Indium-mediated Reformatsky-Claisen rearrangement

Article abstract of DOI:10.1016/j.tet.2011.03.079

A new variant of the Reformatsky-Claisen rearrangement is described. The reaction of substituted allyl α-bromoacetates with indium and indium(III) chloride under ultrasonication provides a general entry into the functionalized synthon.

Full text of DOI:10.1016/j.tet.2011.03.079

Tetrahedron 67 (2011) 3659e3667
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Indium-mediated ReformatskyeClaisen rearrangement
*
Jun Ishihara , Yuki Watanabe, Noriko Koyama, Yukihiro Nishino, Keisuke Takahashi,
*
Susumi Hatakeyama
Nagasaki University, Graduate School of Biomedical Sciences, 1-14 Bunkyo-machi, Nagasaki 852-8521, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 1 March 2011
Received in revised form 23 March 2011
Accepted 23 March 2011
Available online 30 March 2011
A new variant of the ReformatskyeClaisen rearrangement is described. The reaction of substituted allyl
a
-bromoacetates with indium and indium(III) chloride under ultrasonication provides a general entry
into the functionalized synthon.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Claisen rearrangement
ReformatskyeClaisen rearrangement
Indium chloride
1. Introduction
for the indium-mediated ReformatskyeClaisen rearrangement as
well as the mechanistic insight of the reaction.
Development of new methods for the stereoselective carbone
carbon bond formation has been important in the creation of useful
molecules, such as drugs and other chemical entities. The [3,3]-sig-
matropic rearrangements are reliable for selective bond formation,
inparticular, theClaisenrearrangementisoneof themostcompetent
methodstoprovideusefulbuildingblocksforthesynthesisofnatural
products.1 The versatile utilities of their products prompted the
development of a considerable number of variants of the Claisen
Zn
O
PhH, 80 °C
Br
(1)
O
COOH
100%
Zn, TBSCl
COOH
O
THF, HMPA
(2)
O
rearrangement.2 For instance, the rearrangement of allyl
a-bro-
reflux
73%
Br
moacetates with zinc dust was referred as the ReformatskyeClaisen
rearrangement (Scheme 1, Eq. 1).3 This variant of the Claisen
rearrangement also proceeds in the presence of a silylating agent,
in which the silyl ketene acetal is the most likely intermediate
(Scheme 1, Eq. 2).4 In the course of our synthetic study of natural
products, we needed to explore a Claisen rearrangement executable
under non-basic conditions. Therefore, we took a great interest in the
ReformatskyeClaisen rearrangement. The IrelandeClaisen rear-
rangementhasbeenwidelyusedinthesynthesis ofa diverserangeof
natural products,2a,4,5 whereas only several examples of zinc-
mediated ReformatskyeClaisen rearrangement have been utilized
sofar.6 Themainreasonbehindencumberingthedevelopmentof the
ReformatskyeClaisen rearrangement arises from the accompanying
side reaction, which gives the corresponding protonated products.
Recently we reported IneInCl3 is effective for the Reformatskye
Scheme 1. Pioneer works of ReformatskyeClaisen rearrangement.
2. Results and discussion
2.1. Investigation of ReformatskyeClaisen rearrangement of 1
Initially, we examined the ReformatskyeClaisen rearrangement
of a-bromocyclohexanecarboxylate 1 by the conventional method.
However, when 1 was treated with Zn and TMSCleEt3N in THF, the
protonated product 2 was obtained exclusively (Scheme 2). The
scope of the Reformatsky reaction has been considerably extended
bythe developmentofmetalsotherthanzinc. For instance, indium is
knowntoreact readilywith a-halo esterstoinducethe Reformatsky-
type reaction.8 Recently Baba demonstrated that In(I)X is effective
for the Reformatsky-type reactions of ketones and esters to afford
Claisen rearrangement, but this method is feasible only for a-bro-
moisobutyrate derivatives.7 Herein we report an improved method
b
-hydroxyketones and b
-hydroxyesters diastereoselectively.9 These
reports prompted us to investigate the indium-mediated rear-
rangement of 1. In fact, we gratifyingly found that reaction of 1 with
* Corresponding authors. E-mail address: jishi@nagasaki-u.ac.jp (J. Ishihara).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.03.079

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J. Ishihara et al. / Tetrahedron 67 (2011) 3659e3667
IneInCl3 in the presence of TMSCl and Et3N in MeCN under ultra-
sonication at 10e30 ꢀC furnished 3 in 88% yield.
product 9 was again generated (entry 3). On the other hand, the
reaction in THF afforded 10 in 32% yield, but the major product was
9 (entry 4). By the use of a 4:1 mixture of THF and DMPU as a sol-
vent, the yield of the rearranged product 10 was much improved
(entry 5). In addition, we were pleased to find that the reaction in
a 1:1 mixture of THF and DMPU brought us the satisfying result,
giving 10 in 84% yield together with 9 (16% yield) (entry 6). The use
of DMPU alone led to the small decline of the yield of 10 (entry 7). In
contrast, treatment of 8 with indium(III) triflate and indium in
THFeDMPU (1:1) afforded 9 quantitatively (entry 8). The combi-
nation of indium(III) bromide and indium was also found to be
effective in the rearrangement (entry 9), providing 10 in 83% yield,
whereas indium(I) chloride turned out to be ineffective (entry 10).
O
O
Zn (2 eq), TMSCl (2.5 eq),
Et3N (2.5 eq)
Br
H
O
O
THF, rt
reflux
(100%)
1
2
In (2 eq), InCl3 (2 eq),
TMSCl (4 eq), Et3N (4 eq),
COOH
1
MeCN, ultrasonication
(88%)
3
Scheme
2. Preliminary
works
of
indium-mediated
ReformatskyeClaisen
rearrangement.
2.4. Indium-mediated ReformatskyeClaisen rearrangement
of various substrates
2.2. The effect of silylating agents
We next turned our attention to the reaction of various a-bro-
The rearrangement of bromoisobutyrate derivative 4 also pro-
ceeded smoothly to afford the rearranged product 5 in an excellent
yield (Scheme 3). Baldwin and Walker reported that the zinc-me-
diated ReformatskyeClaisen rearrangement proceeded smoothly
without a silylating agent; however, the use of TMSCl and Et3N is
requisite for the rearrangement in our case. For instance, exposure
of 4 to In and InCl3 without TMSCl and Et3N furnished the homo-
coupling compound 6 in 26% yield, along with the protonated
compound 7 and the starting material 4 in 7% and 67% yields. On
the other hand, the indium-mediated reaction of 4 with TMSCl in
the absence of Et3N resulted in a complex mixture.
mopropionate derivatives, which are readily prepared by acylation
of allylic alcohols with 2-bromoisobutyryl bromide or 2-bromo-
propionyl bromide (Table 2). Most reactions afforded rearranged
products along with the protonated compounds
The aromatic compounds 11, 13, 15, and 17 underwent rear-
rangement to carboxylic acids 12, 14, 16, and 18, in moderate to
excellent yields (entries 1e4). However, the diastereoselectivities
were poor (entries 2 and 4). In the case of 11 and 15, the rear-
rangement took place in MeCN rather smoothly, whereas the
rearrangement of 13 and 17 proceeded in THFeDMPU (1:1) but not
in MeCN. Interestingly, 4-nitrocinnamyl derivative 19 did not give
the rearranged product 20 at all (entry 5). On the other hand, the
reactions of aliphatic substrates 21e29 brought about the Refor-
matskyeClaisen rearrangement successfully to give highly func-
tionalized carboxylic acids 22e30 (entries 6e10). In fact, when the
indium-mediated reaction of bulky 2-methylbut-3-en-2-yl esters
21 and 23 were performed, compounds 22 and 24 were yielded in
63% and 62% yields, respectively. Notably, the rearrangement of 25
can install the contiguous quaternary centers, giving compound 26
in 91% yield. In addition, propargyl ester 29 was converted to
1,1-disubstituted allenic compound 30 in 60% yield. In contrast, the
In (2 eq), InCl3 (2 eq)
TMSCl (8 eq), Et3N (8 eq)
O
Br
COOH
96%
O
MeCN, ultrasonication
4
5
O
In (2 eq), InCl3 (2 eq)
MeCN, ultrasonication
+
4
O
2
reactions of the cyclic
a-bromoisobutyrate 31 and 33 gave the
6
26%
O
corresponding carboxylic acids 32 and 34 in low yields. These
disappointing results can be rationalized by the transition states,
which involve highly strained boat forms.
O
+ 4 67%
To illustrate the application of the indium-mediated rearrange-
ment to the complicated substrates,
and 39 were prepared by esterification of cinnamyl alcohol and the
corresponding
-bromocarboxylic acids,10 which were available in
a single step (NaNO2, KBr, aq H2SO4) from
-phenylalanine,11a
-valine,11b and -isoleucine.11c It turned out that indium-mediated
a-bromocarboxylates 35, 37,
7
7%
a
Scheme 3. Effect of silylating agents.
L
L
L
2.3. Indium-mediated ReformatskyeClaisen rearrangement
of -bromopropionate
rearrangements of 35, 37, and 39 provided functionalized carboxylic
acids 36, 38, and 40 in 53%, 63%, and 73% yields, respectively, though
the diastereoselectivities were not satisfying (Table 3). For an ex-
tensive survey of the reactions of dialkylated bromoacetates,12 the
indium-mediated reaction of 41 gave carboxylic acid 42 in 77% yield,
whereas the reaction of 43 afforded the rearrangement product 44
in low yield (entries 4 and 5). The diastereoselectivities of both
reactions were again poor. It should be mentioned that the rear-
rangement of chiral 35 afforded racemic compound 36. This result
implies the reaction did not proceed through a radical intermediate,
which was derived from organoindium species, but [3,3]-sigma-
tropic rearrangement of the ketene acetal (Table 3).
a
To probe the generality of the indium-mediated reaction,
-bromopropionate 8 was next subjected to the optimized reaction
a
conditions. As Table 1 illustrates, the reaction of 8 in MeCN was
unsuccessful, resulting in the exclusive production of unwanted
propionate 9 (entry 1). When MeCN-d3 was used as a solvent,
deuteration product 9a was obtained in 63% yield (entry 2). This
result suggested that a hydrogen atom installed in 9 would be
delivered from MeCN, affording 9a. It should be mentioned that this
condition allowed the production of desired 10 in 37% yield pre-
sumably because of a heavy-atom effect. Considered that the for-
mation of a silyl ketene acetal would compete with the protonation
of an enolate, we next investigated several aprotic polar solvents
and indium species for the reaction of 8. Pivalonitrile, having less
acidic methyl group, was utilized as a solvent; however, only
2.5. The reaction of acyloxy and base-sensitive compounds
The most intriguing feature of the ReformatskyeClaisen rear-
rangement is the feasibility of utilizing base-sensitive substrates.

Table 1
Investigation of the ReformatskyeClaisen rearrangement of a-bromopropionate 8
Entry
Indium source
Solvents
Yielda (%)
9
10 (diastereomeric ratiob)
1
2
3
4
5
6
7
8
9
In (2 equiv), InCl3 (2 equiv)
In (2 equiv), InCl3 (2 equiv)
In (2 equiv), InCl3 (2 equiv)
In (2 equiv), InCl3 (2 equiv)
In (2 equiv), InCl3 (2 equiv)
In (2 equiv), InCl3 (2 equiv)
In (2 equiv), InCl3 (2 equiv)
In (2 equiv), In(OTf)3 (2 equiv)
In (2 equiv), InBr3 (2 equiv)
InCl (2eq.)
MeCN
MeCN-d3
Me3CCN
THF
THF-DMPU (4:1)
THF-DMPU (1:1)
DMPU
THF-DMPU (1:1)
THF-DMPU (1:1)
THF-DMPU (1:1)
100
63 (9a)
80
68
33
16
18
100
17
27
37 (1.9: 1)
32 (2:1)
60 (2:1)
84 (1.5:1)
77 (1.5:1)
83 (2:1)
22 (2.3:1)
10
a
Isolated yields.
b
Determined by 1H NMR spectra. The relative structures of the diastereomeric isomers were not determined.
Table 2
ReformatskyeClaisen rearrangement of various substrates 11e33
Entry
Substrates
R
Yieldc (%)
Rearranged products (diastereomeric ratiod)
Protonated products
1a
2b
3a
4b
11
13
15
17
Me
H
12
14
16
18
94
11a
13a
15a
17a
NDe
32
61 (1.6:1)
71
Me
H
25
54 (1.4:1)
44
5a
19
Me
20
NDe
19a
NDe
6a
21
23
25
27
29
Me
H
22
24
26
28
30
63
62
91
34
60
21a
23a
25a
27a
29a
NDe
24
7b
8a
Me
H
NDe
62
9b
10a
36
11a
31
33
32
34
15
35
31a
33a
36
56
12a
a
The reactions were carried out by using In (2 equiv), InCl3 (2 equiv), TMSCl (8 equiv), and Et3N (8 equiv) in MeCN under ultrasonication.
The reactions were carried out by using In (2 equiv), InCl3 (2 equiv), TMSCl (4 equiv), and Et3N (4 equiv) in THF-DMPU (1:1) under ultrasonication.
b
c
Isolated yields.
d
e
Determined by 1H NMR spectra. The relative structures of the diastereomeric isomers were not determined.
Not detected.

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J. Ishihara et al. / Tetrahedron 67 (2011) 3659e3667
Table 3
ReformatskyeClaisen rearrangement of various substrates 35e43a
Entry
Substrates
Yieldb (%)
Rearranged products (diastereomeric ratioc)
Protonated products %
1
53% (2.0:1)
63% (2.0:1)
42
2
3
27
11
73% (2.4:2.2:1.1:1.0)
4
77% (1.5:1)
22
81
5
19% (1.0:1.3)
a
The reactions were carried out by using In (2 equiv), InCl3 (2 equiv), TMSCl (4 equiv), and Et3N (4 equiv) in THF-DMPU (1:1) under ultrasonication.
Isolated yields.
b
c
Determined by 1H NMR spectra. The relative structures of the diastereomeric isomers were not determined.
The reactions of
a
-bromoisobutyrates E-45 and Z-45 under the
The results shown in Scheme 5 revealed a marked advantage
over the IrelandeClaisen rearrangement. Thus, when compound 51
was subjected to the above mentioned indium-mediated rear-
rangement conditions, the rearranged product 52 was obtained in
64% yield. In contrast, the reaction of 53 with KHMDS in the pres-
ence of TMSCl and Et3N afforded isomer 5413 in place of 52.
optimized conditions proceeded smoothly to afford 46 in 80% and
53% yields, respectively (Scheme 4). In the case of bromopropionate
47, the moderate diastereoselectivity was observed, although the
yield was not satisfying. On the other hand, the reaction of 49
afforded carboxylic acid 50 having contiguous quaternary carbons
in 66% yield. It should be noted that the acetoxy group could survive
under the reaction conditions in stark contrast to IrelandeClaisen
rearrangement.
In, InCl3
O
TMSCl, Et3N
Br
COOH
MeOOC
O
MeOOC
MeCN, ultrasonication
51
52
64%
O
O
AcO
Br
Br
KHMDS
O
O
AcO
O
a
O
TMSCl, Et3N
+
O
52
MeOOC
O
E-45
PhMe
Z-45
0%
-78 °C
70 °C
MeOOC
53
54
a
AcO
COOH
39%
80%
53%
Scheme 5. Attempted rearrangements of 51 and 53.
46
O
b
2.6. Potential for the chirality transfer of the
ReformatskyeClaisen rearrangement
AcO
AcO
COOH
AcO
AcO
O
36%
Br
(3.3:1)
COOH
47
48
An efficient chirality transfer is often observed in the Claisen
rearrangement owing to its fixed chair transition state. To dem-
onstrate a potential for the chirality transfer, the indium-mediated
rearrangement of chiral compounds E-55 and Z-55 were explored
(Scheme 6). The compounds E- and Z-55 in 98% ee were derived
from chiral benzyl glycidol in five steps.14 The ReformatskyeClaisen
rearrangement of E-55 provided S-56 in 97% ee and 69% yield, and
the reaction of Z-55 afforded R-56 in 94% ee and 35% yield. Notably,
O
a
Br
O
66%
49
50
Scheme 4. Reagents and conditions; (a) In (2 equiv), InCl3 (2 equiv), TMSCl (8 equiv),
Et3N (8 equiv), MeCN, ultrasonication; (b) In (2 equiv), InCl3 (2 equiv), TMSCl (4 equiv),
Et3N (4 equiv), THFeDMPU (1:1), ultrasonication.

J. Ishihara et al. / Tetrahedron 67 (2011) 3659e3667
3663
the significant loss of the enantiomeric purity of the substrates was
4. Experimental section
4.1. General information
not observed in these cases. These results suggest that this Claisen
rearrangement would proceed through a chair form transition state
to completely transfer the chirality of the substrate to the product.
Solvents and reagents were dried and distilled before use.
Tetrahydrofuran (THF) and toluene (PhMe) were distilled from
sodium benzophenone ketyl. CH2Cl2, pyridine, and Et3N were
distilled from CaH2. DMSO was distilled under reduced pressure
from CaH2. EtOH and MeOH were distilled from their magnesium
alkoxides. Normal reagent-grade solvents were used for flash
chromatography and extraction. All reactions were monitored by
TLC with precoated Silica gel plates (Merck, silica gel 60 F254
1.05715.25). Visualization was achieved via UV light, a 5.6% etha-
nolic p-anisaldehyde solution containing 5.6% of concentrated
H2SO4-heat, and 10% ethanolic phosphomolybdic acid solution-
heat. For flash chromatography was utilized Silica gel (YMG, silica
gel SIL-60-400/230W or Kanto Kagaku, silica gel 60N, spherical
neutral, 37563-84). Melting points were measured in open cap-
illary tubes and are uncorrected. IR spectra were obtained on
a Hitachi model 270-30 and JASCO model FT/IR-230 infrared
spectrophotometer in neat state. The 1H NMR spectra were
In, InCl3
BnO
O
TMSCl, Et3N
S
Br
Br
HOOC
HOOC
OBn
OBn
MeCN
O
H
ultrasonication
E-55
S-56
(98%ee)
69% (97%ee)
BnO
In, InCl3
O
TMSCl, Et3N
R
O
H
MeCN
ultrasonication
Z-55
R-56
(98%ee)
35% (94%ee)
Scheme 6. ReformatskyeClaisen rearrangements of E- and Z-55.
2.7. Proposed mechanism of indium-mediated
ReformatskyeClaisen rearrangement
recorded on a JEOL model AL-300 (300 MHz), a-400 (400 MHz)
and a VARIAN model Gemini 300 (300 MHz) spectrometers in
CDCl3. The 13C NMR spectra were measured on a VARIAN Gemini
300 (75 MHz), Unity plus 500 (125 MHz), and spectrometer in
As illustrated in Scheme 7, it has been reported that a mixture of
In and InCl3 generates in situ InCl(I), which readily reacts with
CDCl3. Chemical shifts (
d
) were reported with tetramethylsilane
¼7.26 ppm) as internal standards.
a
Both
-bromoacetate 57 to afford
a-In(III) intermediate 58 or
a
-In(I) 59.9
(
d
¼0.00 ppm) or CHCl3
(d
a-indium intermediates can be transformed to indium enolate
Splitting patterns were designated as ‘s, d, t, q, m, and br’; in-
dicating ‘singlet, doublet, triplet, quartet, multiplet, and broad’,
respectively. Optical rotations were recorded on JASCO model DIP-
370 and P-1020 digital polarimeters using CHCl3 as a solvent.
High-resolution mass spectra were obtained on a JEOL model JMS-
HX-110 and JMS-DX303 mass spectrometer under EI condition. All
reactions were carried out under anhydrous conditions and argon
atmosphere, unless otherwise noted.
60, which is converted to silyl ketene acetal 61 by silylation. Since
no rearrangement was observed without TMSCl and Et3N, the di-
rect rearrangement of indium enolates is unlikely. Finally, the
rearrangement of 61 proceeds to generate the corresponding car-
boxylic acid 62. The rearrangement of
rivatives (R3, R4¼Me) smoothly proceeded in MeCN, whereas the
reaction of
-bromopropionates (R3¼Me, R4¼H) in MeCN afforded
a-bromoisobutyrate de-
a
only the protonated products. These results can be rationalized as
follows. Compared to enolate 60 (R3, R4¼Me) derived from iso-
butyrate, the enolate 60 derived from the propionate derivative
(R3¼Me, R4¼H) is more nucleophilic, so that it easily undergoes
protonation with MeCN to form protonated product. The deutera-
tion experiment of 8 in MeCN-d3 (Table 1, entry 2) clearly supported
that the rearrangement would proceed, provided that the pro-
tonation of enolate is relatively slow.
4.2. Typical procedure under condition a
A mixture of TMSCl (0.7 mL, 5.5 mmol) and Et3N (0.7 mL,
5.0 mmol) was centrifuged at 3000 rpm for 5 min. The supernatant
(0.72 mL, containing 2.8 mmol of TMSCl and 2.6 mmol of Et3N) was
added to a mixture of dried InCl3 (156 mg, 0.72 mmol) and In
(81 mg, 0.72 mmol) in CH3CN (2 mL). To a stirred mixture was
added a solution of 4 (100 mg, 0.35 mmol) in CH3CN (3 mL) and the
reaction mixture was stirred at 10e30 ꢀC for 3 h under ultra-
sonication. The stirring mixture was diluted with satd NH4Cl
(4 mL), and the aqueous layer was extracted with AcOEt (30 mLꢁ3).
Drying over MgSO4, concentration, and chromatography (SiO2 15 g,
hexaneeEtOAc, 8:1) afforded 5 (69 mg, 0.34 mmol, 96%).
In + InCl3
R2
O
R2
O
R2
O
InCl
InCl
Br
InBrCl
R4
In
R1
O
R1
O
R1
O
R4
R4
R3
R3
R3
57
58
59
InBrCl2
R1,R2= H, alkyl,aryl
R3,R4= H, alkyl,aryl
Et3N
Me3SiCl
rearrangement
SiMe3
R4
InX
n
R1 R2
R2
O
R2
O
R4
COOH
4.3. Typical procedure under condition b
R1
O
R1
O
R3 R4
R3
R3
InClX
n
n = 0 or 2
62
61
60
A mixture of TMSCl (0.34 mL, 2.7 mmol) and Et3N (0.34 mL,
2.5 mmol) was centrifuged at 3000 rpm for 5 min. The supernatant
(0.34 mL, containing 1.4 mmol of TMSCl and 1.3 mmol of Et3N) was
added to a mixture of dried InCl3 (152 mg, 0.69 mmol) and In
(79 mg, 0.69 mmol) in THF (1.7 mL). To a stirred mixture was added
a solution of 8 (92 mg, 0.34 mmol) in DMPU (1.7 mL) and the re-
action mixture was stirred at 10e30 ꢀC for 4 h under ultra-
sonication. The stirring mixture was diluted with satd NH4Cl
(15 mL) and extracted with AcOEt (15 mLꢁ2). Combined organic
extracts were washed with 1M HCl (15 mL), dried over MgSO4, and
concentrated. The residue was purified by chromatography (SiO2
11 g, hexaneeEtOAc, 5:1 to 1:1) afforded 10 (61 mg, 0.29 mmol,
84%) and 9 (11 mg, 0.05 mmol, 16%).
Scheme 7. Proposed mechanism of ReformatskyeClaisen rearrangement.
3. Conclusion
In conclusion, the indium-mediated ReformatskyeClaisen
rearrangement of -bromoacetate derivatives has been described.
a
This method was found to be feasible to install the quaternary
centers in product. The feasibility of this method for base-sensitive
substrates makes it complementary to the IrelandeClaisen rear-
rangement, and allows a simple access to valuable building blocks
for the synthesis of complex natural products. Further exploration
of this chemistry is underway in our laboratory.

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J. Ishihara et al. / Tetrahedron 67 (2011) 3659e3667
4.4. Preparation of substrates and indium-mediated
4.83 (d, J 6.3 Hz, 2H), 4.42 (q, J 7.0 Hz, 1H), 1.86 (d, J 7.0 Hz, 3H); 13
C
ReformatskyeClaisen rearrangements
NMR (100 MHz, CDCl3) d 170.3, 136.3, 135.2, 128.5, 127.0,122.5, 66.8,
40.3, 22.0; HRMS (EI) m/z 91, 115, 117, 143, 189 (100), 268 (Mþ);
4.4.1. Allyl 1-bromocyclohexanecarboxylate (1). A mixture of cyclo-
hexanecarboxylic acid (1.50 g, 11.7 mmol) and thionyl chloride
(1.07 mL, 14.8 mmol) was heated at 90 ꢀC for 2 h. After cooling to
room temperature, phosphorous red (18.0 mg, 0.58 mmol) was
added to the mixture. The reaction mixture was stirred at 90 ꢀC for
2 h, and 2-methyl-2-butene (2.1 mL, 19.0 mmol) was added. After
HRMS (EI) calcd for C12H1381BrO2 (Mþ) 270.0079, found 270.0087.
4.4.6. 2-Methyl-3-phenylpent-4-enoic acid (10). A white crystal; IR
(neat), nmax 2980, 1715, 1493, 1456, 1417, 1291, 919, 759, 700,
517 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d 7.33e7.17 (m, 5H), 6.06e5.90
(m,1H), 5.16e5.02 (m, 2H), 3.54 (t, J 9.4 Hz, 0.37ꢁ1H), 3.44 (t, J 9.3 Hz,
20 min, to the mixture was added allyl alcohol (0.875 ml,12.0 mmol),
0.63ꢁ1H), 2.87e2.78 (m, 1H), 1.24 (d, J 7.1 Hz, 0.37ꢁ3H), 1.00 (d, J
and stirring was continued for 2 h. The reaction mixture was diluted
with H2O (2 mL) and extracted with Et2O (50 mL). The organic ex-
tracts were dried over Mg2SO4 and concentrated. The residue was
purified by chromatography (SiO2 75 g, hexaneeAcOEt, 65:1)
afforded 1 (2.24 g, 9.0 mmol, 78%) as a brown oil; IR (neat), nmax 3455,
7.1 Hz, 0.63ꢁ3H); 13C NMR (75 MHz, CDCl3)
d 182.2, 182.6, 142.0,
140.9, 139.3, 138.1, 128.7, 128.5, 128.1, 127.6, 126.8, 126.7, 117.0, 115.8,
53.3, 53.1, 45.1, 44.7, 15.8, 15.3; HRMS (EI) m/z 190 (Mþ), 117 (100),
115; HRMS (EI) calcd for C12H14O2 (Mþ) 190.0994, found 190.0976.
3083, 2955, 2667, 1744, 1644, 1438, 822, 694, 555 cmꢂ1
(400 MHz, CDCl3)
10.4 Hz,1H), 4.72 (d, J 7.2 Hz,1H), 2.18 (br s, 4H),1.52 (m, 4H),1.26 (t, J
;
1H NMR
4.4.7. 4-Methoxycinnamyl 2-bromo-2-methylpropanoate (11). A pale
yellow oil; IR (neat), nmax 2933, 1738, 1607, 1513, 1463, 1389, 1274,
d
5.99e5.90 (m,1H), 5.40 (d, J 16.1 Hz,1H), 5.27 (d, J
1167, 1035, 965, 846 cmꢂ1 1H NMR (300 MHz, CDCl3)
; d 7.35 (d, J
7.3 Hz, 2H); 13C NMR (100 MHz, CDCl3)
d
170.4,131.4,118.2, 65.8, 37.7,
8.8 Hz, 2H), 6.87 (d, J 8.8 Hz, 2H), 6.66 (d, J 15.9 Hz, 1H), 6.17 (dt, J
6.6, 15.9 Hz, 1H), 4.81 (dd, J 1.1, 6.6 Hz, 2H), 3.82 (s, 3H), 1.96 (s, 6H);
24.5, 23.5; HRMS (EI) m/z 167 (100), 248 (Mþ); HRMS (EI) calcd for
C10H15BrO2 (Mþ) 248.0226, found 248.0235.
13C NMR (75 MHz, CDCl3)
d 171.4, 159.6, 134.4, 128.7, 127.9, 119.9,
113.9, 66.7, 55.8, 55.2, 30.7; MS (EI) m/z 312(Mþ); HRMS (EI) calcd
4.4.2. 1-Allylcyclohexanecarboxylic acid (3). A colorless oil; IR
(neat), nmax 3400 (br), 2940, 2859, 1702, 1448, 1255, 1051, 925, 844,
for C14H1779BrO3 (Mþ) 312.0361, found 312.0354.
761 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
5.81e5.70 (m, 1H), 5.08 (d, J
16.8 Hz, 1H), 5.04 (d, J 11.6 Hz, 1H), 2.28 (d, J 7.6 Hz, 2H), 1.46e1.35
(m, 2H), 1.30e1.26 (m, 2H); 13C NMR (100 MHz, CDCl3)
182.6,
4.4.8. 3-(4-Methoxyphenyl)-2,2-dimethylpent-4-enoic acid (12). A
white crystal; mp 93.0e94.5 ꢀC; IR (neat), nmax 2979, 1702, 1611,
d
1513, 1469, 1250, 1180, 1037, 922, 832, 540 cmꢂ1 1H NMR
;
133.3, 117.7, 47.1, 44.3, 43.1, 33.4, 25.3, 22.9; HRMS (EI) m/z 123, 168
(300 MHz, CDCl3) d 7.13 (d, J 8.8 Hz, 2H), 6.83 (d, J 8.8 Hz, 2H), 6.21
(Mþ); HRMS (EI) calcd for C10H16O2 (Mþ) 168.1151, found 168.1126.
(dt, J 17.6, 10.1 Hz, 1H), 5.13 (d, J 11.0 Hz, 1H), 5.12 (dd, J 0.9, 15.9 Hz,
1H), 3.71 (s, 3H), 3.59 (d, J 9.6 Hz, 1H), 1.17 (s, 3H), 1.12 (s, 3H); 13C
4.4.3. Cinnamyl 2-bromo-2-methylpropanoate (4). To a solution of
cinnamyl alcohol (100 mg, 0.75 mmol) in CH2Cl2 (2.5 mL) were
added DMAP (9.0 mg, 0.08 mmol), pyridine (0.18 mL, 2.24 mmol),
and 2-bromoisobutyryl bromide (0.14 mL, 1.12 mmol) at 0 ꢀC. After
stirring at 0 ꢀC for 1.5 h, the mixture was diluted with brine (12 mL)
and extracted with AcOEt (30 mLꢁ3). Combined organic extracts
were dried over Mg2SO4 and concentrated. The residue was puri-
fied by chromatography (SiO2 15 g, hexaneeAcOEt, 7:1) afforded 4
(229 mg, 0.81 mmol, quantitatively) as a colorless oil. IR (neat), nmax
2977,1816,1742, 1462,1389,1279, 1170, 968, 746, 693, 490 cmꢂ1; 1H
NMR (75 MHz, CDCl3) d 183.7, 158.4, 136.9, 132.0, 130.2, 117.5, 113.4,
56.5, 55.1, 46.8, 23.1, 21.8; MS (EI) m/z 234 (Mþ); HRMS (EI) calcd for
C14H18O3 (Mþ) 234.1255, found 234.1237.
4.4.9. 4-Methoxycinnamyl 2-bromopropanoate (13). A colorless oil;
IR (neat), nmax 2941, 1739, 1606, 1512, 1449, 1253, 1158, 972, 844,
747 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 7.34 (d, J 8.8 Hz, 2H), 6.86 (d, J
8.8 Hz, 2H), 6.65 (d, J 15.9 Hz,1H), 6.15 (dt, J 15.9, 6.6 Hz,1H), 4.80 (d, J
6.6 Hz, 2H), 4.40 (q, J 6.9 Hz,1H), 3.81 (s, 3H),1.85 (d, J 6.9 Hz, 3H); 13C
NMR (100 MHz, CDCl3) d 170.1, 159.7, 134.8, 128.7, 128.0, 119.8, 114.0,
NMR (300 MHz, CDCl3)
d
7.42e7.26 (m, 5H), 6.72 (d, J 15.9 Hz, 1H),
66.8, 55.3, 40.1, 21.7; HRMS (EI) m/z 91,135,147 (100), 219, 298 (Mþ);
6.30 (dt, J 6.5, 15.9 Hz, 1H), 4.83 (d, J 6.6 Hz, 2H), 1.97 (s, 6H); 13C
HRMS (EI) calcd for C13H1579BrO3 (Mþ) 298.0205, found 298.0202.
NMR (75 MHz, CDCl3) d 171.3, 136.0, 134.5, 128.5, 128.1, 126.6, 122.2,
66.4, 55.7, 30.7; HRMS (EI) m/z 282 (Mþ); HRMS (EI) calcd for
4.4.10. 3-(4-Methoxyphenyl)-2-methylpent-4-enoic acid (14). A
white crystal; IR (neat), nmax 2981, 1722, 1511, 1461, 1264, 1035, 921,
C13H1579BrO2 (Mþ) 282.0255, found 282.0247.
830, 659, 541 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 7.13 (d, J 8.8 Hz,
4.4.4. 2,2-Dimethyl-3-phenylpent-4-enoic acid (5). A white crystal;
mp 79.5e80.3 ꢀC; IR (neat), nmax 2980, 1698, 1470, 1413, 1281, 1184,
0.39ꢁ2H), 7.09 (d, J 8.8 Hz, 0.61ꢁ2H), 6.85 (d, J 8.8 Hz, 0.61ꢁ2H), 6.82
(d, J 8.8 Hz, 0.39ꢁ2H), 6.04e5.85 (m,1H), 5.13e5.00 (m, 2H), 3.77 (d, J
8.0 Hz, 3H), 3.49 (t, J 9.3 Hz, 0.39ꢁ1H), 3.40 (t, J 9.3 Hz, 0.61ꢁ1H),
2.82e2.74 (m, 1H), 1.23 (d, J 6.8 Hz, 0.39ꢁ3H), 1.00 (d, J 6.8 HZ,
926, 742, 706, 513 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d 7.20e7.31 (m,
5H), 6.25 (dt, J 17.6, 9.6 Hz, 1H), 5.15 (dd, J 0.6, 10.9 Hz, 1H), 5.14 (d, J
0.6, 17.5 Hz, 1H), 3.63 (d, J 9.6 Hz, 1H), 1.18 (s, 3H), 1.13 (s, 3H); 13C
0.61ꢁ3H); 13CNMR (100MHz,CDCl3)
d 182.0,181.4,158.4,158.2,139.6,
NMR (75 MHz, CDCl3)
d
183.9, 140.0, 136.6, 129.3, 128.0, 126.8, 117.8,
138.4,134.1,132.9,129.0,128.6,116.6,115.4,114.1,113.9,55.2,55.2, 52.3,
52.3, 45.1, 44.8,15.7,15.4; HRMS (EI) m/z 220 (Mþ),147 (100),132,115,
91, 77; HRMS (EI) calcd for C13H16O3 (Mþ) 220.1100, found 220.1087.
57.3, 46.7, 23.2, 21.8; MS (EI) m/z 204 (Mþ); HRMS (EI) calcd for
C13H16O2 (Mþ) 204.1150, found 204.1146.
4.4.5. Cinnamyl 2-bromopropanoate (8). To a solution of cinnamyl
alcohol (2.10 g, 14.9 mmol) in CH2Cl2 (30 mL) were added DMAP
(182 mg, 1.50 mmol), pyridine (2.4 mL, 30 mmol), and 2-bromo-
propionyl bromide (1.9 mL,18 mmol) at 0 ꢀC. After stirring at 0 ꢀC for
40 min, the mixture was diluted with brine (100 mL) and extracted
with AcOEt (100 mLꢁ2). Combined organic extracts were dried over
Mg2SO4 and concentrated. The residue was purified by chroma-
tography (SiO2 200 g, hexaneeAcOEt, 20:1) afforded 8 (3.99 mg,
14.8 mmol, 98%) as a colorless oil; IR (neat), nmax 3026, 1737, 1447,
4.4.11. 4-Bromocinnamyl 2-bromo-2-methylpropanoate (15). A white
crystal; mp 40.5e42.0 ꢀC; IR (neat), nmax 2930,1743,1487,1371,1280,
1170, 968, 847, 643, 498 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d 7.46 (d, J
8.5 Hz, 2H), 7.27 (d, J 8.5 Hz, 2H), 6.65 (d, J 15.9 Hz, 1H), 6.29 (dt, J 6.3,
15.9 Hz, 1H), 4.82 (d, J 6.2 Hz, 2H), 1.96 (s, 6H); 13C NMR (75 MHz,
CDCl3)
d 171.4, 135.0, 133.1, 131.7, 128.1, 123.2, 122.0, 66.1, 55.7, 30.7;
HRMS (EI) m/z 360 (Mþ); HRMS (EI) calcd for C13H1479Br2O2 (Mþ)
359.9361, found 359.9357.
1334, 1218, 1156, 968, 746, 692 cmꢂ1
;
1H NMR (300 MHz, CDCl3)
4.4.12. 3-(4-Bromophenyl)-2,2-dimethylpent-4-enoic acid (16). A
white crystal; mp 102.0e103.0 ꢀC; IR (neat), nmax 2980, 1707, 1489,
d
7.42e7.27 (m, 5H), 6.71 (d, J 15.9 Hz,1H), 6.29 (dt, J 15.9, 6.3 Hz,1H),

J. Ishihara et al. / Tetrahedron 67 (2011) 3659e3667
3665
1404,1276,1076,1011, 925, 828, 516 cmꢂ1; 1H NMR (300 MHz, CDCl3)
7.42 (d, J 8.5 Hz, 2H), 7.09 (d, J 8.5 Hz, 2H), 6.18 (dt, J 16.8, 9.9 Hz,1H),
5.17 (dd, J 0.9,11.2 Hz,1H), 5.14 (d, J 0.8, 16.7 Hz,1H), 3.60 (d, J 9.3 Hz,
1H), 1.18 (s, 3H), 1.12 (s, 3H); 13C NMR (75 MHz, CDCl3)
183.6,139.0,
(d, J 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d
182.8, 134.1, 120.9,
d
39.7, 31.8, 25.8, 17.8, 16.3; MS (EI) m/z 142 (Mþ), 96, 81, 69 (100),
55, 41; HRMS (EI) calcd for C8H14O2 (Mþ) 142.0994, found
142.0986.
d
136.0,131.2,130.9,120.8,118.3, 56.6, 46.6, 22.9, 22.0; MS (EI) m/z 282
(Mþ); HRMS (EI) calcd for C13H1579BrO2 (Mþ) 282.0255, found
282.0270.
4.4.20. 3-Methylbut-2-enyl
A yellow oil; IR (neat), nmax 2976, 1741, 1463, 1387, 1280, 1169, 1110,
1010, 958, 763, 648 cmꢂ1 1H NMR (300 MHz, CDCl3)
5.36 (t, J
7.1 Hz, 1H), 4.67 (d, J 7.1 Hz, 2H), 1.93 (s, 6H), 1.75 (d, J 12.4 Hz, 6H);
2-bromo-2-methylpropanoate
(25).
;
d
4.4.13. 4-Bromocinnamyl 2-bromopropanoate (17). A colorless oil;
IR (neat), nmax 2932, 1738, 1484, 1446, 1333, 1218, 1153, 1067, 968,
13C NMR (75 MHz, CDCl3)
d 171.2, 129.3, 117.8, 62.6, 55.7, 30.5, 25.5,
843 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
7.45 (d, J 8.5 Hz, 2H), 7.26 (d,
17.9; MS (EI) m/z 234 (Mþ); HRMS (EI) calcd for C9H1679BrO2
(MþHþ) 235.0334, found 235.0302.
J 8.5 Hz, 2H), 6.64 (d, J 15.9 Hz, 1H), 6.28 (dt, J 15.9, 6.3 Hz, 1H), 4.81
(d, J 6.3 Hz, 2H), 4.41 (q, J 6.9 Hz, 1H), 1.85 (d, J 6.9 Hz, 3H); 13C NMR
(100 MHz, CDCl3)
d
169.9, 134.9, 133.4, 131.7, 128.1, 123.0, 122.0, 66.1,
4.4.21. 2,2,3,3-Tetramethylpent-4-enoic acid (26). A colorless oil; IR
(neat), nmax 2978, 1700, 1468, 1375, 1293, 1131, 1009, 915, 740,
40.0, 21.6; HRMS (EI) m/z 115, 116 (100), 142, 211, 297, 346, 348
(MꢂHþ); HRMS (EI) calcd for C12H1281Br2O2 (Mþ) 349.9163, found
349.9162.
553 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
5.98 (dd, J 17.3, 11.0 Hz, 1H),
5.04 (dd, J 10.7, 1.1 Hz, 1H), 5.00 (dd, J 17.3, 1.4 Hz, 1H), 1.16 (s, 6H),
1.10 (s, 6H); 13C NMR (75 MHz, CDCl3)
d 183.9, 144.4, 112.5, 47.8,
4.4.14. 3-(4-Bromophenyl)-2-methylpent-4-enoic acid (18). A white
crystal; IR (neat), nmax 2980, 1711, 1486, 1413, 1292, 1075, 1005, 920,
40.9, 22.9, 21.4; MS (EI) m/z 156 (Mþ); HRMS (EI) calcd for C9H16O2
(Mþ) 156.1150, found 156.1142.
818, 519 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 7.44 (d, J 8.6 Hz,
0.58ꢁ2H), 7.41 (d, J 8.3 Hz, 0.42ꢁ2H), 7.09 (d, J 8.3 Hz, 0.58ꢁ2H),
7.05 (d, J 8.3 Hz, 0.42ꢁ2H), 6.01e5.81 (m, 1H), 5.15e5.05 (m, 1H),
3.51e3.41 (m, 1H), 2.82e2.74 (m, 1H), 1.24 (d, J 7.0 Hz, 0.42ꢁ3H),
4.4.22. 3-Methylbut-2-enyl 2-bromopropanoate (27). A colorless
oil; IR (neat), nmax 2977, 1739, 1447, 1380, 1340, 1223, 1158, 1062,
986, 933 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
5.36 (t, J 7.1 Hz, 1H),
4.66 (d, J 7.1 Hz, 2H), 4.37 (q, J 6.8 Hz, 1H), 1.82 (d, J 6.8 Hz, 3H), 1.77
(s, 3H), 1.73 (s, 3H); 13C NMR (100 MHz, CDCl3)
170.2, 140.1, 117.7,
1.00 (d, J 6.8 Hz, 0.58ꢁ3H); 13C NMR (100 MHz, CDCl3)
d 181.6, 181.2,
141.0, 140.0, 138.7, 137.6, 131.8, 131.6, 129.8, 129.4, 120.7, 120.5, 117.4,
116.3, 52.5, 52.5, 44.8, 44.5, 15.7, 15.4; HRMS (EI) m/z 268 (Mþ), 195,
116 (100), 115; HRMS (EI) calcd for C12H1381BrO2 (Mþ) 270.0078,
found 270.0084.
d
62.8, 40.3, 25.8, 21.7, 18.1; MS (EI) m/z 41, 69, 95, 109, 141 (100), 220,
223 (Mþ); HRMS (EI) calcd for C8H1379BrO2 (Mþ) 220.0099, found
220.0105.
4.4.15. 4-Nitrocinnamyl 2-bromo-2-methylpropanoate (19). A yel-
low crystal; mp 49.0e50.0 ꢀC; IR (neat), nmax 2932, 1741, 1598, 1523,
4.4.23. 2,3,3-Trimethylpent-4-enoic acid (28). A yellow oil; IR
(neat), nmax 2972, 1708, 1462, 1416, 1286, 1243, 1082, 1005, 918,
1462, 1349, 1167, 970, 863, 740, 689 cmꢂ1
;
1H NMR (300 MHz,
694 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
5.86 (dd, J 17.4, 10.8 Hz, 1H),
CDCl3)
d 8.20 (d, J 8.8 Hz, 2H), 7.54 (d, J 8.5 Hz, 2H), 6.79 (d, J 15.9 Hz,
5.02 (d, J 11.0 Hz,1H), 5.00 (d, J 17.3 Hz,1H), 2.39 (q, J 7.1 Hz,1H),1.12
1H), 6.48 (dt, J 5.9, 15.9 Hz, 1H), 4.89 (dd, J 1.7, 5.8 Hz, 2H), 1.98 (s,
(s, 3H), 1.10 (s, 6H); 13C NMR (75 MHz, CDCl3)
d 181.5, 145.5, 112.1,
6H); 13C NMR (75 MHz, CDCl3)
d
171.2, 147.1, 142.4, 131.4, 127.3,
48.7, 38.5, 25.0, 23.6, 12.7; MS (EI) m/z 142 (Mþ), 127, 97, 81, 69
127.1, 123.9, 65.5, 55.5, 30.6; MS (EI) m/z 327 (Mþ); HRMS (EI) calcd
(100); HRMS (EI) calcd for C8H14O2 (Mþ) 142.0994, found 142.0975.
for C13H1479BrO4 (Mþ) 327.0107, found 327.0109.
4.4.24. 4-(Benzyloxy)but-2-ynyl 2-bromo-2-methylpropanoate (29).
A yellow oil; IR (neat), nmax 2856, 1746, 1455, 1371, 1273, 1162, 1011,
4.4.16. 2-Methylbut-3-en-2-yl 2-bromo-2-methylpropanoate (21).
A colorless oil; IR (neat), nmax 2979,1818,1741,1463,1288,1076, 928,
970, 742, 699 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
7.40e7.26 (m, 5H),
848, 739, 641, 486 cmꢂ1
;
1H NMR (300 MHz, CDCl3)
d
6.08 (dd, J
4.84 (s, 2H), 4.60 (s, 2H), 4.22 (s, 2H),1.96 (s, 6H); 13C NMR (100 MHz,
10.9,17.4 Hz,1H), 5.25 (d, J 17.3 Hz,1H), 5.13 (d, J 11.0 Hz,1H),1.90 (s,
CDCl3)
d 170.7, 137.0, 128.2, 127.9, 127.7, 83.2, 79.7, 71.4, 57.0, 55.0,
6H), 1.56 (s, 6H); 13C NMR (75 MHz, CDCl3)
d
169.9, 141.6, 113.1, 82.0,
53.6, 30.5; MS (EI) m/z 324 (Mþ); HRMS (EI) calcd for C15H1779BrO3
57.0, 30.6, 25.9; MS (EI) m/z 235 (Mþ); HRMS (EI) calcd for
C9H1679BrO2 (MþHþ) 235.0333, found 235.0342.
(Mþ) 324.0361, found 324.0363.
4.4.25. 3-((Benzyloxy)methyl)-2,2-dimethylpenta-3,4-dienoic acid (30).
A yellow oil; IR (neat), nmax 2979, 1955, 1705, 1455, 1360, 1284, 1069,
4.4.17. 2,2,5-Trimethylhex-4-enoic acid (22). A yellow oil; IR (neat),
nmax 2974, 1709, 1473, 1409, 1383, 1241, 1201, 1162, 943, 557 cmꢂ1
;
851, 739, 699 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
7.38e7.23 (m, 5H),
1H NMR (300 MHz, CDCl3)
d 5.12 (tt, J 7.7, 1.4 Hz, 1H), 2.26 (d, J
4.94 (t, J 2.1 Hz, 2H), 4.59 (s, 2H), 4.13 (t, J 1.9 Hz, 2H),1.38 (s, 6H); 13C
7.7 Hz, 2H), 1.72 (s, 3H), 1.61 (s, 3H), 1.19 (s, 6H); 13C NMR (75 MHz,
NMR (100 MHz, CDCl3)
d 207.4, 182.0, 137.9, 128.3, 127.7, 127.5,
CDCl3)
d
184.7, 134.6, 119.6, 42.7, 38.4, 26.0, 24.5, 17.9; MS (EI) m/z
104.5, 78.1, 71.9, 68.8, 43.0, 24.9; MS (EI) m/z 246 (Mþ); HRMS (EI)
156 (Mþ); HRMS (EI) calcd for C9H16O2 (Mþ) 156.1151, found
156.1131.
calcd for C15H18O3 (Mþ) 246.1255, found 246.1257.
4.4.26. Cyclohex-2-enyl 2-bromo-2-methylpropanoate (31). A yel-
low oil; IR (neat), nmax 2937, 1737, 1462, 1389, 1281, 1173, 1053, 1010,
4.4.18. 2-Methylbut-3-en-2-yl 2-bromopropanoate (23). A colorless
oil; IR (neat), nmax 2983, 1739, 1448, 1342, 1229, 1127, 989, 929,
912, 728 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
6.00 (dt, J 4.2, 10.2 Hz,
843 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 6.08 (dd, J 17.6, 11.0 Hz, 1H),
1H), 5.73 (dd, J 3.6, 9.9 Hz, 1H), 5.29 (d, J 4.3 Hz, 1H), 2.18e1.53 (m,
5.74 (d, J 17.6 Hz,1H), 5.13 (d, J 11.0 Hz,1H), 4.30 (q, J 6.8 Hz,1H),1.79
12H); 13C NMR (75 MHz, CDCl3)
d 171.1, 133.2, 124.7, 69.5, 56.2, 30.6,
(d, J 6.8 Hz, 3H), 1.55 (s, 6H); 13C NMR (100 MHz, CDCl3)
d
169.2,
27.7, 24.8, 18.6; HRMS (EI) m/z 246 (Mþ); HRMS (EI) calcd for
142.0, 113.8, 82.8, 42.0, 26.5, 26.5, 21.9.
C10H1579BrO2 (Mþ) 246.0256, found 246.0241.
4.4.19. 2,5-Dimethylhex-4-enoic acid (24). A yellow oil; IR (neat),
nmax 2975, 1709, 1459, 1381, 1243, 1121, 937, 811, 640, 562 cmꢂ1; 1H
4.4.27. 2-(Cyclohex-2-enyl)-2-methylpropanoic acid (32). A yellow
oil; IR (neat), nmax 2929, 1702, 1469, 1367, 1279, 1149, 942, 859, 721,
NMR (400 MHz, CDCl3)
d
5.13e5.08 (m, 1H), 2.53e2.44 (m, 1H),
619 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
5.79 (dd, J 10.3, 3.2 Hz, 1H),
2.40e2.33 (m, 1H), 2.20e2.10 (m, 1H), 1.71 (s, 3H), 1.62 (s, 3H), 1.17
5.53 (d, J 9.9 Hz, 1H), 2.60e2.46 (m, 1H), 2.20e1.40 (m, 6H), 1.26 (s,

3666
J. Ishihara et al. / Tetrahedron 67 (2011) 3659e3667
6H); MS (EI) m/z 168 (Mþ); HRMS (EI) calcd for C10H16O2 (Mþ)
168.1150, found 168.1138.
(Mþ), 175, 117 (100), 115, 91; HRMS (EI) calcd for C14H18O2 (Mþ)
218.1307, found 218.1291.
4.4.28. 4,6-Di-O-acetyl-3-O-(2-bromo-2-methylpropionyl)-
(33). A pale yellow oil; IR (neat), nmax 2929, 1758, 1649, 1473, 1371,
1247, 1164, 1108, 759, 600 cmꢂ1 1H NMR (300 MHz, CDCl3)
6.51
D
-glucal
4.4.34. (2S,3S)-Cinnamyl 2-bromo-3-methylpentanoate (39). A col-
24
orless oil; [
a
]
ꢂ11.3 (c 1.06, CHCl3); IR (neat), nmax 2967, 1740,
D
;
d
1454, 1379, 1267, 1147, 969, 743, 698 cmꢂ1
;
1H NMR (300 MHz,
(d, J 6.0 Hz, 1H), 5.38e5.29 (m, 2H), 4.89 (dd, J 3.2, 6.2 Hz, 1H), 4.45
(dd, J 5.8, 12.1 Hz, 1H), 4.30 (dt, J 2.8, 6.6 Hz, 1H), 4.21 (dd, J 2.9,
11.9 Hz, 1H), 2.11 (s, 3H), 2.08 (s, 3H), 1.91 (s, 6H); 13C NMR (75 MHz,
CDCl3) 7.42e7.24 (m, 5H), 6.71 (d, J 15.9 Hz, 1H), 6.29 (dt, J 15.9,
d
6.3 Hz, 1H), 4.83 (d, J 6.3 Hz, 2H), 4.14 (d, J 6.3 Hz, 2H), 2.14e2.00 (m,
1H), 1.83e1.69 (m, 1H), 1.39e1.24 (m, 1H), 1.02 (d, J 6.9 Hz, 3H), 0.92
CDCl3)
20.7.
d
170.6, 169.4, 146.1, 98.0, 73.9, 69.0, 66.6, 61.3, 55.3, 30.4,
(t, J 7.4 Hz, 3H); 13C NMR (100 MHz, CDCl3)
d 169.3, 136.0, 134.9,
128.6, 128.2, 126.6, 122.2, 66.2, 53.0, 38.3, 26.3, 16.2, 10.6; MS(EI) m/
z 115, 117, 231 (100), 310, 311 (MꢂHþ); HRMS (EI) calcd for
C15H1981BrO2 (Mþ) 312.0548, found 312.0554.
4.4.29. 2-((2S,5S,6R)-5,6-Dihydro-5-acetoxy-6-(acetoxymethyl)-2H-
pyran-2-yl)-2-methylpropanoic (34). A yellow oil; IR (neat), nmax
2928, 1732, 1469, 1370, 1225, 1131, 1080, 1043, 794, 642, 605 cmꢂ1
;
4.4.35. 2-sec-Butyl-3-phenylpent-4-enoic acid (40). A white crystal;
IR (neat), nmax 3030, 2967, 1703, 1457, 1421, 1252, 1208, 920, 757,
1H NMR (300 MHz, CDCl3)
d 5.85 (s, 2H), 5.26 (dd, J 9.2, 2.9 Hz, 1H),
4.42 (d, J 2.3 Hz, 1H), 4.25 (dd, J 11.8, 2.7 Hz, 1H), 4.17 (dd, J 11.8,
5.5 Hz, 1H), 3.74 (dt, J 2.7, 3.1 Hz, 1H), 2.09 (s, 3H), 2.07 (s, 3H), 1.20
699 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 7.33e7.16 (m, 5H),
6.07e5.83 (m,1H), 5.16e4.97 (m, 2H), 3.70e3.62 (m,1H), 2.90e2.69
(d, J 8.5 Hz, 6H); 13C NMR (75 MHz, CDCl3)
d 180.5, 171.2, 170.6,
(m, 1H), 1.89e1.41 (m, 1H), 1.41e1.15 (m, 1H), 1.15e0.71 (m, 7H); 13C
128.6, 127.6, 78.7, 74.1, 65.4, 63.2, 46.3, 21.0, 21.7, 20.5; HRMS (EI) m/
NMR (75 MHz, CDCl3) d 180.0, 179.7, 179.1, 178.9, 142.4, 142.4, 141.4,
z 300 (Mþ).
141.1, 139.8, 139.5, 139.2, 139.1, 128.8, 128.7, 128.5, 128.5, 127.9, 127.9,
127.7, 127.7, 126.7, 126.7, 126.5, 116.1, 116.1, 115.9, 115.6, 56.6, 56.0,
53.6, 50.2, 50.1, 49.8, 49.5, 34.8, 34.7, 34.2, 34.0, 28.7, 28.2, 24.3,
23.4, 18.0, 17.5, 14.3, 13.7, 12.4, 12.1, 12.0, 11.7; HRMS (EI) m/z 232
(Mþ), 175, 117 (100), 115, 91; HRMS (EI) calcd for C15H230O2 (Mþ)
232.1463, found 232.1464.
4.4.30. (S)-Cinnamyl 2-bromo-3-phenylpropanoate (35). A colorless
oil; [a
]
25þ17.2 (c 1.05, CHCl3); IR (neat), nmax 3031, 1739, 1494, 1445,
D
1225, 1149, 967, 742, 696, 516 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
7.39e7.20 (m, 10H), 6.63 (d, J 15.9 Hz, 1H), 6.18 (dt, J 15.9, 6.5 Hz,
1H), 4.77 (d, J 6.5 Hz, 2H), 4.44 (dd, J 8.5, 7.0 Hz, 1H), 3.49 (dd, J 14.0,
8.5 Hz, 1H), 3.27 (dd, J 14.0, 7.0 Hz, 1H); 13C NMR (100 MHz, CDCl3)
4.4.36. Cinnamyl 2-bromo-2-methylbutanoate (41). A colorless oil;
IR (neat), nmax 2976, 1734, 1452, 1380, 1251, 1151, 964, 744, 692,
d
169.5, 137.0, 136.3, 135.2, 129.5, 129.0, 128.9, 128.5, 127.7, 127.0,
122.4, 66.7, 45.6, 41.5; HRMS (EI) m/z 91, 117 (100), 133, 265, 345
(Mþ); HRMS (EI) calcd for C18H1781BrO2 (Mþ) 346.0391, found
346.0383.
490 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 7.42e7.26 (m, 5H), 6.71 (d, J
15.9 Hz,1H), 6.30 (dt, J 15.9, 6.6 Hz,1H), 4.84 (d, J 6.6 Hz, 2H), 2.18 (q,
J 7.3 Hz, 2H), 1.92 (s, 3H), 1.01 (t, J 7.3 Hz, 3H); 13C NMR (100 MHz,
CDCl3) d 171.1, 136.1, 134.7, 128.6, 128.6, 126.7, 122.4, 66.4, 62.1, 35.7,
4.4.31. 2-Benzyl-3-phenylpent-4-enoic acid (36). A white crystal;
IR (neat), nmax 3029, 1707, 1495, 1445, 1250, 1077, 920, 757,
27.4, 10.3; MS(EI) m/z 117 (100), 133, 217, 296 (Mþ); HRMS (EI) calcd
for C14H1779BrO2 (Mþ) 296.0411, found 296.0414.
698 cmꢂ1
;
1H NMR (300 MHz, CDCl3) 7.39e7.02 (m, 10H),
6.10e5.95 (m, 1H), 5.25e5.18 (m, 0.33ꢁ1H), 5.18e5.01 (m,
0.67ꢁ1H), 3.59 (t, J 9.2 Hz, 0.33ꢁ1H), 3.51 (t, J 9.6 Hz, 0.67ꢁ1H),
3.08e3.01 (m, 0.33ꢁ1H), 2.84 (dd, J 11.9, 14.4 Hz, 0.33ꢁ1H), 2.72
(dd, J 13.9, 10.9 Hz, 0.67ꢁ1H), 2.57 (dd, J 13.7, 4.1 Hz, 0.67ꢁ1H);
4.4.37. 2-Ethyl-2-methyl-3-phenylpent-4-enoic acid (42). A white
crystal; IR (neat), nmax 3081, 1713, 1460, 1410, 1268, 1163, 922, 789,
741, 704, 540 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 7.41e7.22 (m, 5H),
6.37e6.19 (m, 1H), 5.20e5.12 (m, 2H), 3.68 (d, J 10.0 Hz, 0.61ꢁ1H),
3.62 (d, J 9.5 Hz, 0.39ꢁ1H), 1.92e1.80 (m, 0.61ꢁ2H), 1.56e1.45 (m,
0.39ꢁ1H), 1.15 (s, 0.61ꢁ3H), 1.13 (s, 0.39ꢁ3H), 0.91 (t, J 7.2 Hz,
0.61ꢁ3H), 0.84 (t, J 7.3 Hz, 0.39ꢁ3H); 13C NMR (100 MHz, CDCl3)
13C NMR (75 MHz, CDCl3)
d 180.2, 179.6, 141.3, 141.0, 139.0, 138.8,
138.7, 138.4, 128.9, 128.7, 128.6, 128.5, 128.4, 127.9, 127.7, 127.0,
126.8, 126.4, 126.4, 117.3, 116.3, 53.7, 53.2, 53.1, 36.7, 36.4; MS (EI)
m/z 266 (Mþ), 175, 117 (100), 91; HRMS (EI) calcd for C18H18O2
(Mþ) 266.1307, found 266.1303.
d
183.1, 182.8, 140.6, 140.0, 137.1, 136.2, 129.5, 129.0, 128.1, 128.0,
126.8, 126.7, 118.0, 117.4, 58.1, 57.7, 51.5, 50.9, 31.2, 30.8, 16.2, 16.0,
9.2, 9.0; MS (EI) m/z 218 (Mþ), 117 (100),115, 43; HRMS (EI) calcd for
C14H18O2 (Mþ) 218.1307, found 218.1299.
4.4.32. (S)-Cinnamyl 2-bromo-3-methylbutanoate (37). A colorless
24
oil; [
a
]
ꢂ5.01 (c 1.00, CHCl3); IR (neat), nmax 2968, 1740, 1455,
D
1378, 1290, 1148, 970, 743, 697 cmꢂ1
;
1H NMR (300 MHz, CDCl3)
4.4.38. Cinnamyl 2-bromo-2-phenylpropanoate (43). A colorless oil;
IR (neat), nmax 3029, 1734, 1494, 1447, 1378, 1244, 1119, 965, 741,
d
7.42e7.24 (m, 5H), 6.71 (d, J 15.9 Hz, 1H), 6.29 (dt, J 15.9,
6.5 Hz, 1H), 4.83 (d, J 6.5 Hz, 2H), 4.09 (d, J 7.7 Hz, 1H), 2.36e2.19
695 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
7.36e7.24 (m, 10H), 6.61 (d,
J 15.9 Hz, 1H), 6.22 (dt, J 15.9, 6.3 Hz, 1H), 4.84 (d, J 6.3 Hz, 2H), 2.32
(s, 3H); 13C NMR (100 MHz, CDCl3)
170.7, 140.9, 136.0, 134.6, 128.6,
(m, 1H), 1.11 (d, J 6.6 Hz, 3H), 1.05 (d, J 6.6 Hz, 3H); 13C NMR
(100 MHz, CDCl3)
d
169.2, 136.0, 135.0, 128.6, 128.2, 126.7, 122.2,
d
66.2, 54.6, 32.3, 20.0, 19.9; MS(EI) m/z 115, 117 (100), 133, 217,
296 (Mþ); HRMS (EI) calcd for C14H1781BrO2 (Mþ) 298.0391,
found 298.0400.
128.4, 128.1,126.8, 126.6, 126.0,122.1, 66.8, 61.9, 31.3; HRMS (EI) m/z
103, 117 (100), 132, 265, 344 (Mþ); HRMS (EI) calcd for C18H1779BrO2
(Mþ) 344.0412, found 344.0407.
4.4.33. 2-Isopropyl-3-phenylpent-4-enoic acid (38). A white crystal;
4.4.39. 2-Methyl-2,3-diphenylpent-4-enoic acid (44). A white crys-
tal; IR (neat), nmax 3062, 1701, 1496, 1451, 1383, 1270, 1115, 997, 922,
IR (neat), nmax 2965, 1702, 1420, 1285, 1207, 917, 753, 695, 517 cmꢂ1
;
1H NMR (300 MHz, CDCl3)
d
7.34e7.19 (m, 5H), 6.08e5.80 (m, 1H),
702 cmꢂ1 1H NMR (300 MHz, CDCl3)
; d 7.45e6.85 (m, 10H),
5.18e5.01 (m, 2H), 3.63 (t, J 9.9 Hz, 1H), 2.85e2.80 (m, 0.34ꢁ1H),
2.75 (dd, J 10.6, 4.8 Hz, 0.66ꢁ1H), 2.21e2.00 (m, 0.34ꢁ1H),
1.72e1.56 (m, 0.66H, 1H), 1.04 (dd, J 18.1, 6.9 Hz, 0.34ꢁ6H), 0.92 (t, J
6.34e6.21 (m, 0.43ꢁ1H), 6.01e5.89 (m, 0.57ꢁ1H), 5.18e5.11 (m,
0.43ꢁ2H), 5.00e4.89 (m, 0.57ꢁ2H), 4.34 (d, J 8.7 Hz, 0.57ꢁ1H), 4.23
(d, J 8.7 Hz, 0.43ꢁ1H), 1.62 (d, J 7.5 Hz, 3H); 13C NMR (100 MHz,
7.1 Hz, 0.66ꢁ6H); 13C NMR (100 MHz, CDCl3)
d
177.9, 176.9, 142.4,
CDCl3) d 180.0, 179.8, 140.5, 140.1, 139.9, 139.6, 137.3, 137.0, 130.2,
141.3, 139.4, 139.3, 128.8, 128.6, 127.9, 127.7, 126.7, 126.6, 116.1, 115.9,
129.8, 128.0, 127.9, 127.9, 127.8, 127.5, 127.3, 127.2, 127.1, 126.8, 126.5,
56.0, 55.4, 50.5, 50.0, 27.8, 27.5, 22.0, 21.5, 17.1, 16.2; MS (EI) m/z 218
118.2, 118.1, 57.3, 56.5, 54.9, 54.5, 19.4, 18.8; HRMS (EI) m/z 266

J. Ishihara et al. / Tetrahedron 67 (2011) 3659e3667
3667
(Mþ), 117 (100), 91, 70, 45; HRMS (EI) calcd for C18H18O2 (Mþ)
266.1307, found 266.1283.
(d, J 6.8 Hz, 2H), 1.26 (s, 3H), 1.23 (s, 3H); 13C NMR (100 MHz, CDCl3)
d
21.5, 23.8, 44.4, 51.8, 56.8,120.7,131.7,172.4,182.6; MS (EI) m/z 187
(Mþ1), 189, 155, 127, 99 (100); HRMS (EI) calcd for C9H14O4 (Mþ),
4.4.40. (E)-4-Acetoxybut-2-enyl 2-bromo-2-methylpropanoate (E-45).
A colorless oil; IR (neat), nmax 2978, 1748, 1463, 1372, 1275, 1166,
186.0892, found 186.0875.
1111,1028, 969, 642, 475 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d
5.90 (dt,
4.4.47. (Z)-Methyl 4-(isobutyryloxy)but-3-enoate (54). A colorless
oil; IR (neat), nmax 2982, 1766, 1676, 1472, 1268, 1018, 853, 748,
J 4.4 Hz, 2H), 4.69 (d, J 4.1 Hz, 2H), 4.60 (d, J 4.1 Hz, 2H), 1.97 (s, 3H),
1.95 (s, 6H); 13C NMR (75 MHz, CDCl3)
d
171.2, 170.5, 128.1, 127.1,
593 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d 7.19 (d, J 6.3 Hz, 1H), 5.12 (dt,
65.0, 63.7, 55.4, 30.6, 20.7; MS(EI) m/z 278 (Mþ); HRMS (EI) calcd for
J 6.3, 6.8 Hz, 1H), 3.71 (s, 3H), 3.23 (d, J 6.8 Hz, 2H), 2.65 (quint,
C11H1779BrO3 (Mþ) 278.0154, found 278.0156.
J 6.8 Hz, 1H), 1.22 (d, J 6.8 Hz, 6H); 13C NMR (100 MHz, CDCl3)
d
173.5, 171.1, 136.1, 105.0, 65.8, 33.8, 30.0, 15.2, 14.1; MS (EI) m/z 186
4.4.41. 3-(Acetoxymethyl)-2,2-dimethylpent-4-enoic acid (46). IR
(neat), nmax 3200 (br), 2981, 1744, 1467, 1367, 1243, 1162, 1039, 929,
(Mþ), 84, 71 (100); HRMS (EI) calcd for C9H14O4 (Mþ), 186.0892,
found 186.0869.
686, 606 cmꢂ1; 1H NMR (300 MHz, CDCl3)
d 5.64 (dt, J 16.8, 10.4 Hz,
1H), 5.21 (dd, J 10.4, 1.6 Hz, 1H), 5.19 (dd, J 16.8, 0.6 Hz, 1H),
4.20e4.03 (m, 2H), 2.80 (d, J 8.0 Hz, 1H), 2.75 (d, J 8.0 Hz, 1H), 2.00
Acknowledgements
(s, 3H), 1.17 (s, 6H); 13C NMR (75 MHz, CDCl3)
d 183.4, 170.8, 134.0,
This work was financially supported by Grants-in-Aid for Sci-
entific Research from the Ministry of Education, Culture, Sports,
Science and Technology, Japan (17590009 and 21590012) and by
a Grant-in-Aid for Scientific Research from the President of Naga-
saki University.
119.7, 63.9, 49.7, 43.2, 24.4, 20.2; MS (EI) m/z 200 (Mþ); HRMS (EI)
calcd for C10H16O4 (Mþ) 200.1048, found 200.1027.
4.4.42. (E)-4-Acetoxybut-2-enyl 2-bromopropanoate (47). A pale
yellow oil; IR (neat), nmax 2941, 1740, 447, 1380, 1336, 1229, 1159,
1028, 975, 638 cmꢂ1 1H NMR (300 MHz, CDCl3)
; d 5.97e5.83 (m,
Supplementary data
2H), 4.68 (dd, J 3.8 Hz, 2H), 4.59 (d, J 4.1 Hz, 2H), 4.39 (q, J 7.1 Hz,1H),
2.09 (s, 3H), 1.85 (d, J 7.1 Hz, 3H); MS (EI) m/z 43 (100), 70, 112, 135,
152, 264 (MꢂHþ); HRMS (EI) calcd for C9H1381BrO4 (Mþ) 265.9977,
found 265.9966.
Supplementary data associated with this article can be found in
the online version at doi:10.1016/j.tet.2011.03.079.
References and notes
4.4.43. 3-(Acetoxymethyl)-2-methylpent-4-enoic acid (48). A white
crystal; IR (neat), nmax 3082, 2979, 1741, 1460, 1383, 1250, 1042, 999,
1. See for examples: (a) Ziegler, F. E. Acc. Chem. Res. 1977, 10, 227; (b) Tadano, K.-i.
In Studies in Natural Products Chemistry: Stereoselective Synthesis; Atta-Ur-Rah-
man, Ed.; Elsevier Science: Amsterdam, 1994; Vol. 10, p 405; (Part F); (c) Ito, S.;
Tsunoda, T. Pure Appl. Chem. 1994, 66, 2071; (d) Nubbemeyer, U. Top. Curr. Chem.
2005, 244, 149.
2. (a) For reviews, see:The Claisen Rearrangement: Methods and Applications; Hi-
ersemann, M., Nubbemeyer, U., Eds.; Wiley-VCH GmbH KGaA: Weinheim, 2007;
See also: (b) Bennett, G. B. Synthesis 1977, 589; (c) Blechert, S. Synthesis 1989,
71; (d) Wipf, P. In Comprehensive Organic synthesis; Trost, B. M., Ed.; Pergamon:
Oxford, 1991; Vol. 5, p 827; (e) Martin Castro, A. M. Chem. Rev. 2004, 104, 2939.
3. Baldwin, J. E.; Walker, J. A. J. Chem. Soc., Chem. Commun. 1973, 117.
4. Ireland, R. E.; Mueller, R. H.; Willard, A. K. J. Am. Chem. Soc. 1976, 98, 2868.
5. (a) Ireland, R. E.; Mueller, R. H. J. Am. Chem. Soc. 1972, 94, 5897; (b) Ireland, R. E.;
Wipf, P.; Armstrong, J. D. J. Org. Chem. 1991, 56, 650; (c) Ireland, R. E.; Wipf, P.;
Xiang, J.-N. J. Org. Chem. 1991, 56, 3572 For a review, see: (d) Pereira, S.; Srebnik,
M. Aldrichimica Acta 1993, 26, 17.
927, 680 cmꢂ1 1H NMR (300 MHz, CDCl3)
; d 5.79e5.70 (m,
0.24ꢁ1H), 5.65e5.56 (m, 0.76ꢁ1H), 5.20e5.14 (m, 2H), 4.23e4.13
(m, 2H), 2.79e2.75 (m, 0.24ꢁ1H), 2.73e2.65 (m, 0.76ꢁ2H),
2.63e2.58 (m, 0.24ꢁ1H), 2.04 (s, 3H), 1.19 (d, J 6.8 Hz, 3H); 13C NMR
(75 MHz, CDCl3) d 185.6, 181.4, 180.7, 170.9, 135.4, 134.7, 119.0, 118.4,
65.2, 64.4, 45.3, 45.2, 40.4, 40.3, 14.0, 13.8, 13.8; MS (EI) m/z 187
(Mþ1þ); HRMS (EI) calcd for C9H14O4 (Mþ) 186.0892, found
186.0880.
4.4.44. (E)-4-Acetoxy-3-methylbut-2-enyl 2-bromo-2-methylpropan
oate (49). A pale yellow oil; IR (neat), nmax 2930, 1739, 1460, 1374,
1231, 1161, 1110, 1027, 962, 645, 476 cmꢂ1 1H NMR (300 MHz,
;
6. (a) Wada, M.; Shigehisa, T.; Akiba, K. Tetrahedron Lett. 1985, 26, 5191; (b)
Greuter, H.; Lang, R. W.; Romann, A. J. Tetrahedron Lett. 1988, 29, 3291; (c)
Zaman, S.; Kitamura, M.; Narasaka, K. Bull. Chem. Soc. Jpn. 2003, 76, 1055; (d)
Yang, Y.-Y.; Meng, W.-D.; Qing, F.-L. Org. Lett. 2004, 6, 4257; (e) Yang, Y.-Y.; Xu, J.;
You, Z.-W.; Xu, X.-h.; Qiu, X.-L.; Qing, F.-L. Org. Lett. 2007, 9, 5437; (f) Zheng, F.;
Zhang, X.; Qing, F.-L. Chem. Commun. 2009, 1505.
CDCl3)
d
5.64 (t, J 6.8 Hz, 1H), 4.73 (d, J 6.9 Hz, 2H), 4.51 (s, 2H), 2.10
171.3,
(s, 3H), 1.94 (s, 6H), 1.76 (s, 3H); 13C NMR (75 MHz, CDCl3)
d
170.7, 136.5, 120.8, 68.4, 62.1, 55.7, 30.7, 20.8, 14.2; MS (EI) m/z 292
(MþHþ); HRMS (EI) calcd for C11H1779BrO4 (Mþ) 292.0310, found
292.0304.
7. Ishihara, J.; Koyama, N.; Nishino, Y.; Takahashi, K.; Hatakeyama, S. Synlett 2009,
2351.
8. Chao, L.-C.; Rieke, R. D. J. Org. Chem. 1975, 40, 2253.
4.4.45. 3-(Acetoxymethyl)-2,2,3-trimethylpent-4-enoic acid (50).
A yellow oil; IR (neat), nmax 2984, 1742, 1471, 1417, 1385, 1242, 1037,
9. Babu, S. A.; Yasuda, M.; Shibata, I.; Baba, A. Org. Lett. 2004, 6, 4475; (b) Babu, S.
A.; Yasuda, M.; Shibata, I.; Baba, A. J. Org. Chem. 2005, 70, 10408; (c) Babu, S. A.;
Yasuda, M.; Okabe, Y.; Shibata, I.; Baba, A. Org. Lett. 2006, 8, 3029.
10. Tanasova, M.; Yang, Q.; Olmsted, C. C.; Vasileiou, C.; Li, X.; Anyika, M.; Borhan, B.
Eur. J. Org. Chem. 2009, 25, 4242.
11. (a) Chen, J. G.; Zhu, J. Y.; Skonezny, P. M.; Rosso, V.; Venit, J. J. Org. Lett. 2004, 6,
3233; (b) Kunz, H.; Lerchen, H. G. Tetrahedron Lett. 1987, 28, 1873; (c) Itsuno, S.;
Tanaka, K.; Ito, K. Chem. Lett. 1986, 1133.
921, 606, 452, 440 cmꢂ1 1H NMR (300 MHz, CDCl3)
; d 5.90 (dd,
J 17.4, 10.9 Hz, 1H), 5.20 (dd, J 10.9, 0.8 Hz, 1H), 5.08 (dd, J 17.3,
0.8 Hz, 1H), 4.26 (d, J 11.1 Hz, 1H), 4.13 (d, J 11.1 Hz, 1H), 2.02 (s, 3H),
1.20 (s, 3H), 1.19 (s, 3H), 1.16 (s, 3H); 13C NMR (75 MHz, CDCl3)
d
182.8,171.0,139.5,115.7, 68.1, 46.8, 44.4, 21.6, 20.8,16.7; MS (EI) m/
12. Compounds 41 and 43 were prepared by coupling of cinnamyl alcohol and the
z 214 (Mþ); HRMS (EI) calcd for C11H18O4 (Mþ) 214.1205, found
corresponding a-bromo carboxylic acid, which was derived from its carboxylic
acid by heating with NBS; see Meldal, M.; Porreca, F.; Davis, P.; Tornoe, C. W. J.
Peptide Sci. 2000, 6, 594.
214.1197.
13. For the formation of syn-vinyl ester, see: (a) Inomata, K.; Hirata, T.; Sasada, Y.;
Asada, T.; Senda, H.; Kinoshita, H. Chem. Lett. 1990, 2153; (b) Hirata, T.; Sasada,
Y.; Ohtani, T.; Asada, T.; Kinoshita, H.; Senda, H.; Inomata, K. Bull. Chem. Soc. Jpn.
1992, 65, 75; (c) Inomata, K. J. Synth. Org. Chem. Jpn. 2009, 67, 1172.
14. Takano, S.; Sekiguchi, Y.; Shimazaki, Y.; Takahashi, M.; Ogasawara, K. Chem. Lett.
1987, 1905.
4.4.46. 3-(Methoxycarbonyl)-2,2-dimethylpent-4-enoic acid (52).
A colorless oil; IR (neat), nmax 2987, 1715, 1368, 1474, 1437, 1268,
1027, 932 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
5.88 (dt, J 17.1, 9.8 Hz,
1H), 5.29 (d, J 10.2 Hz, 1H), 5.22 (d, J 17.1 Hz, 1H), 3.69 (s, 3H), 3.42