Cross-coupling of alkyl halides with Grignard reagents using nickel and palladium complexes bearing η3-allyl ligand as catalysts

Article abstract of DOI:10.1039/b612586g

The cross-coupling of Grignard reagents with alkyl bromides and tosylates has been achieved by the use of η³-allylnickel and η³-allylpalladium complexes as catalysts. The Royal Society of Chemistry.

Full text of DOI:10.1039/b612586g

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Cross-coupling of alkyl halides with Grignard reagents using nickel and
3
palladium complexes bearing g -allyl ligand as catalysts{
a
Jun Terao,* Yoshitaka Naitoh, Hitoshi Kuniyasu and Nobuaki Kambe*
b
b
b
Received (in Cambridge, UK) 1st September 2006, Accepted 31st October 2006
First published as an Advance Article on the web 21st November 2006
DOI: 10.1039/b612586g
3
The cross-coupling of Grignard reagents with alkyl bromides
3
To prove the intermediary of bis(g -allyl)metal complexes and
to reveal, if so, whether the ethylene tether (CH CH ) between two
and tosylates has been achieved by the use of g -allylnickel and
2
2
3
allyl ligand is essential or not, we examined the reaction using the
3
simplest bis(g -allyl)metal complexes 2 as catalysts. As a result,
g -allylpalladium complexes as catalysts.
Transition metal-catalyzed cross-coupling reactions of organic
halides with organometallic reagents are among the most
important transformations in organic synthesis, especially for
building complex structures of compounds from readily available
here we disclose that cross-coupling of alkyl bromides and
tosylates with Grignard reagents proceeded efficiently without
using conjugated diene additives in the presence of Pd and Ni
3
complexes having g -allyl ligands (Scheme 2).
1
components. As for the substrates, a variety of organometallic
Table 1 summarizes the results obtained by the reaction of
n-decyl bromide with n-butylmagnesium chloride or methylmag-
nesium bromide (1.3 equiv.) for 3 h using various catalysts in THF.
reagents have been employed, whereas the scope of the coupling
partner had long been limited to aryl and alkenyl halides. The use
of alkyl halides usually gave unsatisfactory results due mainly to
the slow oxidative addition to transition metal catalysts and the
fast b-elimination from the alkylmetal intermediates. During the
2
When PdCl (0.1 equiv.) was employed only a trace amount of the
cross-coupling product was obtained, and significant amounts of
decane (54%) and decenes (26%) were formed (entry 1).
2
,3
past several years, cross-coupling reaction of alkyl halides with
organometallic reagents has been studied extensively, however, and
alkyl halides as well as sulfonates have now become promising
candidates as reagents in transition metal catalyzed cross-coupling
reaction. As a practical method for such transformations, we
developed a unique catalytic system where Ni and Pd catalyzes
cross-coupling of alkyl fluorides, chlorides, bromides and tosylates
with Grignard reagents in the presence of conjugated dienes such
No reaction took place with PdCl (PPh
2
3 2
) (entry 2). Although
3
(g -allyl)palladium chloride gave only 10% yield of tetradecane,
3
bis(g -allyl)palladium complex afforded a moderate yield of
5
cross-coupling product (entries 3 and 4). When a methyl Grignard
3
reagent was employed, both mono- and bis(g -allyl)palladium
complexes gave satisfactory yields of product, whereas Pd
3
complexes having no g -allyl ligands again failed to catalyze this
6
reaction (entries 5–8). Nickel complexes having no g -allyl ligands
3
4
3
were also ineffective (entries 9 and 10). Bis(g -allyl)nickel catalyst
as 1,3-butadiene, isoprene, or bisdienes (Scheme 1).
3
3
In this catalytic system, bis(g -allyl)nickel or bis(g -allyl)palla-
dium complexes (1) formed by the reaction of M(0) [M = Ni, Pd]
with 2 molecules of 1,3-butadienes were proposed to be involved as
key intermediates.
shows by far the highest activity for both butyl and methyl
3
Grignard reagents (entries 12 and 16). Mono(g -allyl)nickel
complex afforded a successful result when MeMgBr was employed
n
but not in the case of Bu-MgCl (entries 11 and 15).
Results of some other representative combinations of substrates
3
using bis(g -allyl)nickel are shown in Table 2. This cross-coupling
reaction also proceeds efficiently by using alkyl tosylates (entries 1,
2
and 5). Aryl Grignard reagents afforded the corresponding
coupling product in good yield (entry 2). When the reaction of
-hexenyl bromide with n-butylmagnesium chloride were carried
5
out, 1-decene was obtained as the sole coupling product in 91%
yield without the formation of pentylcyclopentane, suggesting that
the 5-hexenyl radical, which may undergo ring-closing, was not
7
formed (entry 3). Cyclopropylmethyl bromide gave only non-
8
ylcyclopropane as a coupling product (entry 4). These results rule
Scheme 1
out a radical mechanism. It should be noted that a bromo
substituent on the aryl ring remained intact in this reaction system
a
Science and Technology Centre for Atoms, Molecules and Ions Control,
Graduate School of Engineering, Osaka University, Yamadaoka 2-1,
Suita, Osaka, 565-0871, Japan. E-mail: terao@chem.eng.osaka-u.ac.jp;
Fax: +81-6-6879-7390; Tel: +81-6-6879-7389
b
Department of Applied Chemistry Graduate School of Engineering,
Osaka University, Yamadaoka 2-1, Suita, Osaka, 565-0871, Japan.
E-mail: kambe@chem.eng.osaka-u.ac.jp; Fax: +81-6-6879-7390;
Tel: +81-6-6879-7388
{
Electronic supplementary information (ESI) available: Typical experi-
mental procedures and analytical data of products. See DOI: 10.1039/
b612586g
Scheme 2
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Chem. Commun., 2007, 825–827 | 825

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Table 1 Pd- or Ni-catalyzed cross-coupling reactions of decyl
bromide with Grignard reagents
n
Dec-R + decane + decenes
a
Entry
R
Cat.
T/uC Yield (%)
1
2
3
Bu PdCl
Bu (PPh
2
0
0
0
0
0
0
0
0
3
2
10
58
9
54
1
26
13
26
1
6
3
33
3
33
4
26
1
23
12
26
1
6
1
18
1
24
2
3
)
2
PdCl
PdCl)
Pd
2
b
Bu (C
Bu (C
3
H
H
5
5
2
4
5
6
3
)
2
Me PdCl
Me (PPh
2
3
)
2
PdCl
PdCl)
Pd
2
9
b
7
Me (C
Me (C
3
H
H
5
5
2
83
90
5
1
7
8
9
3
)
2
Bu NiCl
Bu (PPh
2
230
230
230
230 94
230
230
Scheme 3 A plausible reaction pathway.
10
11
12
13
14
15
16
a
3
)
2
NiCl
NiCl)
Ni
2
b
Bu (C
Bu (C
3
H
H
5
2
3
5
)
2
Me NiCl
Me (PPh
2
1
3
8
4
2
0
14
4
3
3
)
2
NiCl
NiCl)
Ni
2
b
Me (C
Me (C
3
H
H
5
2
230 92
230 98
3
5
)
2
2
b
Determined by GC. 5 mol% of catalyst was used.
3
Table 2 Cross-coupling reactions using bis(g -allyl)nickel complex as
a catalyst
Scheme 4
bis(p-allyl)palladium with EtMgBr, reacted with n-hexyl bromide
at 260 uC for 3 h, giving rise to nearly equal amounts of octane
3
38% GC yield) and bis(g -allyl)palladium (35% NMR yield)
(
(
Scheme 4). This result suggests that anionic complex (39)
a
Yield (%)
entry
Alkyl–X
R–MgX
undergoes substitution reaction with alkyl bromides to give the
3
corresponding coupling products along with generation of bis(g -
n
1
2
3
Oct–OTs
Oct–OTs
Et–MgBr
Ph–MgBr
Bu–MgCl
78
87
91
n
allyl)palladium. It should be noted that possible products,
n
1
-pentene or 1-nonene by the reductive elimination of an allyl
n
4
Oct–MgCl
86 (81)
group of intermediate 4 in Scheme 3 were not formed from GC
and NMR analysis. This fact is in accord with the evidence that
reductive elimination proceeds preferentially with alkyl group than
5
Et–MgBr
76 (71)
11
allyl group. When the reaction was conducted using n-decyl
bromide at 230 uC for 20 h, dodecane was formed in 66% yield
but 2b could not be detected in the resulting mixture.
b
6
n
Dec–Br
Me
3
SiCH
2
–MgCl
70 (65)
a
b
Determined by GC. Isolated yield is in parentheses. Reaction was
In conclusion, Ni and Pd catalysts bearing simple allyl ligands
were found to catalyze cross-coupling reaction of Grignard
reagents with alkyl bromides and tosylates. This reaction proceeds
efficiently by the use of alkyl- or arylmagnesium halides. It was
revealed that two allyl ligands are essential to attain high yields of
the cross-coupling products.
carried out at 220 uC for 20 h.
(entry 5). A sterically hindered Grignard reagent also gave a
moderate yield of the corresponding coupling product (entry 6).
3
A plausible reaction pathway is depicted in Scheme 3. Bis(g -
allyl)metal complex 2 reacts with Grignard reagents to form a
Notes and references
1
3
bis(g ,g -allyl)metal complex 3. This anionic complex would
possess enhanced nucleophilicity at the metal centre toward alkyl
halides. Coupling products were formed by nucleophilic attack of
1 For reviews of transition metal-catalyzed cross-coupling reactions, see:
International Symposium on 30 years of the Cross-coupling Reaction,
J. Organomet. Chem., 2002, 653, 1; Metal-Catalyzed Cross-Coupling
Reactions, ed. A. de Meijere and F. Diederich, Wiley-VCH, New York,
2004; Transition Metals for Organic Synthesis, ed. M. Beller and
C. Bolm, Wiley-VCH, Weinheim, 2004; Handbook of Organopalladium
Chemistry for Organic Synthesis, ed. E. Negishi, Wiley-Interscience, New
York, 2002.
3
to alkyl halides yielding dialkylmetal complexes 4 followed by
reductive elimination.
To confirm the validity of this proposed pathway, we examined
the stoichiometric reaction of alkyl halides with the anionic
1
3
1
3
bis(g ,g -allyl) complex 3. As might be expected, bis(g ,g -
2
For reviews of transition metal-catalyzed cross-coupling reactions using
alkyl halides, see: D. J. C a´ rdenas, Angew. Chem., Int. Ed., 2003, 42, 384;
9,10
allyl)palladate complex (39),
formed by the reaction of
8
26 | Chem. Commun., 2007, 825–827
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M. R. Netherton and G. C. Fu, Adv. Synth. Catal., 2004, 346, 1525;
J. Terao and N. Kambe, J. Synth. Org. Chem. Jpn., 2004, 62,
solution at 0 uC. The product was extracted with diethyl ether (10 mL)
and analyzed by GC (dodecane, 90% GC yield).
1
4
1
192–1203; A. C. Frisch and M. Beller, Angew. Chem., Int. Ed., 2005,
4, 67; M. R. Netherton and G. C. Fu, Top. Organomet. Chem., 2005,
4, 85.
For more recent work, see: C. Fischer and G. C. Fu, J. Am. Chem. Soc.,
005, 127, 4549; N. Hadei, E. A. B. Kantchev, C. J. O’brrien and
7 Suzuki–Miyaura reaction can be applied to alkyl–alkyl coupling of alkyl
iodides with alkylboranes, where alkyl radicals are proposed to be
involved as key intermediates: T. Ishiyama, S. Abe, N. Miyaura and
A. Suzuki, Chem. Lett., 1992, 691.
3
2
8 Typical procedure (entry 4 in Table 2): A mixture of cyclopropylmethyl
bromide (270.0 mg, 2.0 mmol) and a catalytic amount of bis(g -
3
M. C. Organ, J. Org. Chem., 2005, 70, 8503; M. Nakamura, S. Ito,
K. Matsuo and E. Nakamura, Synlett, 2005, 11, 1794; F. O. Arp and
G. C. Fu, J. Am. Chem. Soc., 2005, 127, 10482; R. B. Bedford,
D. W. Bruce, R. M. Frost and M. Hird, Chem. Commun., 2005, 4161;
K. Bica and P. Gaertner, Org. Lett., 2006, 8, 733; H. Ohmiya,
K. Wakabayashi, H. Yorimitu and K. Oshima, Tetrahedron, 2006, 62,
allyl)nickel (28.2 mg, 0.2 mmol) was cooled to 278 uC. Then
nonylmagnesium chloride (1 M in THF, 2.6 mL, 2.6 mmol) was added
slowly to the solution and the mixture was warmed to 230 uC. After
stirring for 3 h, 3 M HCl (aq) (2 mL) was added to the solution. The
product was extracted with diethyl ether (10 mL), dried over MgSO
and evaporated to give a clear crude product (86% GC yield).
Purification by HPLC with CHCl as the eluent afforded 272.7 mg
(81%) of 1-cyclopropylnonane. IR (neat): 3076, 3000, 2957, 2923, 2864,
4
,
2
2
2
207; H. Ohmiya, H. Yorimitu and K. Oshima, J. Am. Chem. Soc.,
006, 128, 1886; F. Gonz a´ lez-Bobes and G. C. Fu, J. Am. Chem. Soc.,
006, 128, 5360; R. B. Bedford, M. Betham, D. W. Bruce, S. A. Davis,
3
2
1 1
R. M. Frost and M. Hird, Chem. Commun., 2006, 1398; H. Takahashi,
S. Inagaki, Y. Nishihara, T. Shibata and K. Takagi, Org. Lett., 2006, 8,
2360, 1464, 1378, 1014, 911, 820, 721 cm
CDCl ): d 20.02–0.01 (m, 2H), 0.34–0.43 (m, 2H), 0.60–0.78 (m, 1H),
0.89 (t, J = 6.8 Hz, 3H), 1.15–1.38 (m, 16H), C NMR (100 MHz,
CDCl ): d 11.1, 14.3, d 4.6, 22.9, 29.5, 29.7, 29.8, 29.9, 32.1, 34.9; MS
(EI) m/z (relative intensity, %) 168 (M , 1.48), 125 (4), 111 (19), 97 (49),
; H NMR (400 MHz,
3
13
3037; H. Oshima, H. Yorimitsu and K. Oshima, Org. Lett., 2006, 8,
3093; W. Affo, H. Oshima, T. Fujioka, Y. Ikeda, T. Mizuta and
K. Miyoshi, J. Am. Chem. Soc., 2006, 128, 8068.
J. Terao, H. Watanabe, A. Ikumi and N. Kambe, J. Am. Chem. Soc.,
2002, 124, 4222; J. Terao, Y. Naitoh, H. Kuniyasu and N. Kambe,
3
u
d
+
+
4
83 (74), 69 (91), 55 (100), 41 (59); HR-MS: calc. for C12
H
24 (M ):
168.1878; found: 168.1879; elemental analysis: calc. for C12
H, 14.37; found: C, 85.32; H, 14.02%.
H24: C, 85.63;
Chem. Lett., 2003, 32, 890; J. Terao, A. Ikumi, H. Kuniyasu and
N. Kambe, J. Am. Chem. Soc., 2003, 125, 5646; J. Terao, H. Todo,
H. Watanabe and N. Kambe, Angew. Chem., Int. Ed., 2004, 43, 6180;
J. Terao and N. Kambe, Bull. Chem. Soc. Jpn., 2006, 79, 663.
B. Henc, P. W. Jolly, R. Salz, G. Wilke, R. Benn, E. G. Hoffmann,
R. Mynott, G. Schroth, K. Seevogel, J. C. Sekutowski and C. Kr u¨ ger,
J. Organomet. Chem., 1980, 191, 425.
Typical procedure (entry 8 in Table 1): A 50 mL Pyrex glass vessel
containing a magnetic stirring bar, decyl bromide (442.4 mg, 2.0 mmol),
a catalytic amount of bis(g -allyl)palladium (37.8 mg, 0.2 mmol), and
9 S. Holle, P. W. Jolly, R. Mynott and R. Z. Salz, Z. Naturforsch., Teil B,
1982, 37, 675; P. W. Jolly, Angew. Chem., Int. Ed. Engl., 1985, 24, 283;
B. Bogdanovi c´ , S. C. Huckett, U. Wilczok and A. Rufi nˇ ska, Angew.
Chem., Int. Ed. Engl., 1988, 27, 1513; D. Alberti, R. Goddard,
A. Rufi nˇ ska and K.-R. P o¨ rschke, Organometallics, 2003, 22, 4025.
5
6
1
10 Formation of 39 was confirmed by NMR at 260 uC ( H NMR
8
(400 MHz, THF-d , 260 uC): d 0.6–0.9 (m, 2H) 1.26 (t, J = 7.7 Hz, 3H),
1.51 (d, J = 14.9 Hz, 1H), 1.55 (d, J = 14.4 Hz, 1H), 1.71 (d, J = 8.8 Hz,
2H), 2.01 (d, J = 6.9 Hz, 1H), 2.15 (d, J = 6.6 Hz, 1H), 3.41 (d, J =
9.3 Hz, 1H), 3.91 (d, J = 16.4 Hz, 1H), 4.3–4.6 (m, 1H), 6.1–6.4 (m, 1H);
3
nonane (internal standard, 128.3 mg, 1.0 mmol) was cooled to 278 uC
under nitrogen. Then MeMgBr (0.9 M in THF, 3.2 mL, 2.9 mmol) was
added slowly to the solution at 278 uC, and the mixture was warmed to
13
C NMR (100 MHz, THF-d , 260 uC): d 8.3, 22.8, 23.4, 45.9, 50.0,
8
91.1, 113.3, 152.7). A similar complex was identified by NMR, see ref. 9.
11 L. Abis, A. Sen and J. Halpern, J. Am. Chem. Soc., 1978, 100, 2916.
0
uC. After stirring for 3 h, 3 M HCl (aq) (2 mL) was added to the
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Chem. Commun., 2007, 825–827 | 827