Cross-metathesis of allyl halides with olefins bearing amide and ester groups

Article abstract of DOI:10.1016/j.tet.2011.11.064

An investigation was conducted to determine whether the cross-metathesis (CM) of allyl halides tolerates amide groups. The results show that the ruthenium-based complexes I-III serve as poor catalysts for the CM of allyl halides with olefins that contain an N,N-dimethylamide group. In contrast, the Grubbs-Hoveyda-Blechert second generation catalyst (III) efficiently promotes these processes with olefins bearing a Weinreb amide group. Lastly, a reinvestigation of the ester group tolerance of the allyl halide CM with unsaturated esters demonstrated that III serves as an efficient catalyst for these reactions.

Full text of DOI:10.1016/j.tet.2011.11.064

Tetrahedron 68 (2012) 1177e1184
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Cross-metathesis of allyl halides with olefins bearing amide and ester groupsq
,
,
Jeong In Yun a b, Hyoung Rae Kim a, Sang Kyum Kim b, Deukjoon Kim c, Jongkook Lee a
*
a Bio-Organic Science Division, Korea Research Institute of Chemical Technology, PO Box 107, Yuseong, Deajeon 305-600, Republic of Korea
b College of Pharmacy, Chungnam University, 99 Daehak-ro, Yuseong, Deajeon 305-764, Republic of Korea
c The Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, San56-1, Shillim-Dong, Kwanak-Ku, Seoul 151-742, Republic of Korea
a r t i c l e i n f o
a b s t r a c t
Article history:
An investigation was conducted to determine whether the cross-metathesis (CM) of allyl halides toler-
ates amide groups. The results show that the ruthenium-based complexes IeIII serve as poor catalysts
for the CM of allyl halides with olefins that contain an N,N-dimethylamide group. In contrast, the
GrubbseHoveydaeBlechert second generation catalyst (III) efficiently promotes these processes with
olefins bearing a Weinreb amide group. Lastly, a reinvestigation of the ester group tolerance of the allyl
halide CM with unsaturated esters demonstrated that III serves as an efficient catalyst for these
reactions.
Received 9 September 2011
Received in revised form 22 November 2011
Accepted 22 November 2011
Available online 28 November 2011
Keywords:
Cross-metathesis
Allyl halide
Ó 2011 Elsevier Ltd. All rights reserved.
Weinreb amide
GrubbseHoveydaeBlechert second
generation catalyst
1. Introduction
whether the CM of allyl halides can tolerate an amide group.9 We
now describe our successful use of allyl halide CM to synthesize
The cross-metathesis (CM) of allyl halides serves as a useful
synthetic tool for the introduction of an allyl halide moiety into
organic substances. In natural product syntheses, an allyl halide
moiety is typically incorporated into a structure by performing an
olefinationereductionehalogenation sequence on a preexisting al-
dehyde.1 The CM of allyl halides is both atom- and step-economical
because the process plays the role of a synthetic shortcut,
substituting a single step for several functional group trans-
formations. As a result, following the emergence of ruthenium-
based catalysts, such as the Grubbs catalyst (I),2 Grubbs second
generation catalyst (II),3 and GrubbseHoveydaeBlechert second
generation catalyst (III)4 (Fig. 1), several groups have investigated
the utility of CM in the synthesis of functionalized allyl halides.5 The
results of these studies show that the process tolerates a variety of
functional groups including ester, cyanide, benzyl ether, silyl ether,
and the hydroxyl group. The CM of allyl halides has also been
employed successfully in the syntheses of several natural products,
such as subglutinol B,6 diospongin A,7 and spongidepsin.8 Amide
and ester groups are common functional groups in organic com-
pounds. The tolerance of ester groups to allyl halide CM has been
investigated, but few reports have yet appeared that address
functionalized allyl halides that bear amide and ester groups in the
presence or absence of an
a
-alkoxy amide group.10
Fig. 1. Grubbs catalyst (I), Grubbs second generation catalyst (II), and
GrubbseHoveydaeBlechert second generation catalyst (III).
2. Results and discussion
We first examined the tolerance of allyl halide CM to a-alkoxy
amide groups, which are frequently used in natural product syn-
thesis due to their strong chelation of metal cations, such as Liþ, Naþ,
Mg2þ, and Kþ.11 The examination commenced with the synthesis of
a-alkoxy amide 6b by the SN2 reaction of pentenol 3 with chlor-
oacetamide 1 (Scheme 1).12 The CM of allyl chloride with the N,N-
dimethylamide 6b was performed in the presence of catalysts IeIII.
Contrary to our expectations, the reaction with amide 6b did not
produce allyl halides 13a,b, and most of the starting material was
recovered (Table 1, entry 1). We hypothesized that the N,N-dime-
thylamide group of 6b may behave as a ligand for ruthenium com-
plexes IeIII,13 and reasoned that bulkyalkyl substituents or electron-
q
Taken in part from the Master’s thesis of J.I. Yun, Korea University, 2011.
* Corresponding author. Tel.: þ82 42 860 7178; fax: þ82 42 860 7160; e-mail
address: jongkook@krict.re.kr (J. Lee).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.11.064

1178
J.I. Yun et al. / Tetrahedron 68 (2012) 1177e1184
performed allyl halide CM with N-tosylated amide 12, which was
prepared by coupling of 9b with sulfonamide 11. Amide 12 also un-
derwent smooth CM with allyl halides to produce 13g,h in good
yields (Table 1, entries 9 and 10). These results strongly indicate that
the putative inactivation of ruthenium complexes IeIII is attributed
to the N,N-dimethylamide group of 6b. In contrast to catalyst III, the
CM of allyl halides with Weinreb amide 10b was not promoted to any
appreciable extent by I or II (Table 1, entry 5).
The effect of the distance between the amide group and the
terminal olefin moiety on the success of the CM of unsaturated
amides with allyl halides promoted by III was also explored. Wil-
liamson ether synthesis of alcohols 2, 4, and 5 with chlor-
oacetamide 1 afforded the corresponding N,N-dimethylamides
6a,c,d. Readily available carboxylic acids 9a,c,d14 were converted to
10a,c,d by coupling with N-methoxy-N-methylamine (Scheme 1).
The CM of allyl halides with N,N-dimethylamides 6a,c,d did not
produce 14aec, but the Weinreb amides 10a,c,d were observed to
undergo smooth CM to generate 14dei in good yields (Table 2).
Interestingly, the high E/Z selectivity of the reactions with a-ally-
Scheme 1. Reagent and conditions: (i) NaH, THF, prop-2-en-1-ol (2)/pent-4-en-1-ol
(3)/hept-5-en-1-ol (4)/dec-9-en-1-ol (5), rt, overnight, 63e94%; (ii) Me(MeO)NH, hy-
droxybenzotriazole (HOBt), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDCI),
Et3N, CH2Cl2, rt, overnight, 78e90%; (iii) (COCl)2, DMF, benzene, rt, overnight then
Et3N, CH2Cl2 rt, overnight, 63%.
loxyamide 10a was observed compared to that of the reactions with
10bed (16e20:1 vs 6:1, Table 2, entries 2 and 3). The results further
substantiate our hypothesis that an N,N-dimethylamide group
causes the inactivation of the ruthenium-based catalysts IeIII.
Table 2
Table 1
Effect of the distance between an amide group and olefin moiety on the cross-
metathesis of allyl halides
Cross-metathesis of allyl halides in the presence of a-alkoxy amides
h
, 12
Entry Compound
R
X
Conditions
Yield (%)
Ratio
Entry Compound
R
X
Conditions
Yield %
Ratio
E/Za
E/Za
1
6a, c or d
(n¼1, 5, or 8)
10a, n¼1
10a, n¼1
10c, n¼5
10c, n¼5
10d, n¼8
10d, n¼8
NMe2
Cl 10 mol %, 24 h 14aec, Nb
1
2
6b
8
NMe2
Cl,
I, II or III (10 mol %), 13a,b, Nb
or Br 24 h
Cl
2
3
4
5
6
7
N(OMe)Me Cl 20 mol %,c 3 h
N(OMe)Me Br 10 mol %, 3 h
14d, 74
14e, 65
20:1
16:1
6:1
6:1
6:1
N(i-Pr)2
I or II (10 mol %),
13c, <10
24 h
N(OMe)Me Cl 20 mol %,c 3 h 14f, 97
3
8
N(i-Pr)2
N(i-Pr)2
N(OMe)Me Cl
N(OMe)Me Cl
N(OMe)Me Br
N(OMe)Me Br
Cl
Br
III (20 mol %),c 4 h
III (20 mol %),c 4 h
13c, 53
13d, 44
8:1
5:1
N(OMe)Me Br 10 mol %, 2 h
N(OMe)Me Cl 20 mol %,c 2 h 14h, 95
N(OMe)Me Br 10 mol %, 2 h 14i, 88
14g, 89
4
8
5
6
7
8
10b
10b
10b
10b
12
I or II (10 mol %), 3 h 13e, Nb
6:1
III (20 mol %),c 5 h
III (10 mol %), 2 h
III (10 mol %), 4 h
III (20 mol %), 3 h
III (20 mol %), 3 h
13e, 69
13f, 90
9:1
7:1
a
The ratio was determined by the analysis of 1H 500 MHz NMR spectra.
b
13f, 48d 5:1
No product formation was detected and most of the starting material was
9
N(Ts)Me
N(Ts)Me
Cl
Br
13g, 80
13h, 88
8:1
6:1
recovered.
c
10
12
Total 20 mol % (time 0, 10 mol %; time 2 h, 10 mol %) of III was used to complete
the reaction.
a
The ratio was determined by the analysis of 1H 500 MHz NMR spectra.
b
No product formation was detected and most of the starting material was
recovered.
Encouraged by the results, we investigated the CM of allyl ha-
lides with olefins that possess an amide group, but do not contain
an -alkoxy group. The investigation commenced with the syn-
thesis of substrates for CM with allyl halides. -Octenoic acid (15d)
c
Total 20 mol % (time 0, 10 mol %; time 2 h, 10 mol %) of III was used to complete
the reaction.
a
d
Allyl bromide (3 equiv) was used and 34% of 10b was recovered.
u
was transformed into amides 16d, 17d, and 18d by coupling with
the corresponding amines as shown in Scheme 2. Studies of the CM
of allyl chloride with N,N-dimethylamide 16d showed that catalysts
IeIII promoted inefficient processes that furnished 19a (Table 3,
entry 1) along with mainly the recovered starting material. Like-
wise, the N,N-diisopropylamide 17d underwent highly inefficient
CM with allyl chloride catalyzed by III to generate 19b in low yield.
In contrast, the analogous Weinreb amide 18d was transformed in
high yields to the respective allyl halides 19c and 19d by CM with
allyl chloride and bromide (Table 1, entries 2e4). These results also
indicate that the N,N-dimethylamide group in 16d impedes the CM
of allyl halides catalyzed by IeIII. However, the Weinreb amide
group in 18d, which contains an electron-withdrawing methoxy
group, does not serve to deactivate III. Finally, the results also
suggest that the bulky N,N-diisopropylamide group does not suf-
ficiently hinder disfavored interactions of the amide with catalyst
withdrawing groups might prevent disfavorable interactions with
IeIII. Williamson ether synthesis of pentenol with chlor-
3
oacetamide 7 and coupling of acid 9b with N-methoxymethylamine
led to the formation of amides 8 and 10b, respectively. Although the
conversion was incomplete, bulky N,N-diisopropylamide 8 un-
derwent CM with allyl halides promoted by catalyst III to produce
allyl halides 13c,d in 53% and 44% yields, respectively (50e60%
conversion, Table 1, entries 3 and 4). To our delight, the CM of allyl
halides with Weinreb amide 10b, which contains an electron-
withdrawing N-methoxy group, proceeded completely to generate
allyl halides 13e,f in the presence of III in 69% and 90% yields, re-
spectively (Table 1, entries 6 and 7). It was necessary to use a large
excess of allyl halides for the complete conversion of 10b, probably
due to the homo-CM of allyl halides (Table 1, entry 8). To further
address the effect of electron-withdrawing groups in amides, we
III in the absence of an electron-withdrawing a-alkoxy group.

J.I. Yun et al. / Tetrahedron 68 (2012) 1177e1184
1179
Table 4
Effect of the distance between an amide group and an olefin moiety on the cross-
metathesis of allyl halides
Entry Compound
R
X
Conditions
Ratio E/Za Yield %
20a, <10
Scheme 2. Reagent and conditions: (i) hydroxybenzotriazole (HOBt), 1-ethyl-3-(3-
dimethylaminopropyl)carbodiimide (EDCI), Me2NH/i-Pr2NH/Me(MeO)NH, Et3N,
CH2Cl2, rt, overnight, 78e90%.
1
2
3
4
5
6
7
8
16a, n¼0
16b, n¼1
16c, n¼3
16e, n¼7
18a, n¼0
18a, n¼0
18b, n¼1
18b, n¼1
18c, n¼3
18c, n¼3
18e, n¼7
18e, n¼7
NMe2
NMe2
NMe2
NMe2
Cl III (10 mol %), 24 h
Cl III (10 mol %), 24 h
Cl III (10 mol %), 24 h
Cl III (10 mol %), 24 h
34:1
11:1
20b, 38
20c, 33
20d, <10
20e, 36
20f, 18
20g, 59
20h, 26
20i, 75
20j, 70
20k, 90
20l, 71
N(OMe)Me Cl III (10 mol %), 18 h >99:1
Table 3
N(OMe)Me Br III (10 mol %), 24 h
N(OMe)Me Cl III (10 mol %), 28 h
N(OMe)Me Br III (10 mol %), 24 h
N(OMe)Me Cl III (10 mol %), 1 h
N(OMe)Me Br III (10 mol %), 1 h
N(OMe)Me Cl III (10 mol %), 1 h
N(OMe)Me Br III (10 mol %), 1 h
46:1
10:1
28:1
12:1
6:1
Cross-metathesis of allyl halides in the presence of substituted amides
9
10
11
12
8:1
6:1
a
The ratio was determined by the analysis of 1H 500 MHz NMR spectra.
Entry Compound
R
X
Conditions
Ratio Yield %
E/Za
1
16d
NMe2
Cl IeIII (10 mol %),
24 h
Cl III (10 mol %), 24 h
19a, <20
19b, <10
19c, 68
19d, 75
2
3
4
17d
18d
18d
N(i-Pr)2
N(OMe)Me Cl III (10 mol %), 1 h
N(OMe)Me Br III (10 mol %), 1 h
6:1
6:1
a
The ratio was determined by the analysis of 1H 500 MHz NMR spectra.
Fig. 2. Proposed intermediates of allyl halide CM with Weinreb amides 18a,b.
We next sought to examine the effect of the distance between
the amide group and terminal olefin moiety on the efficiency of CM
of allyl halides with substrates, that do not bear an -alkoxy group,
a
halides with ester group-containing substrates when ruthenium
complex III was employed as a catalyst. In the reported cases,
functionalized allyl halides were formed in moderate to good
yields.5dej We observed that the CM of allyl halides with 22a, pro-
moted by 2 mol % of III utilizing UmanieRonchi’s conditions at room
temperature, generated allyl chloride 24a in only a low yield even
though the starting material was completely consumed (Table 4,
entry 1). An exploration of this reaction using a variety of conditions
demonstrated that 24a is produced in 71% yield when 10 mol % of III
is employed (Table 5, entry 2). We expected that ester 22a would be
efficiently converted to 24a under the conditions that we developed
for the CM of allyl halides with amide-containing olefins (see above).
In fact, Howell and co-workers carried out the CM of allyl halides
catalyzed by III. Coupling reactions of carboxylic acids 15aec,e with
amines were employed to produce the corresponding amides
16aec,e and 18aec,e (Scheme 2). Interestingly, the CM of allyl ha-
lides with N,N-dimethylamides 16b,c generated the expected
products 20b,c in moderately low yields with good E/Z selectivity.
In addition, only trace quantities of 20a,d were generated in the
reactions of the acrylamide 16a and decenoic acid amide 16e, re-
spectively (Table 4, entries 1e4). However, the Weinreb amides
18c,e underwent smooth CM to produce 20iel in high yields (Table
4, entries 9e12). The CM of allyl halides with the Weinreb amides
18a,b proceeded very slowly and produced 20eeh in moderate or
low yields (Table 4, entries 5e7). The slow reaction rates and low
yields of this reaction with 18a,b might be attributed to the for-
mation of the corresponding stable five or six-membered reaction
intermediates IV and V (Fig. 2),3c,4a,15 and/or the instability of the
products 20eeh. The results indicate that the CM of allyl halides
with unsaturated amides is dependent on the distance between the
amide group and the terminal alkene moiety.
with a
-methylene lactones in similar conditions.5f,g Interestingly, we
observed that ester 22a was transformed into 24a by using catalyst
III (10 mol %, reflux, 1 h) in nearly quantitative yield with only
a slight loss of E/Z selectivity (5:1, Table 5, entry 3) compared to the
process performed at room temperature (E/Z, 6:1, Table 5, entry 2).
The CM between allyl bromide and ester 22a also proceeded
smoothly to produce 24b in high yield (Table 5, entry 4). Methyl
esters 22b and 23, generated, respectively, by an SN2 reaction of
It has been reported that ruthenium-based catalysts IeIII pro-
mote the CM of substrates that contain ester groups, although the
level of tolerance has not been investigated thoroughly. As a result,
our attention was next turned to an exploration of the CM of allyl
halides with olefins bearing ester groups. tert-Butyl ester 22a was
prepared from the commercially available bromoacetate 21a by
bromoacetate 21b with pentenol 3 and the esterification of
u-
octenoic acid (15d) (Scheme 3), were both observed to undergo CM
to afford 24cef in moderate to good yields (Table 5, entries 7e10).
The results indicate that an a-alkoxy group improves the reaction
using Williamson ether synthesis with pentenol 3 (Scheme 2).16
A
rates and yields of allyl halide CM with olefins bearing an ester
group. We also investigated the effect of amide groups on the CM of
allyl chloride with ester 22a. The reaction was catalyzed by III in the
presence of either amide 25 or 26 (Fig. 3). N,N-Dimethylamide 25
inhibited the CM of allyl chloride with 22a promoted by III to pro-
duce 24a in 39% yield along with 31% of the recovered starting ma-
terial. However, the reaction proceeded completely to produce 24a
in high yield in the presence of an excess amount of Weinreb amide
26 (Table 5, entries 5 and 6). The results further demonstrate that an
N,N-dimethylamide group is responsible for any disfavorable in-
teractions with catalysts IeIII.
variety of conditions for the CM of 22a with allyl halides were ex-
amined including those described in the literature. We observed that
22a was converted to the allyl chloride 24a in only trace amounts by
CM with allyl chloride, promoted by Grubbs catalyst (I) under a va-
rietyof conditions.5a Inprevious studies, Royand Yamamoto showed
that the CM of allyl halides with olefins bearing an ester group,
promoted by using 10 mol % of II, gave functionalized allyl halides in
good yields.5b,c However, the CM of the unsaturated ester 22a was
inefficiently catalyzed by II, and most of the starting material was
recovered. A few research groups have reported on the CM of allyl

1180
J.I. Yun et al. / Tetrahedron 68 (2012) 1177e1184
Table 5
4. Experimental
Cross-metathesis of allyl halides with unsaturated esters
4.1. General experimental
All reactions were performed under an atmosphere of dry ni-
trogen in dry glassware with magnetic stirring. All compounds were
purified by flash column chromatography on silica gel (Merck Kie-
selgel 60, 230e400 mesh) and reaction progress was monitored by
thin layer chromatography with a Merck pre-coated TLC plate (silica
gel 60 GF254, 0.25 mm). Nuclear magnetic resonance (1H NMR and
13C NMR) spectra were recorded on a Varian Gemini 300 [300 MHz
23
Entry Compound
R
X
Y
Conditions
Ratio Yield %
E/Za
(1H), 75 MHz
(
13C)] spectrometer or Bruker HRMASFT-NMR
1
2
3
4
5
22a
22a
22a
22a
22a
t-Bu Cl
t-Bu Cl
t-Bu Cl
t-Bu Br
t-Bu Cl
O
O
O
O
O
III (2 mol %), rt, 2 h
6:1 24a, 24
6:1 24a, 71
5:1 24a, 94
5:1 24b, 95
III (10 mol %), rt, 3 h
III (10 mol %), reflux, 1 h
III (10 mol %), reflux, 1 h
[500 MHz (1H)] spectrometer, using CDCl3 as the solvent, and
chemical shifts are reported in parts per million downfield from the
TMS internal standard. High-resolution mass spectra (HRMS) were
measured on a JMS-700 mass spectrometer (JEOL Ltd., Tokyo, Japan).
III (10 mol %), 25 (5 equiv), 5:1 24a, 39b
reflux, 24 h
6
22a
t-Bu Cl
O
III (10 mol %), 26 (5 equiv), 5:1 24a, 81
reflux, 5 h
III (10 mol %), reflux, 1 h
III (10 mol %), reflux, 1 h
III (10 mol %), reflux, 2 h
III (10 mol %), reflux, 2 h
4.2. General procedure for the preparation of amides 6aed
and 8
7
8
9
22b
22b
23
Me Cl
Me Br
Me Cl
Me Br
O
O
C
C
10:1 24c, 77
4:1 24d, 87
6:1 24e, 37
8:1 24f, 68
10
23
To a suspension of NaH (344 mg, 60% dispersion in mineral oil)
The ratio was determined by the analysis of 1H 500 MHz NMR spectra.
The reaction proceeded incompletely and 31% of 22a was recovered.
in THF (17 mL) was added allyl alcohol (2) (500 mg, 8.6 mmol) at
a
b
0
ꢀC. After 1 h at the same temperature, chloroacetamide 1
(0.97 mL, 9.5 mmol) was added and the mixture was stirred for
24 h. The mixture was quenched with saturated aqueous NH4Cl and
concentrated at reduced pressure. The resulting residue was dis-
solved in EtOAc and washed with water and brine. The organic layer
was dried over anhydrous MgSO4 and concentrated in vacuo. The
residue was purified by flash column chromatography on silica gel
(hexanes/EtOAc, 3:1) to give 6a (1.05 g, pale yellow oil) in 85% yield.
4.2.1. 2-(Allyloxy)-N,N-dimethylacetamide (6a). 1H NMR (CDCl3,
300 MHz)
d 6.00e5.86 (m, 1H), 5.35e5.17 (m, 2H), 4.15 (s, 2H),
4.10e4.05 (m, 2H), 3.04e2.93 (m, 6H); 13C NMR (CDCl3, 75 MHz)
Scheme 3. Reagent and conditions: (i) 4-penten-1-ol (3), Bu4NHSO4, 40% aqueous
KOH, rt, 24 h, 53%; (ii) NaH, 4-penten-1-ol (3), THF, rt, overnight, 80e95%; (iii) H2SO4,
MeOH, reflux, 24 h, 95%.
d 169.2, 134.1, 117.9, 72.2, 69.1, 36.4, 35.5; HRMS (EI) m/z calcd for
C7H13NO2 (Mþ) 143.0946, found 143.0943.
4.2.2. N,N-Dimethyl-2-(pent-4-enyloxy)acetamide (6b). Pale orange
oil: 94% yield. 1H NMR (CDCl3, 300 MHz)
d 5.89e5.74 (m, 1H),
5.07e4.93 (m, 2H), 4.13 (s, 2H), 3.52 (t, J¼6.5 Hz, 2H), 3.02 (s, 3H),
2.96 (s, 3H), 2.19e2.08 (m, 2H), 1.77e1.66 (m, 2H); 13C NMR (CDCl3,
75 MHz) d 169.4, 138.1, 114.9, 70.9, 70.4, 36.5, 35.6, 20.3, 28.8; HRMS
(EI) m/z calcd for C9H17NO2 (Mþ) 171.1259, found 171.1243.
Fig. 3. Structure of amides 25 and 26.
4.2.3. 2-(Hept-6-enyloxy)-N,N-dimethylacetamide (6c). Pale yellow
oil: 92% yield. 1H NMR (CDCl3, 300 MHz)
d 5.87e5.71 (m, 1H),
3. Conclusion
5.04e4.88 (m, 2H), 4.12 (s, 2H), 3.49 (t, J¼6.6 Hz, 2H), 3.10 (s, 3H),
2.95 (s, 3H), 2.10e2.01 (m, 2H), 1.68e1.57 (m, 2H), 1.48e1.30 (m,
4H); 13C NMR (CDCl3, 75 MHz)
d 169.5, 139.0, 114.4, 71.6, 70.5, 36.6,
In summary, we have prepared functionalized allyl halides that
possess either an amide or ester group by using the CM of allyl
halides promoted by the GrubbseHoveydaeBlechert second gen-
eration catalyst (III) in good yield and with good E/Z selectivity. The
findings arising from this investigation indicate that the CM of allyl
halides promoted by ruthenium complexes IeIII are not efficient
when olefins that bear an N,N-dimethylamide group are employed
as substrates and especially when the amide group is separated
from the terminal alkene moiety by more than three carbons.
However, these limitations were readily overcome by the re-
placement of the N,N-dimethylamide group with a Weinreb amide
group. In addition, a reexamination of the tolerance of the CM of
allyl halides with olefins bearing an ester group demonstrated that
the process is strongly dependent on both the amount of the ru-
thenium complex III employed and the reaction temperature. The
35.6, 33.8, 29.5, 28.8, 25.7; HRMS (EI) m/z calcd for C11H21NO2 (Mþ)
199.1572, found 199.1576.
4.2.4. 2-(Dec-9-enyloxy)-N,N-dimethylacetamide (6d). Pale yellow
oil: 82% yield. 1H NMR (CDCl3, 300 MHz)
d 5.89e5.73 (m, 1H),
5.04e4.89 (m, 2H), 4.13 (s, 2H), 3.49 (t, J¼6.6 Hz, 2H), 3.03 (s, 3H),
2.96 (s, 3H), 2.09e1.98 (m, 2H), 1.68e1.55 (m, 2H), 1.40e1.20 (m,
8H); 13C NMR (CDCl3, 75 MHz)
d 169.6, 139.3, 114.3, 71.7, 70.5, 36.6,
35.6, 33.9, 29.7, 29.53, 29.50, 29.2, 29.0, 26.2; HRMS (EI) m/z calcd
for C14H27NO2 (Mþ) 241.2042, found 241.2072.
4.2.5. N,N-Diisopropyl-2-(pent-4-enyloxy)acetamide (8). Pale or-
ange oil: 63% yield (The reaction was not optimized). 1H NMR
(CDCl3, 300 MHz)
d 5.89e5.73 (m, 1H), 5.08e4.91 (m, 2H),
results suggest that the presence of an
saturated amide and ester substrates positively affects the yields of
CM with allyl halides.
a-alkoxy group in un-
4.10e3.93 (m, 3H), 3.57e3.32 (m, 3H), 2.13 (q, J¼7.1 Hz, 2H), 1.72
(quint, J¼6.8 Hz, 2H), 1.42 (d, J¼6.5 Hz, 6H), 1.19 (d, J¼6.4 Hz, 6H);
13C NMR (CDCl3, 75 MHz)
d 168.2, 138.2, 114.9, 72.2, 70.8, 48.2, 45.9,

J.I. Yun et al. / Tetrahedron 68 (2012) 1177e1184
1181
30.3, 28.9, 20.9, 20.5; HRMS (EI) m/z calcd for C13H25NO2 (Mþ)
227.1885, found 227.1879.
J¼6.7 Hz, 2H),1.69e1.57 (m, 2H),1.48e1.29 (m, 4H); 13C NMR (CDCl3,
75 MHz) d 174.8, 140.0, 114.4, 61.2, 33.7, 32.3, 31.9, 29.0, 28.7, 24.5;
HRMS (EI) m/z calcd for C10H19NO2 (Mþ) 185.1416, found 185.1416.
4.3. General procedure for the preparation of amides 10aed,
16aee, 17d, and 18aee
4.3.8. N-Methoxy-N-methyldec-9-enamide (18e). Pale yellow oil:
89% yield. 1H NMR (CDCl3, 300 MHz)
d
5.80 (dddd, J¼17.1, 10.2, 6.6,
A mixture of acid 9b (399 mg, 2.8 mmol), N,O-dimethylhydrox-
ylamine (270 mg, 2.8 mmol), 1-ethyl-3-(3-dimethylaminopropyl)
carbodiimide (EDCI, 798 mg, 4.2 mmol), hydroxybenzotriazole
(HOBt, 562 mg, 4.2 mmol), and triethylamine (1.2 mL, 8.3 mmol) in
anhydrous CH2Cl2 (28 mL) was stirred overnight and concentrated
at reduced pressure. The residue was dissolved in EtOAc, and
washed with water, saturated aqueous NaHCO3, and brine. The or-
ganic layer was dried over anhydrous MgSO4 and concentrated in
vacuo. The resulting residue was purified by flash column chroma-
tography on silica gel (hexanes/EtOAc, 1:1) to give 10b (461 mg,
brown oil) in 89% yield.
6.6 Hz, 1H), 5.04e4.86 (m, 2H), 3.67 (s, 3H), 3.16 (s, 3H), 2.39 (t,
J¼7.5 Hz, 2H), 2.04 (q, J¼6.9 Hz, 2H), 1.70e1.52 (m, 2H), 1.45e1.20
(m, 8H); 13C NMR (CDCl3, 125 MHz)
d 174.9, 139.2, 114.2, 61.3, 33.8,
31.9, 29.4, 29.3, 29.0, 28.9, 24.7; HRMS (EI) m/z calcd for C12H23NO2
(Mþ) 213.1729, found 213.1722.
4.4. Synthesis of ester 22a,b, 23
4.4.1. tert-Butyl pent-4-enyloxy-acetate (22a). To a mixture of pent-
4-en-1-ol (3) (1.2 mL, 11.6 mmol) in toluene (15.5 mL) and aqueous
40% KOH (15.5 mL) were added Bu4NHSO4 (2.0 g, 5.8 mmol) and
tert-butyl bromoacetate (21a) (2.0 mL, 13.9 mmol) at 0 ꢀC. The
mixture was stirred overnight. The mixture was poured into water
and extracted with ether (50 mLꢁ3). The combined organic layers
were washed with brine, dried over anhydrous MgSO4, and con-
centrated in vacuo. The resulting residue was purified by flash
column chromatography on silica gel (hexanes/EtOAc, 10:1) to give
22a (1.2 g, colorless oil) in 53% (75% based on recovered starting
4.3.1. N-Methoxy-N-methyl-2-(pent-4-enyloxy)acetamide (10b). 1H
NMR (CDCl3, 300 MHz)
d 5.89e5.76 (m, 1H), 5.08e4.93 (m, 2H),
4.26 (s, 2H), 3.69 (s, 3H), 3.56 (t, J¼6.7 Hz, 2H), 3.19 (s, 3H),
2.21e2.10 (m, 2H), 1.80e1.67 (m, 2H); 13C NMR (CDCl3, 75 MHz)
d
171.4, 138.3, 114.9, 71.3, 68.4, 61.5, 32.4, 30.0, 28.9; HRMS (EI) m/z
calcd for C9H17NO3 (Mþ) 187.1208, found 187.1203.
material) yield: 1H NMR (CDCl3, 300 MHz)
d 5.89e5.76 (m, 1H),
4.3.2. 2-(Hept-6-enyloxy)-N-methoxy-N-methylacetamide
5.07e4.94 (m, 2H), 3.95 (s, 2H), 3.53 (t, J¼6.6 Hz, 2H), 2.20e2.10 (m,
(10c). Pale yellow oil: 78% yield. 1H NMR (CDCl3, 300 MHz)
2H), 1.78e1.67 (m, 2H), 1.48 (s, 9H); 13C NMR (CDCl3, 75 MHz)
d
5.89e5.73 (m, 1H), 5.05e4.90 (m, 2H), 4.26 (s, 2H), 3.69 (s, 3H),
3.55 (t, J¼6.7 Hz, 2H), 3.19 (s, 3H), 2.06 (q, J¼5.7 Hz, 2H), 1.72e1.59
(m, 2H), 1.49e1.32 (m, 4H); 13C NMR (CDCl3, 75 MHz)
171.3, 139.1,
d 169.9, 138.3, 114.9, 81.6, 71.2, 68.9, 30.3, 28.9, 28.2; HRMS (EI) m/z
calcd for C11H20O3 (Mþ) 200.1412, found 200.1400.
d
114.4, 72.0, 68.4, 61.5, 33.8, 32.5, 29.6, 28.8, 25.6; HRMS (EI) m/z
4.4.2. Methyl pent-4-enyloxy-acetate (22b). Pent-4-en-1-ol (3)
(6.0 mL, 58.1 mmol) was added dropwise to a stirred suspension of
NaH (2.3 g, 60% in mineral oil, 58.1 mmol) in anhydrous THF
(116 mL) at 0 ꢀC and stirred for 1 h at room temperature. Methyl
bromoacetate (21b) (5 mL, 52.8 mmol) was added at 0 ꢀC and the
mixture was stirred for 3 h at room temperature. To the mixture
was added saturated aqueous NH4Cl solution and the mixture was
concentrated at reduced pressure. The residue was suspended in
EtOAc. The mixture was washed with brine, dried over anhydrous
MgSO4, and concentrated in vacuo. The resulting residue was pu-
rified by flash column chromatography on silica gel (hexanes/
EtOAc, 10:1) to give 22b (3.0 g, colorless oil) in 33% yield (This re-
calcd for C11H21NO3 (Mþ) 215.1521, found 215.1526.
4.3.3. 2-(Dec-9-enyloxy)-N-methoxy-N-methylacetamide
(10d). Pale yellow oil: 90% yield. 1H NMR (CDCl3, 300 MHz)
d
5.89e5.72 (m, 1H), 5.04e4.87 (m, 2H), 4.25 (s, 2H), 3.69 (s, 3H),
3.54 (t, J¼6.8 Hz, 2H), 3.19 (s, 3H), 2.09e1.97 (m, 2H), 1.70e1.48 (m,
2H), 1.45e1.20 (m, 10H); 13C NMR (CDCl3, 75 MHz)
171.3, 139.2,
d
114.1, 72.0, 68.3, 61.5, 33.8, 32.4, 29.6, 29.4, 29.1, 28.9, 26.1, 25.8;
HRMS (EI) m/z calcd for C14H27NO3 (Mþ) 257.1991, found 257.2003.
4.3.4. N,N-Dimethyloct-7-enamide (16d). Pale yellow oil: 87% yield.
1H NMR (CDCl3, 300 MHz)
d
5.90e5.75 (m, 1H), 5.05e4.90 (m, 2H),
action was not optimized.): 1H NMR (CDCl3, 300 MHz)
d 5.90e5.75
3.01 (s, 3H), 2.96 (s, 3H), 2.32 (t, J¼7.5 Hz, 2H), 2.07 (q, J¼6.6 Hz, 2H),
(m, 1H), 5.09e4.98 (m, 2H), 4.10 (s, 2H), 3.77 (s, 3H), 3.55 (t,
1.70e1.61 (m, 2H), 1.46e1.36 (m, 4H); 13C NMR (CDCl3, 75 MHz),
J¼6.6 Hz, 2H), 2.15 (q, J¼7.1 Hz, 2H), 1.80e1.57 (m, 2H); 13C NMR
d
173.2, 139.0, 114.4, 37.4, 35.4, 33.7, 33.4, 29.0, 28.8, 25.1; HRMS (EI)
(CDCl3, 75 MHz) d 171.1, 138.1, 115.0, 71.3, 68.3, 51.9, 30.2, 28.8;
m/z calcd for C10H19NO (Mþ) 169.1467, found 169.1461.
HRMS (EI) m/z calcd for C8H14O3 (Mþ) 158.0943, found 158.0926.
4.3.5. N,N-Dimethyldec-9-enamide (16e). Pale yellow oil: 96% yield.
4.4.3. Methyl oct-7-enoate (23). To a solution of -octenoic acid
u
1H NMR (CDCl3, 300 MHz)
d
5.80 (dddd, J¼17.1,10.2, 6.9, 6.9 Hz,1H),
(15d) (1.0 mL, 7.1 mmol) in methanol (24 mL) was added sulfuric acid
(0.3 mL, 5.7 mmol) at room temperature and the mixture was refluxed
for 24 h. The mixture was concentrated at reduced pressure and the
resulting residue was dissolved in ether. The solutionwas washed with
saturated aqueous NaHCO3 solution and brine, dried over anhydrous
MgSO4, and concentrated in vacuo. The resulting residue was purified
by flash column chromatography on silica gel (hexanes/EtOAc, 5:1) to
give 23 (911 mg, colorless oil) in 95% yield: 1H NMR (CDCl3, 300 MHz)
5.03e4.86 (m, 2H), 3.00 (s, 3H), 2.93 (s, 3H), 2.29 (dd, J¼15.0, 7.2 Hz,
2H), 2.03 (q, J¼7.2 Hz, 2H), 1.70e1.52 (m, 2H), 1.45e1.17 (m, 8H); 13C
NMR (CDCl3, 125 MHz)
d 173.3, 139.2, 114.2, 37.4, 35.4, 33.9, 33.5,
29.5, 29.4, 29.1, 29.0, 25.3; HRMS (EI) m/z calcd for C12H23NO (Mþ)
197.1780, found 197.1780.
4.3.6. N,N-Diisopropyloct-7-enamide (17d). Pale orange oil: 62%
yield. 1H NMR (CDCl3, 300 MHz)
d
5.87e5.82 (m,1H), 5.04e4.94 (m,
d
5.88e5.72 (m, 2H), 5.03e4.91 (m, 1H), 3.67 (s, 3H), 2.31 (t, J¼7.4 Hz,
2H), 4.00e3.98 (m, 1H), 3.55e3.48 (m, 1H), 2.30 (t, J¼7.6 Hz, 2H),
2H), 2.05 (q, J¼6.7 Hz, 2H), 1.70e1.56 (m, 2H) 1.47e1.23 (m, 4H); 13C
2.08 (q, J¼6.9 Hz, 2H), 1.67e1.16 (m, 18H); 13C NMR (CDCl3, 75 MHz)
NMR (CDCl3, 125 MHz) d 174.4, 138.9, 114.5, 51.6, 34.2, 33.7, 28.7, 28.6,
d
172.1, 139.0, 114.4, 45.6, 35.4, 33.8, 29.1, 28.9, 25.4, 21.1, 20.8;
24.9; HRMS (EI) m/z calcd for C9H16O2 (Mþ) 156.1150, found 156.1151.
HRMS (EI) m/z calcd for C14H27NO (Mþ) 225.2093, found 225.2095.
4.5. Typical procedure for the CM of allyl halides
4.3.7. N-Methoxy-N-methyloct-7-enamide (18d). Pale yellow oil:
91% yield. 1H NMR (CDCl3, 300 MHz)
d
5.82e5.77 (m,1H), 5.02e4.92
To a solution of olefin 10b (60 mg, 0.32 mmol) in anhydrous
(m, 2H), 3.68 (s, 3H), 3.18 (s, 3H), 2.42 (t, J¼7.5 Hz, 2H), 2.06 (q,
CH2Cl2 (1.1 mL) were added allyl bromide (0.14 mL, 1.6 mmol) and

1182
J.I. Yun et al. / Tetrahedron 68 (2012) 1177e1184
GrubbseHoveydaeBlechert second generation catalyst (III) (20 mg,
0.032 mmol) at room temperature. The mixture was refluxed for
2 h and concentrated at reduced pressure. The resulting residue
was purified by flash column chromatography on silica gel (hex-
anes/EtOAc, 2:1) to afford 13f (71 mg, brown oil, E/Z¼7:1 by the
analysis of a 1H 500 MHz NMR spectrum) as an inseparable E/Z
mixture in 90% yield.
28.8, 28.6, 21.8; HRMS (EI) m/z calcd for C16H22BrNO4S (Mþ)
403.0453, found 403.0458.
4.5.7. (E/Z)-2-(4-Chlorobut-2-enyloxy)-N-methoxy-N-methyl-
acetamide (14d). Pale brown oil: 74% yield. 1H NMR (CDCl3,
500 MHz)
d 5.93e5.89 (m, 2H), 4.28 (s, 2H), [4.12e4.10 (m) and
4.09e4.03 (m), 2H], 3.69 (s, 3H), 3.19 (s, 3H); 13C NMR (CDCl3,
75 MHz)
d 170.9, 130.7, 129.1, 70.8, 67.4, 61.6, 44.3, 32.4; HRMS (EI)
4.5.1. (E/Z)-2-(6-Bromo-hex-4-enyloxy)-N-methoxy-N-methyl-
m/z calcd for C8H14ClNO3 (Mþ) 207.0662, found 207.0665.
acetamide (13f). 1H NMR (CDCl3, 500 MHz)
d 5.83e5.67 (m, 2H),
4.26 (s, 2H), [4.05e4.01 (m) and 3.95 (d, J¼8.3 Hz), 2H], 3.69 (s, 3H),
4.5.8. (E/Z)-2-(4-Bromobut-2-enyloxy)-N-methoxy-N-methyl-
3.56 (t, J¼6.5 Hz, 2H), 3.19 (s, 3H), [2.30e2.24 (m) and 2.23e2.11
acetamide (14e). Pale brown oil: 65% yield. 1H NMR (CDCl3,
(m), 2H], 1.79e1.69 (m, 2H); 13C NMR (CDCl3, 75 MHz)
d
135.9,
500 MHz)
4.18e4.08 (m, 2H), [4.05 (d, J¼8.4 Hz) and 3.97 (d, J¼7.3 Hz), 2H],
3.69 (s, 3H), 3.19 (s, 3H); 13C NMR (CDCl3, 75 MHz)
131.1, 129.6,
d 6.03e5.94 (m, 1H), 5.93e5.85 (m, 1H), 4.28 (s, 2H),
127.0, 71.1, 68.4, 61.6, 33.6, 32.5, 28.9, 28.7 (One carbon was not
detected due to slow relaxation); HRMS (EI) m/z calcd for
C10H18BrNO3 (Mþ) 279.0470, found 279.0466.
d
70.7, 67.3, 61.6, 32.4, 31.9 (One carbon was not detected due to slow
relaxation); HRMS (EI) m/z calcd for C8H14NO3 (MþꢂBr) 172.0974,
found 172.0970.
4.5.2. (E/Z)-2-(6-Chloro-hex-4-enyloxy)-N,N-diisopropylacetamide
(13c). Pale brown oil: 53% yield. 1H NMR (CDCl3, 500 MHz)
d
5.88e5.61 (m, 2H), 4.10 (d, J¼7.1 Hz, 2H), 4.06e3.97 (m, 5H),
4.5.9. (E/Z)-2-(8-Chlorooct-6-enyloxy)-N-methoxy-N-methyl-
3.64e3.48 (m, 2H), 3.44e3.36 (m, 1H), [2.25e2.20 (m) and
2.15e2.10 (m), 2H], 1.71 (quint, J¼6.8 Hz, 2H), 1.41 (d, J¼6.4 Hz, 6H),
acetamide (14f). Pale brown oil: 97% yield. 1H NMR (CDCl3,
500 MHz)
d 5.81e5.73 (m, 1H), 5.65e5.57 (m, 1H), 4.25 (s, 2H),
1.18 (d, J¼6.3 Hz, 6H); 13C NMR (CDCl3, 75 MHz)
d
168.2, 135.4,
[4.13e4.07 (m) and 4.03 (d, J¼7.1 Hz), 2H], 3.69 (s, 3H), 3.54 (t,
J¼6.7 Hz, 2H), 3.19 (s, 3H), [2.16e2.10 (m) and 2.07 (q, J¼6.7 Hz),
2H],1.71e1.60 (m, 2H),1.48e1.35 (m, 4H); 13C NMR (CDCl3, 75 MHz)
126.6, 72.1 70.7, 48.3, 46.0, 45.5, 29.8, 28.7, 21.0, 20.6 (peaks of Z-
isomer detected separately from those of E-isomer
d 134.5, 126.1,
39.6, 32.1, 29.5, 29.3, 29.0, 33.8, 22.8, 14.2); HRMS (EI) m/z calcd for
d
171.2, 136.1, 126.0, 71.8, 68.3, 61.5, 45.5, 32.4, 32.0, 29.5, 28.6, 25.6
C14H26ClNO2 (Mþ) 275.1652, found 275.1652.
(peaks of Z-isomer detected separately from those of E-isomer
d
135.3, 125.3, 39.6, 29.1, 27.0, 25.7); HRMS (EI) m/z calcd for
4.5.3. (E/Z)-2-(6-Bromohex-4-enyloxy)-N,N-diisopropylacetamide
C12H22ClNO3 (Mþ) 263.1288, found 263.1289.
(13d). Pale brown oil: 44% yield. 1H NMR (CDCl3, 500 MHz)
d
5.81e5.67 (m, 2H), [4.07 (s) and 4.05 (s), 2H], 4.03e3.92 (m, 3H),
4.5.10. (E/Z)-2-(8-Bromooct-6-enyloxy)-N-methoxy-N-methyl-
3.55e3.48 (m, 2H), 3.47e3.34 (m, 1H), [2.28e2.21 (m) and
2.20e2.11 (m), 2H], 1.73e1.66 (m, 2H), 1.41 (d, J¼6.6 Hz, 6H), 1.19 (d,
acetamide (14g). Pale brown oil: 89% yield. 1H NMR (CDCl3,
500 MHz)
d
5.82e5.63 (m, 2H), 4.25 (s, 2H), [4.00 (d, J¼8.3 Hz) and
J¼6.3 Hz, 6H); 13C NMR (CDCl3, 75 MHz)
d
168.2, 135.8, 127.0, 72.1,
3.95 (d, J¼7.4 Hz), 2H], 3.69 (s, 3H), 3.57e3.51 (m, 2H), 3.19 (s, 3H),
[2.18e2.12 (m) and 2.07 (q, J¼6.7 Hz), 2H], 1.69e1.57 (m, 2H),
70.6, 48.3, 46.0, 33.5, 29.0, 28.7, 21.0, 20.6; HRMS (EI) m/z calcd for
C14H26BrNO2 (Mþ) 319.1147, found 319.1150.
1.46e1.31 (m, 4H); 13C NMR (CDCl3, 75 MHz)
d 171.4, 136.6, 126.5,
71.9, 68.4, 61.5, 33.7, 32.4, 32.1, 29.5, 28.7, 25.6 (peaks of Z-isomer
detected separately from those of E-isomer 135.9, 125.5, 32.0,
4.5.4. (E/Z)-2-(6-Chloro-hex-4-enyloxy)-N-methoxy-N-methyl-
d
acetamide (13e). Pale brown oil: 69% yield. 1H NMR (CDCl3,
29.8, 29.4, 29.0, 27.4, 26.9, 25.8, 22.8, 14.2); HRMS (EI) m/z calcd for
500 MHz)
d
5.83e5.75 (m, 1H), 5.68e5.59 (m, 1H), 4.25 (s, 2H),
C12H22BrNO3 (Mþ) 307.0783, found 307.0782.
[4.14e4.10 (m) and 4.03 (dd, J¼7.1, 0.8 Hz), 2H], 3.69 (s, 3H),
3.58e3.53 (m, 2H), 3.19 (s, 3H), 2.18 (q, J¼7.3 Hz, 2H), 1.78e1.70
4.5.11. (E/Z)-2-(11-Chloroundec-9-enyloxy)-N-methoxy-N-methyl-
(m, 2H); 13C NMR (CDCl3, 75 MHz)
d
135.4, 126.5, 71.1, 68.4, 61.5,
acetamide (14h). Pale brown oil: 95% yield. 1H NMR (CDCl3,
45.5, 32.5, 28.9, 28.7 (One carbon was not detected due to slow
500 MHz) d 5.81e5.73 (m, 1H), 5.64e5.56 (m, 1H), 4.27 (s, 2H), [4.10
relaxation; peaks of Z-isomer detected separately from those of
(d, J¼6.6 Hz) and 4.03 (d, J¼7.1 Hz), 2H], 3.69 (s, 3H), 3.54 (t,
E-isomer
d 134.5, 126.1, 70.8, 39.6, 30.3, 29.2, 23.7, 22.8, 14.2);
J¼6.8 Hz, 2H), 3.19 (s, 3H), 2.14e1.99 (m, 2H), 1.68e1.58 (m, 4H),
HRMS (EI) m/z calcd for C10H18ClNO3 (Mþ) 235.0975, found
1.43e1.22(m, 8H); 13C NMR (CDCl3, 75 MHz)
d 171.3, 136.4, 125.9,
235.0978.
72.0, 68.3, 61.5, 45.6, 32.4, 32.1, 29.7, 29.43, 29.41, 29.1, 28.9, 26.1
(peaks of Z-isomer detected separately from those of E-isomer
4.5.5. (E/Z)-2-(6-Chlorohex-4-enyloxy)-N-methyl-N-tosylacetamide
d 135.6, 125.2, 39.6, 29.8, 29.3, 29.2, 27.1); HRMS (EI) m/z calcd for
(13g). Pale brown oil: 80% yield. 1H NMR (CDCl3, 500 MHz)
d
7.78
C15H28ClNO3 (Mþ) 305.1758, found 305.1760.
(d, J¼8.5 Hz, 2H), 7.39 (d, J¼8.0 Hz, 2H), 5.84e5.75 (m, 1H),
5.70e5.61 (m, 1H), 4.54e4.51 (m, 2H), 4.05 (d, J¼7.0 Hz, 2H), 3.53 (t,
J¼6.5 Hz, 2H), 3.22 (s, 3H), 2.46 (s, 3H), [2.23 (q, J¼7.0 Hz) and 2.15
(q, J¼7.0 Hz), 2H], 1.70 (quint, J¼6.5 Hz, 2H); 13C NMR (CDCl3,
4.5.12. (E/Z)-2-(11-Bromoundec-9-enyloxy)-N-methoxy-N-methyl-
acetamide (14i). Pale brown oil: 88% yield. 1H NMR (CDCl3,
500 MHz)
d
5.81e5.63 (m, 2H), 4.25 (s, 2H), [4.00 (d, J¼8.3 Hz) and
75 MHz)
d
170.6, 145.4, 135.5, 135.2, 130.2, 127.4, 126.6, 71.4, 71.2,
3.95 (d, J¼7.5 Hz), 2H], 3.69 (s, 3H), 3.54 (t, J¼6.8 Hz, 2H), 3.19 (s,
3H), [2.16e2.09 (m) and 2.09e1.99 (m), 2H], 1.69e1.56 (m, 4H),
45.4, 32.7, 28.8, 28.6, 21.7; HRMS (EI) m/z calcd for C16H22ClNO4S
(Mþ) 359.0958, found 359.0959.
1.43e1.21 (m, 8H); 13C NMR (CDCl3, 75 MHz)
d 136.9, 126.4, 72.1,
68.4, 61.5, 33.8, 32.5, 32.2, 29.7, 29.49, 29.46, 29.1, 28.9, 26.1 (One
4.5.6. (E/Z)-2-(6-Bromohex-4-enyloxy)-N-methyl-N-tosylacetamide
carbon was not detected due to slow relaxation; peaks of Z-isomer
detected separately from those of E-isomer d 136.2, 125.3, 56.0,
(13h). Pale brown oil: 88% yield. 1H NMR (CDCl3, 500 MHz)
d
7.78
(d, J¼8.5 Hz, 2H), 7.38 (d, J¼8.0 Hz, 2H), 5.83e5.68 (m, 2H),
4.57e4.52 (m, 2H), [4.04 (d, J¼8.0 Hz) and 3.94 (d, J¼7.0 Hz), 2H],
3.58e3.47 (m, 2H), 3.22 (s, 3H), 2.45 (s, 3H), [2.28e2.21 (m) and 2.16
(q, J¼7.0 Hz), 2H], 1.76e1.65 (m, 2H); 13C NMR (CDCl3, 75 MHz)
38.8, 29.3, 29.2, 27.8, 27.6, 27.0); HRMS (EI) m/z calcd for
C15H28BrNO3 (Mþ) 349.1253, found 349.1283.
4.5.13. (E/Z)-9-Chloro-N-methoxy-N-methylnon-7-enamide
d
170.6, 145.4, 135.7, 135.6, 130.2, 127.5, 127.1, 71.4, 71.3, 33.5, 32.7,
(19c). Pale brown oil: 68% yield. 1H NMR (CDCl3, 500 MHz)

J.I. Yun et al. / Tetrahedron 68 (2012) 1177e1184
1183
d
5.80e5.72 (m, 1H), 5.64e5.56 (m, 1H), [4.03 (d, J¼6.7 Hz) and 4.09
HRMS (EI) m/z calcd for C7H12BrNO2 (Mþ) 221.0051, found
221.0045.
(d, J¼7.1 Hz), 2H], 3.68 (s, 3H), 3.18 (s, 3H), 2.41 (t, J¼7.3 Hz, 2H),
[2.18e2.10 (m) and 2.06 (q, J¼7.0 Hz), 2H], 1.68e1.59 (m, 2H),
1.48e1.33 (m, 4H); 13C NMR (CDCl3, 75 MHz)
d
136.1, 126.1, 61.3,
4.5.21. (E/Z)-7-Chloro-N-methoxy-N-methylhept-5-enamide
39.6, 32.4, 32.0, 31.9, 28.97, 28.72, 24.51 (One carbon was not
(20i). Pale brown oil: 75% yield. 1H NMR (CDCl3, 500 MHz)
detected due to slow relaxation; peaks of Z-isomer detected sepa-
d
5.81e5.72 (m, 1H), 5.68e5.60 (m, 1H), [4.10 (d, J¼7.0 Hz) and 4.23
rately from those of E-isomer
d
135.4, 125.4, 45.6, 29.15, 29.05,
(d, J¼7.0 Hz), 2H], 3.79 (s, 3H), 3.68 (s, 3H), 2.42 (t, J¼7.0 Hz, 2H),
27.03); HRMS (EI) m/z calcd for C11H20ClNO2 (Mþ) 233.1183, found
2.16e2.10 (m, 2H), 1.78e1.50 (m, 2H); 13C NMR (CDCl3, 75 MHz)
233.1186.
d 135.3, 126.9, 61.4, 45.4, 31.7, 31.2, 31.1, 23.8 (One carbon was not
detected due to slow relaxation); HRMS (EI) m/z calcd for
4.5.14. (E/Z)-9-Bromo-N-methoxy-N-methylnon-7-enamide
C9H16ClNO2 (Mþ) 205.0870, found 205.0859.
(19d). Pale brown oil: 75% yield. 1H NMR (CDCl3, 500 MHz)
d
5.79e5.64 (m, 2H), [3.95 (d, J¼7.4 Hz) and 4.0 (d, J¼8.4 Hz), 2H],
4.5.22. (E/Z)-7-Bromo-N-methoxy-N-methylhept-5-enamide
3.68 (s, 3H), 3.18 (s, 3H), 2.42 (t, J¼7.2 Hz, 2H), [2.18e2.11 (m) and
2.08 (q, J¼7.2 Hz), 2H], 1.64 (quint, J¼7.6 Hz, 2H), 1.48e1.33 (m, 4H);
(20j). Pale brown oil: 70% yield. 1H NMR (CDCl3, 500 MHz)
d
5.82e5.65 (m, 2H), [4.01 (d, J¼8.5 Hz) and 3.95 (d, J¼7.0 Hz),
13C NMR (CDCl3, 75 MHz)
d
136.6, 126.6, 61.3, 33.6, 32.3, 31.97,
2H], 3.68 (s, 3H), 3.18 (s, 3H), 2.48e2.38 (m, 2H), [2.22 (q,
J¼7.0 Hz) and 2.13 (q, J¼7.0 Hz), 2H], 1.79e1.70 (m, 2H); 13C NMR
31.89, 28.94, 28.68, 24.4 (One carbon was not detected due to slow
relaxation; peaks of Z-isomer detected separately from those of E-
(CDCl3, 75 MHz) d 174.3, 135.7, 127.2, 61.3, 33.4, 31.6, 31.1, 23.9,
isomer
d
135.9, 125.5, 55.7, 38.6, 29.08, 28.78, 27.5, 27.4, 27.0);
23.6; HRMS (EI) m/z calcd for C9H16BrNO2 (Mþ) 249.0364, found
HRMS (EI) m/z calcd for C11H20BrNO2 (Mþ) 277.0677, found
249.0370.
277.0684.
4.5.23. (E/Z)-11-Chloro-N-methoxy-N-methylundec-9-enamide
4.5.15. (E/Z)-5-Chloro-pent-3-enoic acid dimethylamide (20b). Pale
(20k). Pale brown oil: 70% yield. 1H NMR (CDCl3, 500 MHz)
brown oil: 38% yield. 1H NMR (CDCl3, 500 MHz)
d
6.02e5.93 (m,
d
5.81e5.73 (m, 1H), 5.63e5.55 (m, 1H), [4.09 (d, J¼6.5 Hz) and 4.23
1H), 5.77e5.68 (m, 1H), [4.13 (d, J¼7.5 Hz) and 4.62 (d, J¼7.0 Hz),
(d, J¼7.0 Hz), 2H], 3.67 (s, 3H), 3.17 (s, 3H), 2.42 (t, J¼7.0 Hz, 2H),
2H], 3.18 (d, J¼6.5 Hz, 2H), 3.25 (s, 3H), 3.97 (s, 3H); 13C NMR (CDCl3,
2.05 (q, J¼6.0 Hz, 2H), 1.67e1.58 (m, 2H), 1.43e1.21 (m, 8H); 13C
75 MHz)
d
170.5, 129.1, 128.7, 44.7, 37.5, 37.1, 35.6; HRMS (EI) m/z
NMR (CDCl3, 125 MHz) d 174.9, 136.4, 126.0, 61.3, 45.7, 32.3, 32.1,
calcd for C7H12ClNO (Mþ) 161.0607, found 161.0615.
32.0, 29.44, 29.33, 29.06, 28.89, 24.7 (peaks of Z-isomer detected
separately from those of E-isomer 135.6, 125.2, 39.7, 39.0, 29.81,
d
4.5.16. (E/Z)-7-Chloro-hept-5-enoic acid dimethylamide (20c). Pale
29.50, 29.37, 29.12, 28.99, 27.16); HRMS (EI) m/z calcd for
brown oil: 33% yield. 1H NMR (CDCl3, 500 MHz)
d
5.80e5.72 (m,
C13H24ClNO2 (Mþ) 261.1496, found 261.1494.
1H), 5.68e5.60 (m, 1H), [4.10 (d, J¼7.5 Hz) and 4.02 (d, J¼7.0 Hz),
2H], 2.99 (s, 3H), 2.94 (s, 3H), 2.32 (t, J¼7.5 Hz, 2H), 2.13 (q, J¼7.0 Hz,
4.5.24. (E/Z)-11-Bromo-N-methoxy-N-methylundec-9-enamide
2H), 1.75 (quint, J¼7.5 Hz, 2H); 13C NMR (CDCl3, 75 MHz)
d
172.8,
(20l). Pale brown oil: 90% yield. 1H NMR (CDCl3, 500 MHz)
135.4, 126.9, 45.4, 37.4, 35.5, 32.5, 31.7, 24.3; HRMS (EI) m/z calcd for
d
5.83e5.74 (m, 1H), 5.73e5.64 (m, 1H), [4.02 (d, J¼8.0 Hz) and 3.96
C9H16ClNO (Mþ) 189.0920, found 189.0927.
(d, J¼7.0 Hz), 2H], 3.68 (s, 3H), 3.18 (s, 3H), 2.41 (t, J¼7.0 Hz, 2H),
[2.13 (q, J¼7.0 Hz) and 2.05 (q, J¼7.0 Hz), 2H], 1.67e1.57 (m, 2H),
4.5.17. (E/Z)-4-Chloro-N-methoxy-N-methylbut-2-enamide
1.43e1.24 (m, 8H); 13C NMR (CDCl3, 75 MHz)
d 136.8, 126.4, 61.3,
(20e). Pale brown oil: 36% yield. 1H NMR (CDCl3, 500 MHz)
d
7.00
33.8, 32.1, 32.0, 29.5, 29.3, 29.2, 29.0, 28.9, 24.7 (peaks of Z-isomer
(ddd, J¼15.0, 6.0, 6.0 Hz, 1H), 6.72 (d, J¼15.0 Hz, 1H), [4.24 (dd,
detected separately from those of E-isomer d 136.1, 125.4, 55.9, 38.8,
J¼6.0, 1.5 Hz) and 4.19e4.16 (m), 2H], 3.77e3.71 (m, 3H), 3.26
32.3, 27.7, 27.5, 27.0); HRMS (EI) m/z calcd for C13H24BrNO2 (Mþ)
(s, 3H); 13C NMR (CDCl3, 75 MHz)
d
165.7, 140.4, 121.7, 62.0, 43.2,
305.0990, found 305.0995.
32.5; HRMS (EI) m/z calcd for C6H10ClNO2 (Mþ) 163.0400, found
163.0400.
4.5.25. tert-Butyl (E/Z)-(6-chloro-hex-4-enyloxy)-acetate (24a).
Colorless oil: 94% yield. 1H NMR (CDCl3, 500 MHz)
d 5.81e5.60 (m,
4.5.18. (E/Z)-4-Bromo-N-methoxy-N-methylbut-2-enamide
2H), [4.14 (d, J¼7.2 Hz) and 4.03 (d, J¼7.0 Hz), 2H], 3.96e3.94 (m,
2H), 3.50 (t, J¼6.5 Hz, 2H), [2.50 (q, J¼7.1 Hz) and 2.21e2.14 (m),
2H], 2.72 (quint, J¼6.6 Hz, 2H), 1.50 (s, 9H); 13C NMR (CDCl3,
(20f). Pale brown oil: 18% yield. 1H NMR (CDCl3, 500 MHz)
d
7.09e6.99 (m, 1H), 6.63 (d, J¼15 Hz, 1H), [4.23 (d, J¼6.0 Hz) and
4.06 (dd, J¼7.5, 1.0 Hz), 2H], 3.74 (s, 3H), 3.28 (s, 3H); 13C NMR
75 MHz) d 169.9, 135.3, 126.6, 81.6, 70.9, 68.9, 45.4, 28.9, 28.7, 28.2
(CDCl3, 75 MHz)
d
165.7, 140.5, 122.4, 62.1, 32.5, 30.1; HRMS (EI) m/z
(peaks of Z-isomer detected separately from those of E-isomer
calcd for C6H10BrNO2 (Mþ) 206.9895, found 206.9895.
d 134.4, 126.1, 70.6, 39.6, 29.2, 23.7); HRMS (EI) m/z calcd for
C12H21ClO3 (Mþ) 248.1179, found 248.1167.
4.5.19. (E/Z)-5-Chloro-N-methoxy-N-methylpent-3-enamide
(20g). Pale brown oil: 59% yield. 1H NMR (CDCl3, 500 MHz)
4.5.26. tert-Butyl (E/Z)-(6-bromo-hex-4-enyloxy)-acetate (24b).
d
6.03e5.94 (m, 1H), 5.82e5.72 (m, 1H), [4.14 (d, J¼7.0 Hz) and 4.09
(d, J¼7.0 Hz), 2H], [3.72 (s) and 3.70 (s), 3H], 3.28 (d, J¼6.5 Hz, 2H),
3.19 (s, 3H); 13C NMR (CDCl3, 75 MHz)
171.9, 129.5, 128.1, 61.5,
44.8, 35.5, 32.3 (peaks of Z-isomer detected separately from those
of E-isomer
127.1, 39.3); HRMS (EI) m/z calcd for C7H12ClNO2 (Mþ)
Colorless oil: 95% yield. 1H NMR (CDCl3, 500 MHz)
d 5.84e5.70 (m,
2H), 3.99e3.95 (m, 4H), 3.57e3.51 (m, 2H), [2.32e2.25 (m) and
d
2.23e2.17 (m), 2H], 1.84e1.70 (m, 2H), 1.50 (s, 9H); 13C NMR (CDCl3,
75 MHz)
d 169.9, 135.8, 127.0, 81.7, 70.9, 68.9, 33.5, 31.1, 28.9, 28.7,
d
28.3; HRMS (EI) m/z calcd for C8H14BrO3 (MHþ2 ꢂC4H9) 237.0126,
177.0557, found 177.0558.
found 237.0120.
4.5.20. (E/Z)-5-Bromo-N-methoxy-N-methylpent-3-enamide
4.5.27. Methyl (E/Z)-(6-chloro-hex-4-enyloxy)-acetate (24c). Colorless
(20h). Pale brown oil: 26% yield. 1H NMR (CDCl3, 500 MHz)
oil: 77% yield. 1H NMR (CDCl3, 500 MHz),
d 5.83e5.64 (m, 2H), [4.13
d
6.01e5.92 (m, 1H), 5.88e5.79 (m, 1H), [4.09 (d, J¼7.0 Hz) and 3.98
(d, J¼7.5 Hz), 2H], 3.70 (s, 3H), 3.27 (d, J¼6.5 Hz, 2H), 3.19 (s, 3H);
13C NMR (CDCl3, 75 MHz)
172.1, 129.9, 128.4, 61.5, 35.5, 32.5;
(d, J¼7.3 Hz) and 4.05 (d, J¼7.0 Hz), 2H], 4.10 (s, 2H), 3.78 (s, 3H), 3.55
(t, J¼6.5 Hz, 2H), 2.26 (q, J¼7.2 Hz, 2H), 2.20 (q, J¼7.2 Hz, 2H), 1.74
d
(quint, J¼6.6 Hz, 2H); 13C NMR (CDCl3, 75 MHz)
d 171.1, 135.2, 126.7,

1184
J.I. Yun et al. / Tetrahedron 68 (2012) 1177e1184
71.1, 69.4, 51.9, 45.4, 28.8, 28.6; HRMS (EI) m/z calcd for C9H14O3
(MþꢂHCl) 170.0943, found 170.0945.
overnight and concentrated at reduced pressure. The residue was
dissolved in EtOAc, and washed with water and brine. The organic
layer was dried over anhydrous MgSO4 and concentrated in vacuo.
The resulting residue was purified by flash column chromatography
on silica gel (hexanes/EtOAc, 5:1) to give 12 (274.5 mg, colorless oil)
4.5.28. Methyl(E/Z)-(6-bromo-hex-4-enyloxy)-acetate(24d). Colorless
oil: 87% yield. 1H NMR (CDCl3, 500 MHz)
d 5.84e5.73 (m, 2H),
4.13e4.09 (m, 2H), [4.04 (d, J¼7.7 Hz) and 3.96 (d, J¼7.1 Hz), 2H], 3.79
in 63% yields: 1H NMR (CDCl3, 300 MHz)
d
7.75 (d, J¼8.1 Hz, 2H), 7.35
(s, 3H), 3.59e3.54 (m, 2H), [2.28 (q, J¼7.9 Hz) and 2.20 (q, J¼7.4 Hz),
(d, J¼7.8 Hz, 2H), 5.90e5.70 (m, 1H), 5.10e4.90 (m, 2H), 4.50 (s, 2H),
3.50 (t, J¼6.6 Hz, 2H), 3.22 (s, 3H), 2.46 (s, 3H), 2.13 (q, J¼6.9 Hz, 2H),
2H], 1.80e1.71 (m, 2H); 13C NMR (CDCl3, 75 MHz)
d 171.0, 135.6, 127.1,
71.1, 68.4, 51.9, 33.4, 28.8, 28.6 (peaks of Z-isomer detected separately
2.70 (quint, J¼6.9 Hz, 2H); 13C NMR (CDCl3, 75 MHz)
d170.7, 145.5,
from those of E-isomer
d
134.5, 126.3, 70.9, 68.3, 55.4, 35.3, 29.0, 27.9,
138.3, 135.7, 130.3, 127.6, 115.1, 71.6, 71.5, 32.8, 30.3, 21.6; HRMS (EI)
27.3, 23.5); HRMS (EI) m/z calcd for C9H15BrO3 (Mþ) 250.0205, found
m/z calcd for C15H21NO4S (Mþ) 311.1191, found 311.1186.
250.0229.
Acknowledgements
4.5.29. Methyl (E/Z)-9-chloro-non-7-enoate (24e). Colorless oil: 37%
yield. 1H NMR (CDCl3, 500 MHz)
d 5.78e5.73 (m, 1H), 5.64e5.57 (m,
1H), [4.09 (d, J¼7.0 Hz) and 4.03 (d, J¼7.1 Hz), 2H] 3.68 (s, 3H),
2.33e2.28 (m, 2H), [2.12 (q, J¼6.8 Hz) and 2.06 (q, J¼7.0 Hz), 2H],
1.67e1.58 (m, 2H), 1.44e1.28 (m, 4H); 13C NMR (CDCl3, 75 MHz)
This work was financially supported by the Korea Research In-
stitute of Chemical Technology and the National Research Foun-
dation of Korea (NRF) grant funded by the Government of Korea
(MEST) (R01-2008-000-20205-0).
d
174.3, 136.0, 126.3, 51.6, 45.6, 34.1, 32.0, 28.7, 28.6, 24.9; HRMS (EI)
m/z calcd for C10H17ClO2 (Mþ) 204.0917, found 204.0937.
References and notes
1. For some recent examples, see (a) Morris, C. L.; Hu, Y.; Head, G. D.; Brown, L. J.;
Whittingham, W. G.; Brown, R. C. D. J. Org. Chem. 2009, 74, 981; (b) Miyaoka, H.;
Hara, Y.; Shinohara, I.; Kurokawa, T.; Kawashima, E.; Yamada, Y. Heterocycles
2009, 77, 1185; (c) Yadav, J. S.; Kumar, M. R.; Sabitha, G. Tetrahedron Lett. 2008,
49, 463; (d) Davoren, J. E.; Harcken, C.; Martin, S. F. J. Org. Chem. 2008, 73, 391;
(e) Davoren, J. E.; Martin, S. F. J. Am. Chem. Soc. 2007, 129, 510; (f) Janssen, D.;
Kalesse, M. Synlett 2007, 2667; (g) Noguchi, N.; Nakada, M. Org. Lett. 2006, 8,
2039; (h) Zou, Y.; Che, Q.; Snider, B. B. Org. Lett. 2006, 8, 5605; (i) Yohsimura, T.;
Yakushiji, F.; Kondo, S.; Wu, X.; Shindo, M.; Shishido, K. Org. Lett. 2006, 8, 475;
(j) Canesi, S.; Berthiaume, G.; Deslongchamps, P. Eur. J. Org. Chem. 2006, 3681.
2. (a) Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R. H. Angew. Chem., Int. Ed.
Engl. 1995, 34, 2039; (b) Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc.
1996, 118, 100.
4.5.30. Methyl (E/Z)-9-bromo-non-7-enoate (24f). Colorless oil:
68% yield. 1H NMR (CDCl3, 500 MHz)
d 5.80e5.65 (m, 2H), [3.98 (d,
J¼8.5 Hz) and 3.96e3.93 (m), 2H], 3.67 (s, 3H), 2.40e2.28 (m, 2H),
[2.17e2.15 (m) and 2.07 (q, J¼7.0 Hz), 2H], 1.68e1.59 (m, 2H),
1.46e1.28 (m, 4H); 13C NMR (CDCl3, 75 MHz)
d 174.3, 136.4, 126.7,
51.6, 24.1, 33.6, 31.9, 28.7, 28.5, 24.5 (peaks of Z-isomer detected
separately from those of E-isomer
d 135.8, 125.6, 31.0, 28.8, 27.4,
26.8); HRMS (EI) m/z calcd for C10H16O2 (MþꢂHBr) 168.1150, found
168.1150.
3. (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953; (b)
Chatterjee, A. K.; Grubbs, R. H. Org. Lett. 1999, 1, 1751; (c) Chatterjee, A. K.; Choi,
T.-L.; Sanders, D. P.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 11360.
4. (a) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc.
2000, 122, 8168; (b) Gessler, S.; Randl, S.; Blechert, S. Tetrahedron Lett. 2000, 41,
9973.
5. (a) Blanco, O. M.; Castedo, L. Synlett 1999, 557; (b) Liu, B.; Das, S. K.; Roy, R. Org.
Lett. 2002, 4, 2723; (c) Eustache, J.; Weghe, P. V.; Nouen, D. L.; Uyehara, H.; Kabuto,
C.; Yamamoto, Y. J. Org. Chem. 2005, 70, 4043; (d) Bandini, M.; Cozzi, P. G.; Licciulli,
S.; Umani-Ronchi, A. Synthesis 2004, 409; (e) Thibaudeau, S.; Fuller, R.; Gou-
verneur, V. Org. Biomol. Chem. 2004, 2,1110; (f) Raju, R.; Allen, L. J.; Le, T.; Taylor, C.
D.; Howell, A. R. Org. Lett. 2007, 9,1699; (g) Raju, R.; Howell, A. R. Org. Lett. 2006, 8,
2139; (h) Pietraszuk, C.; Marciniec, B.; Fischer, H. Tetrahedron Lett. 2003, 44, 7121;
(i) Jacobs, T.; Rybak, A.; Meier, M. A. R. Appl. Catal., A 2009, 353, 32; (j) Vulovic, B.;
Bihelovic, F.; Matovic, R.; Saicic, R. N. Tetrahedron 2009, 65, 10485.
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G.; Lee, D.-S.; Kim, Y.; Kim, S. H.; Hong, J. J. Am. Chem. Soc. 2009, 131, 3192; (b)
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M. C.; Lee, D.-S.; Hong, J. Chem.dAsian J. 2010, 5, 1902.
4.6. Synthesis of 9d and 12
4.6.1. 2-(Dec-9-enyloxy)acetic acid (9d). Decenol
5
(1.2 mL,
6.4 mmol) was added dropwise to a stirred suspension of NaH
(282 mg, 60% dispersion in mineral oil, 7.1 mmol) in anhydrous THF
(4.6 mL) at 0 ꢀC. After 15 min at the same temperature, the mixture
was stirred for 15 min at room temperature. A solution of chloro-
acetic acid (605 mg, 6.4 mmol) in anhydrous THF (2.3 mL) was
added to a separate suspension of NaH (282 mg, 60% in mineral oil,
7.1 mmol) in anhydrous THF (2.3 mL) at 0 ꢀC was added. After 10 min
of stirring at 0 ꢀC, the previously prepared alkoxide solution was
added to the reaction mixture. The reaction mixture was stirred for
24 h at 70 ꢀC. After cooling to room temperature, the reaction
mixture was poured into water and THF was evaporated under re-
duced pressure. The mixture was acidified until pH 3e4 with 1 N
aqueous HCl and extracted with CH2Cl2 (30 mLꢁ3). The combined
organic layers were washed with brine, dried over anhydrous
MgSO4 and concentrated in vacuo. The resulting residue was puri-
fied by flash column chromatography on silica gel (hexanes/EtOAc,
1:1) to give 9d (1.10 g, colorless oil) in 73% yield: 1H NMR (CDCl3,
7. Lee, K.; Kim, H.; Hong, J. Org. Lett. 2009, 11, 5202.
8. Ghosh, A. K.; Xu, X. Org. Lett. 2004, 6, 2055.
9. Artman, G. D., III; Grubbs, A. W.; Williams, R. M. J. Am. Chem. Soc. 2007, 129,
6336.
10. Preliminary results from this study have been reported: Yun, J. I.; Kim, D.; Lee, J.
Tetrahedron Lett. 2011, 52, 1928.
11. For some recent examples, see (a) Sohn, T.; Kim, M. J.; Kim, D. J. Am. Chem. Soc.
2010, 132, 12226; (b) Jeong, W.; Kim, M. J.; Kim, H.; Kim, S.; Kim, D.; Shin, K. J.
Angew. Chem., Int. Ed. 2010, 49, 752; (d) Prasad, K. R.; Gandi, V. R. Synlett 2009,
2593; (e) Ribes, C.; Falomir, E.; Murga, J.; Carda, M.; Marco, J. A. Org. Biomol.
Chem. 2009, 7, 1355; (f) Paek, S.-M.; Yun, H.; Kim, N.-J.; Jung, J.-W.; Chang, D.-J.;
300 MHz)
4.09 (s, 2H), 3.57 (t, J¼6.6 Hz, 2H), 2.12e1.97 (m, 2H), 1.71e1.53 (m,
2H), 1.46e1.20 (m, 10H); 13C NMR (CDCl3, 75 MHz)
175.1, 139.3,
d 9.50 (br s, 1H), 5.90e5.72 (m, 1H), 5.06e4.88 (m, 2H),
d
€
Lee, S.; Yoo, J.; Park, H.-J.; Suh, Y.-G. J. Org. Chem. 2009, 74, 554; (g) Furstner, A.;
114.3, 72.3, 67.9, 33.9, 29.53, 29.50, 29.45, 29.16, 29.02, 26.0; HRMS
ꢀ
Bouchez, L. C.; Morency, L.; Funel, J.-A.; Liepins, V.; Poree, F.-H.; Gilmour, R.;
(EI) m/z calcd for C12H22O3 (Mþ) 214.1569, found 214.1549.
Laurich, D.; Beaufils, F.; Tamiya, M. Chem.dEur. J. 2009, 15, 3983.
12. (a) Kim, H.; Choi, W. J.; Jung, J.; Kim, S.; Kim, D. J. Am. Chem. Soc. 2003, 125,
10238; (b) Lugtenberg, R. J. W.; Egberink, R. J. M.; Engbersen, J. F. J.; Reinhoudt,
D. N. J. Chem. Soc., Perkin Trans. 2 1997, 1353.
4.6.2. N-Methyl-2-(pent-4-en-1-yloxy)-N-tosylacetamide (12). To
a solution of acid 9b (200 mg, 1.4 mmol), in anhydrous benzene
(1.4 mL) were successively added a catalytic amount of DMF (one
drop) and oxalyl chloride (0.1 mL, 1.5 mmol). The reaction mixture
was stirred overnight at room temperature. The mixture was con-
centrated at reduced pressure and the residue was dissolved in an-
hydrous CH2Cl2 (5 mL). N-Methyl-p-toluenesulfonamide (200 mg,
1.1 mmol) and triethylamine (1 mL, 7 mmol) were added to the so-
lution at room temperature. The reaction mixture was stirred
13. (a) Toste, F. D.; Chatterjee, A. K.; Grubbs, R. H. Pure Appl. Chem. 2002, 74, 7; (b)
~
McNaughton, B. R.; Bucholtz, K. M.; Camaano-Moure, A.; Miller, B. L. Org. Lett.
2005, 7, 733; (c) Harrity, J. P. A.; La, D. S.; Cefalo, D. R.; Visser, M. S.; Hoveyda, A.
H. J. Am. Chem. Soc. 1998, 120, 2343.
14. (a) Petit, F.; Furstoss, R. Tetrahedron: Asymmetry 1993, 4, 1341; (b) Taillier, C.;
Hameury, T.; Bellosta, V.; Cossy, J. Tetrahedron 2007, 63, 4472; (c) Broadhurst,
M. J.; Brown, S. J.; Percy, J. M.; Prime, M. E. J. Chem. Soc., Perkin Trans. 1 2000,
3217; (d) Simonot, B.; Rousseau, G. J. Org. Chem. 1994, 59, 5912.
15. Wakamatsu, H.; Blechert, S. Angew. Chem., Int. Ed. 2002, 41, 2403.
16. Pietraszkiewicz, M.; Jurczak, J. Tetrahedron 1984, 40, 2967.