Iron-catalyzed alkenylation of Grignard reagents by enol phosphates

Article abstract of DOI:10.1055/s-2008-1067194

Stereoselective preparation of trisubstituted olefins can be easily performed from an Z/E-mixture of enol phosphates by reacting only the E-isomer with a Grignard reagent in the presence of Fe(acac)₃. This procedure combines a kinetic differentiation and a stereoselective reaction. The coupling is very chemoselective in the presence of an alkyl chloride, an ester, a ketone or a nitrile. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2008-1067194

2636
SPECIAL TOPIC
Iron-Catalyzed Alkenylation of Grignard Reagents by Enol Phosphates
I
ron-Catalyzed A
l
é
r
f
G
rign
a
r
ts by
E
n
d
Laboratoire de Synthèse Organique Sélective et de Chimie Organométallique (SOSCO), UMR 8123 CNRS-UCP-ESCOM,
5 Mail Gay-Lussac, Neuville sur Oise, 95031 Cergy-Pontoise cedex, France
E-mail: gerard.cahiez@u-cergy.fr
Received 20 March 2008
iron-catalyzed reactions have received considerable inter-
Abstract: Stereoselective preparation of trisubstituted olefins can
est as indicated by the increasing number of reports from
be easily performed from an Z/E-mixture of enol phosphates by re-
us5c,7 and others.6,8
acting only the E-isomer with a Grignard reagent in the presence of
Fe(acac)3. This procedure combines a kinetic differentiation and a
The alkenylation reaction previously described is very ef-
stereoselective reaction. The coupling is very chemoselective in the
ficient and offers many economical and environmental
presence of an alkyl chloride, an ester, a ketone or a nitrile.
advantages. However, the starting alkenyl halides are not
always easy to prepare. To circumvent this problem in the
case of the palladium- and nickel-catalyzed reactions, a
Key words: cross-coupling, Grignard reactions, iron, alkenes,
stereoselectivity
classical alternative is to replace alkenyl bromides or
iodides by the corresponding enol triflates, which often
react similarly.9 However, these substrates are not very
convenient for preparative chemistry. Indeed, although
triflates are very useful on a laboratory scale, they do not
constitute a valuable industrial alternative to alkenyl ha-
lides since they are expensive and relatively difficult to
handle and purify on a large scale. From this point of
view, enol phosphates are much more attractive since they
are less expensive. Moreover, they are stable enough to be
prepared, stored and isolated without problem. Thus, they
can often be purified by distillation or by chromatography
on a silica gel column. To extend the scope of the iron-cat-
alyzed alkenylation of Grignard reagents for large-scale
applications we have thus developed the iron-catalyzed
coupling of organomagnesium reagents with enol phos-
phates.10
The first example of iron-catalyzed cross-coupling reac-
tions between a Grignard reagent and a vinylic halide was
described by Kharasch in 1945.1 Kochi, in 1971, studied
the mechanism of the coupling between alkylmagnesium
reagents and vinyl or propenyl bromide.2 Unfortunately,
from a preparative point of view, the reaction was not very
attractive since its scope was limited to reactive vinylic
halides such as propenyl bromide or b-bromostyrene.3
Moreover, as a rule, a large excess of these substrates (3
to 9 equivalents) had to be used in order to obtain satisfac-
tory yields. Twenty years later, the chemistry of iron-cat-
alyzed cross-coupling reactions was still in its infancy
since no general preparative procedure had been de-
scribed. At this time, we were convinced that iron salts
such as FeCl3, and Fe(acac)3 were a valuable alternative to
the palladium and nickel complexes commonly used as
catalysts for many coupling procedures since they were
cheaper and much more environmentally sound. Thus, we
have reinvestigated the iron-catalyzed coupling of Grig-
nard reagents with alkenyl halides and have finally dis-
covered that, in the presence of N-methyl-2-pyrrolidinone
(NMP) as an additive, the reaction occurs almost instanta-
neously to give excellent yields, even from the less reac-
tive alkenyl chlorides.4,5 In addition, the reaction is highly
chemo- and stereoselective (Scheme 1).
A preliminary experiment (Scheme 2) showed that enol
phosphate 1 reacted with octylmagnesium bromide in the
presence of 6% Fe(acac)3 and nine equivalents of NMP, in
tetrahydrofuran, to give the coupling product 2 in 67%
yield (Scheme 2). The yield was improved by replacing
NMP by N,N¢-dimethylpropylene urea (DMPU; 78%).
Oct
OPO(OPh)2
n-OctMgBr, Fe(acac)3 (6 mol%)
solvent, –20 °C, 1.5 h
Pr
Pr
Pr
Pr
1
2
The use of NMP is a major advance in the field of iron-
catalyzed cross-coupling reactions. Thus, our conditions
have since been used by Fürstner to couple alkylmagne-
sium reagents with aryl chlorides.6 In the last few years,
THF: 58%
THF–NMP (9 equiv): 67%
THF–DMPU (9 equiv): 78%
Scheme 2
n-BuMgCl
Fe(acac)3 (1 mol%)
O
O
It should be underscored that a 58% yield was obtained in
tetrahydrofuran alone, which is surprising since alkenyl
halides give very poor yields under these conditions. In
fact, it seems that enol phosphates are able to replace, at
least partially, NMP. It is interesting to note that enol tri-
flates behave similarly (Scheme 3).
Cl
Bu
THF–NMP (9 equiv)
–5 to 0 °C, 15 min
>99% E
80% (>99% E)
Scheme 1
SYNTHESIS 2008, No. 16, pp 2636–2644
Advanced online publication: 24.07.2008
x
x.
x
x
.
2
0
0
8
DOI: 10.1055/s-2008-1067194; Art ID: C02408SS
© Georg Thieme Verlag Stuttgart · New York

SPECIAL TOPIC
Iron-Catalyzed Alkenylation of Grignard Reagents by Enol Phosphates
2637
Table 1 Iron-Catalyzed Alkenylation of RMgCl by Enol
Phosphates
OTf
Bu
n-BuMgBr, Fe(acac)3 (5 mol%)
solvent, –30 to 20 °C
OPO(OR)2
R2
R
RMgCl, Fe(acac)3 (3 mol%)
THF, –20 °C, 1.5 h
R2
R1
R1
THF: 66%
THF–NMP (9 equiv): 80%
R = Et, Ph
Scheme 3
Entry Enol phosphate
R
Product
(E/Z)
Yield
(%)a
(E/Z)
The above hypothesis was confirmed by the following ex-
periment (Scheme 4). Thus, the coupling between alkenyl
chloride 3 and n-BuMgBr gave a poor yield in tetrahydro-
furan alone, whereas excellent yields of olefin 4 were ob-
tained in the presence of NMP or triethylphosphate as a
cosolvent (9 equiv).
1
Bu
Ph
87
81
OPO(OEt)2
Bu
5 (90:10)
(84:16)
OPO(OEt)2
Ph
2
3
2
2
(70:30)
5 (85:15)
Bu
Bu
Bu
Bu
n-BuMgBr, Fe(acac)3 (3 mol%)
–20 °C, 1.5 h
Bu
OPO(OPh)2
Cl
Bu
Bu
Bu
90
3
4
THF: 14%
THF–NMP (9 equiv): 85%
THF–PO(OEt)3 (9 equiv): 88%
6
Bu
OPO(OPh)2
Scheme 4
4
75b,c
3
3
7
8
9
The scope of the reaction is very broad; various enol phos-
phates derived from aldehydes (Table 1, entries 1 and 2)
or ketones (entries 3 to 15) have been used successfully.
The reaction conditions depend on the reactivity of the
substrate. Thus, enol phosphates derived from aldehydes
or acetophenone are reactive enough to give satisfactory
yields in tetrahydrofuran alone (entries 1 to 3), whereas
the less reactive a,b-disubstituted enol phosphates require
the presence of NMP (entries 4 to 9) or even DMPU (en-
tries 10 to 15). Although aromatic and linear aliphatic
Grignard reagents lead to good yields of coupling product,
secondary and tertiary alkylmagnesium halides either did
not couple (entry 12, R = t-Bu) or led to poor yields (entry
6, R = c-Hex).
Oct
OPO(OPh)2
5
6
Oct
82b,c
20b
c-Hex
OPO(OPh)2
OPO(OPh)2
c-Hex
Oct
7
Oct
75b,d
10
11
12
Bu
OPO(OPh)2
8
9
Bu
90b
n-OctMgBr
Fe(acac)3 (6 mol%)
OPO(OPh)2
Oct
Oct
OPO(OPh)2
Oct
90b
80c
70e
Pr
Pr
Pr
Pr
THF–DMPU (9 equiv)
–20 °C, 1.5 h
1
2
62%
>99% Z
E/Z = 42:58
OPO(OPh)2
Bu
Bu
Bu
Scheme 5
10
11
12
13
Bu
Pr
Pr
(68:32)
13
While considering the results presented in Table 1, it
seems that the reaction is not stereoselective (entries 10 to
15) and indeed this is true for the Z-enol phosphates
(Scheme 5). However, by following the evolution of the
reaction (GC monitoring, Figure 1) between octylmagne-
sium bromide and a mixture of Z- and E-enol phosphates
1 (entry 11), it is clear that the E-isomer reacts much faster
than the Z-isomer. Thus, after 25 minutes, 98.5% of the E-
isomer was consumed whereas less than 5% of the Z-iso-
mer reacted. Moreover, it is interesting to note that at the
beginning of the reaction, the E-enol phosphate reacts al-
most exclusively to give the coupling product stereoselec-
tively (≥99% E).
OPO(OPh)2
Bu
Ph
Bu
Ph
Pr
Pr
(68:32)
14 (94:6)
OPO(OPh)2
Bu
t-Bu
Bu
Oct
c
t-Bu
Oct
0
Pr
Pr
(68:32)
OPO(OPh)2
75e
(70:30)
15 (88:12)
Synthesis 2008, No. 16, 2636–2644 © Thieme Stuttgart · New York

2638
G. Cahiez et al.
SPECIAL TOPIC
Table 1 Iron-Catalyzed Alkenylation of RMgCl by Enol Phos-
phates (continued)
Table 2 Stereoselective and Stereodifferentiating Iron-Catalyzed
Cross-Coupling Reactions
OPO(OR)2
R2
R
OPO(OPh)2
R
RMgCl, Fe(acac)3 (3 mol%)
THF, –20 °C, 1.5 h
RMgBr, Fe(acac)3 (4 mol%)
THF–DMPU, –20°C, 30 min
R2
R1
R1
R1
R2
R1
R2
R = Et, Ph
Entry Enol phosphate (E/Z)
Product
Yield (%)a
Entry Enol phosphate
R
Product
(E/Z)
Yield
Oct
Et
(%)a
OPO(OPh)2
(E/Z)
81
(≥99% E)
1
Me
Me
Et
OPO(OPh)2
Oct
(68:32)
16
14
Oct
81e
Oct
Pr
OPO(OPh)2
86
(71:29)
OPO(OPh)2
15
16 (83:17)
2
3
(≥98% E)b
Et
Ph
Et
Pr
Ph
73e
15
Oct
Bu
OPO(OPh)2
90
(≥98% E)
(71:29)
17 (93:7)
Pr
a Yield of isolated product.
Pr
Bu
b The reaction was performed in the presence of NMP (9 equiv).
c The reaction was performed with RMgBr.
(65:35)
2
Et
OPO(OPh)2
Pent
91
(93% Z)
d OctMgCl (2 equiv) was used.
4
e The reaction was performed in the presence of DMPU (9 equiv).
Bu
Pent
Bu
18
(69:31)
a
Yield of isolated product based on the E-enol phosphate using
RMgBr (1.2 equiv based on the E-enol phosphate).
b OctMgBr (1.4 equiv) was used.
Interestingly, the stereoselectivity can be improved by ad-
justing the amount of Grignard reagent. Thus in the last
example (entry 4), the use of 1.05 instead of 1.2 equiva-
lents of EtMgBr led to only 68% yield but the stereochem-
ical purity jumped from 93% to 98%. It should be noted
that when the reaction was performed on a mixture of the
corresponding Z- and E-alkenyl bromides, which are
much more reactive, the selectivity was clearly lower
(Scheme 7).
Figure 1
n-OctMgBr (0.6 equiv)
Fe(acac)3 (3 mol%)
Br
Oct
Pr
THF–NMP (9 equiv)
–20 °C, 1 h
In the light of these observations, we performed the same
reaction using only a stoichiometric amount of Grignard
reagent based on the E-enol phosphate (Scheme 6). Under
these conditions, the coupling took place quickly and ste-
reoselectively to give the pure E-olefin 2 in excellent yield
(90%). Moreover, at the end of the reaction the unreacted
Z-enol phosphate was recovered in 95% yield (≥95% Z).
Et
Pr
Et
15
E/Z = 60:40
50%*
(E/Z = 74:26)
* GC yield based on OctMgBr.
Scheme 7
From b-monosubstituted alkenyl phosphates such as 19,
which are more reactive than the a,b-disubstituted ana-
logues, the formation of the E-coupling product was also
favored. However, the kinetic differentiation was less
clear cut and the E-selectivity could not be improved by
lowering the amount of Grignard reagent used
(Scheme 8).
n-OctMgBr (0.78 equiv)
Fe(acac)3 (4 mol%)
OPO(OPh)2
Oct
90%*
>98% E
THF–DMPU (9 equiv)
–20 °C, 1.5 h
Pr
Pr
Pr
Pr
E/Z = 65:35
* The unreacted (Z) enol phosphate was recovered in 95% yield (>95% Z).
Scheme 6
n-BuMgCl, Fe(acac)3 (3 mol%)
OPO(OPEt)2
Bu
It should be noted that this procedure combines a kinetic
differentiation and a stereoselective reaction. From a pre-
parative point of view, this is very interesting since it is
possible to avoid the tedious preparation of pure E-enol
phosphates. Other applications of this procedure are pre-
sented in Table 2.
Bu
Bu
THF, –20 °C, 1 h
19
20
E/Z = 70:30
1.2 equiv BuMgBr: 71% (E/Z = 91:9)
0.85 equiv BuMgBr: 56% (E/Z = 91:9)
Scheme 8
Synthesis 2008, No. 16, 2636–2644 © Thieme Stuttgart · New York

SPECIAL TOPIC
Iron-Catalyzed Alkenylation of Grignard Reagents by Enol Phosphates
2639
It is interesting to note that the iron- and palladium-cata-
lyzed reactions are complementary. Indeed, Rossi has
shown that, under palladium catalysis, it is possible to ob-
tain the E-olefin with excellent selectivity (≥98% E) from
a mixture of (E)- and (Z)-1-bromo-1-alkenes.11 Unfortu-
nately, this procedure is not applicable to either the a,b-
disubstituted alkenyl halides or phosphates, which are
clearly less reactive and give unsatisfactory yields
(Scheme 9).
Table 4 Preparation and Coupling of the Enol Phosphate in a One-
Pot Procedure
O
R2
1) LDA, –20 °C
2) CIPO(OPh)2
R1
R1
3) R2MgBr, Fe(acac)3 (6 mol%)
THF–NMP (9 equiv),
–20 °C, 3 h
( )1,2
( )1,2
Entry
1
Starting ketone
Product
Yield (%)a
82
n-OctMgBr (0.65 equiv)
PdCl2(dppf) (2 mol%)
Oct
Z
Oct
Pr
O
23
THF, 30 °C, 2 h
Et
Pr
Et
Bu
15
O
E/Z = 60:40
Z = Br: 26%* (>99% E)
Z = OPO(OPh)2: 28%* (>99% E)
2
3
88
94
* GC yield based on OctMgBr.
24
25
Scheme 9
Bu
O
In fact, the iron-catalyzed procedure is currently the only
way to prepare a stereodefined trisubstituted olefin selec-
tively from an E/Z mixture of a,b-disubstituted alkenyl
phosphates.
a Yield of isolated product.
The alkenylation reaction described above can be per-
formed chemoselectively in the presence of aliphatic
chlorides, nitrile or ester groups (Table 3, entries 1, 3 and
4). However, in the presence of aliphatic bromides (entry
2) the reaction gave a mixture of b-elimination products
characteristic of the reaction of alkyl Grignard reagents
with alkyl bromides in the presence of iron salts.12
In summary, we have shown that the cross-coupling reac-
tion between Grignard reagents and enol phosphates is ef-
ficiently catalyzed by Fe(acac)3. These results extend the
scope of the iron-catalyzed alkenylation of Grignard re-
agents by alkenyl halides described previously.3 The use
of enol phosphates is especially interesting when the cor-
responding alkenyl halide is difficult to prepare. It should
be noted that olefins of defined configuration are easily
prepared via this procedure from a mixture of Z- and E-
enol phosphates since the E-isomer reacts exclusively and
stereoselectively. This is important since the tedious prep-
aration of pure E-enol phosphates can thus be avoided.
The procedure represents the first examples of transition-
metal-catalyzed alkenylation of organometallics involv-
ing a stereoselective kinetic differentiation to give trisub-
stituted alkenes. From an economical and environmental
point of view, this procedure is an interesting alternative
to the nickel- and palladium-catalyzed reactions.
Table 3 Chemoselectivity of the Cross-Coupling Reaction
n-BuMgBr
Fe(acac)3 (3 mol%)
Bu
OPO(OPh)2
Z
Z
THF–NMP (9 equiv)
–5 to 0 °C, 1.5 h
21
22a–c
Entry
Product
Yield (%)
90
Bu
1
2
3
Cl
22a
Bu
0
Br
THF was purchased from Merck and freshly distilled from sodium/
benzophenone under a nitrogen atmosphere before use. Iron(III)
acetylacetonate (99+%) was purchased from Acros. Products were
purified by distillation or by chromatography on a silica gel column
(40–63mm). All reactions were performed under a nitrogen atmo-
sphere. Enol phosphates were prepared from the corresponding ke-
tones according to the procedures described in the literature.14
Bu
96
CN
22b
Bu
COOMe
4
84
GC analyzes were performed on a Hewlett–Packard HP 6890 chro-
matograph equipped with a capillary column HP-5MS (30 m × 0.25
mm × 0.25 mm) and a flame ionization detector. Mass spectra (MS)
were obtained on a Hewlett–Packard HP 5973 mass spectrometer
via a GC/MS coupling with a Hewlett–Packard HP 6890 chromato-
graph equipped with a capillary column HP-5MS. Ionization was
performed by electron impact (EI) or chemical ionization with
methane (IC, CH4). Mass spectra are reported as m/z (% relative in-
tensity). 1H and 13C NMR spectra (d, 1H 0.01 ppm, 13C 0.05 ppm,
TMS as internal standard, J values in Hz 0.3 Hz) were recorded ei-
22c
Interestingly, both the preparation of the enol phosphates
and the iron-catalyzed cross-coupling reaction can be per-
formed in good yields according to a one-pot procedure
(Table 4).13
Synthesis 2008, No. 16, 2636–2644 © Thieme Stuttgart · New York

2640
G. Cahiez et al.
SPECIAL TOPIC
ther on a JEOL JNM-EX 270 (270 MHz for 1H) spectrometer or a
JEOL ECX 400 (400 MHz for H) spectrometer. FT-IR spectra
were recorded on a Nicolet Impact 400 instrument (OMNIC soft-
ware).
Preparation of 6-Ethylundec-5-ene (18);15 Typical Procedure C
A dried four-necked flask equipped with a mechanical stirrer, a
thermometer and a septum was charged with a solution of Fe(acac)3
(433 mg, 1.2 mmol, 4%) in THF (30 mL), DMPU (30 mL, 248
mmol, 8.3 equiv) and 6-diphenoxyphosphoryloxyundec-5-ene
(12.07 g, 30 mmol, 1 equiv). After stirring for 1 min, ethylmagne-
sium bromide (24.8 mL, 24.8 mmol, 0.83 equiv) was added drop-
wise in 2 h at –20 °C. The resulting mixture was then stirred at
20 °C for 2 h and hydrolyzed with aq HCl (1 M, 100 mL). After ex-
traction with Et2O (3 × 30 mL), the combined organic layers were
washed successively with aq HCl (1 M, 50 mL) and brine (50 mL).
The organic layer was dried over MgSO4 and concentrated under re-
duced pressure. The residue was purified by flash chromatography
on silica gel (cyclohexane) to give the product as a mixture of ste-
reoisomers (E/Z = 3:97).
1
Cross-Coupling of Enol Phosphates with Grignard Reagents;
Typical Procedure A
Preparation of 2-(3-Chloropropyl)hex-1-ene (22a)
A dried four-necked flask equipped with a mechanical stirrer, a
thermometer and a septum was charged with a solution of Fe(acac)3
(60 mg, 0.17 mmol, 3%) in THF (5 mL), N-methylpyrrolidinone
(4.9 mL, 51.1 mmol, 9 equiv) and 5-chloro-2-diphenoxyphosphoryl-
oxypent-1-ene (2 g, 5.67 mmol, 1 equiv). After stirring for 1 min,
butylmagnesium bromide (5 mL, 6.8 mmol, 1.2 equiv) was added
dropwise at –20 °C. The resulting mixture was then stirred at 20 °C
for 2 h then hydrolyzed with aq HCl (1 M, 20 mL). After extraction
with Et2O (3 × 30 mL), the combined organic layers were washed
successively with aq HCl (1 M, 50 mL) and brine (50 mL). The or-
ganic layer was dried over MgSO4 and concentrated under reduced
pressure. The residue was purified by flash chromatography on sil-
ica gel (cyclohexane) to give the pure product 22a.
Yield: 3.2 g (71%); colorless oil.
IR (neat): 2940, 1650, 1440 cm–1.
1H NMR (400 MHz, CDCl3): d = 5.10 (1 H, t, J = 7.3 Hz), 2.02–
1.96 (6 H, m, 2), 1.38–1.23 (10 H, m), 0.98 (3 H, t, J = 7.3 Hz), 0.89
(6 H, t, J = 7.3 Hz).
13C NMR (100 MHz, CDCl3): d = 141.1 (C), 123.5 (CH), 36.7
(CH2), 32.5 (CH2), 32.0 (CH2), 30.2 (CH2), 29.6 (CH2), 28.2 (CH2),
27.4 (CH2), 23.9 (CH2), 22.6 (CH2), 22.4 (CH2), 14.0 (2 × C, CH3),
13.0 (CH3).
MS (EI, 70 eV): m/z (%) = 182 (39) [M + H]+, 126 (6), 111 (26), 97
(74), 83 (61), 69 (100), 55 (73).
Yield: 0.83 g (90%); yellow oil.
IR (neat): 2940, 1660, 750 cm–1.
1H NMR (270 MHz, CDCl3): d = 4.81 (1 H, s), 4.74 (1 H, s), 3.54
(2 H, t, J = 7.3 Hz), 2.16 (2 H, t, J = 7.3 Hz), 2.00 (2 H, t, J = 7.3
Hz), 1.91 (2 H, quint, J = 7.3 Hz), 1.41 (2 H, quint, J = 7.3 Hz), 1.32
(2 H, sext, J = 7.3 Hz), 0.91 (3 H, t, J = 7.3 Hz).
13C NMR (68 MHz, CDCl3): d = 148.2 (C), 109.6 (CH2), 44.6
(CH2), 35.7 (CH2), 33.0 (CH2), 30.6 (CH2), 29.9 (CH2), 22.4 (CH2),
14.0 (CH3).
MS (EI, 70 eV): m/z (%) = 160 (64) [M + H]+, 118 (66), 95 (26), 81
(43), 69 (92), 56 (100).
HRMS: m/z [M + H]+ calcd for C9H17Cl: 160.1019; found:
160.1022.
Preparation of 1-Octylcyclopent-1-ene (23);16 Typical Proce-
dure D
A dried four-necked flask equipped with a mechanical stirrer and a
thermometer was charged with a solution of diisopropylamine (4.2
mL, 30 mmol, 1.2 equiv) in THF (40 mL). A solution of n-BuLi (1.6
M in hexanes, 17.2 mL, 27.5 mmol, 1.1 equiv) was added dropwise
at –40 °C. After stirring at 0 °C for 30 min, cyclopentanone (2.1 g,
41.5 mmol, 1 equiv) and, 30 min later, diphenylchlorophosphate
(5.8 mL, 27.5 mmol, 1.1 equiv) was added dropwise. The reaction
mixture was stirred at 20 °C for 2 h then Fe(acac)3 (441 mg, 1.25
mmol, 5%) and NMP (22 mL, 225 mmol, 9 equiv) were added. Fi-
nally, a solution of octylmagnesium bromide (0.8 M in THF, 40.6
mL, 32.5 mmol, 1.3 equiv) was added dropwise at –15 °C and stir-
ring was continued for 30 min at –5 °C and for 1.5 h at 20 °C. The
reaction mixture was then hydrolyzed with aq HCl (1 M, 50 mL),
extracted with Et2O (3 × 40 mL) and the combined organic layers
were washed successively with aq HCl (1 M, 80 mL) and brine (80
mL). The organic layer was dried over MgSO4 and concentrated un-
der reduced pressure. The residue was purified by flash chromatog-
raphy on silica gel (pentane) to give 23.
Preparation of 3-Ethylundec-2-ene (16); Typical Procedure B
A dried four-necked flask equipped with a mechanical stirrer, a
thermometer and a septum was charged with a solution of Fe(acac)3
(212 mg, 0.6 mmol, 3%) in THF (20 mL), DMPU (21.8 mL, 180
mmol, 9 equiv) and 3-diphenoxyphosphoryloxypent-2-ene (6.36 g,
20 mmol, 1 equiv). After stirring for 1 min, octylmagnesium bro-
mide (20 mL, 24 mmol, 1.2 equiv) was added dropwise at –20 °C.
The resulting mixture was then stirred at 20 °C for 2 h then hydro-
lyzed with aq HCl (1 M, 50 mL). After extraction with Et2O (3 × 30
mL), the combined organic layers were washed successively with
aq HCl (1 M, 50 mL) and brine (50 mL). The organic layer was
dried over MgSO4 and concentrated under reduced pressure. The
residue was purified by flash chromatography on a silica gel column
(cyclohexane) to give 16 as a mixture of stereoisomers (E/
Z = 83:17).
Yield: 3.68 g (82%); colorless oil.
IR (neat): 2940, 1660, 1452 cm–1.
1H NMR (400 MHz, CDCl3): d = 5.30 (1 H, m), 2.28 (2 H, m), 2.21
(2 H, t, J = 7.3 Hz), 2.04 (2 H, t, J = 7.3 Hz), 1.84 (2 H, quint,
J = 7.3 Hz), 1.43 (2 H, quint, J = 7.3 Hz), 1.30–1.20 (10 H, m), 0.88
(3 H, t, J = 7.3 Hz).
13C NMR (100 MHz, CDCl3): d = 145.1 (C), 122.9 (CH), 35.1
(CH2), 32.4 (CH2), 31.9 (CH2), 31.2 (CH2), 29.6 (CH2), 29.5 (CH2),
29.3 (CH2), 27.9 (CH2), 23.5 (CH2), 22.7 (CH2), 14.1 (CH3).
Yield: 2.96 g (81%); colorless oil.
IR (neat): 2945, 1640 cm–1.
1H NMR (270 MHz, CDCl3): d = 5.14 (1 H, q, J = 6.9 Hz), 1.94
(2 H, q, J = 7.3 Hz), 1.90 (2 H, t, J = 7.3 Hz), 1.67 (3 H, d, J = 6.9
Hz), 1.33 (2 H, quint, J = 7.3 Hz), 1.19 (10 H, m), 0.88 (3 H, t,
J = 7.3 Hz), 0.81 (3 H, t, J = 7.1 Hz).
13C NMR (68 MHz, CDCl3): d = 142.1 (C), 117.5 (CH), 116.9 (CH),
36.7 (CH2), 31.9 (CH2), 29.6 (CH2), 29.5 (CH2), 29.3 (CH2), 28.3
(CH2), 22.7 (2 × C, CH2), 14.1 (CH3), 12.8 (2 × C, CH3).
MS (EI, 70 eV): m/z (%) = 182 (16) [M + H]+, 153 (4), 111 (4), 97
(18), 84 (100), 69 (78), 55 (65).
MS (EI, 70 eV): m/z (%) = 180 (32) [M + H]+, 123 (8), 95 (32), 82
(80), 67 (100), 55 (12).
Preparation of 1-Phenylhex-1-ene (5);17 Typical Procedure E
A dried four-necked flask equipped with a mechanical stirrer and a
thermometer was charged with a solution of Fe(acac)3 (35 mg, 0.10
mmol, 1%) in THF (20 mL) and 1-diethoxyphosphoryloxy-2-phe-
Anal. Calcd for C13H26: C, 85.63; H, 14.37. Found: C, 85.25; H,
14.49.
Synthesis 2008, No. 16, 2636–2644 © Thieme Stuttgart · New York

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Iron-Catalyzed Alkenylation of Grignard Reagents by Enol Phosphates
2641
nylethene (2.562 g, 10 mmol). After stirring for 1 min, butylmagne-
sium bromide (10 mL, 12 mmol, 1.2 equiv) was added dropwise
over 20 min. After stirring for 15 min, the reaction mixture was
quenched with aq HCl (1 M, 50 mL) and the aqueous phase was ex-
tracted with cyclohexane (3 × 30 mL), dried with MgSO4 and con-
centrated under reduced pressure. The residue was purified by flash
chromatography on silica gel (cyclohexane) to give 5 as a mixture
of stereoisomers (E/Z = 90:10).
Yield: 4.311 g (90%); colorless oil.
IR (neat): 2940, 1627, 1580, 1494 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.42–7.12 (5 H, m), 5.25 (1 H, s),
5.05 (1 H, s), 2.48 (2 H, t, J = 7.3 Hz), 1.42 (2 H, quint, J = 7.3 Hz),
1.33 (2 H, sext, J = 7.3 Hz), 0.79 (3 H, t, J = 7.3 Hz).
13C NMR (100 MHz, CDCl3): d = 148.7 (C), 141.4 (C), 128.2 (CH),
127.2 (CH), 126.1 (CH), 112.0 (CH2), 35.0 (CH2), 30.4 (CH2), 22.4
(CH2), 13.9 (CH3).
Yield: 694 mg (87%); colorless oil.
IR (neat): 2957, 1598, 1494, 1448, 964 cm–1.
MS (EI, 70 eV): m/z (%) = 160 (9) [M + H]+, 131 (5), 118 (100), 103
(14), 91 (14), 77 (8), 65 (2), 51 (3).
1H NMR (400 MHz, CDCl3): d = 7.35–7.15 (5 H, m), 6.39 (0.1 H,
d, J = 11.9 Hz), 6.37 (0.9 H, d, J = 16.1 Hz), 6.22 (0.9 H, dt,
J = 16.1, 6.9 Hz), 5.66 (0.1 H, dt, J = 11.9, 6.9 Hz), 2.32 (0.2 H, dt,
J = 7.3, 6.9 Hz), 2.18 (1.8 H, dt, J = 7.3, 6.9 Hz), 1.47 (2 H, quint,
J = 7.3 Hz), 1.39 (2 H, sext, J = 7.3 Hz), 0.94 (2.7 H, t, J = 7.3 Hz),
0.91 (0.3 H, t, J = 7.3 Hz).
2-Butyloct-1-ene (7)21
Prepared according to typical procedure A.
The residue was purified by flash chromatography on a silica gel
column (cyclohexane).
13C NMR (100 MHz, CDCl3): d = 137.9 (C), 137.8 (C), 133.2 (CH),
131.2 (CH), 129.6 (CH), 128.7 (2 × C, CH), 128.6 (CH), 128.4 (2 ×
C, CH), 128.1 (2 × C, CH), 126.7 (CH), 126.4 (CH), 125.9 (2 × C,
CH), 32.7 (CH2), 32.2 (CH2), 31.5 (CH2), 28.3 (CH2), 22.4 (CH2),
22.3 (CH2), 14.0 (CH3).
MS (EI, 70 eV): m/z (%) = 160 (30) [M + H]+, 131 (5), 117 (100),
104 (58), 91 (28), 77 (5), 65 (4), 51 (3).
Yield: 1.26 g (75%); colorless oil.
IR (neat): 2960, 2932, 1652, 1468, 1376 cm–1.
1H NMR (270 MHz, CDCl3): d = 4.68 (2 H, s), 1.99 (4 H, t, J = 6.9
Hz), 1.50–1.26 (12 H, m), 0.87 (6 H, t, J = 6.9 Hz).
13C NMR (68 MHz, CDCl3): d = 150.2 (C), 108.4 (CH2), 36.1
(CH2), 35.8 (CH2), 31.9 (CH2), 30.1 (CH2), 29.2 (CH2), 27.8 (CH2),
22.6 (2 × CH2), 14.0 (2 × CH3).
MS (EI, 70 eV): m/z (%) = 168 (20) [M + H]+, 126 (5), 111 (32), 98
(17), 83 (20), 69 (51), 56 (100).
5-Butyltridec-4-ene (2)18
Prepared according to typical procedure B.
The residue was purified by flash chromatography on a silica gel
column (cyclohexane) to give the product as a mixture of stereoiso-
mers (E/Z = 74:26).
2-Ethyldec-1-ene (8)22
Prepared according to typical procedure A.
The residue was purified by flash chromatography on a silica gel
column (cyclohexane).
Yield: 5.57 g (78%); colorless oil.
IR (neat): 2940, 1650 cm–1.
1H NMR (270 MHz, CDCl3): d = 5.10 (1 H, t, J = 7.3 Hz), 1.97
(6 H, m), 1.41–1.26 (18 H, m), 0.93–0.85 (9 H, m).
13C NMR (68 MHz, CDCl3): d = 140.3 (C), 126.7 (CH), 37.5 (CH2),
37.2 (CH2), 32.5 (CH2), 31.3 (CH2), 31.2 (CH2), 30.4, 30.3, 30.2,
30.1, 29.9 (5 × C, CH2), 29.1 (CH2), 28.9 (CH2), 23.8 (CH2), 23.4
(CH2), 23.2 (CH2), 23.1 (CH2), 14.6 (3 × C, CH3).
MS (EI, 70 eV): m/z (%) = 238 (33) [M + H]+, 196 (4), 154 (8), 140
(24), 125 (11), 111 (25), 98 (59), 83 (74), 70 (100), 55 (90).
Yield: 0.86 g (82%); colorless oil.
IR (neat): 2960, 1646, 1460 cm–1.
1H NMR (270 MHz, CDCl3): d = 4.61 (2 H, s), 1.93 (4 H, m), 1.38–
1.18 (12 H, m), 0.95 (3 H, t, J = 6.3 Hz), 0.81 (3 H, t, J = 6.9 Hz).
13C NMR (68 MHz, CDCl3): d = 151.6 (C), 107.3 (CH2), 36.4
(CH2), 32.0 (CH2), 29.7 (CH2), 29.6 (CH2), 29.5 (CH2), 28.8 (CH2),
27.9 (CH2), 22.8 (CH2), 14.1 (CH3), 12.3 (CH3).
MS (EI, 70 eV): m/z (%) = 168 (4) [M + H]+, 139 (7), 97 (7), 83
(22), 70 (100), 55 (45).
Anal. Calcd for C17H34: C, 85.63; H, 14.37. Found: C, 85.45; H,
14.58.
2-Cyclohexylbut-1-ene (9)23
Prepared according to typical procedure A.
5-Butyldec-5-ene (4)19
The residue was purified by flash chromatography on a silica gel
column (cyclohexane).
Prepared according to typical procedure A.
The residue was purified by flash chromatography on a silica gel
column (cyclohexane).
Yield: 0.18 g (20%); colorless oil.
IR (neat): 2940, 1640, 1462 cm–1.
1H NMR (270 MHz, CDCl3): d = 4.63 (1 H, s), 4.60 (1 H, s), 1.96
(2 H, q, J = 7.3 Hz), 1.76 (1 H, quint, J = 7.3 Hz), 1.48 (10 H, m),
0.95 (3 H, t, J = 7.3 Hz).
13C NMR (68 MHz, CDCl3): d = 157.0 (C), 105.5 (CH2), 44.5 (CH),
43.5 (CH2), 32.6 (2 × C, CH2), 30.2 (CH2), 26.9 (2 × C, CH2), 12.6
(CH3).
Yield: 1.67 g (85%); colorless oil.
IR (neat): 2940, 1650, 1452 cm–1.
1H NMR (400 MHz, CDCl3): d = 5.10 (1 H, t, J = 6.9 Hz), 2.01–
1.93 (6 H, m), 1.40–1.22 (12 H, m), 0.90–0.80 (9 H, m).
13C NMR (100 MHz, CDCl3): d = 139.5 (C), 124.6 (CH), 36.7
(CH2), 32.5 (CH2), 30.6 (CH2), 30.2 (CH2), 29.8 (CH2), 27.4 (CH2),
22.9 (2 × C, CH2), 22.5 (CH2), 14.1 (3 × C, CH3).
MS (EI, 70 eV): m/z (%) = 196 (34) [M + H]+, 154 (6), 139 (6), 112
(24), 97 (75), 83 (84), 69 (80), 55 (100).
MS (EI, 70 eV): m/z (%) = 138 (34) [M + H]+, 123 (2), 109 (92), 96
(34), 91 (4), 81 (69), 67 (100), 55 (34).
2-(1,1-Dimethylethyl)dec-1-ene (10)24
Prepared according to typical procedure A.
2-Phenylhex-1-ene (6)20
Prepared according to typical procedure A.
The residue was purified by flash chromatography on a silica gel
column (cyclohexane).
The residue was purified by flash chromatography on a silica gel
column (cyclohexane).
Synthesis 2008, No. 16, 2636–2644 © Thieme Stuttgart · New York

2642
G. Cahiez et al.
SPECIAL TOPIC
Yield: 0.69 g (75%); colorless oil.
IR (neat): 2960, 1638, 1468 cm–1.
1H NMR (270 MHz, CDCl3): d = 4.84 (1 H, s), 4.68 (1 H, s), 2.01
(2 H, t, J = 7.6 Hz), 1.43 (2 H, quint, J = 7.6 Hz), 1.36–1.28 (10 H,
m), 1.05 (9 H, s), 0.88 (3 H, t, J = 7.3 Hz).
The residue was purified by flash chromatography on a silica gel
column (cyclohexane) to give the product as a mixture of stereoiso-
mers (E/Z = 94:6).
Yield: 3.27 g (70%); colorless oil.
IR (neat): 2940, 1660, 1594, 1450 cm–1.
13C NMR (68 MHz, CDCl3): d = 157.8 (C), 105.5 (CH2), 36.1 (C),
31.9 (CH2), 31.3 (CH2), 29.9, 29.7, 29.5, 29.4, 29.3 (7 × C, CH2 or
CH3), 22.7 (CH2), 14.1 (CH3).
MS (EI, 70 eV): m/z (%) = 196 (5) [M + H]+, 138 (7), 111 (5), 98
(28), 83 (100), 69 (21), 55 (28).
1H NMR (270 MHz, CDCl3): d = 7.36–7.17 (5 H, m), 5.60 (1 H, t,
J = 7.1 Hz), 2.50 (2 H, t, J = 6.9 Hz), 2.16 (2 H, q, J = 7.1 Hz), 1.50
(2 H, sext, J = 7.1 Hz), 1.31–1.29 (4 H, m), 0.96 (3 H, t, J = 7.3 Hz),
0.86 (3 H, t, J = 7.1 Hz).
13C NMR (68 MHz, CDCl3): d = 143.5 (C), 140.3 (C), 128.9 (CH),
128.1 (2 × C, CH), 126.3 (2 × C, CH2), 30.9 (CH2), 30.6 (CH2), 29.5
(CH2), 23.1 (CH2), 22.7 (CH2), 13.9 (2 × C, CH2).
1-Butylcyclohex-1-ene (11)25
Prepared according to typical procedure A.
MS (EI, 70 eV): m/z (%) = 202 (13) [M + H]+, 160 (9), 145 (57), 131
The residue was purified by flash chromatography on a silica gel
column (cyclohexane).
(17), 118 (100), 103 (8), 91 (46), 77 (9).
4-Propyldodec-3-ene (15)
Prepared according to typical procedure B.
Yield: 0.85 g (90%); yellow oil.
IR (neat): 2940, 1660 cm–1.
1H NMR (270 MHz, CDCl3): d = 5.38–5.32 (1 H, m), 1.97–1.91
(6 H, m), 1.65–1.50 (4 H, m), 1.37 (2 H, quint, J = 7.3 Hz), 1.28
(2 H, sext, J = 7.3 Hz), 0.90 (3 H, t, J = 7.3 Hz).
13C NMR (68 MHz, CDCl3): d = 137.9 (C), 120.5 (CH), 37.7 (CH2),
30.0 (CH2), 28.3 (CH2), 25.5 (CH2), 23.1 (CH2), 23.0 (CH2), 22.7
(CH2), 14.0 (CH3).
The residue was purified by flash chromatography on a silica gel
column (cyclohexane) to give the product as a mixture of stereoiso-
mers (E/Z = 88:12).
Yield: 0.92 g (75%); colorless oil.
IR (neat): 2952, 1644 cm–1.
1H NMR (270 MHz, CDCl3): d = 5.01 (1 H, t, J = 7.3 Hz), 1.90
(6 H, m), 1.28 (4 H, m), 1.19 (10 H, m), 0.86 (3 H, t, J = 7.6 Hz),
0.81 (6 H, t, J = 7.1 Hz).
13C NMR (68 MHz, CDCl3): d = 138.7 (C), 126.7 (CH), 39.2 (CH2),
37.0 (CH2), 32.1 (CH2), 29.9 (CH2), 29.8 (CH2), 29.7 (CH2), 29.5
(CH2), 28.7 (CH2), 28.5 (CH2), 22.8 (CH2), 21.7 (CH2), 21.4 (CH2),
21.1 (CH2), 14.16 (CH3), 14.12 (2 × C, CH3).
MS (EI, 70 eV): m/z (%) = 138 (50) [M + H]+, 109 (10), 96 (55), 81
(100), 67 (55), 55 (17).
1-Octylcyclohex-1-ene (12)16
Prepared according to typical procedure A.
The residue was purified by flash chromatography on a silica gel
column (cyclohexane).
Anal. Calcd for C15H30: C, 85.63; H, 14.37. Found: C, 85.24; H,
14.72.
Yield: 0.87 g (90%); yellow oil.
IR (neat): 2960, 2930, 1670, 1460 cm–1.
3-Phenylpent-2-ene (17)28
1H NMR (270 MHz, CDCl3): d = 5.40–5.34 (1 H, m), 1.97–1.89
(6 H, m), 1.65–1.52 (4 H, m), 1.45–1.30 (12 H, m), 0.91 (3 H, t,
J = 7.3 Hz).
13C NMR (68 MHz, CDCl3): d = 138.0 (C), 120.5 (CH), 38.1 (CH2),
32.0 (CH2), 29.8 (CH2), 29.6 (CH2), 29.5 (CH2), 28.3 (CH2), 27.8
(CH2), 25.2 (CH2), 22.7 (3 × C, CH2), 14.1 (CH3).
Prepared according to typical procedure B.
The residue was purified by flash chromatography on a silica gel
column (cyclohexane) to give the product as a mixture of stereoiso-
mers (E/Z = 93:7).
Yield: 2.13 g (73%); colorless oil.
IR (neat): 2948, 1642, 1599 cm–1.
1H NMR (270 MHz, CDCl3): d = 7.47–7.18 (5 H, m), 5.70 (1 H, q,
J = 6.9 Hz), 2.50 (2 H, q, J = 7.6 Hz), 1.80 (3 H, d, J = 6.9 Hz), 0.98
(3 H, t, J = 7.6 Hz).
13C NMR (68 MHz, CDCl3): d = 143.3 (C), 142.3 (C), 128.2 (2 × C,
CH), 127.1 (CH), 126.2 (2 × C, CH), 122.0 (CH), 22.6 (CH2), 13.9
(CH3), 13.2 (CH3).
MS (EI, 70 eV): m/z (%) = 194 (40) [M + H]+, 109 (13), 96 (90), 81
(100), 67 (40), 55 (18).
5-Butylnon-4-ene (13)26
Prepared according to typical procedure B.
The residue was purified by flash chromatography on a silica gel
column (cyclohexane).
MS (EI, 70 eV): m/z (%) = 146 (62) [M + H]+, 131 (20), 117 (100),
103 (4), 91 (29), 77 (7).
Yield: 2.92 g (80%); colorless oil.
IR (neat): 2940, 1660 cm–1.
1H NMR (270 MHz, CDCl3): d = 5.10 (1 H, t, J = 7.3 Hz), 1.97–
1.92 (6 H, m), 1.43–1.25 (10 H, m), 0.93–0.85 (9 H, m).
Dec-5-ene (20)29
Prepared according to typical procedure A.
13C NMR (68 MHz, CDCl3): d = 139.7 (C), 124.5 (CH), 36.7 (CH2),
30.6 (2 × C, CH2), 29.8 (2 × C, CH2), 23.3 (CH2), 22.9 (CH2), 22.5
(CH2), 14.0 (2 × C, CH3), 13.9 (CH2).
The residue was purified by flash chromatography on a silica gel
column (cyclohexane) to give the product as a mixture of stereoiso-
mers (E/Z = 91:9).
MS (EI, 70 eV): m/z (%) = 182 (47) [M + H]+, 140 (18), 125 (7), 111
Yield: 496 mg (71%); colorless oil.
IR (neat): 2940, 1671, 1468, 1378, 967 cm–1.
(11), 98 (39), 83 (69), 69 (100), 55 (92).
1H NMR (400 MHz, CDCl3): d = 5.38 (1.8 H, m), 5.34 (0.2 H, m),
1.97 (4 H, m), 1.30 (8 H, m), 0.88 (6 H, t, J = 7.3 Hz).
13C NMR (100 MHz, CDCl3): d = 130.3 (CH), 129.8 (CH), 32.3
(CH2), 31.8 (CH2), 26.9 (CH2), 22.2 (CH2), 14.0 (CH3).
5-Phenylnon-4-ene (14)27
Prepared according to typical procedure B.
Synthesis 2008, No. 16, 2636–2644 © Thieme Stuttgart · New York

SPECIAL TOPIC
Iron-Catalyzed Alkenylation of Grignard Reagents by Enol Phosphates
2643
MS (EI, 70 eV): m/z (%) = 140 (37) [M + H]+, 111 (4), 97 (17), 83
Hz), 2.22 (2 H, dt, J = 7.8, 1.5 Hz), 1.51 (2 H, quint, J = 7.3 Hz),
(15), 69 (51), 55 (100).
1.37 (2 H, sext, J = 7.3 Hz), 0.92 (3 H, t, J = 7.3 Hz).
13C NMR (100 MHz, CDCl3): d = 136.9 (C), 136.7 (C), 135.2 (C),
127.6 (CH), 126.5 (CH), 126.3 (CH), 124.7 (CH), 122.8 (CH), 32.6
(CH2), 30.8 (CH2), 28.6 (CH2), 23.2 (CH2), 22.8 (CH2), 14.1 (CH3).
2-(3-Cyanopropyl)hex-1-ene (22b)30
Prepared according to typical procedure A.
The residue was purified by flash chromatography on a silica gel
column (cyclohexane).
MS (EI, 70 eV): m/z (%) = 186 (25) [M + H]+, 144 (100), 129 (93),
115 (18), 102 (2), 91 (4), 77 (3).
Yield: 0.85 g (96%); yellow oil.
IR (neat): 2940, 1660, 1200 cm–1.
1H NMR (270 MHz, CDCl3): d = 4.73 (1 H, s), 4.69 (1 H, s), 2.27
(2 H, t, J = 7.3 Hz), 2.10 (2 H, t, J = 7.3 Hz), 1.93 (2 H, t, J = 7.3
Hz), 1.73 (2 H, quint, J = 7.3 Hz), 1.33 (2 H, quint, J = 7.3 Hz), 1.28
(2 H, sext, J = 7.3 Hz), 0.84 (3 H, t, J = 7.3 Hz).
Acknowledgment
The authors thank the CNRS and the Ecole Supérieure de Chimie
Organique et Minérale (ESCOM) for their financial support and the
Fondation de France for a grant to O.G and V.H.
13C NMR (68 MHz, CDCl3): d = 147.1 (C), 119.5 (C), 110.2 (CH2),
35.2 (CH2), 34.4 (CH2), 29.7 (CH2), 23.1 (CH2), 22.2 (CH2), 16.3
(CH2), 13.8 (CH3).
MS (EI, 70 eV): m/z (%) = 151 (2) [M + H]+, 136 (13), 122 (22), 109
(63), 94 (34), 81 (39), 69 (67), 56 (100).
References
(1) Kharasch, M. S.; Fuchs, C. F. J. Org. Chem. 1945, 10, 292.
(2) (a) Tamura, M.; Kochi, J. K. J. Am. Chem. Soc. 1971, 93,
1487. (b) Tamura, M.; Kochi, J. K. Synthesis 1971, 303.
(c) Tamura, M.; Kochi, J. K. J. Organomet. Chem. 1971, 31,
289. (d) Tamura, M.; Kochi, J. K. Bull. Chem. Soc. Jpn.
1971, 44, 3063. (e) Kochi, J. K. Acc. Chem. Res. 1974, 7,
351. (f) Neumann, S.; Kochi, J. K. J. Org. Chem. 1975, 40,
599. (g) Smith, R. S.; Kochi, J. K. J. Org. Chem. 1976, 41,
502.
(3) For coupling of aromatic Grignard reagents with 2-bromo-
styrene, see: Molander, G. A.; Rahn, B. J.; Shubert, D. C.;
Bonde, S. E. Tetrahedron Lett. 1983, 24, 5449.
(4) (a) Cahiez, G.; Avedissian, H. Synthesis 1998, 1199.
(b) The iron-catalyzed alkenylation of RMnX has also been
reported, see: Cahiez, G.; Marquais, S. Pure Appl. Chem.
1996, 68, 53.
(5) We have shown that the use of NMP or DMPU as a co-
solvent also has a remarkable beneficial influence on the Cu-
catalyzed alkylation of RMnX or RMgX, see: (a) Cahiez,
G.; Marquais, S. Synlett 1994, 45. (b) Cahiez, G.;
Chaboche, C.; Jézéquel, M. Tetrahedron 2000, 56, 2733.
For Co-catalyzed alkenylation of RMgX, see: (c) Cahiez,
G.; Marquais, S. Tetrahedron Lett. 1996, 37, 1773.
(6) Fürstner, A.; Leitner, A. Angew. Chem. Int. Ed. 2002, 41,
609.
(7) (a) Cahiez, G.; Chavant, P. Y.; Metais, E. Tetrahedron Lett.
1992, 33, 5245. (b) Dohle, W.; Kopp, F.; Cahiez, G.;
Knochel, P. Synlett 2001, 1901. (c) Duplais, C.; Bures, F.;
Korn, T.; Sapountzis, I.; Cahiez, G.; Knochel, P. Angew.
Chem. Int. Ed. 2004, 43, 2968. (d) Cahiez, G.; Chaboche,
C.; Mahuteau-Betzer, F.; Ahr, M. Org. Lett. 2005, 7, 1943.
(e) Cahiez, G.; Habiak, V.; Duplais, C.; Moyeux, A. Angew.
Chem. Int. Ed. 2007, 46, 4364. (f) Cahiez, G.; Duplais, C.;
Moyeux, A. Org. Lett. 2007, 9, 3253. (g) Cahiez, G.;
Moyeux, A.; Buendia, J.; Duplais, C. J. Am. Chem. Soc.
2007, 129, 13788.
Methyl 4-Methenyloctanoate (22c)31
Prepared according to typical procedure A.
The residue was purified by flash chromatography on silica gel (cy-
clohexane–EtOAc, 90:10).
Yield: 0.91 g (84%); yellow oil.
IR (neat): 2940, 1730, 1650, 1200, 1180 cm–1.
1H NMR (270 MHz, CDCl3): d = 4.67 (1 H, s), 4.63 (1 H, s), 3.61
(3 H, s), 2.37 (2 H, dt, J = 6.9, <1 Hz), 2.26 (2 H, t, J = 6.9 Hz), 1.95
(2 H, t, J = 6.9 Hz), 1.34–1.30 (4 H, m), 1.23 (2 H, t, J = 6.9 Hz),
0.83 (3 H, t, J = 7.3 Hz).
13C NMR (68 MHz, CDCl3): d = 173.5 (C), 149.9 (C), 108.9 (CH2),
51.3 (CH3), 35.8 (CH2), 32.3 (CH2), 30.6 (CH2), 29.5 (CH2), 22.2
(CH2), 13.7 (CH3).
MS (EI, 70 eV): m/z (%) = 170 (4) [M + H]+, 141 (2), 128 (56), 113
(2), 101 (100), 84 (11), 71 (34), 55 (8).
1-Butyl-6-methylcyclohex-1-ene (24)32
Prepared according to typical procedure D.
The residue was purified by flash chromatography on a silica gel
column (cyclohexane).
Yield: 3.38 g (88%); colorless oil.
IR (neat): 2950, 1660 cm–1.
1H NMR (400 MHz, CDCl3): d = 5.35 (1 H, m), 2.11 (1 H, m), 2.08–
1.85 (4 H, m), 1.73–1.22 (8 H, m), 0.98 (3 H, d, J = 7.0 Hz), 0.89
(3 H, t, J = 7.3 Hz).
13C NMR (68 MHz, CDCl3): d = 142.2 (C), 120.6 (CH), 34.9 (CH2),
31.6 (CH2), 31.3 (CH), 30.2 (CH2), 25.7 (CH2), 22.6 (CH2), 19.9
(CH2), 19.6 (CH3), 14.1 (CH3).
(8) (a) Fürstner, A.; Leitner, A.; Méndez, M.; Krause, H. J. Am.
Chem. Soc. 2002, 124, 13856. (b) Quintin, J.; Frank, X.;
Hocquemiller, R.; Figadère, B. Tetrahedron Lett. 2002, 43,
3547. (c) Martin, R.; Fürstner, A. Angew. Chem. Int. Ed.
2004, 43, 3955. (d) Scheiper, B.; Bonnekessel, M.; Krause,
H.; Fürstner, A. J. Org. Chem. 2004, 69, 3943.
MS (EI, 70 eV): m/z (%) = 152 (38) [M + H]+, 109 (39), 95 (100),
81 (49), 67 (39), 55 (14).
1-Butyl-3,4-dihydronaphthalene (25)33
Prepared according to typical procedure D.
The residue was purified by flash chromatography on a silica gel
column (pentane).
(e) Nakamura, M.; Matsuo, K.; Ito, S.; Nakamura, E. J. Am.
Chem. Soc. 2004, 126, 3686. (f) Dos Santos, M.; Franck,
X.; Hocquemiller, R.; Figadère, B.; Peyrat, J.-F.; Provot, O.;
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Yield: 4.4 g (94%); colorless oil.
IR (neat): 2950, 1640, 1490, 1450, 740 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.26–7.10 (4 H, m), 5.83 (1 H, t,
J = 1.5, 1.4 Hz), 2.72 (2 H, t, J = 7.8 Hz), 2.42 (2 H, dt, J = 7.3, 1.4
Synthesis 2008, No. 16, 2636–2644 © Thieme Stuttgart · New York

2644
G. Cahiez et al.
SPECIAL TOPIC
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Synthesis 2008, No. 16, 2636–2644 © Thieme Stuttgart · New York