Palladium-catalyzed coupling of haloalkynes with allyl acetate: A regio- and stereoselective synthesis of (Z)-β-haloenol acetates

Article abstract of DOI:10.1021/jo2005318

A Pd-catalyzed coupling of haloalkynes with allyl acetate has been reported, providing a convenient method for the stereoselective synthesis of (Z)-β-haloenol acetates in good yields. The synthetic utility of this method is demonstrated by the formation of functionalized enol acetates via the Suzuki-Miyaura or Sonogashira coupling of the resulting (Z)-β-haloenol acetate products.

Full text of DOI:10.1021/jo2005318

NOTE
pubs.acs.org/joc
Palladium-Catalyzed Coupling of Haloalkynes with Allyl Acetate:
A Regio- and Stereoselective Synthesis of (Z)-β-Haloenol Acetates
Xiaoyi Chen, Dongxu Chen, Zenghui Lu, Lichun Kong, and Gangguo Zhu*
Department of Chemistry, Zhejiang Normal University, 688 Yingbin Road, Jinhua 321004, China
S Supporting Information
b
ABSTRACT: A Pd-catalyzed coupling of haloalkynes with allyl acetate has
been reported, providing a convenient method for the stereoselective synth-
esis of (Z)-β-haloenol acetates in good yields. The synthetic utility of this
method is demonstrated by the formation of functionalized enol acetates via
the SuzukiꢀMiyaura or Sonogashira coupling of the resulting (Z)-β-haloenol
acetate products.
aloalkenes are a fundamental and pivotal class of com-
pounds that undergo numerous chemical transformations.1ꢀ6
Scheme 1. Two Nucleopalladation-Initiated Reactions of
Haloalkynes
H
In this respect, the β-haloenol acetates encompass the reactivity
of enol acetates and carbonꢀhalide bonds, which renders them
as one of the most important building blocks in organic synthesis.
The versatile scopes of the applications include the transition-
metal-catalyzed cross-coupling reactions, the halogen-metal ex-
change reactions,7,8 the precursors for β-keto dianions,9ꢀ11 and
others. However, there are only a few methods that exist for the
effective synthesis of stereodefined β-haloenol acetates.12 In
1990, Barluenga13 described a facile protocol for the synthesis
of (E)-haloenol acetates via the electrophilic addition of terminal
alkynes. More recently, Jiang and co-workers14 discovered an
elegant method for the stereoselective synthesis of (Z)-β-haloenol
acetates based on the silver-catalyzed difunctionalization reaction
of terminal alkynes.
We have recently15 reported a regio- and stereoselective
synthesis of (Z)-1,2-dihalo-1,4-dienes through the Pd-catalyzed
coupling of alkynyl halides and allyl halides, with the alkenyl
palladium intermediate I as the key intermediate (path a,
Scheme 1). On the other hand, pioneered by Lu et al.,16ꢀ23
the acetoxypalladation of acetylenes24ꢀ30 is witnessing a great
deal of interest because of the formation of carbonꢀcarbon bond
and carbonꢀoxygen bond in a rather efficient and atom-eco-
nomic fashion. As such, we envisioned that the employment of
allyl acetates as the capture reagents for the palladium inter-
mediate I would eventually offer facile access to (Z)-β-haloenol
acetates (path b, Scheme 1). Herein, we reported our recent work
on Pd-catalyzed coupling of alkynyl halides with allyl acetate, in
which the (Z)-β-haloenol acetates were synthesized in a highly
regio- and stereoselective manner.
At the outset of this investigation, we examined the coupling
reaction between phenylethynyl chloride (1a) and allyl acetate
(2a) using 5 mol % of PdCl2, 2.0 equiv of LiOAc, and 10 mol %
of 2,20-bipyridine (L1) (see Figure 1) as the ligand. Gratifyingly,
the reaction gave the desired (Z)-β-haloenol acetate (Z)-3aa in
50% GC yield, after stirring for 8 h in HOAc at 80 °C. The
regiochemistry of this reaction was determined by the NOE
Figure 1. The Structure of Ligands.
measurements and further confirmed by X-ray diffraction anal-
ysis of (Z)-3ka. Inspired by this promising result, we further
examined the reaction conditions, and the results are summar-
ized in Table 1.
First, we tested a variety of palladium sources for this reaction
using HOAc as the solvent. The employment of Pd(OAc)2
resulted in the best yield, giving the (Z)-β-haloenol acetate
product (Z)-3aa in 60% GC yield, while decreased yields were
observed when other palladium catalysts such as PdBr2, Pd-
(MeCN)2Cl2, and Pd(PhCN)2Cl2 were employed (entries
1ꢀ4, Table 1). A brief survey of the solvents revealed that
HOAc was critical for this reaction, and the use of other
solvents, such as CH3CN or DMSO, failed to give the desired
products (entries 6 and 7, Table 1). Interestingly, a significant
increase of the yield was observed when the reaction was
Received: March 15, 2011
Published: June 15, 2011
r
2011 American Chemical Society
6338
dx.doi.org/10.1021/jo2005318 J. Org. Chem. 2011, 76, 6338–6343
|

The Journal of Organic Chemistry
NOTE
Table 1. Selected Results of Screening the Reaction
Conditionsa
Table 2. Scope and Limits of the Reactiona
entry
1
R
X
3
yield (%)b
entry
PdX2
solvent LiOAc (equiv) ligand yield (%)b,c
1
1a
1b
1c
1d
1e
1f
Ph
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Cl
Cl
Cl
Cl
I
(Z)-3aa
(Z)-3ba
(Z)-3ca
(Z)-3da
(Z)-3ea
(Z)-3fa
(Z)-3ga
(Z)-3ha
(Z)-3ia
(Z)-3ja
(Z)-3ka
(Z)-3la
(Z)-3ma
(Z)-3na
(Z)-3oa
(Z)-3pa
(Z)-3qa
(Z)-3ra
(Z)-3sa
(Z)-3ta
(Z)-3ua
(Z)-3aa
(Z)-3aa
86
76
80
74
81
71
85
70
73
65
77
72
71
80
74
77
75
72
82
0
1
PdCl2
PdBr2
HOAc
HOAc
2.0
2.0
2.0
2.0
2.0
2.0
2.0
ꢀ
L1
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L5
L5d
pyr
L6
L7
50
2
p-F-C6H4
2
52
3
p-Cl-C6H4
o-Cl-C6H4
p-Br-C6H4
o-Br-C6H4
p-Me-C6H4
p-OMe-C6H4
m-OMe-C6H4
o-OMe-C6H4
3,4-OMe2-C6H3
2,4-Cl2-C6H3
4-i-Pr-C6H4
4-t-Bu-C6H4
Ph
3
Pd(MeCN)2Cl2 HOAc
Pd(PhCN)2Cl2 HOAc
55
4
4
56
5
5
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
HOAc
CH3CN
DMSO
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
HOAc
60
6
6
NR
0
7
1g
1h
1i
7
8
8
73
9
9
ꢀ
55
10
11
12
13
14
15
16
17
18
19
20
21
22c
23d
1j
10
11
12
13
14
15
16
ꢀ
45
1k
1l
ꢀ
74
89 (86)c
ꢀ
1m
1n
1o
1p
1q
1r
1s
1t
ꢀ
57
ꢀ
47
ꢀ
18
p-Cl-C6H4
CH3(CH2)4
TBSOCH2CH2
BnOCH2CH2
(CH3CH2)3Si
Ph
ꢀ
75
a Reaction conditions: 1a, 0.5 mmol; 2a, 0.75 mmol; ligand, 0.05 mmol;
and Pd catalyst, 0.025 mmol, in 2.5 mL of solvent at 80 °C. b GC yield,
with naphthalene as the internal standard. c Isolated yield. d 6 mol % of
L5 was used.
1u
1a
1a
0
conducted without adding LiOAc, and the yield was increased
to 73% (entry 8, Table 1).
Ph
Cl
52
Ph
Cl
trace
a Reaction conditions: 1, 0.5 mmol; 2a, 1.5 mmol; L5, 0.05 mmol; and
Pd(OAc)2, 0.025 mmol, in 2.5 mL of HOAc at 80 °C. b Isolated yield.
c Allyl benzoate was used. d Allyl ethyl ether was used.
We then focused on screening the ligands for this reaction.
As clearly demonstrated in Table 1, the electronic nature of ligands
plays an important role in the Pd-catalyzed coupling of alkynyl
halides with allyl acetate. The utilization of electron-deficient
ligands, such as 4,40-dicarboxylic-2,20-bipyridine (L2) and 4,
40-dicyano-2,20-bipyridine (L3), led to a substantial decrease of the
yields to 55% and 45%, respectively (entries 9 and 10, Table 1).
In sharp contrast, when the electron-rich ligand 4,40-dimethoxy-
2,20-bipyridine (L5), for example, was chosen as the ligand for
this reaction, the desired product (Z)-3aa was obtained in a much
higher yield (86%) (entry 12, Table 1). Notably, the 2/1 ligand/
metal ratio turned out to be essential for achieving the high yield,
and the use of 5 mol % of Pd(OAc)2 and 6 mol % of ligand (L5)
resulted in a dramatic decrease of the yield to 57% (entry 13,
Table 1). Other ligands, such as pyridine, L6, and L7, led to no
improvement of the yields (entries 14ꢀ16, Table 1). Further-
more, the reaction had to be performed at 80 °C, because at a
lower temperature (60 °C), the conversions remained incom-
plete. Finally, we chose 5 mol % of Pd(OAc)2 as the catalyst,
10 mol % of 4,40-dimethoxy-2,20-bipyridine (L5) as the ligand,
and 80 °C for the optimal reaction conditions.
stereoselectivity. For example, the reaction of chloroalkynes 1b
and 1c afforded the desired (Z)-β-haloenol acetates (Z)-3ba and
(Z)-3ca in 76% and 80% yields, respectively (entries 2 and 3,
Table 2). The reaction of substances possessing a substituent
ortho to the CꢀC triple bond was effective as well, producing the
(Z)-β-haloenol acetates in good yields (entries 4, 6, and 10,
Table 2). Moreover, bromoalkynes 1o and 1p were converted
into the (Z)-β-bromoenol acetates (Z)-3oa and (Z)-3pa in 74%
and 77% yields, respectively (entries 15 and 16, Table 2).
Aliphatic haloalkynes also participated well in this reaction.
For example, the (Z)-β-haloenol acetate (Z)-3qa was gene-
rated from alkynyl chloride 1q in 75% yield (entry 17,
Table 2). In contrast, the reaction of phenylethynyl iodide
(1u) only led to the decomposition of the starting materials,
probably due to the worse stability of the CꢀI bond in the
presence of palladium catalyst (entry 21, Table 2). Interestingly,
allyl benzoate reacted smoothly with 1a to give the (Z)-β-haloenol
acetate (Z)-3aa in 52% yield, while only a trace of the desired
product was obtained when allyl ethyl ether was used (entries 22
and 23, Table 2).
After establishing the optimized conditions, the scope and
limitations of this reaction were then investigated in detail with
other haloalkynes under the optimal conditions. As outlined
in Table 2, the reaction was found to be widely applicable to
various functionalized chloroalkynes, except triethylsilylethynyl
chloride (1t) (entry 20, Table 2). Either electron-rich or electron-
deficient chloroalkynes were smoothly converted into the
(Z)-β-haloenol acetate products in good yields with excellent
Then, we carried out the coupling reactions of 1a with
substituted allyl acetates, such as 2b, 2c, 2d, and 2e (Figure 2);
however, the starting material 1a was mostly intact in these cases,
probably due to the sluggish carbopalladation of the alkenyl
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NOTE
utility of the resulting (Z)-β-haloenol acetate products was well-
demonstrated in the followed Pd-catalyzed cross-coupling reac-
tions, such as Suzuki and Sonogashira coupling reactions. Further
synthetic applications of this reaction are on the way.
Figure 2. The structure of 2.
’ EXPERIMENTAL SECTION
Scheme 2. Pd-Catalyzed Cross-Coupling Reactions of
(Z)-3
General. Unless otherwise noted, all reactions and manipulations
were conducted under air atmosphere. Column chromatography was
1
performed using silica gel (300ꢀ400 mesh). H NMR and 13C NMR
spectra were recorded on a 400 MHz NMR spectrometers. Chemical
shifts were reported in ppm downfield from tetramethylsilane with the
solvent resonance as the internal standard. MS and microanalysis were
performed in the state-authorized analytical center of Zhejiang Normal
University.
General Procedure for the Pd-Catalyzed Coupling of
Haloalkynes with Allyl Acetate. To a solution of 2a (75 mg,
0.75 mmol), Pd(OAc)2 (6.5 mg, 0.025 mmol), and 4,40-dimethoxy-2,20-
bipyridine (9.2 mg, 0.05 mmol) in 2.0 mL of HOAc was added 1a
(69 mg, 0.50 mmol) at rt. After stirring for 8 h at 80 °C, the reaction
mixture was quenched with water, extracted with dichloromethane,
washed with saturated NaHCO3 and brine, and dried over anhydrous
Na2SO4. Column chromatography on silica (petroleum ether/ethyl
acetate = 100/1) gave 101 mg (yield: 86%) of (Z)-3aa as a yellow oil.
1H NMR (CDCl3, 400 MHz): δ 2.21 (s, 3 H), 3.18 (d, J = 6.0 Hz, 2 H),
5.22 (dd, J = 10.0, 1.2 Hz, 1 H), 5.25 (dd, J = 16.0, 1.2 Hz, 1 H),
5.86ꢀ5.93 (m, 1 H), 7.36ꢀ7.42 (m, 5 H). 13C NMR (CDCl3, 100 MHz):
δ 20.4, 38.3, 117.5, 123.7, 128.1 (2 C), 128.2 (2 C), 128.9, 132.8, 133.4,
143.6, 167.7. MS (EI, m/z): 236 (M+, 2), 201 (18), 196 (22), 194 (100),
179 (13). Anal. Calcd for C13H13ClO2. HRMS (ESI): calcd 236.0604,
found 236.0605.
Scheme 3. Proposed Mechanism for Pd-Catalyzed Coupling
of Haloalkynes with Allyl Acetate
(Z)-2-Chloro-1-(4-fluorophenyl)penta-1,4-dienyl Acetate [(Z)-3ba].
Yield: 76% as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 2.20 (s, 3 H),
3.13 (dd, J = 5.6, 1.6 Hz, 2 H), 5.22 (dd, J = 10.2, 1.6 Hz, 1 H), 5.24
(dd, J = 17.2, 1.6 Hz, 1 H), 5.84ꢀ5.89 (m, 1 H), 7.03ꢀ7.08 (m, 2 H),
7.38ꢀ7.41 (m, 2 H). 13C NMR (CDCl3, 100 MHz): δ 20.3, 38.2, 115.3
(d, J = 21.0 Hz, 2 C), 117.5, 123.8, 129.4, 130.2 (d, J = 8.0 Hz, 2 C), 132.6,
142.7, 162.7 (d, J = 240.0 Hz), 167.7. MS (EI, m/z): 219 (M+ ꢀ 35Cl, 22),
214 (30), 212 (100), 197 (11), 177 (48). Anal. Calcd for C13H12ClFO2.
HRMS (ESI): calcd 254.0510, found 254.0511.
(Z)-2-Chloro-1-(4-chlorophenyl)penta-1,4-dienyl Acetate [(Z)-3ca].
Yield: 80% as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 2.20 (s, 3 H),
3.14 (d, J = 6.0 Hz, 2 H), 5.23 (dd, J = 17.2, 1.6 Hz, 1 H), 5.25 (dd, J =
10.8, 1.2 Hz, 1 H), 5.84ꢀ5.91 (m, 1 H), 7.33 (s, 4 H). 13C NMR
(CDCl3, 100 MHz): δ 20.3, 38.2, 117.6, 124.2 (2 C), 128.4 (2 C), 129.5,
131.8, 132.5, 134.9, 142.6, 167.7; MS (EI, m/z): 237 (10), 235 (M+ ꢀ
35Cl, 24), 230 (58), 228 (100), 195 (20), 193 (70). Anal. Calcd for
C13H12Cl2O2. HRMS (ESI): calcd 270.0214, found 270.0211.
(Z)-2-Chloro-1-(2-chlorophenyl)penta-1,4-dienyl Acetate [(Z)-3da].
Yield: 74% as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 2.17 (s, 3 H),
2.96 (d, J = 6.0 Hz, 2 H), 5.13 (dd, J = 11.2, 1.2 Hz, 1 H), 5.15 (dd, J =
17.2, 1.2 Hz, 1 H), 5.75ꢀ5.79 (m, 1 H), 7.25ꢀ7.33 (m, 2 H), 7.41ꢀ7.49
(m, 1 H), 7.50ꢀ7.51 (m, 1 H). 13C NMR (CDCl3, 100 MHz): δ 20.6,
38.4, 118.0, 126.1, 126.7, 129.8, 130.8, 132.3, 132.5, 132.6, 134.1, 140.9,
168.1. MS (EI, m/z): 237 (8), 235 (M+ ꢀ 35Cl, 24), 230 (62), 228 (100),
195 (23), 193 (75). Anal. Calcd for C13H12Cl2O2. HRMS (ESI): calcd
270.0214, found 270.0217.
palladium intermediate with the substituted allyl acetates (see the
proposed mechanism).
To demonstrate the synthetic utility of this protocol, we
further examined the resulting products in the transition-metal-
catalyzed cross-coupling reactions (Scheme 2). For instance,
(Z)-β-haloenol acetates (Z)-3aa and (Z)-3oa underwent the
SuzukiꢀMiyaura coupling31 with PhB(OH)2 in the presence of
Xphos32,33 to produce the highly functionalized enol acetate 4 in
72% and 81% yields, respectively. The X-ray analysis of 4 clearly
demonstrated the structure of the product. On the other hand,
the Sonogashira coupling34,35 of (Z)-3aa and (Z)-3oa occurred
uneventfully as well, providing the enol acetate 5 in 67% and 73%
yields, respectively. The generated enol acetate products may be
amenable to further chemical transformations.36ꢀ40
In view of the previous reports on the acetoxypalladation
reactions, we proposed a plausible mechanism in Scheme 3 to
account for this reaction. The reaction was initiated by the trans-
acetoxypalladation16ꢀ23 of haloalkyne 1 to form the alkenyl
palladium intermediate II. Then, the following carbopalladation
reaction of alkenylpalladium intermediate II with allyl acetate
resulted in an alkylpalladium complex III. Finally, the β-hetero-
atom elimination in the presence of nitrogen-containing ligand
furnished the (Z)-β-haloenol acetate product (Z)-3 and closed
the catalytic cycle (Scheme 3).
(Z)-2-Chloro-1-(4-bromophenyl)penta-1,4-dienyl Acetate [(Z)-3ea].
Yield: 81% as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 2.20 (s, 3 H),
3.14 (dt, J = 6.0, 1.2 Hz, 2 H), 5.21 (dd, J = 10.0, 1.6 Hz, 1 H), 5.24
(dd, J = 17.2, 1.6 Hz, 1 H), 5.84ꢀ5.91 (m, 1 H), 7.27ꢀ7.29 (m, 2 H),
7.50 (dd, J = 6.8, 2.0 Hz, 2 H). 13C NMR (CDCl3, 100 MHz): δ 20.3,
38.2, 117.6, 123.2, 124.3, 129.8 (2 C), 131.4 (2 C), 132.3, 132.5, 142.7,
167.7. MS (EI, m/z): 281 (13), 279 (M+ ꢀ 35Cl, 13), 276 (20), 274
In summary, we have developed a convenient and practical
method for the regio- and stereoselective synthesis of (Z)-
β-haloenol acetates via the palladium-catalyzed coupling of alkynyl
halides with allyl acetate under mild conditions. The synthetic
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NOTE
(100), 272 (72). Anal. Calcd for C13H12BrClO2. HRMS (ESI): calcd
313.9709, found 313.9713.
wR2 = 0.1373, largest diff peak and hole 0.225 and ꢀ0.266 e Åꢀ3
.
Crystallographic data for the structure (Z)-3ka have been deposited with
the Cambridge Crystallographic Data Centre as supplementary publica-
tion no. CCDC-823487.
(Z)-2-Chloro-1-(2-bromophenyl)penta-1,4-dienyl Acetate [(Z)-3fa].
Yield: 71% as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 2.18 (s, 3 H),
2.94 (d, J = 6.0 Hz, 2 H), 5.15 (dd, J = 16.8, 6.0 Hz, 2 H), 5.73ꢀ5.83 (m,
1 H), 7.21ꢀ7.26 (m, 1 H), 7.30ꢀ7.34 (m, 1 H), 7.49ꢀ7.51 (m, 1 H),
7.60ꢀ7.62 (m, 1 H). 13C NMR (CDCl3, 100 MHz): δ 20.6, 38.4, 118.0,
123.8, 126.0, 127.3, 130.9, 132.5, 132.8, 133.0, 134.3, 142.2, 168.0. MS
(EI, m/z): 281 (14), 279 (M+ ꢀ 35Cl, 14), 276 (20), 274 (79), 272 (60).
Anal. Calcd for C13H12BrClO2. HRMS (ESI): calcd 313.9709, found
313.9702.
(Z)-2-Chloro-1-p-tolylpenta-1,4-dienyl Acetate [(Z)-3ga]. Yield:
85% as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 2.21 (s, 3 H), 2.35
(s, 3 H), 3.20 (dd, J = 5.6, 1.2 Hz, 2 H), 5.23 (dd, J = 10.4, 1.2 Hz,
1 H), 5.26 (dd, J = 18.4, 1.2 Hz, 1 H), 5.87ꢀ5.94 (m, 1 H), 7.19 (d, J =
8.0 Hz, 2 H), 7.32 (d, J = 8.0 Hz, 2 H). 13C NMR (CDCl3, 100 MHz):
δ 20.4, 21.1, 38.3, 117.4, 123.2, 128.0 (2 C), 128.9 (2 C), 130.5, 133.0,
139.0, 143.7, 167.8. MS (EI, m/z): 210 (25), 208 (100), 193 (28), 173
(29), 157 (11). Anal. Calcd for C14H15ClO2. HRMS (ESI): calcd
250.0761, found 250.0768.
(Z)-2-Chloro-1-(4-methoxyphenyl)penta-1,4-dienyl Acetate [(Z)-3ha].
Yield: 70% as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 2.20 (s, 3 H),
3.16 (dd, J = 6.0, 1.6 Hz, 2 H), 3.81 (s, 3 H), 5.20 (dd, J = 10.0, 1.2 Hz,
1 H), 5.24 (dd, J = 17.6, 1.6 Hz, 1 H), 5.85ꢀ5.90 (m, 1 H), 6.88 (dd, J =
6.8, 2.0 Hz, 2 H), 7.33 (dd, J = 6.8, 2.0 Hz, 2 H). 13C NMR (CDCl3,
100 MHz): δ 20.4, 38.3, 55.0, 113.5 (2 C), 117.3, 122.7, 125.7, 129.6
(2 C), 133.0, 143.5, 159.9, 167.8. MS (EI, m/z): 268 (4), 266 (M+, 12),
226 (32), 224 (100), 189 (52). Anal. Calcd for C14H15ClO3. HRMS:
calcd 266.0710, found 266.0711.
(Z)-2-Chloro-1-(3-methoxyphenyl)penta-1,4-dienyl Acetate [(Z)-
3ia]. Yield: 73% as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 2.21
(s, 3 H), 3.20 (d, J = 5.6 Hz, 2 H), 3.79 (s, 3 H), 5.23 (d, J = 11.2 Hz,
1 H), 5.26 (d, J = 17.2 Hz, 1 H), 5.87ꢀ5.94 (m, 1 H), 6.89ꢀ7.00
(m, 3 H), 7.28ꢀ7.30 (m, 1 H). 13C NMR (CDCl3, 100 MHz): δ 20.6,
38.6, 55.3, 113.8, 114.9, 117.7, 120.8, 124.0, 129.5, 133.1, 134.8,
143.7, 159.4, 168.0. MS (EI, m/z): 266 (M+, 1), 231 (9), 226 (16),
224 (48), 209 (100). Anal. Calcd for C14H15ClO3. HRMS: calcd
266.0710, found 266.0711.
(Z)-2-Chloro-1-(2-methoxyphenyl)penta-1,4-dienyl Acetate [(Z)-
3ja]. Yield: 65% as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 2.15
(s, 3 H), 2.98 (d, J = 6.0 Hz, 2 H), 3.84 (s, 3 H), 5.13 (d, J = 16.0 Hz, 1 H),
5.15 (d, J = 10.0 Hz, 1 H), 5.75ꢀ5.83 (m, 1 H), 6.90ꢀ6.96 (m, 3 H),
7.33ꢀ7.37 (m, 1 H). 13C NMR (CDCl3, 100 MHz): δ 20.7, 38.6, 55.6,
111.0, 117.6, 120.3, 122.2, 124.8, 130.9, 131.6, 133.3, 140.5, 157.2, 168.0.
MS (EI, m/z): 266 (M+, 4), 233 (2), 231 (16), 226 (31), 224 (100).
Anal. Calcd for C14H15ClO3. HRMS: calcd 266.0710, found 266.0707.
(Z)-2-Chloro-1-(3,4-dimethoxyphenyl)penta-1,4-dienyl Acetate [(Z)-
3ka]. Yield: 77% as a colorless solid. Mp: 74ꢀ76 °C. 1H NMR (CDCl3,
400 MHz): δ 2.19 (s, 3 H), 3.16 (dd, J = 7.2, 3.2 Hz, 2 H), 3.84 (s, 3 H),
3.87 (s, 3 H), 5.20 (dd, J = 10.4, 1.6 Hz, 1 H), 5.25 (dd, J = 17.6, 1.2 Hz,
1 H), 5.86ꢀ5.90 (m, 1 H), 6.83 (d, J = 8.0 Hz, 1 H), 6.90 (d, J = 2.0 Hz,
1 H), 6.95ꢀ6.98 (m, 1 H). 13C NMR (CDCl3, 100 MHz): δ 20.7, 38.7,
55.9 (2 C), 110.7, 111.3, 117.6, 121.3, 123.1, 126.1, 133.3, 143.8, 148.6,
149.7, 168.2. MS (EI, m/z): 298 (10), 296 (M+, 30), 256 (30), 254
(100), 239 (83). Anal. Calcd for C15H17ClO4. HRMS: calcd 296.0815,
found 296.0816.
(Z)-2-Chloro-1-(2,4-dichlorophenyl)penta-1,4-dienyl Acetate [(Z)-
3la]. Yield: 72% as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 2.17
(s, 3 H), 2.94 (d, J = 6.0 Hz, 2 H), 5.12 (dd, J = 11.6, 1.2 Hz, 1 H), 5.14
(dd, J = 15.6, 1.6 Hz, 1 H), 5.78ꢀ5.80 (m, 1 H), 7.24ꢀ7.27 (m, 1 H),
7.43 (dd, J = 8.4, 1.6 Hz, 2 H). 13C NMR (CDCl3, 100 MHz): δ 20.5,
38.3, 118.1, 126.6, 127.1, 129.7, 130.8, 132.3, 133.3, 135.0, 136.2, 139.9,
168.0. MS (EI, m/z): 273 (3), 271 (16), 269 (M+ ꢀ 35Cl, 26), 266 (31),
264 (96), 262 (100). Anal. Calcd for C13H11Cl3O2. HRMS (ESI): calcd
303.9825, found 303.9833.
(Z)-2-Chloro-1-(4-isopropylphenyl)penta-1,4-dienyl Acetate [(Z)-
3ma]. Yield: 71% as a yellow oil. 1H NMR (CDCl3, 400 MHz):
δ 1.22 (d, J = 8.8 Hz, 3 H), 1.25 (d, J = 6.0 Hz, 3 H), 2.18 (s, 3 H),
2.88ꢀ2.92 (m, 1 H), 3.18 (dd, J = 5.6, 1.2 Hz, 2 H), 5.21 (dd, J = 12.0, 1.6
Hz, 1 H), 5.25 (dd, J = 17.6, 1.6 Hz, 1 H), 5.86ꢀ5.93 (m, 1 H), 7.21
(d, J = 8.4 Hz, 2 H), 7.31 (d, J = 8.0 Hz, 2 H). 13C NMR (CDCl3,
100 MHz): δ 20.7, 23.8 (2 C), 34.0, 38.6, 117.7, 123.5, 126.5 (2 C),
128.3 (2 C), 130.0, 133.3, 144.0, 150.0, 168.1. MS (EI, m/z): 280 (1),
278 (M+, 3), 238 (32), 236 (100), 193 (62). Anal. Calcd for C16H19ClO2.
HRMS: calcd 278.1074, found 278.1073.
(Z)-2-Chloro-1-(4-tert-butylphenyl)penta-1,4-dienyl Acetate [(Z)-
1
3na]. Yield: 80% as a yellow oil. H NMR (CDCl3, 400 MHz): δ
1.34 (s, 9 H), 2.21 (s, 3 H), 3.22 (dt, J = 6.0, 1.6 Hz, 2 H), 5.24 (dd, J =
10.6, 1.6 Hz, 1 H), 5.28 (dd, J = 17.2, 1.6 Hz, 1 H), 5.88ꢀ5.93 (m, 1 H),
7.34ꢀ7.41 (m, 4H). 13C NMR (CDCl3, 100 MHz): δ 20.7, 31.2 (2 C),
34.8, 38.6, 117.7, 123.5, 125.4 (2 C), 128.1 (2 C), 130.7, 133.3, 144.0,
152.3, 168.1. MS (EI, m/z): 294 (1), 292 (M+, 3), 257 (14), 252 (32),
250 (100), 235 (70). Anal. Calcd for C17H21ClO2. HRMS: calcd
292.1230, found 292.1231.
(Z)-2-Bromo-1-phenylpenta-1,4-dienyl Acetate [(Z)-3oa]. Yield:
1
74% as a yellow oil. H NMR (CDCl3, 400 MHz): δ 2.20 (s, 3 H),
3.28 (dd, J = 5.6, 4.4 Hz, 2 H), 5.22 (dd, J = 10.0, 1.6 Hz, 1 H), 5.26
(dd, J = 17.2, 1.2 Hz, 1 H), 5.85ꢀ5.92 (m, 1 H), 7.35ꢀ7.43 (m, 5 H). 13C
NMR (CDCl3, 100 MHz): δ 20.5, 39.8, 115.9, 117.4, 128.1 (2 C), 128.2
(2 C), 128.3, 128.9, 133.4, 145.5, 167.7. MS (EI, m/z): 240 (32), 238
(34), 202 (13), 201 (100), 159 (31). Anal. Calcd for C13H13BrO2.
HRMS (ESI): calcd 280.0099, found 280.0102.
(Z)-2-Bromo-1-(4-chlorophenyl)penta-1,4-dienyl Acetate [(Z)-3pa].
Yield: 77% as a yellow oil. 1H NMR (CDCl3, 400 MHz): δ 2.24 (s, 3 H),
3.25 (dd, J = 4.0, 1.2 Hz, 2H), 5.23 (dd, J = 11.2, 1.2 Hz, 1 H), 5.26
(dd, J = 16.0, 1.6 Hz, 1 H), 5.82ꢀ5.90 (m, 1 H), 7.34 (s, 4 H). 13C NMR
(CDCl3, 100 MHz): δ 20.5, 39.8, 116.3, 117.6, 128.5 (2 C), 129.4 (2 C),
131.8, 133.1, 135.0, 144.4, 167.7. MS (EI, m/z): 276 (11), 274 (50),
272 (40), 195 (5), 193 (16). Anal. Calcd for C13H12BrClO2. HRMS
(ESI): calcd 313.9709, found 313.9707.
(Z)-2-Chloro-1-pentyl-penta-1,4-dienyl Acetate [(Z)-3qa]. Yield:
75% as a colorless oil. 1H NMR (CDCl3, 400 MHz): δ 0.88 (t, J = 6.8
Hz, 3 H), 1.25ꢀ1.34 (m, 4 H), 1.41ꢀ1.48 (m, 2 H), 2.20 (s, 3 H), 2.29
(t, J = 7.6 Hz, 2 H), 3.13 (d, J = 6.0 Hz, 2 H), 5.14 (dd, J = 10.2, 1.6 Hz, 1
H), 5.20 (dd, J = 17.2, 1.6 Hz, 1 H), 5.74ꢀ5.85 (m, 1 H). 13C NMR
(CDCl3, 100 MHz): δ 13.7, 20.3, 22.1, 26.2, 30.2, 31.0, 37.7, 117.0,
120.2, 132.6, 145.3, 167.8. MS (EI, m/z): 195 (M+
(30), 188 (100), 161 (3), 159 (7). Anal. Calcd for C12H19ClO2. HRMS
(ESI): calcd 230.1074, found 230.1068.
ꢀ
35Cl, 22), 190
Crystal data for (Z)-3ka (C15H17ClO4, 296.08): triclinic, space group
P1, a = 8.9785(9) Å, b = 11.6414(12) Å, c = 14.8917(17) Å, U =
1486.9(3) Å3, Z = 4, specimen 0.254 ꢁ 0.102 ꢁ 0.045 mm3, T = 296(2)
(Z)-4-Chloro-1-tert-butyldimethylsilyloxy-hepta-3,6-dien-3-yl Acet-
ate [(Z)-3ra]. Yield: 72% as a colorless oil. 1H NMR (CDCl3, 400 MHz):
δ 0.04 (s, 6 H), 0.88 (s, 9 H), 2.19 (s, 3 H), 2.52 (t, J = 6.4 Hz, 2 H), 3.15
(d, J = 6.0 Hz, 2 H), 3.70 (t, J = 6.6 Hz, 2 H), 5.14 (dd, J = 10.0, 1.2 Hz, 1
H), 5.21 (dd, J = 17.2, 1.6 Hz, 1 H), 5.78ꢀ5.85 (m, 1 H). 13C NMR
(CDCl3, 100 MHz):δ ꢀ5.7, 18.0, 20.3, 25.6, 34.1, 37.7, 59.7, 117.1, 122.1,
132.6, 142.4, 167.8. MS (EI, m/z): 263 (14), 261 (M+ ꢀ But, 40),
K, SIEMENS P4 diffractometer, absorption coefficient 0.267 mmꢀ1
,
reflections collected 23 798, independent reflections 6784 [R(int) =
0.0337], refinement by full-matrix least-squares on F2, data/restraints/
parameters 6784/0/367, goodness-of-fit on F2 = 1.029, final R indices
[I > 2σ(I)] R1 = 0.0446, wR2 = 0.1188, R indices (all data) R1 = 0.0797,
6341
dx.doi.org/10.1021/jo2005318 |J. Org. Chem. 2011, 76, 6338–6343

The Journal of Organic Chemistry
NOTE
221 (34), 219 (100), 189 (67). Anal. Calcd for C15H27ClO3Si. HRMS
(ESI): calcd 318.1418, found 318.1414.
(Z)-4-Chloro-1-phenoxyhepta-3,6-dien-3-yl Acetate [(Z)-3sa].
’ AUTHOR INFORMATION
Corresponding Author
*E-mail: gangguo@zjnu.cn
1
Yield: 82% as a colorless oil. H NMR (CDCl3, 400 MHz): δ 2.17
(s, 3 H), 2.64 (t, J = 6.4 Hz, 2 H), 3.17 (t, J = 6.0 Hz, 2 H), 3.58 (t, J = 6.4
Hz, 2 H), 4.52 (s, 2 H), 5.13 (dd, J = 10.4, 1.6 Hz, 1 H), 5.21 (dd, J = 17.2,
1.6 Hz, 1 H), 5.78ꢀ5.82 (m, 1 H), 7.30ꢀ7.37 (m, 5 H). 13C NMR
(CDCl3, 100 MHz): δ 20.6, 31.5, 38.1, 66.9, 73.1, 117.4, 122.4, 127.6
(2 C), 127.7, 128.4 (2 C), 132.8, 138.1, 142.6, 168.1. MS (EI, m/z): 294
(M+, 1) 259 (8), 252 (12), 234 (10), 163 (32), 161 (94). Anal. Calcd for
C16H19ClO3. HRMS: calcd 294.1023, found 294.1022.
’ ACKNOWLEDGMENT
We greatly thank the National Natural Science Foundation of
China (No. 20902084), Qianjiang Talents Project of the Science
and Technology Office in Zhejiang Province (2010R10016) and
Zhejiang Normal University for their financial support.
Compound 4. To a mixture of PhB(OH)2 (92 mg, 1.5 mmol),
Pd(OAc)2 (5.6 mg, 0.025 mmol), K3PO4 (1.5 mmol), and Xphos
(23.8 mg, 0.05 mmol) in 1 mL of toluene was added a solution of
(Z)-3aa (119 mg, 0.5 mmol) in 1 mL of toluene under nitrogen. After
stirring at 110 °C for 10 h, the reaction mixture was quenched with
water, extracted with ethyl acetate, washed with brine, dried over
Na2SO4, and concentrated. Column chromatography on silica (petroleum
ether/ethyl acetate = 70/1) gave 100 mg (yield: 72%) of 4 as a yellow
solid. The β-haloenol acetate (Z)-3oa was subjected to the same
procedure to yield compound 4 in 81% yield. Mp: 69ꢀ71 °C. 1H
NMR (CDCl3, 400 MHz): δ 1.87 (s, 3 H), 3.25 (dt, J = 4.8, 1.2 Hz, 2 H),
5.04 (dd, J = 10.4, 1.6 Hz, 1 H), 5.12 (dd, J = 17.2, 1.6 Hz, 1 H), 5.75ꢀ
5.79 (m, 1 H), 7.32ꢀ7.40 (m, 8 H), 7.52ꢀ7.55 (m, 2 H). 13C NMR
(CDCl3, 100 MHz): δ 20.8, 37.6, 116.7, 127.2, 128.1 (2 C), 128.2 (2 C),
128.3 (2 C), 128.5 (2 C), 128.6 (2 C), 135.2, 135.5, 138.7, 143.7, 169.7.
MS (EI, m/z): 278 (M+, 3), 237 (100), 236 (32), 195 (62), 194 (15).
Anal. Calcd for C19H18O2. HRMS: calcd 278.1307, found 278.1310.
Crystal data for 4 (C19H18O2, 278.35): orthorhombic, space group
P2(1)2(1)2(1), a = 9.4980(5) Å, b = 16.8744(8) Å, c = 19.4763(10)Å,
U = 3121.5(3) Å3, Z = 8, specimen 0.431 ꢁ 0.282 ꢁ 0.153 mm3,
T = 296(2) K, SIEMENS P4 diffractometer, absorption coefficient
0.076 mmꢀ1, reflections collected 42 922, independent reflections 5503
[R(int) = 0.0416], refinement by Full-matrix least-squares on F2, data/
restraints/parameters 5503/2/381, goodness-of-fit on F2 = 1.057, final R
indices [I > 2σ(I)] R1 = 0.0426, wR2 = 0.1107, R indices (all data)
R1 = 0.0499, wR2 = 0.1159, largest diff peak and hole 0.185 and
ꢀ0.146 e Åꢀ3. Crystallographic data for the compound 4 have been
deposited with the Cambridge Crystallographic Data Centre as supple-
mentary publication no. CCDC-816364.
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Compound 5. To a mixture of (Z)-3aa (119 mg, 0.50 mmol),
Pd(CH3CN)2Cl2 (6.5 mg, 0.025 mmol), Cs2CO3 (2 equiv), and Xphos
(23.8 mg, 0.05 mmol) in 1 mL of toluene was added a solution of
phenylacetylene (110 μL, 1 mmol) in 1 mL of dry toluene under
nitrogen. After stirring at 110 °C for 10 h, the reaction mixture was
quenched with water, extracted with ethyl acetate, washed with saturated
brine, and dried over Na2SO4. Column chromatography on silica
(petroleum ether/ethyl acetate = 70/1) gave 102 mg (yield: 67%) of
5 as a yellow oil. The β-haloenol acetate (Z)-3oa was subjected to the
1
same procedure at 80 °C to generate compound 5 in 73% yield. H
NMR (CDCl3, 400 MHz): δ 2.26 (s, 3 H), 3.12 (d, J = 6.0 Hz, 2 H), 5.19
(dd, J = 10.4, 1.2 Hz, 1 H), 5.27 (dd, J = 16.8, 1.2 Hz, 1 H), 5.98ꢀ6.05
(m, 1 H), 7.32ꢀ7.46 (m, 10 H). 13C NMR (CDCl3, 100 MHz): δ 20.9,
35.8, 86.3, 95.8, 112.0, 116.8, 123.2, 128.2 (2 C), 128.3 (3 C), 128.4 (2 C),
129.1, 131.5 (2 C), 134.1, 134.7, 151.7, 168.7. MS (EI, m/z): 302 (M+, 4),
261 (16), 260 (14), 219 (3), 201 (3). Anal. Calcd for C21H18O2. HRMS:
calcd 302.1307, found 302.1313.
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S
Supporting Information. Spectroscopic data of the pro-
b
ducts and crystallographic data of (Z)-3ka and compound 4.
This material is available free of charge via the Internet at
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