Cobalt-catalyzed cross-coupling reactions of alkyl halides with allylic and benzylic grignard reagents and their application to tandem radical cyclization/cross-coupling reactions

Article abstract of DOI:10.1002/chem.200400545

Details of cobalt-catalyzed cross-coupling reactions of alkyl halides with allylic Grignard reagents are disclosed. A combination of cobalt(II) chloride and 1,2-bis(diphenylphosphino)ethane (DPPE) or 1,3-bis(diphenylphosphino)propane (DPPP) is suitable as a precatalyst and allows secondary and tertiary alkyl halides-as well as primary ones-to be employed as coupling partners for allyl Grignard reagents. The reaction offers a facile synthesis of quaternary carbon centers. which has practically never been possible with palladium, nickel, and copper catalysts. Benzyl, methallyl, and crotyl Grignard reagents can all couple with alkyl halides. The benzylation definitely requires DPPE or DPPP as a ligand. The reaction mechanism should include the generation of an alkyl radical from the parent alkyl halide. The mechanism can be interpreted in terms of a tandem radical cyclization/cross-coupling reaction. In addition, serendipitous tandem radical cyclization/cyclopropanation/carbonyl allylation of 5-alkoxy-6-halo-4-oxa-1-hexene derivatives is also described. The intermediacy of a carbon-centered radical results in the loss of the original stereochemistry of the parent alkyl halides, creating the potential for asymmetric cross-coupling of racemic alkyl halides.

Full text of DOI:10.1002/chem.200400545

FULL PAPER
Cobalt-Catalyzed Cross-Coupling Reactions of Alkyl Halides with Allylic
and Benzylic Grignard Reagents and Their Application to Tandem Radical
Cyclization/Cross-Coupling Reactions
Hirohisa Ohmiya, Takashi Tsuji, Hideki Yorimitsu, and Koichiro Oshima*[a]
Abstract: Details of cobalt-catalyzed
cross-coupling reactions of alkyl hal-
ides with allylic Grignard reagents are
disclosed. A combination of cobalt(ii)
chloride and 1,2-bis(diphenylphosphi-
no)ethane (DPPE) or 1,3-bis(diphenyl-
phosphino)propane (DPPP) is suitable
as a precatalyst and allows secondary
and tertiary alkyl halides—as well as
primary ones—to be employed as cou-
pling partners for allyl Grignard re-
agents. The reaction offers a facile syn-
thesis of quaternary carbon centers,
which has practically never been possi-
ble with palladium,nickel,and copper
catalysts. Benzyl,methallyl,and crotyl
Grignard reagents can all couple with
alkyl halides. The benzylation definite-
ly requires DPPE or DPPP as a ligand.
The reaction mechanism should include
the generation of an alkyl radical from
the parent alkyl halide. The mechanism
can be interpreted in terms of
a
tandem radical cyclization/cross-cou-
pling reaction. In addition,serendipi-
tous tandem radical cyclization/cyclo-
propanation/carbonyl allylation of 5-
alkoxy-6-halo-4-oxa-1-hexene deriva-
tives is also described. The intermedia-
cy of a carbon-centered radical results
in the loss of the original stereochemis-
try of the parent alkyl halides,creating
the potential for asymmetric cross-cou-
pling of racemic alkyl halides.
Keywords: allylation · benzylation ·
cobalt · cross-coupling reaction ·
radical reaction
Introduction
disproportionation,and cross-coupling of alkyl groups from
the combination of the alkyl Grignard reagent and the alkyl
halide. Since the cross-coupling product was produced
though the coupling of two radicals,one formed by the prior
homolysis of the alkylmetal species and the other formed by
single-electron transfer to organic halide,the cross-coupling
reaction was virtually uncontrollable. Later,Kochi and co-
workers reported selective cross-coupling reactions under
copper and iron catalysis conditions.[8] Aside from the prog-
ress in copper-catalyzed cross-coupling reactions,[9] little at-
tention had been paid to other transition metals such as iron
and cobalt since Kochiꢀs findings. Very recently though,a
renaissance in the base metal-catalyzed coupling reaction
has commenced.[10] Fürstner and co-workers have reported
that ligandless iron salts function as catalysts in cross-cou-
pling reactions between aryl chlorides and alkyl Grignard
reagents,[11] and Nakamura and co-workers[12] and Hayashi
and Nagano[13] have also developed cross-coupling reactions
with iron catalysis,in which primary and secondary alkyl
halides are usable as coupling partners for aryl Grignard re-
agents. These iron catalyst systems are superior to palladium
or nickel catalyst systems in terms of the efficiency of the re-
action,including the yields of the products and the speed of
the synthesis,the ready availability of secondary alkyl hal-
ides under quite simple reaction conditions,and the use of
inexpensive and toxicologically benign iron salts. Such iron-
catalyzed reactions have thus attracted increasing attention.
Palladium- and nickel-catalyzed cross-coupling reactions are
among the most powerful methods for carbon–carbon bond
formation.[1] Their significance has been demonstrated in the
syntheses not only of biologically active compounds,but
also in those of high-performance organic materials. With
regard to their scope,one of the most apparent limitations
in the cross-coupling reactions had been the lack of capabili-
ty to couple alkyl halides possessing b hydrogens. Recently,
however,several groups have overcome the difficulty of b-
hydride elimination.[2–6] Palladium- and nickel-catalyzed
cross-coupling reactions have already moved on to the next
stage and continue to develop.
Cross-coupling reactions can also be catalyzed by transi-
tion metals other than palladium and nickel. More than half
a century ago,Kharasch and co-workers investigated the
effect of transition metal salts such as iron and cobalt in re-
actions between organic halides and Grignard reagents.[7]
The reaction was identified as a mixture of homo-coupling,
[a] H. Ohmiya,T. Tsuji,Dr. H. Yorimitsu,Prof. K. Oshima
Department of Material Chemistry,Graduate School of Engineering
Kyoto University
Kyoto-daigaku Katsura,Nishikyo-ku,Kyoto 615-8510 (Japan)
Fax : (+81)75-383-2438
E-mail: oshima@orgrxn.mbox.media.kyoto-u.ac.jp
5640
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
DOI: 10.1002/chem.200400545
Chem. Eur. J. 2004, 10,5640 – 5648

5640 – 5648
Table 1. Effects of ligand and reaction temperature.[a]
We have been interested in cobalt-catalyzed carbon–
carbon bond-formation reactions.[14] Most of these reactions
offer unprecedented coupling potential,generally impossible
with palladium,nickel,copper,or even iron catalysts.
Among them,cobalt-catalyzed coupling between alkyl hal-
ides and allyl Grignard reagents allows tertiary alkyl halides
to be employed,resulting in facile formation of quaternary
carbons.[15,16] Our cobalt catalyst system does not suffer from
the difficulties of oxidative addition to alkyl halides and
rapid b-hydride elimination,both of which are usually prob-
lematic in palladium-catalyzed reactions. Motivated by our
early success,we have continued to explore the generality of
cobalt-catalyzed allylation reactions. Here we report full de-
tails of the reaction,including its scope,the curious effects
of the ligand and solvent,and couplings of alkyl halides with
benzyl Grignard reagents.
Entry
Ligand[b]
Temp [8C]
Yield of 2a [%]
2a/3
1
2
3
4
5
6
7
8
9
DPPM
DPPE
DPPP
DPPB
DPPE
DPPP
DPPP
DPPP
DPPP
0
0
0
39
73
80
46:54
91:9
82:18
50:50
–
92:8
86:14
–
0
41
À20
À20
À30
À40
À20
N.R.[c]
90
64
N.R.[c]
60[d]
93/7
[a] 1a/Grignard reagent/cobalt cat. = 1:3:0.1 [b] Ligands DPPM–DPPB
denote Ph2P(CH2)nPPh2, n = 1,DPPM; n = 2,DPPE; n = 3,DPPP; n
=
4,DPPB. [c] No reaction proceeded. [d] 1.5 equivalents of the
Grignard reagent.
Results and Discussion
balt complex (vide infra). While [CoCl2(dppe)] did not func-
tion as a precatalyst at À208C,the reaction at À208C in the
presence of [CoCl2(dppp)] provided 2 in excellent yield with
the highest selectivity. Use of triphenylphosphine resulted in
low 2a/3 selectivity. The choice of bidentate ligand and reac-
tion temperature proved to be crucial for achieving high
yields of the coupling product. THF was the best solvent,
while the reaction in diethyl ether or 1,2-dimethoxyethane
also yielded 2 in broadly comparable but slightly lower
yields. No 2 was obtained when the cobalt catalyst was omit-
ted. The amount of the Grignard reagent used has consider-
able influence: treatment with 1.5 equivalents of the
Grignard reagent afforded 2a in 60% yield (Table 1,
entry 9).
Cross-coupling between alkyl halides and allyl Grignard re-
agents: As a model reaction,the allylation of 2-bromo-2-
methyldecane (1a) with allylmagnesium chloride was inves-
tigated first (Table 1). Allylmagnesium chloride (3 equiv)
was added to a solution of 1a in THF in the presence of
[CoCl2(dppp)] (0.1 equiv; dppp=1,3-bis(diphenylphosphi-
no)propane) at 08C. After the resulting mixture had been
stirred for 2 h at 08C,conventional workup followed by
silica gel column purification afforded 2a in 80% yield,
along with 2-methyl-1-decene (3,18% yield,entry 3). The
use of several bidentate ligands to restrain the formation of
3 was surveyed. Use of DPPE instead of DPPP increased
the 2a/3 ratio up to 91:9,but a proportion of 1a remained
unchanged (entry 2). Significant amounts of 3 were obtained
when DPPM and DPPB were employed (entries 1,4). Reac-
tions at lower temperatures might have allowed the forma-
Allylation of a variety of alkyl halides proceeded smooth-
[17]
ly,as shown in Table 2.
Benzylic allylation of 1d required
DPPE in place of DPPP for a satisfactory result to be at-
tained. Secondary bromides were also subjected to allylation
to afford the corresponding coupling products (Table 2,en-
tries 4,5),while a primary alkyl bromide was less reactive
(Table 2,entry 6). Instead,use of alkyl iodides such as 1h
gave high yields at À408C. Use of the tertiary alkyl chloride
1i resulted in low conversion even at higher temperatures. It
is worth noting that haloacetaldehyde dibutyl acetals 1j and
1k,which have butoxy groups at the b-position to the halide
atom,participated in the allylation.
tion of dehydrobromination product
3 to be avoided
(Table 1,entries 5–8). Alkene 3 may be produced by con-
ventional base-induced E2 dehydrobromination or through
b-hydride elimination from the corresponding tert-alkylco-
Abstract in Japanese:
Attempts to transform iodoarenes met with much more
limited success (Scheme 1),the highest yield (32%) of 2j
being obtained in the presence of [CoCl2(PPh3)2] at 208C
under reaction conditions otherwise the same as above. In-
3
À
terestingly,highly selective conversion of sp C Br over
2
À
sp C Br was achieved, 2a being selectively produced and
1n completely recovered when a mixture of 1n and 1a was
subjected to the allylation. Unfortunately,amide,ester,and
carbonate functionalities could not survive under the reac-
tion conditions. Attacks on the carbonyl groups of com-
pounds 1o, 1p,and 1q took place even at À788C,with none
of the desired products being obtained.
Cross-coupling reaction with methallyl, crotyl, prenyl, and
benzyl Grignard reagents: Methallylation of 1a and 1h
Chem. Eur. J. 2004, 10,5640 – 5648
www.chemeurj.org
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
5641

K. Oshima et al.
FULL PAPER
Table 2. Allylation of various alkyl halides.
benzene or 2-methyl-1-decene and 2-methyl-2-decene being
produced as the only by-product in each experiment.
A variety of phosphine ligands were screened for benzyla-
tion of alkyl halides,to reveal that DPPE or DPPP was
again the best ligand (Table 4). It is noteworthy that 1,2-bis-
(dimethylphosphino)ethane,a highly electron-donating bi-
dentate ligand,acted as an effective ligand,while no reac-
tion occurred with DPPM and DPPB. The number of meth-
ylene units between the two phosphorus atoms seems to be
important. In contrast,12,-bis(diphenylphosphino)ethylene,
a conformationally restricted ligand,interfered with the ben-
zylation,indicating that a spacer of some flexibility is re-
quired. None of the monodentate ligands tested—such as
PPh3 and P(2-furyl)3—served as a ligand for the benzylation,
no conversion being observed. Unlike in the allylation reac-
tion,solvent and reaction temperature are not significant
variables in the benzylation reaction. Use of ether or diox-
ane did not affect the yield of 7a (with DPPP,45% and
53% yields,respectively). Benzylation reactions either at
À108C or at reflux gave no significant effects (with DPPP,
47%,15 h and 50%,5 min,respectively). Unlike in the ally-
lation,use of a lower temperature (below À208C) complete-
ly blocked the benzylation.
Entry
1
Substrate
1
Temp. [8C]
À20
2
Yield [%]
83
1b
2b
2
1c
0
2c
76[a]
3
4
5
1d
1e
1 f
À20
0
2d
2e
2 f
73[b]
57
À20
84
6
7
1g
1h
0
2 g
2 g
30
82
À40
8
9
1i
1j
20
2a
2h
31
49
0
Use of 1.5 equivalents of benzylmagnesium chloride was
sufficient for satisfactory yields of products to be attained.
Several alkyl halides were subjected to the benzylation reac-
tion (Table 5). Secondary alkyl halides underwent the benzy-
lation in good to modest yields,while coupling with a terti-
ary alkyl group encountered difficulty.[18] p-Methoxybenzyl
and p-fluorobenzyl Grignard reagents participated in the re-
action given in Equation (1).
10
11
1k
1l
À40
À40
2h
2i
82
76[c]
[a] trans/cis
[c] trans/cis = 86:14 for 2i.
= 82:18 for 2c. [b] DPPE was used instead of DPPP.
Tandem cyclization/cross-coupling reaction: clue to reaction
mechanism: Substrates possessing carbon–carbon double
bonds themselves such as 8 were then subjected to the reac-
tion conditions (Scheme 2). Consequently,tandem cycliza-
tion/cross-coupling occurred,thereby affording 3-butenyl-
substituted lactones after Jones oxidation of the cyclic
acetal. For instance,iodoacetal 8c was converted into lac-
tone 10c bearing a quaternary carbon center. Cyclization of
8d exclusively provided the trans isomer 10d. A cyclization/
benzylation sequence was also established in the reaction of
8a,but afforded the product only in 26% yield [Eq. (2)].
Scheme 1. Other transformations.
yielded 4a and 4b in 50 and 68% yields,respectively
(Table 3,entries 1,2). Treatment of 1a with crotylmagnesi-
um chloride predominantly afforded methyl-branched prod-
uct 5a in modest yield along with linear 5a’ (Table 3,
entry 3). Excellent regioselectivity was observed upon treat-
ment of 1h with crotylmagnesium chloride (Table 3,
entry 4). Similar couplings with prenylmagnesium chloride
gave moderate to poor yields (Table 3,entries 5,6). The re-
gioselectivities were far from satisfactory. In all the reac-
tions,the substrates were completely consumed,with allyl-
Interestingly,treatment of 8e with allylmagnesium chloride
in the presence of [CoCl2(dppp)] furnished the ring-opened
product 10e (Scheme 3). Given that intramolecular carbo-
cobaltation proceeds to yield cyclopropylmethylcobalt, b-
carbon elimination could provide a route to 10e. However,
5642
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10,5640 – 5648

Cobalt-Catalyzed Cross-Coupling
5640 – 5648
Table 3. Methallylation,crotylation,and prenylation of alkyl halides 1a and 1h.
tive addition proceeds through
a single-electron transfer from
an electron-rich allyl- or benzyl-
cobalt complex to the alkyl
halide.
Entry
1
RMgCl
Product
Yield [%]
50
1[a]
1a
2[b]
1h
68
An unexpected tandem radical
cyclization/cyclopropanation/al-
lylation affording allyl cyclopro-
pylmethyl ketone: During the
course of our study of the sol-
vent and ligand effects on the
3[a]
4[b]
5[a]
6[b]
1a
1h
1a
1h
60 (5a),12 ( 5a’)
93 (5b),1 ( 5b’)
11 (6a),29 ( 6a’)
10 (6b),9( 6b’)
tandem
cyclization/cross-cou-
pling reactions of 5-alkoxy-6-
halo-4-oxa-1-hexene derivatives
8,we serendipitously observed
the formation of cyclopropane
[a] Performed at À208C. [b] Performed at À408C.
Table 4. Screening of ligands for benzylation.[a]
Entry
Ligand
Yield [%]
1
2
3
4
5
6
7
8
DPPM
DPPE
DPPP
N.R.
46
51
N.R.
N.R.
29
N.R.
N.R.
DPPB
DPPH[b]
Me2PCH2CH2PMe2
cis-Ph2PCH=CHPPh2
(R)-BINAP
Scheme 2. Tandem cyclization/cross-coupling reactions with substrates 8
possessing carbon–carbon double bonds.
[a] 1r/Grignard reagent/cobalt cat. = 1:3.0:0.1. [b] 1,6-Bis(diphenylphos-
phino)hexane.
Table 5. Cobalt-catalyzed benzylation reaction.[a]
Entry
1
Substrate
Product
Yield [%]
70
2
3
40
7c
7a
61[b]
Scheme 3. Reaction between 8e and allylmagnesium chloride,furnishing
the ring-opened product 10e.
4
5
62
37
ring in a crude reaction mixture. After further investigation,
we found that treatment of 8d with allyl Grignard reagent
in diethyl ether at 208C in the presence of [CoCl2(dppb)] af-
forded cyclopropane 13a in 67% yield (Scheme 4). Oxida-
tion of the alcohol 13a yielded allyl cyclopropylmethyl
ketone 14a as a single isomer. A plausible reaction mecha-
nism is as follows. Single-electron transfer to 8d,followed
by loss of the bromide,could result in the formation of the
corresponding radical. Sequential 5-exo radical cyclization
and recombination of a cobalt complex would then afford
(4-butoxy-3-oxacyclopentyl)methylcobalt. The cobalt species
and/or the corresponding magnesium species 15 that would
[a] 1/Grignard reagent/cobalt cat.
the Grignard reagent.
= 1:1.5:0.1. [b] Three equivalents of
b-carbon elimination seems unlikely,since b-hydride and b-
alkoxy eliminations were minor processes in the reactions of
1. Alternatively,the ring-opening may be accounted for by
the existence of radical intermediates 11 and 12.[19] Taking
all the experimental facts into consideration,we believe that
the reaction mechanism should involve oxidative addition of
alkyl halide by a radical mechanism.[20] Namely,the oxida-
Chem. Eur. J. 2004, 10,5640 – 5648
www.chemeurj.org
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
5643

K. Oshima et al.
FULL PAPER
excess to 22%. Unfortunately,use of ( À)-DIOP (DIOP=
[(2,2-dimethyl-1,3-dioxolane-4,5-diyl)bis(methylene)]bis(di-
phenylphosphine)) or (R)-BINAP (BINAP= [1,1’-binaph-
thalene]-2,2’-diylbis(diphenylphosphine)) resulted in the ex-
clusive formation of the corresponding dehydrobromination
product. The cobalt-catalyzed asymmetric allylation thus
represents a new aspect of transition metal-catalyzed radical
reactions.[21,22]
Conclusion
We have found that the cobalt complexes [CoCl2(dppe)] and
[CoCl2(dppp)] effected allylation of secondary and tertiary
alkyl bromides and iodides with allyl Grignard reagents. The
introduced allyl moiety could undergo a number of transfor-
mations,so this reaction should greatly increase the utility
of cross-coupling reactions. The reaction is highly reliable,
so far unique to cobalt complexes,and superior to the palla-
dium- and nickel-catalyzed versions with respect to the
availability of tertiary alkyl halides. The benzylation is also
useful to install a benzyl unit on an alkyl chain. In both of
the reactions,the specificity of DPPE and DPPP as ligands
is curious and deserves further investigation. The accessibili-
ty of the coupling between sp3 carbon atoms is thanks to
facile oxidative addition through a single-electron transfer
mechanism and fast reductive elimination of the product
from cobalt(alkyl)allyl without suffering from b-elimination.
The electron transfer mechanism was verified by the tandem
radical cyclization/cross-coupling reaction,which resulted in
the efficient synthesis of 3-butenyl- or 2-phenylethyl-substi-
tuted lactones. The cobalt-catalyzed cross-coupling reaction
may be extended to highly enantioselective asymmetric cou-
pling of racemic alkyl halides with organometallic reagents.
Scheme 4. Formation of the cyclopropanated products.
be formed by transmetalation would be converted,in diethyl
ether,into the corresponding cyclopropane 16. In THF
these species did not participate in intramolecular cyclopro-
panation (vide supra). The reaction in the less strongly coor-
dinating diethyl ether could enhance the coordination of the
oxygen atom(s) of 15 to Lewis acidic magnesium. The re-
sulting aldehyde 16 would undergo carbonyl allylation to
afford 13a. The bromo analogue of 8d would also undergo
a similar conversion to afford 13a in 59% yield. g-Adducts
14b and 14c were similarly formed exclusively upon corre-
sponding treatment of prenyl- and crotylmagnesium bro-
mides.
Experimental Section
Potential for asymmetric cross-coupling of racemic alkyl hal-
ides with allylmagnesium chloride: The intermediacy of a
carbon-centered radical results in the loss of the original
stereochemistry of the parent alkyl halides,and so the
cobalt-catalyzed cross-coupling reaction offers potential for
asymmetric cross-coupling of racemic alkyl halides. Treat-
ment of racemic 1d with allylmagnesium chloride in the
presence of [CoCl2{(À)-chiraphos}] at À208C afforded 2d
(Scheme 5). Hydroboration of 2d followed by conventional
oxidation provided 17 in 70% yield and 14% ee,while use
of a lower temperature (À788C) increased the enantiomeric
1H NMR (300 MHz) and 13C NMR (75.3 MHz) spectra were taken on a
Varian GEMINI 300 spectrometer in CDCl3 as a solvent,and chemical
shifts are given as d values with tetramethylsilane as an internal standard.
IR spectra were determined on a JASCO IR-810 spectrometer. TLC
analyses were performed on commercial glass plates with 0.25 mm layers
of Merck silica gel (60F254). Wakogel silica gel (200 mesh) was used for
column chromatography. Mass spectra (EI unless otherwise noted) were
determined on a JEOL Mstation 700 spectrometer. The elemental analy-
ses were carried out at the Elemental Analysis Center of Kyoto Universi-
ty.
Unless otherwise noted,materials obtained from commercial suppliers
were used without further purification. Phosphine ligands were purchased
from Tokyo Kasei Kogyo. Anhydrous CoCl2 was purchased from Wako
Pure Chemicals and was used after removal of water. Commercially
available anhydrous CoCl2 may contain some water. The completely an-
hydrous salt is clear blue,whereas purchased CoCl is somewhat reddish-
2
blue. Handling of CoCl2 under air as usual also caused a low yield.
Hence,in each experiment,CoCl
was carefully dried under reduced
2
pressure (0.5 Torr) by heating with a hair dryer for 2 min in a reaction
flask immediately before use.
A typical procedure for cobalt-catalyzed allylation of alkyl halide: Anhy-
drous cobalt(ii) chloride (6.5 mg,0.050 mmol) was placed in a 20 mL
flask and heated in vacuo with a hair dryer for 2 min. After the color of
the cobalt salt had changed to blue,dppp (25 mg,0.060 mmol) and anhy-
drous THF (1.0 mL) were sequentially added under argon. The mixture
Scheme 5. Asymmetric allylation of racemic 1d. Ar=C6H4-4-OCH3.
5644
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10,5640 – 5648

Cobalt-Catalyzed Cross-Coupling
5640 – 5648
was stirred for about 10 min at room temperature. 2-Bromo-2-methylde-
cane (1a,0.12 g,0.50 mmol) and allylmagnesium chloride (1.0 m THF so-
lution,1.5 mL,1.5 mmol) were successively added dropwise to the reac-
tion mixture at À208C. While the Grignard reagent was being added,the
mixture turned reddish-brown. After having been stirred at À208C for
2 h,the reaction mixture was poured into saturated ammonium chloride
solution. The products were extracted with ethyl acetate (20 mL”2). The
combined organic layers were dried over Na2SO4 and concentrated. Silica
gel column purification (hexane) of the crude product provided 4,4-di-
methyl-1-dodecene (2a) and 2-methyl-1-decene (3a) (94 mg,90% and
8% yields,respectively,as judged by 1H NMR spectra).
The products were extracted with ethyl acetate,and the combined organ-
ic layers were dried and concentrated. Silica gel column purification
(hexane/ethyl acetate 40:1) provided 2d (0.13 g,0.57 mmol) in 57%
yield,in addition to 0.17 mmol of the corresponding dehydrobromination
product and 0.10 mmol of the corresponding protodebromination prod-
uct. The allylated product 2d,dissolved in THF (2 mL),was added at
08C to 9-borabicyclo[3.3.1]nonane (0.5m THF solution,4.6 mL,
2.3 mmol). The mixture was stirred at 208C for 15 h. Sodium hydroxide
(6m aqueous solution,2.0 mL) and hydrogen peroxide (30% aqueous so-
lution,2.0 mL) were sequentially added dropwise at 0 8C. After having
been stirred for 1 h at 208C,the reaction mixture was diluted with water
(50 mL),and a saturated aqueous solution of sodium thiosulfate was
added. Extraction followed by silica gel column purification (hexane/
ethyl acetate 3:1) yielded the corresponding alcohol 17 quantitatively.
A typical procedure for cobalt-catalyzed benzylation of alkyl halide: Co-
balt(ii) chloride (13 mg,0.10 mmol) was placed in a 20 mL flask and
heated in vacuo with a hair dryer for 2 min. DPPP (50 mg,0.12 mmol)
and anhydrous THF (3.0 mL) were then added under argon. After the
mixture had been stirred at room temperature for about 10 min,2-bro-
HPLC analysis of 17 (CHIRALCELꢂ OD column 4.6 mm”250 mm
À1
Daicel Chemical Industries,hexane/2-propanol 90:10,1.0 mLmin
208C,and RI detector) showed that the ratio of the two enantiomers (re-
tention time = 6.2 and 8.6 min) was 42.5:57.5.
,
mooctane (1r,0.19 g,1.0 mmol) and benzylmagnesium chloride (1.06
m
THF solution,2.83 mL,3.00 mmol) were sequentially added dropwise at
08C. While the Grignard reagent was being added,the mixture turned
brown. After having been stirred at 08C for 2 h,the reaction mixture was
quenched with saturated ammonium chloride solution. The products
were extracted with ethyl acetate (20 mL”2). The combined organic
layers were dried over Na2SO4 and concentrated. Purification of the
crude oil by silica gel column chromatography (hexane) provided the cor-
responding benzylated product 7a in 51% yield (104 mg,0.51 mmol).
Characterization data: Tertiary bromides 1a–1d were prepared from the
corresponding alcohols by treatment with PBr3 in ether at À108C. Secon-
dary bromides 1e and 1 f were prepared in a similar fashion at À148C.
Chloride 1i was obtained from the corresponding alcohol by treatment
with conc. HCl at room temperature. Haloacetals 1j, 1k,and 8 were pre-
pared according to the literature.[23] Bromides 1p and 1q were prepared
by sequential nucleophilic dimethylation of e-caprolactone,selective es-
terification,and bromination. Bromide 1c and iodide 1l were found in
the literature.[24,25] Products 7a—7e[26–30] and 10a’[31] were identical with
the corresponding authentic samples.
Tandem cyclization/cross-coupling reaction: Anhydrous cobalt(ii) chlo-
ride (6.5 mg,0.050 mmol) was placed in a 20 mL flask and dried. DPPP
(25 mg,0.060 mmol) and anhydrous THF (1.0 mL) were added under
argon. The mixture was stirred for about 10 min at room temperature. Io-
2-Bromo-2-methyldecane (1a): 1H NMR (CDCl3): d
= 0.89 (t, J =
doacetal (8c,0.18 g,0.50 mmol) and allylmagnesium chloride (0.91
THF solution,1.7 mL,1.5 mmol) were successively added to the reaction
m
6.6 Hz,3H),1.24–1.36 (m,12H),1.44–1.56 (m,2H),1.75 ppm (s,6H);
13C NMR (CDCl3): d = 13.99,22.55,26.19,29.17,29.40,29.52,31.78,
mixture at À408C. While the Grignard reagent was being added,the mix-
ture turned reddish-brown. After having been stirred at À408C for 2 h,
the reaction mixture was poured into saturated ammonium chloride so-
lution. The products were extracted with ethyl acetate (20 mL”2). The
combined organic layers were dried over Na2SO4 and concentrated. The
crude oil was passed through a pad of silica gel with hexane/ethyl acetate
5:1 as eluent. The appropriate fractions were collected and concentrated,
and the residue mainly containing 9c was dissolved in acetone (10 mL).
Jones oxidant was added dropwise until the reaction mixture had turned
greenish red. After the mixture had been stirred for 1 h,the reaction was
quenched with isopropyl alcohol. Extraction with ether and silica gel
column purification (hexane/ethyl acetate 20:1) provided 10c (76 mg,
0.49 mmol) in 98% yield.
34.15,47.56,68.75 ppm; IR (neat):
n˜ = 1101,1138,1369,1387,1466,
2341,2361,2856,2928 cm À1; elemental analysis calcd (%) for C11H23Br: C
56.17,H 9.86; found: C 56.35,H 10.09.
2-Bromo-2-cyclohexyl-4-phenylbutane (1b): 1H NMR (CDCl3):
1.10–1.32 (m,6H),1.60–1.74 (m,4H),1.76 (s,3H),2.04–2.26 (m,3H),
d =
2.78–2.90 (m,2H),7.17–7.23 (m,3H),7.26–7.33 ppm (m,2H);
(CDCl3): d = 26.27,26.52,26.80,28.53,28.59,29.08,30.09,32.09,45.53,
79.05,126.02,128.51,128.54,141.99 ppm; IR (neat): n˜ = 698,746,895,
1049,1379,1450,1497,1603,2853,2928,3026 cm
2-Bromo-2-(4-methoxyphenyl)-3,3-dimethylbutane (1d): 1H NMR
(CDCl3): d = 1.07 (s,9H),2.77 (s,3H),3.81 (s,3H),6.80 (d, J = 9.0 Hz,
2H),7.51 ppm (d, J = 9.0 Hz,2H); 13C NMR (CDCl3): d = 27.08,29.52,
41.17,55.23,82.99,112.01,130.67,135.99,158.34 ppm; IR (Nujol):
696,741,831,1040,1051,1186,1256,1298,1512,1611,2343,2360 cm
elemental analysis calcd (%) for C13H19BrO: C 57.57,H 7.06; found: C
57.29,H 6.88.
13C NMR
À1
.
n˜ =
À1
Tandem radical cyclization/cyclopropanation/allylation affording allyl cy-
clopropylmethyl ketone: Cobalt(ii) chloride (6.5 mg,0.050 mmol,reddish-
blue) was placed in a 20 mL flask and was heated with a hair dryer in
vacuo for 2 min. DPPB (26 mg,0.060 mmol) and anhydrous diethyl ether
(1 mL) were sequentially added under argon. The mixture was stirred for
;
2-Bromo-1-(4-methoxyphenyl)octane (1 f): 1H NMR (CDCl3): d = 1.88
(t, J = 6.9 Hz,3H),1.18–1.40 (brs,8H),1.70–1.85 (m,2H),3.11 (dd,
7.2,3.6 Hz,2H),3.71 (s,3H),4.12–4.21 (m,1H),6.85 (d, J = 8.4 Hz,
J =
about 30 min.
A bright blue mixture was obtained. Iodoacetal 8d
(177 mg,0.50 mmol) and allylmagnesium bromide (0.90 m ether solution,
2.2 mL,2.0 mmol) were successively added dropwise to the reaction mix-
ture at 08C. While the Grignard reagent was being added,the mixture
turned brown. After having been stirred at 208C for 5 h,the reaction
mixture was poured into a saturated NH4Cl solution. The products were
extracted with ethyl acetate (3”20 mL),and the combined organic layers
were dried over Na2SO4 and concentrated. Silica gel column purification
(hexane/ethyl acetate 10:1) yielded 13a (65.6 mg,0.33 mmol) in 67%
yield,and Jones oxidation of 13a (0.33 mmol) in acetone (10 mL) at
room temperature followed by conventional workup and purification
provided the ketone-substituted cyclopropane 14a (58.4 mg,0.30 mmol)
in 90% yield.
2H),7.12 ppm (d, J = 8.4 Hz,2H); 13C NMR (CDCl3): d = 13.92,22.45,
27.44,28.53,31.56,37.97,44.77,55.16,58.40,113.81,130.28,130.84,
158.53 ppm; IR (neat): n˜ = 818,1038,1178,1250,1302,1441,1466,1512,
1012,2856,2930 cm À1; HRMS found 298.0932 [M]+; C15H2379BrO calcd
298.0938.
2-Chloro-2-methyldecane (1i): 1H NMR (CDCl3): d
= 0.89 (t, J =
9.6 Hz,3H),1.22–1.39 (m,10H),1.40–1.54 (m,2H),1.57 (s,6H),1.68–
1.78 (m,2H) ppm; 13C NMR (CDCl3): d = 13.97,22.55,25.04,29.17,
29.43,29.66,31.79,32.33,46.08,71.29 ppm; IR (neat):
1369,1386,1468,2341,2856,2928 cm
n˜ = 1107,1138,
À1; elemental analysis calcd (%) for
C11H23Cl: C 69.26,H 12.15; found: C 69.40,H 12.37.
6-Bromo-6-methylheptyl pivalate (1p): 1H NMR (CDCl3): d = 1.19 (s,
Asymmetric cross-coupling of racemic alkyl halides with allylmagnesium
chloride: Anhydrous cobalt(ii) chloride (13 mg,0.10 mmol) was placed in
a 20 mL flask,which was filled with argon. ( À)-CHIRAPHOS (51 mg,
0.12 mmol) and anhydrous THF (2.0 mL) were sequentially added under
argon,and the mixture was stirred for about 10 min at room temperature.
Bromide 1d (0.27 g,1.0 mmol) and allylmagnesium chloride (1.0 m THF
solution,3.0 mL,3.0 mmol) were successively added dropwise to the re-
action mixture at À408C. After having been stirred for 4 h at À408C,the
reaction mixture was poured into saturated ammonium chloride solution.
9H),1.32–1.43 (m,2H),1.52–1.85 (m,6H),1.75 (s,6H),4.06 ppm (t,
J =
6.6 Hz,2H); 13C NMR (CDCl3): d = 26.2 (2C),27.4,28.8,34.5,47.6,
64.4,64.5,68.3,178.5 ppm; IR (neat):
n˜ = 1155,1284,1369,1458,1481,
1730,2869,2937,3438 cm
À1; HRMS found 293.1115 (FAB,[ M+H+]);
C13H2679BrO2 calcd 293.1116.
Benzyl 6-bromo-6-methylheptyl carbonate (1q): 1H NMR (CDCl3): d =
1.35–1.47 (m,2H),1.45–1.60 (m,2H),1.65–1.85 (m,4H),1.74 (s,6H),
4.16 (t, J = 6.6 Hz,2H),5.16 (s,2H),7.32–7.40 ppm (m,5H);
13C NMR
Chem. Eur. J. 2004, 10,5640 – 5648
www.chemeurj.org
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
5645

K. Oshima et al.
FULL PAPER
(CDCl3): d = 25.7,26.0,28.6,34.3,47.3,68.0,68.1,69.5,128.2,128.3,
128.4,135.1,155.0 ppm; IR (neat): n˜ = 696,910,952,1255,1369,1398,
135.97 ppm; IR (neat): n˜ = 1084,1333,1439,1641,2858,2932,
3076 cmÀ1; HRMS found 234.1984 [M]+; C16H26O calcd 234.1976.
1498,1745,2862,2941 cm
À1; HRMS found 343.0905 (FAB,[ M+H+]);
2,4,4-Trimethyl-1-dodecene (4a): 1H NMR (CDCl3): d = 0.85–0.90 (m,
9H),1.20–1.27 (brs,14H),1.76 (s,3H),1.93 (m,2H),4.62 (brs,1H),
4.82 ppm (brs,1H); 13C NMR (CDCl3): d = 14.4,23.0,24.4,25.7,27.8,
C16H2479BrO3 calcd 343.0909.
1
4,4-Dimethyl-1-dodecene (2a): H NMR (CDCl3): d = 0.84 (s,6H),0.88
(t, J = 6.6 Hz,3H),1.10–1.40 (brs,14H),1.94 (d,
5.04 (m,2H),5.81 ppm (ddt, 16.8,10.5,7.2 Hz,1H);
(CDCl3): d = 13.98,22.59,23.87,26.91,29.28,29.60,30.52,31.51,31.85,
J = 7.2 Hz,2H),4.94–
29.7,30.0,30.9,32.2,34.0,43.0,49.8,113.9,144.0 ppm; IR (neat):
n˜
=
À1; HRMS found
J
=
13C NMR
891,1363,1467,1641,2854,2927,2958,3074,3398 cm
210.2352 [M]+; C15H30 calcd 210.2348.
2-Methyl-6-phenyl-1-hexene (4b): 1H NMR (CDCl3): d = 1.44–1.55 (m,
2H),1.58–1.69 (m,2H),1.71 (s,3H),2.05 (t, J = 7.2 Hz,2H),2.64 (t,
7.2 Hz,2H),4.68 (s,1H),4.71 (s,1H),7.16–7.21 (m,3H),7.26–
7.32 ppm (m,2H); 13C NMR (CDCl3): d = 22.22,27.13,30.98,35.75,
41.95,46.44,116.45,136.12 ppm; IR (neat):
n˜ = 912,995,1366,1468,
1639,2855,2928,3076 cm À1; elemental analysis calcd (%) for C14H28: C
85.63,H 14.37; found C 85.61,H 14.63.
J
=
4-Cyclohexyl-4-methyl-6-phenyl-1-hexene (2b): 1H NMR (CDCl3): d =
0.86 (s,3H),0.90–1.32 (m,5H),1.47–1.58 (m,2H),1.58–1.84 (m,6H),
2.03–2.18 (m,2H),2.15 (t, J = 9.0 Hz,2H),5.03–5.10 (m,2H),5.85 (ddt,
J = 16.5,11.1,7.2 Hz,1H),7.12–7.21 (m,3H),7.21–7.30 ppm (m,2H);
13C NMR (CDCl3): d = 21.78,26.76,26.92,27.20,29.92,37.74,39.48,
41.45,44.59,116.71,125.61,128.39,128.40,135.90,143.80 ppm; IR (neat):
n˜ = 698,741,910,995,1377,1450,1497,1600,1638,2341,2361,2853,
2928,3026,3063 cm À1; elemental analysis calcd (%) for C19H28: C 88.99,
H 11.01; found: C 88.98,H 11.10.
37.55,109.87,125.69,128.32,128.48,142.84,146.03 ppm; IR (neat):
698,746,885,1030,1373,1454,1497,1605,1649,2345,2858,2934,3026,
n˜ =
3072 cmÀ1; elemental analysis calcd (%) for C13H18: C 89.59,H 10.41;
found C 89.30,H 10.27.
3,4,4-Trimethyl-1-dodecene (5a): 1H NMR (CDCl3): d = 0.79 (brs,9H),
0.90 (t, J = 6.6 Hz,3H),1.12–1.37 (brs,14H),1.97 (m,1H),4.90–5.15
(m,2H),5.77 ppm (ddd, J = 18.6,9.0,8.7 Hz,1H);
13C NMR (CDCl3):
d = 14.4,15.1,22.9,23.0,23.9,24.6,24.9,29.7,30.0,31.0,32.2,40.9,46.4,
113.8,142.1 ppm; IR (neat): n˜ = 721,887,910,997,1365,1467,1637,
2854,2925,2958,3074 cm À1; HRMS found 210.2342 [M]+; C15H30 calcd
210.2348.
3-Methyl-6-phenyl-1-hexene (5b): 1H NMR (CDCl3): d = 0.98 (d, J =
6.6 Hz,3H),1.30–1.37 (m,2H),1.55–1.67 (m,2H),2.09–2.19 (m,1H),
cis-4-tert-Butyl-1-methyl-1-(2-propenyl)cyclohexane (2c): 1H NMR
(CDCl3): d = 0.82 (s,3H),0.85 (s,9H),1.03–1.22 (m,5H),1.49–1.57 (m,
4H),2.02 (s,1H),2.04 (s,1H),4.95 (m,2H),5.79 (ddt,
7.5 Hz,1H) ppm; 13C NMR (CDCl3): d
22.48,27.25,27.60,29.46,
32.48,38.30,40.03,47.99,116.39,135.78 ppm; IR (neat): n˜ = 910,997,
1366,1452,1639,2844,2868,2941,3074 cm
À1; elemental analysis calcd
(%) for C14H26: C 86.52,H 13.48; found: C 86.46,H 13.51. The stereo-
chemistry of 1c and 2c was determined by 13C NMR experiments accord-
ing to the literature.[32]
J = 15.9,10.8,
=
2.59 (t, J = 7.8 Hz,2H),4.88–4.98 (m,2H),5.68 (ddd,
7.5 Hz,1H),7.15–7.22 (m,3H),7.24–7.32 ppm (m,2H);
J = 17.6,9.9,
13C NMR
(CDCl3): d = 20.09,29.06,35.97,36.20,37.62,112.54,125.68,128.32,
128.48,142.88,144.81 ppm; IR (neat): n˜ = 698,746,910,995,1373,1419,
4-(4-Methoxyphenyl)-4,5,5-trimethyl-1-hexene (2d): 1H NMR (CDCl3): d
1454,1497,1605,1639,2858,2932,3028,3065 cm
À1; elemental analysis
= 0.83 (s,9H),1.27 (s,3H),2.24 (dd,
= 14.1,3.6 Hz,1H),3.80 (s,3H),4.88 (d,
17.1 Hz,1H),5.42–5.55 (m,1H),6.81 (d,
J = 14.1,8.4 Hz,1H),3.00 (dd,
J
calcd (%) for C13H18: C 89.59,H 10.41; found: C 89.66,H 10.57.
J = 10.2 Hz,1H),5.01 (d, J =
J = 9.0 Hz,2H),7.20 ppm (d,
1
1-(4-Fluorophenyl)-2-methylbutane (7 f): H NMR (CDCl3): d = 0.83 (d,
J = 6.6 Hz,3H),0.9 (t, J = 9.2 Hz,3H),1.04–1.41 (m,2H),1.62 (m,
J = 9.0 Hz,2H); 13C NMR (CDCl3): d = 21.26,26.26,36.51,39.47,
1H),2.35 (dd, J = 13.5,8.1 Hz,1H),2.60 (dd,
J = 13.5,6.3 Hz,1H),
45.22,55.08,112.15,116.43,130.12,136.33,136.85,157.11 ppm; IR (neat):
6.90–6.99 (m,2H),7.04–7.13 ppm (m,2H); 13C NMR (CDCl3): d = 11.8,
19.1,29.3,37.0,42.7,114.7,114.9,130.4,130.5,137.2,137.3 ppm; IR
(neat): n˜ = 837,1157,1222,1379,1461,1510,1600,2856,2875,2925,
2962 cmÀ1; HRMS found 166.1159 [M]+; C11H15F calcd 166.1158.
n˜
= 831,910,1038,1188,1252,1294,1375,1464,1514,1611,2361,
2955 cmÀ1; HRMS found 232.1828 [M]+; C16H24O calcd 232.1831.
4-(4-Methoxybenzyl)-1-decene (2 f): 1H NMR (CDCl3): d = 0.87 (t, J =
6.6 Hz,3H),1.16–1.38 (brs,10H),1.60–1.70 (m,1H),2.01 (dd,
J = 7.8,
4-(3-Butenyl)-4,5-dihydro-2(3H)-furanone (10a): 1H NMR (CDCl3): d =
7.2 Hz,2H),2.48 (d, J = 7.2 Hz,2H),3.79 (s,3H),4.97–5.03 (m,2H),
5.72–5.85 (m,1H),6.82 (d, J = 9.0 Hz,2H),7.06 ppm (d, J = 9.0 Hz,
2H); 13C NMR (CDCl3): d = 13.96,22.55,26.54,29.49,31.78,32.81,
37.39,39.14,39.68,55.18,113.62,116.03,129.31,130.16,137.35,
147.81 ppm; IR (neat): n˜ = 804,910,1040,1177,1246,1300,1466,1512,
1612,2854,2926 cm À1; elemental analysis calcd (%) for C18H28O: C 83.02,
H 10.84; found: C 83.02,H 11.03.
4-Pentenal dibutyl acetal (2h): 1H NMR (CDCl3): d
7.2 Hz,6H),1.38 (m,4H),1.56 (m,4H),1.70 (m,2H),2.11 (m,2H),
3.41 (dt, J = 6.6,9.3 Hz,2H),3.58 (dt, J = 6.6,9.6 Hz,2H),4.48 (t, J =
1.56–1.63 (m,2H),2.06–2.25 (m,3H),2.53–2.68 (m,2H),3.94 (dd,
9.0,7.5 Hz,1H),4.43 (dd, 9.0,7.8 Hz,1H),5.00–5.09 (m,2H),
5.78 ppm (ddt, J = 19.8,7.2,6.6 Hz,1H); 13C NMR (CDCl3): d = 31.31,
J =
J
=
32.02,34.24,34.96,73.12,115.65,137.18,177.14 ppm; IR (neat):
814,1001,1173,1379,1420,1641,1778,2856,2924,3078 cm
n˜ = 839,
À1; elemental
analysis calcd (%) for C8H12O2: C 68.54,H 8.63; found: C 68.45,H 8.45.
4-(3-Butenyl)-5,5-dimethyl-4,5-dihydro-2(3H)-furanone (10b): 1H NMR
(CDCl3): d = 1.25 (s,3H),1.43 (s,3H),1.38–1.46 (m,1H),1.51–1.65 (m,
1H),1.95–2.32 (m,4H),2.59–2.69 (m,1H),4.98–5.10 (m,2H),5.77 ppm
= 0.92 (t, J =
(ddt, J = 16.8,10.5,6.9 Hz,1H);
28.77,32.26,34.49,45.08,86.64,115.70,137.39,175.67 ppm; IR (neat):
13C NMR (CDCl3): d = 21.79,27.35,
n˜
5.7 Hz,1H),4.94–5.06 (m,2H),5.82 ppm (ddt,
J = 17.1,10.5,6.6 Hz,
1H); 13C NMR (CDCl3): d = 13.77,19.34,28.94,31.93,32.59,65.32,
102.62,114.69,138.27 ppm; IR (neat): n˜ = 912,1049,1074,1128,1261,
=
918,959,1096,1128,1217,1258,1375,1389,1641,1771,2934,
2978 cmÀ1; elemental analysis calcd (%) for C10H16O2: C 71.39,H 9.59;
1350,1379,1458,1641,2933,2959 cm
À1; elemental analysis calcd (%) for
found: C 71.36,H 9.78.
4-(1,1-Dimethyl-3-butenyl)-4,5-dihydro-2(3H)-furanone (10c): 1H NMR
C13H26O2: C 72.84,H 12.23; found: C 72.72,H 12.11.
cis-2-(1-Octynyl)-3-(2-propenyl)-1-oxacyclohexane (cis-2i): 1H NMR
(CDCl3): d = 0.90 (t, J = 6.9 Hz,3H),1.22–1.36 (m,4H),1.36–1.48 (m,
2H),1.48–1.66 (m,6H),1.72–1.86 (m,1H),1.93–2.03 (m,1H),2.07–2.16
(m,1H),2.26 (dt, J = 1.8,7.2 Hz,2H),3.59–3.70 (m,1H),3.85–3.95 (m,
(CDCl3): d = 0.90 (s,3H),0.91 (s,3H),1.98 (d,
2.58 (m,3H),4.11 (dd, J = 9.0,8.1 Hz,1H),4.32 (dd,
1H),5.03–5.12 (m,1H),5.72–5.86 ppm (m,2H);
13C NMR (CDCl3): d =
J = 7.5 Hz,2H),2.31–
J = 9.6,8.1 Hz,
23.38,23.67,29.63,34.22,44.00,45.29,69.37,118.32,133.87,177.37 ppm;
IR (neat): n˜ = 918,1003,1026,1175,1470,1639,1780,2964,3076 cm
elemental analysis calcd (%) for C10H16O2: C 71.39,H 9.59; found: C
71.11,H 9.74.
1H),4.54 (brs,1H),4.99–5.09 (m,2H),5.75 (ddt,
J = 16.8,10.2,7.2 Hz,
À1
1H) ppm; 13C NMR (CDCl3): d = 13.90,18.64,22.47,25.28,25.37,28.46,
28.70,31.23,36.71,39.19,62.71,69.60,75.84,89.00,116.30,136.28 ppm;
IR (neat): n˜ = 1078,1350,1439,1641,2239,2341,2858,2932,3076 cm
HRMS found 234.1984 [M]+; C16H26O calcd 234.1979.
;
À1
;
1
trans-4-(3-Butenyl)-5-pentyl-4,5-dihydro-2(3H)-furanone (10d): H NMR
(CDCl3): d = 0.89 (t, J = 6.3 Hz,3H),1.24–1.72 (m,10H),1.98–2.25 (m,
trans-2-(1-Octynyl)-3-(2-propenyl)-1-oxacyclohexane (trans-2i): 1H NMR
(CDCl3): d = 0.88 (t, J = 6.9 Hz,3H),1.08–1.45 (m,7H),1.45–1.70 (m,
5H),1.84–1.98 (m,2H),2.24 (m,2H),2.40–2.49 (m,1H),3.39 (m,1H),
4H),2.71 (m,1H),4.10 (ddd,
J = 7.8,7.2,4.2 Hz,1H),4.99–5.07 (m,
= 16.8,10.5,6.9,6.6 Hz,1H);
13C NMR
2H),5.77 ppm (dddd,
J
(CDCl3): d = 14.2,22.7,25.6,31.8,31.9,32.4,34.8,35.4,40.8,86.0,115.7,
137.2,176.4 ppm; IR (neat): n˜ = 912,945,995,1172,1261,1421,1454,
1641,1778,2860,2931 cm À1; HRMS found 210.1619 [M]+; C13H22O2 calcd
210.1620.
3.80 (dt, J = 9.0,2.7 Hz,1H),3.98 (dt, J = 11.1,2.7 Hz,1H),5.03 (d,
J
= 8.7 Hz,1H),5.05 (d, J = 17.4 Hz,1H),5.79 ppm (ddt, J = 17.4,8.7,
1.8 Hz,1H); 13C NMR (CDCl3): d = 13.89,18.62,22.41,25.29,27.93,
28.46,28.49,31.21,36.71,41.07,67.64,72.65,78.42,86.61,116.57,
5646
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10,5640 – 5648

Cobalt-Catalyzed Cross-Coupling
5640 – 5648
4-(1-Methyl-1,6-heptadienyl)-4,5-dihydro-2(3H)-furanone
(10e,
E
mon Press,New York, 1991,Chapter 2.1–2.5; e) Cross-coupling Re-
actions. A Practical Guide (Ed.: N. Miyaura),Springer,Berlin, 2002.
isomer): 1H NMR (CDCl3): d = 1.45 (tt, J = 7.2,7.2 Hz,2H),1.63 (s,
3H),2.00–2.09 (m,4H),2.46 (dd,
17.7,8.7 Hz,1H),3.18 (tt,
7.5 Hz,1H),4.41 (dd, J = 8.7,7.5 Hz,1H),4.94–5.05 (m,2H),5.28 (t,
= 7.2 Hz,1H),5.80 ppm (ddt, J = 17.1,10.2,6.9 Hz,1H);
(CDCl3): d 13.50,27.09,28.52,32.80,33.19,43.81,71.77,114.74,
J = 17.7,8.7 Hz,1H),2.60 (dd,
8.1,8.1 Hz,1H),4.08 (dd, J =
J =
8.7,
J
[2] a) R. Giovannini,T. Stüdemann,G. Dussin,P. Knochel,
Angew.
J
=
Chem. 1998, 110,2512–2515; Angew. Chem. Int. Ed. 1998, 37,2387–
2390; b) R. Giovannini,T. Stüdemann,A. Devasagayaraj,G.
Dussin,P. Knochel, J. Org. Chem. 1999, 64,3544–3553; c) A. E.
Jensen,P. Knochel, J. Org. Chem. 2002, 67,79–85.
13C NMR
=
127.20,132.02,138.61,177.04 ppm; IR (neat):
1439,1639,1782,2341,2361,2858,2926 cm
(%) for C12H18O2: C 74.19,H 9.34; found: C 73.93,H 9.57. The stereo-
chemistry was assigned by NOE.
1-(2-Pentylcyclopropyl)-4-penten-2-one (14a): 1H NMR (CDCl3): d
n˜ = 847,910,1013,1171,
[3] a) J. Terao,H. Watanabe,A. Ikumi,H. Kuniyasu,N. Kambe,
J. Am.
À1; elemental analysis calcd
Chem. Soc. 2002, 124,4222–4223; b) J. Terao,A. Ikumi,H. Kuniya-
su,N. Kambe, J. Am. Chem. Soc. 2003, 125,5646–5647; c) J. Terao,
Y. Naito,H. Kuniyasu,N. Kambe, Chem. Lett. 2003, 32,890–891.
[4] a) M. R. Netherton,C. Dai,K. Neuschütz,G. C. Fu,
J. Am. Chem.
=
Soc. 2001, 123,10099–10100; b) J. H. Kirchhoff,M. R. Netherton,
I. D. Hills,G. C. Fu, J. Am. Chem. Soc. 2002, 124,13662–13663;
c) K. Menzel,G. C. Fu, J. Am. Chem. Soc. 2003, 125,3718–3719;
d) J.-Y. Lee,G. C. Fu, J. Am. Chem. Soc. 2003, 125,5616–5617; e) J.
Zhou,G. C. Fu, J. Am. Chem. Soc. 2003, 125,12527–12530; f) M.
Eckhardt,G. C. Fu, J. Am. Chem. Soc. 2003, 125,13642–13643;
g) J. Zhou,G. C. Fu, J. Am. Chem. Soc. 2003, 125,14726–14727; h)
S. L. Wiskur,A. Korte,G. C. Fu, J. Am. Chem. Soc. 2004, 126,82–
83; i) J. Zhou,G. C. Fu, J. Am. Chem. Soc. 2004, 126,1340–1341.
[5] a) K. Park,K. Yuan,W. J. Scott, J. Org. Chem. 1993, 58,4866–4870;
0.25 (ddd, J = 5.1,5.1,8.1 Hz,1H),0.32 (ddd,
0.44–0.54 (m,1H),0.66–0.76 (m,1H),0.87 (t,
(m,8H),2.27 (dd, J = 7.2,22.2 Hz,1H),2.35 (dd,
J = 5.1,5.1,8.1 Hz,1H),
J = 6.9 Hz,3H),1.16–1.43
J = 7.2,15.9 Hz,
1H),3.21 (d, J = 6.9 Hz,2H),5.09–5.20 (m,2H),5.29 ppm (ddt, J =
10.2,17.1,6.9 Hz,1H); 13C NMR (CDCl3): d = 11.90,13.76,14.19,18.92,
22.74,29.16,31.77,33.96,47.26,47.35,118.58,130.58,198.51 ppm; IR
(neat): n˜ = 3065,2957,2924,2855,1717,1638,1458,1398,1325,1028,
993,918 cm À1; elemental analysis calcd (%) for C13H22O: C 80.35,H
11.41; found: C 80.43,H 11.63. The trans stereochemistry of the cyclopro-
panes 14 was deduced by coupling constants according to the litera-
ture.[33]
3,3-Dimethyl-1-(2-pentylcyclopropyl)-4-penten-2-one (14b): 1H NMR
(CDCl3): d = 0.16 (ddd, J = 4.2,4.2,8.4 Hz,1H),0.26 (ddd,
4.8,8.4 Hz,1H),0.34–0.45 (m,1H),0.66–0.78 (m,1H),0.87 (t,
b) T. Ishiyama,S. Abe,N. Miyaura,A. Suzuki,
Chem. Lett. 1992,
691–694; c) J. G. Donkervoort,J. L. Vicario,J. T. B. H. Jastrzebski,
R. A. Gossage,G. Cahiez,G. van Koten, J. Organomet. Chem. 1998,
558,61–69.
J = 4.8,
J =
[6] For overviews of the difficulty of achieving cross-coupling reaction
of alkyl halides: a) D. J. Cꢃrdenas, Angew. Chem. 1999, 111,3201–
3203; Angew. Chem. Int. Ed. 1999, 38,3018–3020; b) D. J. Cꢃrdenas,
Angew. Chem. 2003, 115,398–401; Angew. Chem. Int. Ed. 2003, 42,
384–387; c) T.-Y. Luh,M. Leung,K.-T. Wong, Chem. Rev. 2000, 100,
3187–3204.
7.2 Hz,3H),1.20 (s,6H),1.16–1.40 (m,8H),2.35 (d,
5.08–5.14 (m,2H),5.87 ppm (dd, 9.9,16.8 Hz,1H);
(CDCl3): d = 11.72,13.76,14.20,18.81,22.74,23.45,23.45,29.14,31.77,
34.00,42.22,50.59,114.07,142.36,212.52 ppm; IR (neat): n˜ = 2961,2926,
À1; elemental analysis
J = 6.9 Hz,2H),
J
=
13C NMR
2855,1713,1636,1468,1379,1364,1018,997,918 cm
calcd (%) for C15H26O: C 81.02,H 11.79; found: C 81.18,H 11.54.
[7] a) M. S. Kharasch,E. K. Fields, J. Am. Chem. Soc. 1941, 63,2316–
2320; b) M. S. Kharasch,J. K. Hambling,T. P. Rudy, J. Org. Chem.
1959, 24,303–305; c) F. A. Cotton, Chem. Rev. 1955, 55,551–594.
[8] a) M. Tamura,J. K. Kochi, J. Am. Chem. Soc. 1971, 93,1487–1489;
b) M. Tamura,J. K. Kochi, Synthesis 1971,303–305; c) M. Tamura,
J. K. Kochi, J. Organomet. Chem. 1971, 31,289–309; d) S. M. Neu-
mann,J. K. Kochi, J. Org. Chem. 1975, 40,599–606; e) R. S. Smith,
J. K. Kochi, J. Org. Chem. 1976, 41,502–509; f) C. L. Kwan,J. K.
Kochi, J. Am. Chem. Soc. 1976, 98,4903–4912; g) J. K. Kochi, Acc.
Chem. Res. 1974, 7,351–360.
3-Methyl-1-(2-pentylcyclopropyl)-4-penten-2-one (14c,diastereomer
ratio is 1:1): 1H NMR (CDCl3): d = 0.18–0.24 (m,1H),0.26–0.33 (m,
1H),0.38–0.52 (m,1H),0.66–0.76 (m,1H),0.87 (t,
(d, J = 4.5 Hz,3H),1.16–1.42 (m,8H),2.36 (d,
J = 6.6 Hz,3H),1.17
J = 6.9 Hz,2H),3.25
(dq, J = 6.9,6.9 Hz,1H),5.11–5.17 (m,2H),5.79 ppm (ddd,
J = 5.1,
9.9,17.1 Hz,1H); 13C NMR (CDCl3) for mixture of diastereomers: d =
(11.76,11.91,assigned to each diastereomer),13.62,14.19,15.83,(18.77,
18.94,assigned to each diastereomer),22.74,29.15,31.77,33.99,45.66,
50.85,116.63,137.42,211.01 ppm; IR (neat): n˜ = 3063,2959,2926,2855,
1715,1636,1458,1371,995,918 cm
À1; elemental analysis calcd (%) for
[9] a) G. H. Posner, Org. React. 1975, 22,253–400; b) Organocopper
Reagents (Ed.: R. J. K. Taylor),Oxford University Press,Oxford,
1994.
C14H24O: C 80.71,H 11.61; found: C 80.56,H 11.84.
4-(4-Methoxyphenyl)-4,5,5-trimethyl-1-hexanol (17): 1H NMR (CDCl3):
d = 0.83 (s,9H),1.10–1.50 (m,3H),1.29 (s,3H),1.59 (dt,
J = 5.1,
[10] a) G. Cahiez,H. Avedissian, Synthesis 1998,1199–1205; b) G.
Cahiez,S. Marquais, Pure Appl. Chem. 1996, 68,53–60.
[11] a) A. Fürstner,A. Leitner, Angew. Chem. 2002, 114,632–635;
Angew. Chem. Int. Ed. 2002, 41,609–612; b) A. Fürstner,A. Leit-
ner,M. Mꢄndez,H. Krause, J. Am. Chem. Soc. 2002, 124,13856–
13863 and cited therein.
12.6 Hz,1H),2.17 (dt, J = 3.0,12.6 Hz,1H),3.61 (t,
J = 6.6 Hz,2H),
3.80 (s,3H),6.81 (d, J = 9.0 Hz,2H),7.18 ppm (d, J = 9.0 Hz,2H); 13C
NMR (CDCl3): d = 21.00,26.12,28.37,30.51,36.67,45.29,55.06,63.89,
112.35,129.93,136.66,157.32 ppm; IR (neat): n˜ = 829,1040,1188,1252,
À1
1292,1375,1466,1514,1611,2876,2955,3342 cm
; HRMS found
250.1934 [M]+; C16H26O2 calcd 250.1939.
[12] M. Nakamura,K. Matsuo,S. Ito,E. Nakamura,
J. Am. Chem. Soc.
2004, 126,3686–3687.
[13] T. Nagano,T. Hayashi, Org. Lett. 2004, 6,1297–1299.
[14] a) K. Wakabayashi,H. Yorimitsu,K. Oshima, J. Am. Chem. Soc.
2001, 123,5374–5375; b) Y. Ikeda,T. Nakamura,H. Yorimitsu,K.
Oshima, J. Am. Chem. Soc. 2002, 124,6514–6515; c) T. Fujioka,T.
Nakamura,H. Yorimitsu,K. Oshima, Org. Lett. 2002, 4,2257–2259;
d) K. Mizutani,H. Shinokubo,K. Oshima, Org. Lett. 2003, 5,3959–
3961.
[15] T. Tsuji,H. Yorimitsu,K. Oshima, Angew. Chem. 2002, 114,4311–
4313; Angew. Chem. Int. Ed. 2002, 41,4137–4139.
[16] Other cobalt-catalyzed cross-coupling: a) G. Cahiez,H. Avedissian,
Tetrahedron Lett. 1998, 39,6159–6162; b) H. Avedissian,L. Bꢄril-
lon,G. Cahiez,P. Knochel, Tetrahedron Lett. 1998, 39,6163–6166;
c) Y. Nishii,K. Wakasugi,Y. Tanabe, Synlett 1998,67–69; d) L. F.
Acknowledgment
This work was supported by Grants-in-Aid for Scientific Research and
COE Research from the Ministry of Education,Culture,Sports,Science
and Technology,Government of Japan. Drs. Kawashima,Nakao,and
Kurahashi of Prof. Hiyamaꢀs group at Kyoto University are acknowl-
edged for helping with HPLC analysis.
[1] a) Metal-catalyzed Cross-coupling Reactions (Eds.: F. Diederich,P. J.
Stang),Wiley-VCH,Weinheim, 1998; b) J. Organomet. Chem. (Spe-
Elsom,J. D. Hunt,A. McKillop,
Organomet. Chem. Rev. Sect. A
1972, 8,135–152; e) B. Sezen,D. Sames, Org. Lett. 2003, 5,3607–
3610.
[17] In each experiment we confirmed that the reaction does not proceed
in the absence of the cobalt catalyst. All the products were contami-
cial issue,Eds.: K. Tamao,T. Hiyama,E. Negishi),
2002, 653(1–2) ;
c) J. Tsuji, Palladium Reagents and Catalysts. Innovations in Organic
Synthesis,Wiley,Chichester, 1996; d) Comprehensive Organic Syn-
thesis, Vol. 3 (Eds.: B. M. Trost,I. Fleming,C. H. Heathcock),Perga-
Chem. Eur. J. 2004, 10,5640 – 5648
www.chemeurj.org
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
5647

K. Oshima et al.
FULL PAPER
nated with about 10% of the corresponding dehydrobromination
products.
[24] W. Damm,B. Giese,J. Hartung,T. Hasskerl,K. N. Houk,O. Hüter,
H. Zipse, J. Am. Chem. Soc. 1992, 114,4067–4079.
[18] Reactions in Table 4 conducted in the absence of the cobalt catalyst
afforded less than 5% of the benzylated products. To our surprise,
primary alkyl iodide was quantitatively converted into the corre-
sponding benzylated product in the absence of the cobalt catalyst
even at À208C.
[25] A. Inoue,K. Maeda,H. Shinokubo,K. Oshima,
53,665–674.
Tetrahedron 1999,
[26] L. Herbert,R. Dieter,B. Josef,S. Gerald,
1973, 57,39–47.
J. Organomet. Chem.
[27] R. Gelin,B. Chantegrel,S. Gelin, Bull. Soc. Chim. Fr. 1969,4136–
[19] M. Newcomb,S. Y. Choi,J. H. Horner,
1225–1231.
J. Org. Chem. 1999, 64,
4147.
[28] T. G. Savino,K. Kanakarajan,M. S. Platz, J. Org. Chem. 1986, 51,
[20] R. H. Crabtree, The Organometallic Chemistry of the Transition
Metals,Wiley,New York, 1988,Chapter 6.3.
1305–1309.
[29] M. Ohno,K. Shimizu,K. Ishizaki,T. Sasaki,S. Eguchi,
J. Org.
[21] Reviews of asymmetric creation of quaternary carbon: a) K. Fuji,
Chem. Rev. 1993, 93,2037–2066; b) E. J. Corey,A. Guzman-Perez,
Angew. Chem. 1998, 110,402–415; Angew. Chem. Int. Ed. 1998, 37,
388–401; c) J. Christoffers,A. Mann, Angew. Chem. 2001, 113,
4725–4732; Angew. Chem. Int. Ed. 2001, 40,4591–4732.
Chem. 1988, 53,729–733.
[30] C. F. Nutaitis,J. E. Bernardo, Synth. Commun. 1990, 20,487–493.
[31] T. Satoh,S. Sugiyama,Y. Kamide,H. Ota,
4327–4336.
[32] P. Crews,S. Naylor,F. J. Hanke,E. R. Hogue,E. Kho,R. Braslau,
Tetrahedron 2003, 59,
J.
[22] Reviews of enantioselective radical reactions: a) M. P. Sibi,N. A.
Porter, Acc. Chem. Res. 1999, 32,163–171; b) M. P. Sibi,S.
Manyem,J. Zimmerman, Chem. Rev. 2003, 103,3263–3295.
Org. Chem. 1984, 49,1371–1377. Also see ref. 24.
[33] A. B. Charette,H. Juteau,H. Lebel,C. Molinaro, J. Am. Chem. Soc.
1998, 120,11943–11952.
[23] a) R. Inoue,J. Nakao,H. Shinokubo,K. Oshima,
Bull. Chem. Soc.
Jpn. 1997, 70,2039–2049; b) J. Nakao,R. Inoue,H. Shinokubo,K.
Oshima, J. Org. Chem. 1997, 62,1910–1911; c) H. Yorimitsu,H. Shi-
nokubo,K. Oshima, Bull. Chem. Soc. Jpn. 2001, 74,225–235.
Received: June 1,2004
Published online: September 30,2004
5648
ꢁ 2004 Wiley-VCH Verlag GmbH & Co. KGaA,Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10,5640 – 5648