl3):
d 172.82 (s), 148.25 (s), 137.77 (d), 129.00 (d), 124.79 (s),
3.3.4. (E)-2-Ethylidene-4-methylenenonanoic acid (5d).
Yield: 78%; colorless oil; E/Z>97:3. IR (neat, n/cmꢀ1):
w3000, 2932, 1686, 1644, 1420, 1290, 1225. 1H NMR
(300 MHz, CDCl3): d 7.16 (q, J¼7.2 Hz, 1H), 4.74 (d,
J¼1.8 Hz, 1H), 4.61 (d, J¼1.8 Hz, 1H), 3.02 (s, 2H), 2.04
(t, J¼7.5 Hz, 2H), 1.82 (d, J¼7.2 Hz, 3H), 1.54–1.44 (m,
2H), 1.35–1.27 (m, 4H), 0.91 (t, J¼6.3 Hz, 3H). 13C NMR

9612
Y. Li et al. / Tetrahedron 63 (2007) 9605–9613
121.39 (d), 120.23 (t), 27.15 (q), 19.12 (q). HRMS: m/z calcd
for C9H12O2 [M+]: 152.0837; found: 152.0840.
J1¼15.0 Hz, J2¼7.2 Hz, 1H), 6.14–6.04 (m, 1H), 5.38 (dt,
J1¼10.5 Hz, J2¼6.6 Hz, 1H), 5.33 (dt, J1¼10.8 Hz,
J2¼6.9 Hz, 1H), 5.03 (dd, J1¼19.2 Hz, J2¼1.5 Hz, 1H),
5.02 (dd, J1¼10.2 Hz, J2¼1.5 Hz, 1H), 3.46 (dt,
J1¼7.2 Hz, J2¼7.2 Hz, 1H, 2E,4E-isomer), 3.23 (dt,
J1¼7.2 Hz, J2¼7.2 Hz, 1H, 2E,4Z-isomer), 2.08–1.97 (m,
4H), 1.90 (d, J¼6.6 Hz, 3H), 1.81 (dq, J1¼7.8 Hz,
J2¼7.8 Hz, 2H), 0.95 (t, J¼7.5 Hz, 3H). 13C NMR
(75 MHz, CDCl3): d 173.56 (s), 142.09 (d), 140.44 (d),
140.33 (d), 132.21 (d), 129.91 (s), 128.55 (d), 126.92 (d),
114.63 (t), 42.17 (d), 33.37 (t), 25.08 (t), 20.50 (t), 19.04
(q), 14.37 (q) (2E,4E-isomer); 173.64 (s), 141.50 (d),
138.54 (d), 136.68 (d), 132.17 (d), 132.16 (s), 129.22 (d),
124.21 (d), 115.03 (t), 46.08 (d), 33.98 (t), 25.35 (t), 20.59
(t), 18.64 (q), 13.97 (q) (2E,4Z-isomer). HRMS: m/z calcd
for C15H22O2 [M+]: 234.1620; found: 234.1629.
3.4. General procedure for Ireland–Claisen
rearrangement of 10
To a solution of allyl hexa-3,5-dienoate 10 (containing minor
amount of the respective allyl hexa-2,4-dienoate 11)
(8 mmol) in acetonitrile (10 mL/g of 10) were added DBU
(2.44 g, 16 mmol) and TMSCl (2.61 g, 24 mmol). The mix-
ture was heated under reflux and stirred for 4.5–8.5 h, and
then concentrated under reduced pressure. The residue was
dissolved in ether (30 mL) and washed with 3 M hydrogen
chloride (15 mL) and brine, and dried with anhydrous
MgSO4. Concentration under reduced pressure and silica
gelcolumnchromatography(hexane/acetone¼10:1)afforded
13b–c as colorless oils and 13a, 13d–f as colorless solids.
3.4.4. (2E,4E)-2-((E)-But-2-enylidene)-4-methylenenona-
noic acid (13d). Yield: 80%; colorless solid; 2E,4E/
2E,4Z>97:3; mp 56–58 ꢁC. IR (KBr, n/cmꢀ1): w3000,
3.4.1. 2-Allylhexa-2,4-dienoic acid (13a). Yield: 91%; col-
orless solid; 2E,4E/2E,4Z>90:10; mp 58–60 ꢁC. IR (neat,
n/cmꢀ1): w3000, 2937, 1687, 1425, 1258, 975, 912. 1H
NMR (400 MHz, CDCl3): d 7.75 (d, J¼11.4 Hz, 1H,
2E,4Z-isomer), 7.36 (d, J¼11.4 Hz, 1H, 2E,4E-isomer),
6.35 (dd, J1¼14.9 Hz, J2¼11.4 Hz, 1H), 6.20 (dq,
J1¼15.1 Hz, J2¼6.9 Hz, 1H), 6.03–5.88 (m, 1H, 2E,4E-
isomer), 5.90–5.80 (m, 1H, 2E,4Z-isomer), 5.05 (dd,
J1¼18.8 Hz, J2¼1.4 Hz, 1H), 5.01 (dd, J1¼9.6 Hz,
J2¼1.4 Hz, 1H), 3.17 (d, J¼8.0 Hz, 2H), 1.90 (d,
J¼6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3): d 173.98
(s), 142.30 (d), 140.52 (d), 135.43 (d), 127.18 (d), 125.87
(s), 115.38 (t), 30.38 (t), 19.14 (q) (2E,4E-isomer); 173.96
(s), 143.50 (d), 139.32 (d), 136.06 (d), 128.20 (d), 124.53
(s), 115.48 (t), 30.48 (t), 14.15 (q) (2E,4Z-isomer). HRMS:
m/z calcd for C9H12O2 [M+]: 152.0837; found: 152.0841.
1
1697, 1442, 1264, 883, 637. H NMR (300 MHz, CDCl3):
d 7.42 (d, J¼11.1 Hz, 1H), 6.29 (dd, J1¼16.1 Hz,
J2¼11.1 Hz, 1H), 6.22 (dq, J1¼15.0 Hz, J2¼6.6 Hz, 1H),
4.76 (s, 1H), 4.62 (s, 1H), 3.09 (s, 2H), 2.06 (t, J¼7.8 Hz,
2H), 1.89 (d, J¼6.9 Hz, 3H), 1.55–1.45 (m, 2H), 1.34–
1.28 (m, 4H), 0.91 (t, J¼6.6 Hz, 3H). 13C NMR (75 MHz,
CDCl3): d 173.90 (s), 147.16 (s), 142.57 (d), 140.06 (d),
127.41 (d), 126.11 (s), 109.38 (t), 36.74 (t), 32.46 (t),
31.60 (t), 27.42 (t), 22.59 (t), 19.02 (q), 14.09 (q). HRMS:
m/z calcd for C14H22O2 [M+]: 222.1620; found: 222.1620.
3.4.5. (2E,4E)-2-(3-Methylbut-2-enyl)hexa-2,4-dienoic
acid (13e).16 Yield: 85%; white solid; 2E,4E/2E,4Z>97:3;
mp 76–77 ꢁC. IR (KBr, n/cmꢀ1): w3000, 2967, 1674,
1426, 1307, 1258, 972. 1H NMR (300 MHz, CDCl3):
d 7.28 (d, J¼11.1 Hz, 1H), 6.41 (dd, J1¼15.3 Hz,
J2¼11.1 Hz, 1H), 6.17 (dq, J1¼15.0, J2¼6.9 Hz, 1H), 5.06
(t, J¼6.9 Hz, 1H), 3.09 (d, J¼6.6 Hz, 2H), 1.90 (d,
J¼6.9 Hz, 3H), 1.73 (s, 3H), 1.69 (s, 3H). 13C NMR
(75 MHz, CDCl3): d 173.85 (s), 140.86 (d), 139.67 (d),
132.40 (s), 127.89 (s), 127.29 (d), 121.83 (d), 25.73 (t),
25.65 (q), 19.08 (q), 17.92 (q). HRMS: m/z calcd for
C11H16O2 [M+]: 180.1150; found: 180.1144.
3.4.2. 2-(Hex-1-en-3-yl)hexa-2,4-dienoic acid (13b).
Yield: 81%; colorless oil; 2E,4E/2E,4Z¼72:28. IR (neat,
n/cmꢀ1): w3000, 1654, 1413, 1299, 1177, 908, 767, 682.
1H NMR (300 MHz, CDCl3): d 7.71 (d, J¼11.1 Hz, 1H,
2E,4Z-isomer), 7.34 (d, J¼11.1 Hz, 1H, 2E,4E-isomer),
6.49 (dd, J1¼14.8 Hz, J2¼11.4 Hz, 1H), 6.19 (dq,
J1¼14.8 Hz, J2¼6.6 Hz, 1H), 6.14–6.04 (m, 1H), 5.03 (dd,
J1¼20.1 Hz, J2¼1.2 Hz, 1H), 5.00 (dd, J1¼10.2 Hz,
J2¼1.2 Hz, 1H), 3.46 (dt, J1¼7.2 Hz, J2¼7.2 Hz, 1H,
2E,4E-isomer), 3.23 (dt, J1¼7.2 Hz, J2¼7.2 Hz, 1H,
2E,4Z-isomer), 1.91 (d, J¼6.6 Hz, 3H), 1.72 (dt,
J1¼7.8 Hz, J2¼7.8 Hz, 2H), 1.60–1.47 (m, 2H, 2E,4Z-iso-
mer), 1.35–1.25 (m, 2H, 2E,4E-isomer), 0.91 (t, J¼7.2 Hz,
3H). 13C NMR (75 MHz, CDCl3): d 173.79 (s), 141.90 (d),
140.73 (d), 140.21 (d), 130.26 (s), 126.95 (d), 114.43 (t),
42.43 (d), 35.53 (t), 21.02 (t), 19.02 (q), 14.02 (q) (2E,4E-
isomer); 173.71 (s), 141.35 (d), 138.38 (d), 136.20 (d),
132.27 (s), 124.27 (d), 114.69 (t), 46.07 (d), 36.23 (t),
20.61 (t), 18.62 (q), 13.99 (q) (2E,4Z-isomer). HRMS: m/z
calcd for C12H18O2 [M+]: 194.1307; found: 194.1310.
3.4.6. (2E,4E)-2-(2-Cyclohexylideneethyl)hexa-2,4-di-
enoic acid (13f). Yield: 87%; colorless solid; 2E,4E/
2E,4Z>98:2; mp 99–101 ꢁC. IR (KBr, n/cmꢀ1): 2915,
1
1676, 1635, 1424, 1313, 1256, 975. H NMR (400 MHz,
CDCl3): d 7.25 (d, J¼11.4 Hz, 1H), 6.40 (dd, J1¼16.5 Hz,
J2¼11.4 Hz, 1H), 6.15 (dq, J1¼14.7 Hz, J2¼6.9 Hz, 1H),
4.99 (t, J¼7.4 Hz, 1H), 3.10 (d, J¼6.9 Hz, 2H), 2.25 (t,
J¼5.0 Hz, 2H), 2.04 (t, J¼6.0 Hz, 2H), 1.89 (d, J¼6.8 Hz,
3H), 1.55–1.51 (m, 6H). 13C NMR (100 MHz, CDCl3):
d 173.83 (s), 140.89 (d), 140.31 (s), 139.65 (d), 128.09 (s),
127.38 (d), 118.40 (d), 37.19 (t), 28.96 (t), 28.60 (t), 27.77
(t), 26.98 (t), 24.84 (t), 19.16 (q). HRMS: m/z calcd for
C14H20O2 [M+]: 220.1463; found: 220.1470.
3.4.3. (2E,6Z)-2-((E)-But-2-enylidene)- and (2E,6Z)-2-
((Z)-but-2-enylidene)-3-vinylnon-6-enoic acid (13c).
Yield: 79%; colorless oil; 2E,4E/2E,4Z¼88:12. IR (neat,
n/cmꢀ1): w3000, 2964, 1681, 1637, 1416, 1251, 971, 915,
Acknowledgements
1
730. H NMR (300 MHz, CDCl3): d 7.71 (d, J¼11.7 Hz,
1H, 2E,4Z-isomer), 7.34 (d, J¼11.4 Hz, 1H, 2E,4E-isomer),
6.50 (dd, J1¼15.9 Hz, J2¼6.6 Hz, 1H), 6.18 (dq,
Y.L., R.W., and Q.W. are grateful to the Givaudan Schweiz
AG for financial support under the Discovery-Project (No.

Y. Li et al. / Tetrahedron 63 (2007) 9605–9613
9613
Kobayashi, M.; Masumoto, K.; Nakai, E.; Nakai, T.
Tetrahedron Lett. 1996, 37, 3005; Koch, G.; Janser, P.;
Kottirsch, G.; Romero-Giron, E. Tetrahedron Lett. 2002, 43,
4837.
04174). The diligent assistance of Mr. Yongjun Wang
(Spring 2006) as undergraduate research participant is
much appreciated.
6. (a) Hoye, T. R.; Magee, A. S.; Trumper, W. S. Synth. Commun.
1982, 12, 183; (b) Lombardo, L. Tetrahedron Lett. 1985, 26,
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