A New Coupling Reaction of Alkyl Iodides with Electron Deficient Alkenes Nickel Boride (cat.) - Borohydride Exchange Resin in Methanol

Article abstract of DOI:10.1021/jo961751f

The radical addition reaction of alkyl iodides with α,β-unsaturated esters, nitriles, and ketones proceeds in moderate to excellent yields (50-95%) using Ni(OAc)₂ (0.05-0.2 equiv) - BER (3-5 equiv) in methanol in 1-9 h at room temperature or at 65°C. Nickel boride on borohydride exchange resin (BER) is a good alternative reagent to tributyltin hydride for the coupling of alkyl iodides with the electron deficient alkenes in methanol. Compared with tributyltin hydride method, this method has an advantage of simple workup, since nickel boride - BER can be removed readily by filtration.

Full text of DOI:10.1021/jo961751f

J . Org. Chem. 1997, 62, 2357-2361
2357
A New Cou p lin g Rea ction of Alk yl Iod id es w ith Electr on Deficien t
Alk en es Usin g Nick el Bor id e (ca t.)-Bor oh yd r id e Exch a n ge Resin
in Meth a n ol
Tae Bo Sim, J aesung Choi, Meyoung J u J oung, and Nung Min Yoon*
Department of Chemistry, Sogang University, Seoul 121-742, Korea
Received September 11, 1996X
The radical addition reaction of alkyl iodides with R,â-unsaturated esters, nitriles, and ketones
proceeds in moderate to excellent yields (50-95%) using Ni(OAc)2 (0.05-0.2 equiv)-BER (3-5
equiv) in methanol in 1-9 h at room temperature or at 65 °C. Nickel boride on borohydride exchange
resin (BER) is a good alternative reagent to tributyltin hydride for the coupling of alkyl iodides
with the electron deficient alkenes in methanol. Compared with tributyltin hydride method, this
method has an advantage of simple workup, since nickel boride-BER can be removed readily by
filtration.
In tr od u ction
The carbon-carbon bond formation via radical addition
or radical cyclization of alkyl halides with alkenes is one
of important steps in the construction of organic mol-
ecules and has been successfully carried out using
tributyltin hydride.1 However, this reaction requires
high temperature initiators or photolytic conditions, and
although simpler methods have been devised,2 the puri-
fication of the products from tributyltin halides is
troublesome.1c,2 Recently, we have found strong evidence
suggesting that the reduction of alkyl halides with
borohydride exchange resin (BER)-nickel boride pro-
ceeds via a radical reaction: Thus, BER-nickel boride
(cat.) not only readily reduces secondary and tertiary
bromides in rates comparable with the case of primary
bromides, but also gives a coupled product, 2,3-diphe-
nylbutane (30%), besides the expected reduction product
ethylbenzene (70%), in the reaction with R-phenethyl
bromide.3 We also observed a 38% yield of methylcyclo-
pentane from the reaction of 5-hexenyl iodide with nickel
boride (cat.)-BER. We report here a new radical cou-
pling reaction of alkyl iodides with R,â-unsaturated
esters,4 nitriles, and ketones using nickel boride (cat.)-
BER in methanol.
F igu r e 1. Rate of decomposition of BER (circle) and NaBH4
(square) at methanol in the presence (black) and absence
(white) of Ni(OAc)2 (0.02 equiv).
Resu lts a n d Discu ssion
P r ep a r a tion a n d Sta bility of BER. BER can be
readily prepared by treating a chloride form anion-
exchange resin (Amberlite IRA 400) with aqueous NaBH4
solution (1). The borohydride form anion exchange resin
was dried in vacuo, and the dried resin was analyzed for
borohydride content by hydrogen evolution on acidifica-
tion with HCl using gas burette. The borohydride
content of BER is usually 3 mmol/g of dry BER, and the
BER is stable for more than 6 weeks if kept under
nitrogen in a refrigerator. The stability of BER in the
absence and presence of nickel boride was studied in
methanol and compared with that of NaBH4. As shown
in Figure 1, BER decomposes much more slowly than
NaBH4 in methanol. Particularly in the presence of Ni-
(OAc)2 (0.02 equiv) at room temperature, nearly 50% of
BER remained active after 1 h, in contrast to the
complete decomposition of NaBH4 in a few minutes.
Cou p lin g Rea ction s Usin g Nick el Bor id e-BER.
First, we tested the coupling reactions of alkyl bromides
and alkyl iodides with representative alkenes such as
1-octene, styrene, ethyl acrylate and crotononitrile and
found that only the coupling of alkyl iodides with electron
deficient alkenes could be carried out successfully. Then
the coupling reactions of representative alkyl iodides with
R,â-unsaturated esters, nitriles, and ketones were studied
in more detail. Unlike the tin hydride method, the double
bonds of these R,â-unsaturated compounds are readily
hydrogenated with nickel boride-BER in methanol (â-
substituted R,â-unsaturated compounds are much more
X Abstract published in Advance ACS Abstracts, March 15, 1997.
(1) (a) Giese, B. Radicals in Organic Synthesis: Formation of Carbon-
Carbon Bonds; Pergamon Press: Oxford, 1986. (b) Giese, B. Angew.
Chem., Int. Ed. Engl. 1985, 24, 553. (c) Neumann, W. P. Synthesis
1987, 665. (d) Curran, D. P. Radical Addition Reaction; Radical
Cyclization and Sequential Radical Reaction. In Comprehensive
Organic Synthesis; Trost, B. M., Ed.; Pergamon Press: New York, 1991;
Vol. 4, pp 715-831.
(2) (a) Weinshenker, N. M.; Crosby, G. A.; Wong, J . Y. J . Org. Chem.
1975, 40, 1966. (b) Leibner, J . E.; J acobus, J . J . Org. Chem. 1979, 44,
449. (c) Schumann, H.; Pachaly, B. Angew. Chem., Int. Ed. Engl. 1981,
20, 1043. (d) Curran, D. P.; Chang, C. T. J . Org. Chem. 1989, 54, 3140.
(3) Yoon, N. M.; Lee, H. J .; Ahn, J . H.; Choi, J . J . Org. Chem. 1994,
59, 4687.
(4) A part of ester couplings has been communicated: Sim, T. B.;
Choi, J .; Yoon, N. M. Tetrahedron Lett. 1996, 37, 3137.
S0022-3263(96)01751-3 CCC: $14.00 © 1997 American Chemical Society

2358 J . Org. Chem., Vol. 62, No. 8, 1997
Sim et al.
Ta ble 1. Cou p lin g Rea ction of Alk yl Iod id es w ith r,â-Un sa tu r a ted Ester s Usin g Nick el Bor id e (ca t.)-BER in
Meth a n ol a t Room Tem p er a tu r e (20 °C)a
entry
alkyl halide (1)
R,â-unsaturated ester (2)
Ni(OAc)2 (equiv)
time (h)
yield of 3 (%)b
1
2
cyclo-C6H11
cyclo-C6H11
I
I
CH3CHdCHCO2CH3
CH2dC(CH3)CO2CH3
0.05
0.05
0.2
6
9
1
85
93
93
3
4
5
cyclo-C6H11
I
CH2dCHCO2CH2CH3
CH2dCHCO2CH2CH3
CH3CHdCHCO2CH3
0.2
0.2
0.05
0.2
0.05
0.2
3
1
9
1
9
1
20
3
95
92
sec-C6H13
I
n-C8H17
n-C8H17
n-C8H17
I
I
I
68, 52c
42
6
7
CH2dC(CH3)CO2CH3
CH2dCHCO2CH2CH3
88
80
45
86
0.05
0.2
8
9
10
11
12
CH3(CH2)3OCH(OCH2CH3)CH2I
CH3CH2O2C(CH2)3I
NC(CH2)4I
cis-CH3CH2CHdCH(CH2)2I
(CH3)2CdCH(CH2)2I
CH2dCHCO2CH2CH3
CH2dCHCO2CH2CH3
CH2dCHCO2CH2CH3
CH2dC(CH3)CO2CH3
CH2dCHCO2CH2CH3
0.2
0.2
0.2
0.2
3
3
3
3
79
76
78
70d
65d
0.2
3
a
Alkyl iodides (5 mmol) were reacted with enoates (20 equiv) using Ni(OAc)2 (0.05-0.2 equiv) and BER (3 equiv) at room temperature
in methanol. Isolated yield. c Reaction was carried out with 10 equiv of methyl crotonate. Reaction was carried out with 5 equiv of
b
d
BER.
slowly hydrogenated than unsubstituted ones). There-
fore larger amounts of unsaturated compounds (20 equiv)
have to be used than in the case of the tin hydride
method.
nitrile functional group (entries 8, 9, and 10). Finally
we studied the reaction of homoallylic iodides. Simple
addition products were obtained in moderate yields (70-
65%) accompanying 5-15% of the corresponding sequen-
tial cyclization products (entries 11 and 12). This will
be discussed in the next section (coupling with nitriles).
2. Cou p lin g w ith r,â-Un sa tu r a ted Nitr iles. Cy-
clohexyl iodide, 2-hexyl iodide, octyl iodide, â-phenethyl
iodide, and functionalized alkyl iodides were reacted with
representative R,â-unsaturated nitriles, namely, croto-
nonitrile, methacrylonitrile, and acrylonitrile in methanol
for 1 h at 65 °C. The results are summarized in Table 2.
First the reaction was carried out at room temperature,
using 0.05 equiv of Ni(OAc)2 and 3 equiv of BER; how-
ever, the formation of alkyl radical was too slow as shown
in the reaction of cyclohexyl iodide with crotononitrile.
Only 25% yield of 3-cyclohexylbutyronitrile was obtained
in 12 h, leaving 70% of cyclohexyl iodide unreacted
(detected by GC) (entry 1). This slow reaction is probably
due to the preferential adsorption6 and/or reduction of
crotononitrile on nickel boride, which hinders the radical
formation reaction of cyclohexyl iodide at room temper-
ature since cyclohexyl iodide is reduced with BER-nickel
boride (cat.) quantitatively in 1 h at room temperature
in the absence of excess (20 equiv) crotononitrile.3 This
problem was resolved simply by carrying out the reaction
at 65 °C. Cyclohexyl iodide, 2-hexyl iodide, octyl iodide,
and â-phenethyl iodide were all smoothly coupled with
crotononitrile and methacrylonitrile in methanol in 1 h
using 0.05 equiv of Ni(OAc)2 and 3 equiv of BER at 65
°C (condition A) (entries 1, 2, 5, 6, 7, 9, and 12). On the
other hand, the reaction of cyclohexyl iodide with acry-
lonitrile gave only a 65% yield of the addition product,
3-cyclohexylpropiononitrile at condition A, but the yield
could be improved to 90% by increasing the amount of
Ni(OAc)2 (0.2 equiv) and BER (5 equiv) (condition B,
entry 3). Since the radical formation from cyclohexyl
1. Cou p lin g w ith r,â-Un sa tu r a ted Ester s. Cyclo-
hexyl iodide, 2-hexyl iodide, octyl iodide, and function-
alized alkyl iodides were reacted with representative
R,â-unsaturated esters: methyl crotonate, methyl meth-
acrylate, and ethyl acrylate at room temperature using
20 equiv of esters. The results are summarized in Table
1. As shown in Table 1, alkyl iodides were coupled
smoothly with methyl crotonate and methyl methacrylate
in methanol in 6-9 h using 0.05 equiv of Ni(OAc)2 and 3
equiv of BER (entries 1, 2, 5, and 6). In the couplings
with ethyl acrylate, however, better yields (86-95%) were
observed by increasing the amount of Ni(OAc)2 from 0.05
equiv to 0.2 equiv (entries 3, 4, and 7). Presumably, since
the double bond of ethyl acrylate is rapidly hydrogenated
even at 0 °C by this system,5 octyl iodide cannot compete
successfully with ethyl acrylate for the small amount
(0.05 equiv) of nickel boride catalyst. On the other hand,
the increase of nickel boride results in a decrease in the
yields in the coupling with methyl crotonate, a hindered
unsaturated ester (entry 5). In this case, methyl croto-
nate is hydrogenated rather slowly under the reaction
conditions,5 and the coupling of the alkyl radical with this
hindered enoate must compete with the reduction of the
radical to the corresponding alkanes, and thus the
increase of nickel boride results in decreased coupling.
Excess (20 equiv) unsaturated esters favors the coupling
reaction. Indeed, when 10 equiv of unsaturated esters
were used, a somewhat lower yield (52 vs 68%) was
observed (entry 5). In the case of methyl methacrylate,
an increase in nickel boride increased the rate of coupling
without affecting the yields substantially (entries 2 and
6). Equally good yields (76-78%) were observed in the
couplings of alkyl iodides containing acetal, ester, or
(5) Ethyl acrylate and acrylonitrile can be selectively hydrogenated
in the presence of methyl crotonate and crotononitrile by nickel boride-
BER in methanol at 0 °C: Choi, J .; Yoon, N. M. Synthesis 1996, 597.
(6) 1-Octene (20 mmol) was hydrogenated over nickel boride (1
mmol) on BER in 1 h; however, it was not hydrogenated in the presence
of benzonitrile (5 mmol).

Coupling Reaction of Alkyl Iodides with Alkenes
J . Org. Chem., Vol. 62, No. 8, 1997 2359
Ta ble 2. Cou p lin g Rea ction of Alk yl Ha lid es w ith r,â-Un sa tu r a ted Nitr iles Usin g Nick el Bor id e (ca t.)-BER in
Meth a n ol a t 65 °Ca
entry
1
alkyl halide (1)
R,â-unsaturated nitrile (2)
CH3CHdCHCN
condition
yield of 3 (%)b
cyclo-C6H11
I
A
B
A
A
B
A
B
C
A
A
A
A
B
A
B
B
A
B
93, 25,c 78d
90
2
3
cyclo-C6H11
cyclo-C6H11
I
I
CH2dC(CH3)CN
CH2dCHCN
91
65
90, 47f
15 (79)
29 (60)
40 (41)
92
4
cyclo-C6H11Bre
CH3CHdCHCN
5
6
7
8
sec-C6H13
I
CH3CHdCHCN
CH3CHdCHCN
CH2dC(CH3)CN
PhCHdCHCN
n-C8H17
n-C8H17
n-C8H17
I
I
I
80
81
30
77
68
81
65
76
9
10
11
12
13
PhCH2CH2I
CH3CHdCHCN
CH2dCHCN
CH2dCHCN
CH2dC(CH3)CN
CH2dCHCN
CH3(CH2)3OCH(OCH2CH3)CH2I
(CH3CH2)2NOC(CH2)4I
cis-CH3CH2CHdCH(CH2)2I
(CH3)2CdCH(CH2)2I
74
a
Alkyl halides (5 mmol) were reacted with R,â-unsaturated nitriles (20 equiv) using (A) Ni(OAc)2 (0.05 equiv) and BER (3 equiv), (B)
b
Ni(OAc)2 (0.2 equiv) and BER (5 equiv), or (C) Ni(OAc)2 (0.5 equiv) and BER (10 equiv) all for 1 h at 65 °C in methanol (20 mL). Isolated
yield. c Reaction was carried out at room temperature for 12 h, and 70% of cyclohexyl iodide remained. Reaction was carried out under
d
a blanket of purified oxygen, and 5% of cyclohexanol was also obtained. e Reaction was carried out for 3 h, and the amount of cyclohexyl
bromide unreacted is shown in parentheses. f Reaction was carried out with 10 equiv of acrylonitrile.
iodide has to occur on the surface of nickel boride,7 and
acrylonitrile is reduced much more readily by BER-
nickel boride than crotononitrile or methacrylonitrile,5
the radical reaction of cyclohexyl iodide might not proceed
successfully in competition with the reduction of acry-
lonitrile over the small amount of nickel boride produced
by 0.05 equiv of Ni(OAc)2. Higher yield was also observed
in the reaction of octyl iodide with cinnamonitrile (entry
8). However, the reaction of cyclohexyl iodide with
crotononitrile was not influenced by the amount of Ni-
(OAc)2 or BER (entry 1). In the case of cyclohexyl
bromide, the radical reaction of cyclohexyl bromide might
not compete successfully with the reduction of crotono-
nitrile even in the presence of Ni(OAc)2 (0.5 equiv)-BER
(10 equiv), presumably due to the slow reaction of
cyclohexyl bromide compared with cyclohexyl iodide.
Considerable amounts of cyclohexyl bromide (41%) re-
mained unreacted even after 3 h (entry 4). Decrease in
the amount of R,â-unsaturated nitriles resulted in a
significant decrease in the yield. For example, only 47%
yield of 3-cyclohexylpropiononitrile was obtained when
cyclohexyl iodide was reacted with 10 equiv of acryloni-
trile (entry 3). Iodides containing acetal or amide
functional group also resulted in good yields (entries 10
and 11). Finally two homoallylic iodides were reacted
with unsaturated nitriles. As in the reaction with
unsaturated esters, simple addition products were ob-
tained in good yields (76-74%) (entries 12 and 13). The
coupling of homoallylic iodides with nickel boride should
be valuable for the synthesis of simple addition products
(A and A′), since in the tributyltin hydride method
sequential cyclization products (B and B′) are the major
products.8
3. Cou p lin g w tih r,â-Un sa tu r a ted Keton es. Rep-
resentative acyclic and cyclic enones were coupled with
alkyl iodides. All the reactions were completed in 1 h,
using excess (20 equiv) enones in methanol. The results
are summarized in Table 3. Enones such as trans-4-
hexen-3-one and 2-methyl-2-cyclopenten-1-one (entries 1,
2, 8, 11, 13, and 14) were coupled smoothly with alkyl
iodides, using 0.1 equiv of Ni(OAc)2 and 3 equiv of BER
at room temperature (condition A). As these enones are
reduced rather slowly, the reduction does not appear to
interfere with the radical formation by the reaction of
alkyl iodides and nickel boride-BER. However, enones
such as trans-4-phenyl-3-buten-2-one, methyl vinyl ke-
tone, ethyl vinyl ketone, 2-cyclopenten-1-one, and 2-cy-
clohexen-1-one (entries 3, 4, 5, 6, 9, 10, and 12) have
rather unhindered carbon-carbon double bonds and/or
carbonyl groups and are reduced rapidly by this system.
Therefore the radical formation of alkyl iodides might not
compete with the reduction of these enones when small
amounts of nickel boride were used at room temperature
(condition A). For successful coupling of these unhin-
dered enones, increased amounts of Ni(OAc)2 (0.3 equiv)
and BER (5.0 equiv) as well as an increase in the reaction
temperature to 65 °C were required (condition B). Indeed
when some of these reactions were carried out under
condition A, most of the alkyl iodides remained unreacted
while the hydride was rapidly consumed in the reduction
of enones (entries 3, 5, and 7). In the coupling reactions
of iodocyclohexane with alkyl vinyl ketones, higher yields
(7) Cyclohexyl iodide was not reduced with BER in the absence of
nickel boride.
(8) Cekovic, J .; Saicic, R. S. Tetrahedron Lett. 1986, 27, 5893.

2360 J . Org. Chem., Vol. 62, No. 8, 1997
Sim et al.
Ta ble 3. Cou p lin g Rea ction of Alk yl Ha lid es w ith r,â-Un sa tu r a ted Keton es Usin g Nick el Bor id e
(ca t.)-BER in Meth a n ola
entry
alkyl halide (1)
R,â-unsaturated ketone (2)
condition
yield of 3 (%)b
1
2
cyclo-C6H11
cyclo-C6H11
I
I
CH3CHdCHCOCH2CH3
OC(CH2)2CHdCCH3
A
A
81
85,c 71d
3
cyclo-C6H11
I
CH2dCHCOCH3
A
B
B
A
B
B
(2)(96e)
54
4
5
cyclo-C6H11
cyclo-C6H11
I
I
CH2dCHCOCH2CH3
OC(CH2)2CHdCH
84
(17)(75e)
72
6
7
cyclo-C6H11
I
OC(CH2)3CHdCH
66
cyclo-C6H11Br
OC(CH2)2CHdCCH3
A
B
A
B
B
(6)(88e)
56
84
89
80
8
9
10
sec-C8H17
sec-C8H17
sec-C8H17
I
I
I
CH3CHdCHCOCH2CH3
CH2dCHCOCH2CH3
OC(CH2)2CHdCH
11
12
13
n-C8H17
n-C8H17
n-C8H17
I
I
I
CH3CHdCHCOCH2CH3
PhCHdCHCOCH3
OC(CH2)2CHdCCH3
A
B
A
73
60
72f
14
NC(CH2)4I
CH3CHdCHCOCH2CH3
A
68
a
Alkyl halides (3 mmol) were reacted with enones (20 equiv) in methanol (12 mL) for 1 h using (A) Ni(OAc)2 (0.1 equiv) and BER (3
b
equiv) at room temperature, (B) Ni(OAc)2 (0.3 equiv) and BER (5 equiv) at 65 °C. Isolated yield, yields in the parentheses were estimated
using capillary GC. c Cis/ trans ratio was 28/72 as revealed by capillary GC. Reaction was carried out with 10 equiv of 2-methyl-2-
d
cyclopenten-1-one. e Amount of alkyl halide remained. f Cis/ trans ratio was 26/74.
were obtained in the case of ethyl vinyl ketone compared
with methyl vinyl ketone (entries 3 and 4). This might
be also due to the slower reduction of ethyl vinyl ketone
compared with methyl vinyl ketone. The coupling of
bromocyclohexane resulted in a much lower yield com-
pared with cyclohexyl iodide as observed in nitrile
coupling (entry 7). Similar trends were also reported in
the tributyltin hydride reactions.1b
Con clu sion
A new coupling reaction of alkyl iodides with R,â-
unsaturated esters, nitriles, and ketones has been de-
veloped using nickel boride-BER in methanol. This new
coupling method allows simpler workup as well as higher
yields in the simple coupling of alkyl iodides with R,â-
unsaturated esters, nitriles, and ketones, although about
twice the amount of alkenes are required compared with
the tributyltin hydride method. Therefore the heteroge-
neous catalyst, nickel boride (cat.)-BER in methanol is
a good alternative reagent to tributyltin hydride for the
coupling of alkyl iodides with R,â-unsaturated esters,
nitriles, and ketones.
Since we obtained practically the same yield of product
whether the reaction of cyclohexyl iodide with crotono-
nitrile was carried out with or without nitrogen, we did
not endeavor to maintain an inert atmosphere. In the
nickel boride (cat.)-BER-methanol system, oxygen free
inert atmosphere seems to be automatically obtained by
hydrogen evolution due to the decomposition of BER.
When the same reaction was carried out under a blanket
of purified oxygen, 3-cyclohexylbutyronitrile (78%) was
accompanied with 5% of cyclohexanol, produced by
oxygen trapping of the cyclohexyl radical (entry 1 in
Table 2). Finally we attempted the reaction using NaBH4
instead of BER. When the reaction of cyclohexyl iodide
with crotononitrile was repeated using 0.05 equiv of Ni-
(OAc)2 and 3 equiv of NaBH4 in the presence of charcoal,
only 15% yield of 3-cyclohexylbutyronitrile was obtained,
accompanied by 55% of unreacted cyclohexyl iodide.
Similarly in the coupling reaction of octyl iodide with
trans-4-hexen-3-one, octyl iodide remained unreacted,
and only trans-4-hexen-3-one was reduced. Therefore
BER is essential for the nickel boride-catalyzed radical
coupling reaction.
Exp er im en ta l Section
P r ep a r a tion of BER. An aqueous solution of sodium
borohydride (1 M, 500 mL) was stirred with wet chloride form
anion-exchange resin (Amberlite IRA-400 [20 - 50 mesh], 200
g) for 15 min. The resulting resin was washed thoroughly with
distilled water until free from excess NaBH4 and once with
ethanol. The borohydride form anion-exchange resin9 was
then dried in vacuo at 60 °C for 5 h to give 102 g of dried
borohydride exchange resin (BER). The dried resin was
analyzed for borohydride content by hydrogen evolution on
acidification with 2 N HCl, and the average hydride content
of BER was found to be 3.0 mmol of BH4- per gram. The dried
resin was stored under nitrogen in refrigerator (∼4 °C). The
hydride content was constant over 6 weeks.
Sta bility of BER. To the two reaction flasks which contain
1 mmol each of BER were added methanol (10 mL) and
(9) This BER could be directly used without drying. The same yields
were obtained with dried BER.

Coupling Reaction of Alkyl Iodides with Alkenes
J . Org. Chem., Vol. 62, No. 8, 1997 2361
methanol (10 mL) containing 0.02 mmol of Ni(OAc)2, and the
rate of decomposition was followed by measuring the hydrogen
evolution at room temperature. The measurement was re-
peated with NaBH4 in the place of BER. BER decomposed
16% in 1 h, 23% in 2 h, and 45% in 1 h, and 56% in 2 h in the
presence of Ni(OAc)2. In contrast, NaBH4 decomposed com-
pletely in 2 min and 30 min, respectively, in the presence and
absence of Ni(OAc)2.
Cycliza tion of 5-Hexen yl Iod id e. BER (1.03 g, 3 mmol)
was added to a methanol solution (5 mL) of Ni(OAc)2‚4H2O
(0.025 g, 0.1 mmol), and the mixture was stirred slowly at room
temperature. Immediately a black coating of nickel boride and
a slow hydrogen evolution due to decomposition of BER were
observed. After 1 min, a methanol solution (1 mL) of 5-hexenyl
iodide (0.21 g, 1 mmol) was added, and the mixture was stirred
at room temperature. After 0.5 h, the GC analysis of the
mixture on column HP-1 showed 38% of methylcyclopentane
and 62% of n-hexane.
Gen er a l P r oced u r e. 1. Ester Cou p lin g. The prepara-
tion of methyl 3-cyclohexylbutyrate is representative. BER
(5.17 g, 15 mmol) was added to a methanol solution (10 mL)
of Ni(OAc)2‚4H2O (0.25 g, 1 mmol), and the mixture was stirred
slowly at room temperature. Immediately a black coating of
nickel boride and a slow hydrogen evolution due to decomposi-
tion of BER were observed. After 1 min, ethyl crotonate (10.01
g, 100 mmol) and a methanol solution (10 mL) of iodocyclo-
hexane (1.05 g, 5 mmol) were added, and the mixture was
stirred at room temperature. After 6 h, the resin was removed
by filtration, and excess ethyl crotonate, reduction products
(cyclohexane and ethyl butyrate), and methanol were evapo-
rated under reduced pressure to yield the pure methyl 3-cy-
clohexylbutyrate (0.78 g, 85%): IR (neat) 1739 cm-1; 1H NMR
(200 MHz, CDCl3) δ 0.82-1.89 (m, 15 H), 2.08 (dd, 1 H, J )
14.6, 11.9 Hz), 2.38 (dd, 1 H, J ) 14.6, 5.2 Hz), 3.69 (s, 3 H);
MS m/z (relative intensity) (EI, 70 eV) 153 (18), 141 (5), 111
(100), 101 (67), 87 (37), 74 (60), 69 (37), 55 (66). Anal. Calcd
for C11H20O2: C, 71.70; H, 10.94. Found: C, 71.59; H, 11.03.
In some cases, when the reduction products and/or side
products were not removed easily by evaporation, flash chro-
matography was carried out.
mL) of iodocyclohexane (1.05 g, 5 mmol) were added, and the
mixture was stirred at 65 °C. After 1 h, the resin was removed
by filtration, and filtrate was evaporated under reduced
pressure. The crude residue was purified by flash chroma-
tography (SiO2, hexane/EtOAc ) 12:1) to yield the pure
3-cyclohexylbutyronitrile (0.70 g, 93%): IR (neat) 2245 cm-1
;
1H NMR (200 MHz, CDCl3) δ 0.88-1.18 (m, 2 H), 1.15 (d, 3 H,
J ) 6.6 Hz), 1.17-1.42 (m, 4 H), 1.68-1.80 (m, 6 H), 2.26 (dd,
1 H, J ) 16.8, 7.7 Hz), 2.39 (dd, 1 H, J ) 16.8, 5.9 Hz); MS
m/z (relative intensity) (EI, 70 eV) 151 (M+ 4), 150 (18), 135
(10), 95 (23), 82 (68), 68 (76), 54 (100). Anal. Calcd for
C10H17N: C, 79.41; H, 11.33; N, 9.26. Found: C, 79.18; H,
11.08; N, 9.37.
3. Keton e Cou p lin g. The preparation of 5-cyclohexyl-3-
hexanone is representative. BER (2.90 g, 9 mmol) was added
to a methanol solution (6 mL) of Ni(OAc)2‚4H2O (0.08 g, 0.3
mmol), and the mixture was stirred slowly at room tempera-
ture. Immediately a black coating of nickel boride and a slow
hydrogen evolution due to decomposition of BER were ob-
served. After 1 min, trans-4-hexen-3-one (5.89 g, 60 mmol)
and a methanol solution (6 mL) of iodocyclohexane (0.63 g, 3
mmol) were added, and the mixture was stirred at room
temperature. After 1 h, the resin was removed by filtration,
the filtrate was concentrated under reduced pressure, and the
residue was purified by flash chromatography (SiO2, hexane/
EtOAc ) 49:1) to afford 5-cyclohexyl-3-hexanone (0.44 g,
81%): IR (neat) 1736 cm-1; 1H NMR (200 MHz, CDCl3) δ 0.84-
1.32 (m, 6 H), 0.85 (d, 3 H, J ) 7.1 Hz), 1.07 (t, 3 H, J ) 7.3
Hz), 1.61-1.98 (m, 6 H), 2.14-2.55 (m, 4 H); MS m/z (relative
intensity) (EI, 70 eV) 182 (M+ 1), 153 (10), 135 (31), 110 (100),
99 (47), 81 (46), 69 (49), 57 (44), 55 (38). Anal. Calcd for
C12H22O: C, 79.06; H, 12.16. Found: C, 78.98; H, 12.44.
Ack n ow led gm en t. We are grateful to Organic
Chemistry Research Center/KOSEF and to the Daewoo
Foundation for the Post Graduate Scholarship given to
Tae Bo Sim.
Su p p or tin g In for m a tion Ava ila ble: Experimental data
for IR, NMR, MS, and elemental analyses of new compounds
(5 pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
2. Nitr ile Cou p lin g. The preparation of 3-cyclohexylbu-
tyronitrile is representative. BER (5.0 g, 15 mmol) was added
to a methanol solution (10 mL) of Ni(OAc)2‚4H2O (0.13 g, 0.5
mmol) with gentle stirring at room temperature. Immediately
a black coating of nickel boride and a slow hydrogen evolution
due to decomposition of BER were observed. After 1 min,
crotononitrile (6.7 g, 100 mmol) and a methanol solution (10
J O961751F