SN2′ reaction of organozinc reagents activated by catalytic tBu-P4 base in the presence of LiCl

Article abstract of DOI:10.1002/chem.200900556

The tBu-P4 base was found to be an excellent catalyst for the activation of organozinc reagents. The base was used to promote the S_N2′ reaction of α,β-unsaturated esters bearing a γ-chloride in the reactions with various organozinc reagents in

Full text of DOI:10.1002/chem.200900556

FULL PAPER
DOI: 10.1002/chem.200900556
SN2’ Reaction of Organozinc Reagents Activated by Catalytic tBu-P4 Base in
the Presence of LiCl
Koji Kobayashi,[a] Masahiro Ueno,[a] Hiroshi Naka,[b] and Yoshinori Kondo*[a]
Abstract: The tBu-P4 base was found to be an excellent catalyst for the activation
of organozinc reagents. The base was used to promote the SN2’ reaction of a,b-un-
saturated esters bearing a g-chloride in the reactions with various organozinc re-
agents in the presence of LiCl. The reactions proceeded in high yield with excel-
lent chemo-and regioselectivity. The role of LiCl appears to be the activation of
the g-chloride of the a,b-unsaturated esters, which was confirmed by NMR spec-
troscopic study.
Keywords: lithium · nucleophilic
substitution · phosphazene bases ·
zinc
Introduction
clic carbenes as Lewis base catalyst.[4] However, for the SN2’
reaction of organozinc reagents the use of transition-metal
catalyst seemed still essential.[5]
Organozinc reagents are one of the most useful class of or-
ganometallic reagents for organic synthesis.[1] The easy ac-
cessibility and high functional group compatibility of orga-
nozinc compounds allow numerous applications in synthetic
chemistry. However, they occasionally require a catalyst to
react smoothly with electrophiles. Many activation methods
of organozinc reagents have been reported and one of the
most prevalent activation methods is transmetalation using
transition-metal catalysts.[2] However, transition metals are
often expensive and sometimes their removal from the prod-
uct after the reaction is detrimental, especially in multistep
reactions in medicinal chemistry research. It seems still very
important to provide a novel activation method without the
help of transition-metal catalyst.
We recently reported that the use of catalytic tBu-P4
base[6] dramatically improved the performance of halogen-
zinc exchange of aryl iodides (Scheme 1).[7] This activation is
considered to closely relate to the donation of tBu-P4 base
to zinc atom of dialkylzinc reagents, which increases the
electron density of alkyl group to enhance the reactivity.
Herein we wish to report the tBu-P4 base catalyzed SN2’ re-
action of organozinc reagents in the presence of LiCl with-
out using transition metal catalysts.[8]
The SN2’ reaction is an important synthetic transformation
for creating highly substituted sp3 carbon centers effective-
ly.[3] Recently, Lee and Hoveyda reported Cu-free allylic al-
kylation reactions with Grignard reagents using N-heterocy-
Scheme 1. tBu-P4 base catalyzed halogen–zinc exchange.
Results and Discussion
The SN2’ reaction was first examined with a,b-unsaturated
esters bearing a g-chloride (1a), two equivalents of diethyl-
zinc, and 10 mol% of tBu-P4 base in various organic sol-
vents (Table 1, entries 1–4). It was suggested that the cata-
lytic activity was solvent dependent; among the solvents,
DMF was found to be the best for the catalytic activity
(Table 1, entry 4). In this case, no SN2 reaction product was
detected in the NMR analysis of the crude material. By low-
ering the reaction temperature to 08C, the yield of 2a in-
creased to 75% (Table 1, entry 5). The use of a weaker
[a] K. Kobayashi, Dr. M. Ueno, Prof. Dr. Y. Kondo
Graduate School of Pharmaceutical Sciences
Tohoku University, Aramaki-aza Aoba 6-3
Aoba-ku, Sendai 980-8578 (Japan)
Fax : (+81)22-795-6804
E-mail: ykondo@mail.pharm.tohoku.ac.jp
[b] Prof. Dr. H. Naka
Department of Chemistry and Research Center for Materials Science
Nagoya University, Hurou-tyo, Chikusa-ku, Nagoya, 464-8602 (Japan)
Fax : (+81)52-789-5904
Chem. Eur. J. 2009, 15, 9805 – 9809
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
9805

phosphazene base such as 2-tert-butylimino-2-diethylamino-
1,3-dimethylperhydro-1,3,2-diazaphosphorine (BEMP; see
below) resulted in lower yields (Table 1, entry 6); the reac-
to be difficult using conventional transition-metal catalyzed
processes, especially in the presence of the iodo group.
Our next interest focused on the study of the substituent
effect at the a-position of the a,b-unsaturated esters. Alkyl-,
Table 2. SN2’ reaction of functionalized substrates.
Entry
R1
t [h]
Yield [%]
1
2
3
4
5
6
7
Ph
Bn
2
2
2
2
2
8
3
87
93
91
84
88
66
88
tion did not proceed in the absence of a phosphazene base
(Table 1, entry 7). The use of an additive was then examined
to facilitate the reaction. When LiCl was used as an addi-
tive, the reaction proceeded more smoothly, and the yield of
2a was improved up to 90% (Table 1, entry 7).
4-MeO-Bn
4-NC-Ph
4-Bz-Ph
4-O2N-Ph
3-I-Bn
Table 1. Optimization of SN2’ reaction conditions.
allyl-substituted substrates and an unsubstituted substrate
were reacted with diethylzinc under the same conditions
and the desired products were obtained in good yields
(Table 3, entries 1–3). But, when phenyl-substituted sub-
strate was used, the selectivity was siginificantly lowered
and desired product was isolated in only 38% yield together
with SN2 product in 61% yield (Table 3, entry 4).
Entry Base
Additive Solvent
T
t [h] Yield [%]
1
2
3
4
5
6
7
8
tBu-P4 base
–
–
–
–
–
–
–
THF
toluene RT
RT
24
24
2
32[a]
18[a]
71
tBu-P4 base
tBu-P4 base
tBu-P4 base
tBu-P4 base
BEMP
DMF
DMF
DMF
DMF
DMF
DMF
RT
08C
2
75
À408C 12
63[a]
29
Table 3. Influence of a-substituents on SN2’ reaction.
08C
08C
08C
2
2
2
–
0
90
tBu-P4 base LiCl
[a] Yield based on NMR peak analysis.
Entry
R1
R2
t [h]
Yield [%]
1
2
3
4
tBu
tBu
Bn
nBu
Allyl
H
2
4
2
2
88
74
94
As shown in Table 1, it was found that tBu-P4 base is an
excellent catalyst for the SN2’ reaction of organozinc re-
agents; the presence of LiCl was also found to be favorable
for a smooth conversion. With the aim to further develop
the synthetic utility of this method, reactions with other sub-
strates were investigated.
Me
Ph
38 (SN2: 61)
Other a,b-unsaturated esters bearing a g-chloride sub-
strate, such as phenyl and benzyl esters, were reacted with
diethylzinc under the same conditions to give the corre-
sponding esters in 87 (2b) and 93% (2c), respectively
(Table 2, entries 1 and 2). Various substituents on the a,b-
unsaturated esters bearing a g-chloride were compatible in
the SN2’ reaction. The substitution with metal coordinating
functional groups such as a methoxy group did not affect
the reaction, and the corresponding ester 2d was obtained
in good yields (Table 2, entry 3). The presence of electro-
philic functional groups was examined and the tolerance of
cyano, carbonyl, nitro and iodo groups during the SN2’ reac-
tion is considered to be synthetically important and attrac-
tive (Table 2, entries 4–7). These highly chemoselective con-
versions in the presence of functional groups are considered
We next examined the reaction of another alkylzinc with
a,b-unsaturated esters bearing a g-chloride. When di-n-bu-
tylzinc, prepared from n-butyllithium and zinc chloride, was
used, the corresponding ester (2m) was obtained in 74%
yield (Scheme 2).
Scheme 2. Reaction using dibutylzinc.
9806
www.chemeurj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 9805 – 9809

SN2’ Reaction of Organozinc Reagents
FULL PAPER
1H NMR spectra of dimethylzinc in the presence of tBu-
P4 base was measured for the preliminary estimation of the
activation mechanism. As a result, the methyl signals of di-
methylzinc in presence of tBu-P4 base and no additive in
THF at À208C were observed as sharp singlets at d À1.06
and À0.89 ppm, respectively (Figure 1). This result suggested
that dimethylzinc exist as the more anionically activated
form in the presence of tBu-P4 base by the electron-donat-
ing coordination to dimethylzinc. It has been known that the
coodination of donors to alkylzinc compounds causes
Figure 2. 1H NMR spectra of dimethylzinc in the presence of LiCl (THF,
À208C).
1
higher-field shifts of alkyl protons in H NMR spectra.[9] It is
assumed that the high reactivity in the presence of tBu-P4
base is attributed to this enhanced anionic character.
Figure 3. 13C NMR spectra of substrate in the presence of LiCl (THF,
RT).
Figure 1. 1H NMR spectra of dimethylzinc in the presence of tBu-P4 base
(THF, À208C).
Scheme 3. First, tBu-P4 base activates organozinc reagents
anionically. Then, the activated organozinc reagents react
with a,b-unsaturated esters bearing a g-chloride coordinated
by LiCl in a push–pull SN2’ fashion. The coordination of
LiCl to the carbonyl of the substrates is also considered to
be important, which would facilitate alkylation by the en-
hancement of electrophilicity at the a carbon.
Next, the effect of LiCl was investigated. The activating
effect of LiCl to organometallic reagents was reported by
Knochel et al.,[10] but the exact role of the salt still seemed
1
unclear. To disclose the role of LiCl in our reaction, the H
and 13C NMR spectrum of dimethylzinc or substrate with
LiCl were examined carefully (Figures 2 and 3). The chemi-
cal shift of dimethylzinc in the presence of LiCl was the
same chemical shift of dimethylzinc in the absence of LiCl
(Figure 2). This result indicates that LiCl have little interac-
tion with the organozinc reagents. On the other hand, the
apparent changes of the chemical shifts of the substrate in
the presence of LiCl were observed (Figure 3). In 13C NMR
spectra of the substrate with LiCl and without LiCl, the
chemical shifts of carbonyl carbon were almost the same
(Figure 3, c). However, the signals of alkenyl sp2 carbons
and allyl sp3 carbon shifted (Figure 3, e, d and g). The signal
shift of allyl sp3 carbon was the largest (Figure 3g). This ob-
servation suggests that LiCl activates the substrate by coor-
dinating to the g-chloride of the substrate.
Conclusions
The use of tBu-P4 base as a catalyst was found to improve
the performance of SN2’ reaction with organozinc reagents
dramatically. 1H NMR and 13C NMR study suggested that
this high reactivity is reflected by the coordination of tBu-
P4 base to organozinc and the activation of the substarate
by LiCl, but the interaction of LiCl with organozinc reagents
was not observed in our case. LiCl is known to change the
aggregation state of organometallic compounds; an active
species undetectable by NMR analysis may also be involved
in the substitution. The efficient tBu-P4 base and LiCl are
considered to function independently, but still cooperatively
in this SN2’ reaction. Further investigations on the scope and
Based on these results which suggest that the tBu-P4 base
activates the organozinc reagents and LiCl activates the sub-
strate, a possible catalytic cycle is proposed as shown in
Chem. Eur. J. 2009, 15, 9805 – 9809
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9807

Y. Kondo et al.
9H), 1.49 (s, 3H), 1.49–1.88 (m, 1H,),
1.68–1.80 (m, 1H), 5.02–5.09 (m, 2H),
5.98 ppm (dd, J=18.1, 10.5 Hz, 1H);
IR (neat): n˜ = 2973, 2933, 1725, 1459,
1368, 1246, 1136, 914, 850 cmÀ1; LRMS
(EI): m/z: 184 [M+]; HRMS: m/z:
calcd for C11H20O2: 184.1463; found:
184.1447.
Phenyl
2-ethyl-2-methyl-3-enoate
(2b): The crude material was purified
by column chromatography on silica
gel (hexane/ethyl acetate 10:1) to give
the title compound as a colorless oil
(53.3 mg, 87%). 1H NMR (400 MHz,
CDCl3/TMS): d = 0.98 (t, J=7.2 Hz,
H), 1.38 (s, 3H), 1.70–1.82 (m, 1H),
1.90–2.11 (m, 1H), 5.17–5.27 (m, 2H),
6.14 (dd, J=17.6, 10.8 Hz, 1H), 7.04
(d, J=7.6 Hz, 2H), 7.21 (t, J=7.6 Hz,
Scheme 3. A possible catalytic cycle.
1H), 7.35 ppm (t, J=7.6 Hz, 2H);
13C{1H} NMR (100 MHz, CDCl3): d =
limitation of the tBu-P4 base promoted reactions of organo-
zinc compounds and mechanistic studies are currently un-
derway.
9.1, 20.0, 31.9, 49.2, 114.2, 121.4, 125.6, 129.2, 141.0, 150.9, 174.2 ppm; IR
(neat): n˜ = 2977, 1723, 1640, 1457, 1368, 1167, 1136, 914, 849, 766 cmÀ1
;
LRMS (EI): m/z: 204 [M+]; HRMS: m/z: calcd for C13H16O2: 204.1150;
found: 204.1149.
Benzyl 2-ethyl-2-methylbut-3-enoate (2c): The crude material was puri-
fied by column chromatography on silica gel (hexane/ethyl acetate 10:1)
to give the title compound as yellowish oil (60.9 mg, 93%). 1H NMR
(400 MHz, CDCl3/TMS): d = 0.83 (t, J=7.6 Hz, 3H), 1.28 (s, 3H), 1.58–
1.69 (m, 1H), 1.74–1.83 (m, 1H), 5.05–5.19 (m, 2H), 5.12 (s, 2H), 6.03
(dd, J=17.4 Hz, J=10.8 Hz, 1H), 7.27–7.38 ppm (m, 5H); 13C{1H} NMR
(100 MHz, CDCl3): d = 8.9, 19.9, 31.9, 49.0, 66.2, 113.7, 127.7, 128.4,
136.1, 141.3, 175.4 ppm; LRMS (EI): m/z: 218 [M+]; HRMS: Calcd. for
C14H18O2: 218.1307, Found: 218.1325. IR (neat): n˜ = 2970, 1727, 1457,
Experimental Section
General methods: Reactions were carried out under Ar atmosphere
using dry solvents. Melting points (m.p.) were determined with a Yazawa
micro melting point apparatus and uncorrected. Infrared (IR) data were
recorded on SensIR ATR (Attenuated Total Reflectance) FT-IR. The
spectra were acquired in 32 scans per spectrum at a resolution of four
using system ReactIR 2.20 software. Absorbance frequencies are report-
ed in cmÀ1. NMR data were recorded on either a JEOL AL400 spectrom-
eter (395.75 MHz for 1H, 99.50 MHz for 13C). Chemical shifts are ex-
pressed in d (parts per million, ppm) values, and coupling constants are
expressed in hertz (Hz). 1H NMR spectra were referenced to a tetrame-
1231, 1133, 1003, 916, 731, 696 cmÀ1
.
para-Methoxybenzyl 2-ethyl-2-methylbut-3-enoate (2d): The crude mate-
rial was purified by column chromatography on silica gel (hexane/ethyl
acetate 10:1) to give the title compound as a colorless oil (67.8 mg,
91%). 1H NMR (400 MHz, CDCl3/TMS): d = 0.81 (t, J=7.2 Hz, 3H),
1.26 (s, 3H), 1.55–1.67 (m, 1H), 1.71–1.83 (m, 1H), 3.81 (s, 3H), 5.01–
5.12 (m, 4H), 6.01 (dd, J=17.6 Hz, J=11.2 Hz, 1H), 6.87 (d, J=8.4 Hz,
2H), 7.27 ppm (d, J=8.4 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3): d =
8.9, 19.9, 31.9, 49.0, 55.2, 66.1, 113.5, 113.8, 128.3, 129.6, 141.4, 159.3,
175.5 ppm; IR (neat): n˜ = 2966, 1725, 1613, 1515, 1459, 1245, 1133, 1034,
920, 822 cmÀ1; LRMS (EI): m/z: 248 [M+]; HRMS: m/z: calcd for
C15H20O3: 248.1412; found: 248.1395.
thylsilane as an internal standard or to
a solvent signal (CDCl3:
7.26 ppm). 13C NMR spectra were referenced to a tetramethylsilane as an
internal standard or to a solvent signal (CDCl3: 77.0 ppm). The following
abbreviations are used: s=singlet, d=doublet, t=triplet, q=quartet,
m=multiplet, dd=double doublet, dt=double triplet, td=triple doublet,
dq=double quartet, br=broad singlet. Low and high resolution mass
spectra (LRMS and HRMS) were obtained from Mass Spectrometry Re-
source, Graduate School of Pharmaceutical Sciences, Tohoku University,
on a JEOL JMS-DX303 and JMS-700 spectrometer respectively.
para-Cyanophenyl 2-ethyl-2-methylbut-3-enoate (2e): The crude material
was purified by column chromatography on silica gel (hexane/ethyl ace-
tate 10:1) to give the title compound as a colorless oil (57.8 mg, 84%).
1H NMR (400 MHz, CDCl3/TMS): d = 0.97 (t, J=7.2 Hz, 3H), 1.40 (s,
3H), 1.71–1.82 (m, 1H), 1.90–2.00 (m, 1H), 5.19–5.26 (m, 2H), 6.09 (dd,
J=17.2 Hz, J=10.4 Hz, 1H), 7.19 (d, J=8.8 Hz, 2H), 7.68 ppm (d, J=
8.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3): d = 9.0, 19.9, 31.8, 49.3,
109.5, 114.8, 118.1, 122.6, 133.5, 140.2, 154.2, 173.4 ppm; IR (neat): n˜ =
2970, 2231, 1752, 1602, 1497, 1206, 1167, 1092, 901, 862 cmÀ1; LRMS (EI):
m/z: 229 [M+]; HRMS: m/z: calcd for C14H15NO2: 229.1103; found:
229.1103.
Materials: Unless otherwise noted, materials were purchased from Tokyo
Kasei Co., Aldrich Inc., and other commercial suppliers and were used
after appropriate purification (distillation or recrystallization). Flash
column chromatographies were performed with Kanto silica gel 60N
(spherical, neutral, 70–230 mesh).
General procedure: Under argon atmosphere, tBu-P4 base (0.03 mL 1.0m
in hexane, 0.03 mmol) was added to a mixture of electrophile (0.3 mmol),
diethyl zinc (0.60 mL 0.6 mmol), LiCl (1.3 mg 0.03 mmol) and dry DMF
(0.4 mL) at 08C and the mixture was stirred 2–8 h at 08C. After the reac-
tion, saturated aq. NH4Cl and H2O were added to the mixture. The mix-
ture was extracted with AcOEt or Et2O (3ꢁ30 mL). The combined or-
ganic layers were then washed with saturated aq. NaCl (50 mL). The so-
lution was dried with MgSO4, filtered, and concentrated in vacuo. The
crude material was purified by SiO2 column chromatography. All g-
chloro-a,b-unsaturated esters were synthesized using literature proce-
dures.[4]
para-Benzoylphenyl 2-ethyl-2-methylbut-3-enoate (2 f): The crude mate-
rial was purified by column chromatography on silica gel (hexane/ethyl
acetate 10:1) to give the title compound as a colorless oil (81.4 mg,
88%). 1H NMR (400 MHz, CDCl3/TMS): d = 0.99 (t, J=7.6 Hz, 3H),
1.42 (s, 3H), 1.73–1.84 (m, 1H), 1.92–2.02 (m, 1H), 5.21–5.28 (m, 2H),
6.13 (dd, J=17.6 Hz, J=10.4 Hz, 1H), 7.17 (d, J=8.8 Hz, 2H), 7.48 (t,
J=7.6 Hz, 2H), 7.59 (t, J=7.6 Hz, 1H), 7.79 (d, J=7.6 Hz, 2H),
7.85 ppm (d, J=8.8 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3): d = 9.0,
20.0, 31.8, 49.3, 114.6, 121.3, 128.2, 129.8, 131.5, 132.3, 134.8, 137.6, 140.5,
154.1, 173.7, 195.2 ppm; IR (neat): n˜ = 2968, 1750, 1657, 1598, 1275,
tert-Butyl 2-ethyl-2-methylbut-3-enoate (2a): The crude material was pu-
rified by column chromatography on silica gel (hexane/ethyl acetate
10:1) to give the title compound as a colorless oil (49.8 mg, 90%).
1H NMR (400 MHz, CDCl3/TMS): d = 0.85 (t, J=7.5 Hz, 3H), 1.44 (s,
9808
www.chemeurj.org
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 9805 – 9809

SN2’ Reaction of Organozinc Reagents
FULL PAPER
1200, 1148, 1098, 924, 735, 704 cmÀ1; LRMS (EI): m/z: 308 [M+]; HRMS:
m/z: calcd for C20H20O3: 308.1412; found: 308.1399.
7.6 Hz, 2H), 3.72 (s, 3H), 7.08 (t, J=7.6 Hz, 1H), 7.13–7.19 (m, 2H),
7.30–7.40 ppm (m, J=3H); IR (neat): n˜ = 2958, 1715, 1495, 1434, 1245,
1223, 1023, 764, 700 cmÀ1; LRMS (EI): m/z: 204 [M+]; HRMS: m/z:
calcd. for C13H16O2: 204.1150; found 204.1144.
para-Nitrobenzyl 2-ethyl-2-methylbut-3-enoate (2g): The crude material
was purified by column chromatography on silica gel (hexane/ethyl ace-
tate 10:1) to give the title compound as a yellow oil (52.1 mg, 66%).
1H NMR (400 MHz, CDCl3/TMS): d = 0.84 (t, J=7.6 Hz, 3H), 1.31 (s,
3H), 1.61–1.72 (m, 1H), 1.77–1.87 (m, 1H), 5.09–5.29 (m, 2H), 5.21 (s,
2H), 6.02 (dd, J=17.6 Hz, 10.8 Hz, 1H), 7.49 (d, J=9.2 Hz, 2H),
8.22 ppm (d, J=9.2 Hz, 2H); 13C{1H} NMR (100 MHz, CDCl3/TMS): d =
8.92, 19.80, 31.78, 49.02, 64.77, 114.12, 123.64, 127.98, 140.86, 143.36,
147.44, 175.14 ppm; IR (neat): n˜ = 3085, 2970, 1729, 1607, 1520, 1345,
1229, 1111, 735 cmÀ1; LRMS (EI): m/z: 263 [M+]; HRMS: m/z: calcd for
C14H17NO4: 263.1158; found 263.1158.
tert-Butyl 2-butyl-2-ethylbut-3-enoate (2m): The crude material was puri-
fied by column chromatography on silica gel (hexane/ethyl acetate 10:1)
to give the title compound as a colorless oil (47.1 mg, 74%). 1H NMR
(400 MHz, CDCl3/TMS): d = 0.89 (t, J=7.2 Hz, 3H), 1.16–1.35 (m, 4H),
1.21 (s, 3H), 1.43 (s, 9H), 1.49–1.58 (m, 2H), 1.62–1.72 (m, 1H), 5.01–
5.08 (m, 2H), 5.99 ppm (dd, J=17.6, 10.8 Hz, 1H); 13C{1H} NMR
(100 MHz, CDCl3/TMS): d
= 14.04, 20.49, 23.23, 26.84, 28.02, 39.03,
49.08, 80.11, 112.72, 142.44, 174.98 ppm; IR (neat): n˜ = 2958, 2933, 1725,
1459, 1366, 1272, 1254, 1135, 914, 850 cmÀ1; LRMS (EI): m/z: 212 [M+];
HRMS: m/z: calcd for C13H24O2: 212.1776; found 212.1774.
ortho-Iodobenzyl 2-ethyl-2-methylbut-3-enoate (2h): The crude material
was purified by column chromatography on silica gel (hexane/ethyl ace-
tate 8:2) to give the title compound as a colorless oil (90.9 mg, 88%).
1H NMR (400 MHz, CDCl3/TMS): d = 0.85 (t, J=7.6 Hz, 3H), 1.31 (s,
3H), 1.61–1.72 (m, 1H), 1.78–1.88 (m, 1H), 5.08–5.20 (m, 2H), 5.12 (s,
2H), 6.65 (dd, J=17,6 Hz, J=10.8 Hz, 1H), 7.01 (td, J=6.8 Hz, J=
2.4 Hz, 1H), 7.31–7.39 (m, 2H), 7.84 ppm (d, J=7.6 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3/TMS): d = 8.93, 19.83, 31.83, 49.11, 70.10, 98.14,
113.89, 128.23, 129.26, 129.66, 138.52, 139.42, 141.32, 175.30 ppm; IR
Acknowledgements
This work was partly supported by the Grant-in Aid for Scientific Re-
search on Priority Areas “Advanced Molecular Transformations of
Carbon Resources” (No. 19020005) and “Synergistic Effects for Creation
of Functional Molecules” (No. 20036007) and other Research Grants
(No. 19390002, No. 18659001) from the Ministry of Education, Science,
Sports and Culture, Japan.
(neat): n˜ = 3064, 2970, 1727, 1459, 1437, 1229, 1129, 1015, 918, 746 cmÀ1
;
LRMS (EI): m/z: 344 [M+]; HRMS: m/z: calcd for C14H17IO2: 344.0273;
found 344.0287.
tert-Butyl 2-butyl-2-ethylbut-3-enoate (2i): The crude material was puri-
fied by column chromatography on silica gel (hexane/ethyl acetate 10:1)
to give the title compound as a colorless oil (59.8 mg, 88%). 1H NMR
(400 MHz, CDCl3/TMS): d = 0.89 (t, J=7.2 Hz, 3H), 1.16–1.35 (m, 4H),
1.21 (s, 3H), 1.43 (s, 9H), 1.49–1.58 (m, 2H), 1.62–1.72 (m, 1H), 5.01–
5.08 (m, 2H), 5.99 ppm (dd, J=17.6 Hz, J=10.8 Hz, 1H); 13C{1H} NMR
[1] P. Knochel, P. Jones, Organozinc Reagents, Oxford University Press,
Oxford, 1999.
[2] P. Knochel, R. D. Singer, Chem. Rev. 1993, 93, 2117–2188.
[3] R. M. Magid, Tetrahedron 1980, 36, 1901–1930, and references
therein.
(100 MHz, CDCl3/TMS): d
= 14.04, 20.49, 23.23, 26.84, 28.02, 39.03,
[4] Y. Lee, A. H. Hoveyda, J. Am. Chem. Soc. 2006, 128, 15604–15605.
[5] a) A. O. Larsen, W. Leu, C. Nieto-Oberhuber, J. E. Campbell, A. H.
Hoveyda, J. Am. Chem. Soc. 2004, 126, 11130–11131; b) J. J. Van
Veldhuizen, J. E. Campbell, R. E. Giudici, A. H. Hoveyda, J. Am.
Chem. Soc. 2005, 127, 6877–6882; c) K. E. Murphy, A. H. Hoveyda,
J. Am. Chem. Soc. 2003, 125, 4690–4691; d) K. E. Murphy, A. H.
Hoveyda, Org. Lett. 2005, 7, 1255–1258; e) H. Malda, A. W. van Zi-
ji, L. A. Arnold, B. L. Feringa, Org. Lett. 2001, 3, 1169–1171; f) F.
Dꢂbner, P. Knochel, Tetrahedron Lett. 2000, 41. 9233–9237; g) F.
Dꢂbner, P. Knochel, Angew. Chem. 1999, 111, 391–393; Angew.
Chem. Int. Ed. 1999, 38, 379–381.
[6] a) R. Schwesinger, H. Schlemper, Angew. Chem. 1987, 99, 1212–
1214; Angew. Chem. Int. Ed. Engl. 1987, 26, 1167–1169; b) R.
Schwesinger, H. Schlemper, C. Hasenfratz, J. Willaredt, T. Dam-
bacher, T. Breuer, C. Ottaway, M. Fletschinger, J. Boele, H. Fritz, D.
Putzas, H. W. Rotter, F. G. Bordwell, A. V. Satish, G. Z. Ji, E. M.
Peters, K. Peters, H. G. von Schnering, L. Walz, Liebigs Ann. 1996,
1055–1081.
[7] M. Ueno, A. E. H. Wheatley, Y. Kondo, Chem. Commun. 2006,
3549–3550.
[8] A part of this work has been published as a communication: K. Ko-
bayashi, M. Ueno, H. Naka, Y. Kondo, Chem. Commun. 2008,
3780–3782.
[9] a) M. Uchiyama, M. Koike, M. Kameda, Y. Kondo, T. Sakamoto, J.
Am. Chem. Soc. 1996, 118, 8733–8794; b) M. Ishimori, T. Tsuruta,
Kogyo Kagaku Zasshi 1967, 70, 152–158.
49.08, 80.11, 112.72, 142.44, 174.98 ppm; IR (neat): n˜ = 2958, 2933, 1725,
1459, 1366, 1272, 1254, 1135, 914, 850 cmÀ1; LRMS (EI): m/z: 212 [M+];
HRMS: m/z: calcd for C13H24O2: 212.1776; found 212.1774.
tert-Butyl 2-ethyl-2-(2-propenyl) but-3-enoate (2j): The crude material
was purified by column chromatography on silica gel (hexane/ethyl ace-
tate 10:1) to give the title compound as an yellow oil (46.7 mg, 74%).
1H NMR (400 MHz, CDCl3/TMS): d = 0.83 (t, J=7.2 Hz, 3H), 1.44 (s,
9H), 1.69 (q, J=7.2 Hz, 2H), 2.42 (d, J=7.2 Hz, 2H), 5.00–5.20 (m, 4H),
5.64–5.76 (m, 1H), 5.94 ppm (dd, J=17.6 Hz, J=10.8 Hz, 1H); 13C{1H}
NMR (100 MHz, CDCl3): d
= 8.6, 28.1, 28.6, 39.9, 52.7, 80.4, 114.3,
117.4, 134.1, 139.9, 173.8 ppm; IR (neat): n˜ = 2977, 1723, 1640, 1368,
1243, 1167, 1136, 914, 849 cmÀ1; LRMS (EI): m/z: 210 [M+]; HRMS:
m/z: calcd for C13H22O2: 210.1620; found: 210.1578.
Benzyl 2-ethylbut-3-enoate (2k): The crude material was purified by
column chromatography on silica gel (hexane/ethyl acetate 10:1) to give
1
the title compound as a colorless oil (57.6 mg, 94%). H NMR (400 MHz,
CDCl3/TMS): d = 0.90 (t, J=7.6 Hz, 3H), 1.54–1.65 (m, 1H), 1.75–1.87
(m, 1H), 2.97 (dt, J=8.3 Hz, J=7.3 Hz, 1H), 5.10–5.20 (m, 4H), 5.76–
5.88 (m, 1H), 7.30–7.39 ppm (m, 5H); 13C{1H} NMR (100 MHz, CDCl3):
d
= 11.6, 25.4, 51.9, 66.2, 117.2, 127.9, 128.0, 128.4, 135.7, 135.9,
173.7 ppm; IR (neat): n˜ = 2694, 1733, 1457, 1167, 1144, 991, 920, 735,
696 cmÀ1; LRMS (EI): m/z: 204 [M+]; HRMS: m/z: calcd for C13H16O2:
204.1150; found: 204.1137.
Methyl 2-ethyl-2-phenylbut-3-enoate (2l): The crude material was puri-
fied by column chromatography on silica gel (hexane/ethyl acetate 20:1)
to give the title compound as a colorless oil (23.3 mg, 38%). 1H NMR
(400 MHz, CDCl3/TMS): d = 0.83 (t, J=7.6 Hz, 3H), 2.07–2.27 (m, 2H),
3.69 (s, 3H), 5.02 (d, J=18.0 Hz, 1H), 5.31 (d, J=10.8 Hz, 1H), 6.38 (dd,
J=18.0, 10.8 Hz, 1H), 7.20–7.27 (m, 3H), 7.29–7.35 ppm (m, 5H); IR
[10] a) F. F. Kneisel, M. Dochnahl, P. Knochel, Angew. Chem. 2004, 116,
1032–1036; Angew. Chem. Int. Ed. 2004, 43, 1017–1021; b) A. Kra-
sovskiy, V. Malakhov, A. Gavryushin, P. Knochel, Angew. Chem.
2006, 116, 6186–6190; Angew. Chem. Int. Ed. 2006, 45, 6040–6044;
c) A. Metzger, M. A. Schade, P. Knochel, Org. Lett. 2008, 10, 1107–
1110; d) F. M. Piller, P. Appukkuttan, A. Gavryushin, M. Helm, P.
Knochel, Angew. Chem. 2008, 116, 6907–6911; Angew. Chem. Int.
Ed. 2008, 47, 6802–6806.
(neat): n˜
= ;
3087, 2950, 1731, 1459, 1434, 1227, 1123, 739, 698 cmÀ1
LRMS (EI): m/z: 204 [M+]; HRMS: m/z: calcd for C13H16O2: 204.1150;
found 204.1149.
Methyl 2-phenyl-2-hexenoate: The crude material was purified by
column chromatography on silica gel (hexane/ethyl acetate 20:1) to give
the title compound as a colorless oil (37.4 mg, 61%). H NMR (400 MHz,
Received: March 2, 2009
Revised: March 31, 2009
1
CDCl3/TMS): d = 0.87 (t, J=7.2 Hz, 3H), 1.44 (m, 2H), 2.05 (q, J=
Published online: August 13, 2009
Chem. Eur. J. 2009, 15, 9805 – 9809
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9809