984
Table 1. Optimization of the cross-coupling reaction catalyzed
Table 2. The reaction of various arylmagnesium bromides with
cyclohexyl bromide catalyzed by 1a
by 1a
1
1 (1.0 mol%)
PhMgBr
Br
Ph Ph Ph
+
+
ArMgBr
Cy Br
Cy Ar
+
Et2O, rt, 5 min
3a
4a
5a
6a
Yield/%b
3
4a
5
Catalyst PhMgBr Addition Time Temp
/mol % /equiv rate/min /min /°C
Entry
1
ArMgBr 3
Product 5
Yield/%
77
Entry Solvent
5a 6a
Cy
MgBr
1
2
3
4
5
6
7
8
9
Et2O
CPME
THF
DME
Et2O
Et2O
Et2O
Et2O
Et2O
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.5
2.0
3.0
5.0
1.0
1.0
1.0
1.0
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.2
1.0
1.5
2.0
1.2
fast
fast
fast
fast
10
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
5
4
4
4
4
4
4
rt
88 11
81 12
34
5
57
Cy
2
3
MgBr
MgBr
20 26
81 20
65 26
88 11
91
Cy
OMe
MeO
20
fast
fast
fast
fast
fast
fast
fast
fast
fast
fast
33b
Cy
4
MgBr
OMe
35 84 12
rt
rt
rt
rt
rt
rt
rt
rt
83 16
88 15
81 14
79 18
78 18
84 14
85 11
87 11
MeO
Cy
10 Et2O
11 Et2O
12 Et2O
13 Et2O
14 Et2O
15 Et2O
16 Et2O
5
6
89
85
F
MgBr
F
MgBr
Cy
7
95
MgBr
Cy
aThe reaction was carried out on a 1.8 mmol scale of 4a.
bCompounds 5a and 6a were isolated as a mixture. The ratio of
5a/6a was determined by 1H NMR. Yield of 5a was based on
4a. Yield of 6a was based on 3a.
aThe reaction was carried out with 3 (2.2 mmol) and 4a
(1.8 mmol) in the presence of the catalyst 1 (0.018 mmol).
Arylmagnesium bromide 3 was added at once (fast addition).
b
Cy: cyclohexyl. Reaction time was 1 h.
bonding to the iron center is that the bond to the aminoketonato
nitrogen N(1) (2.0345(15) ¡) is substantially shorter than that of
the amino nitrogen N(2) (2.2566(16) ¡).
To demonstrate the efficiency of the cross-coupling reaction
catalyzed by complex 1, we investigated the scope of the
reaction of various arylmagnesium bromides with bromocyclo-
hexane under optimized reaction conditions. The results are
summarized in Table 2. para-Substituted arylmagnesium bro-
mides, such as 4-methyl-, 4-methoxy-, and 4-fluorophenylmag-
nesium bromides, afforded the desired products 5 in good yields
(Entries 1, 3, and 5). However, the decrease of the product yield
was observed in the reactions of ortho-substituted arylmagne-
sium bromides (Entries 2 and 4). In the case of 2-methoxy-
phenylmagnesium bromide, the desired product was obtained
in 33% even after 1 h (Entry 4). By the reaction of 1- and
2-naphthylmagnesium bromide with bromocyclohexane, 1- and
2-cyclohexylnaphthalene were obtained in 85% and 95%,
respectively (Entries 6 and 7).
Then, we examined the reaction of phenylmagnesium
bromide with various alkyl halides (Table 3). In the case of
iodocyclohexane, the desired product 5a was obtained in a good
yield (Entry 1). The chlorinated substrate resulted in the
decrease of the product yield (43%) under the same reaction
conditions, whereas elongation of the reaction time (3 h) led
to the increase of the yield up to 77% (Entry 2). Acyclic
bromoalkanes were also used in the cross-coupling reaction with
phenylmagnesium bromide. In the case of 1-bromooctane as a
primary alkyl halide, 1-phenyloctane was obtained in 77% yield
(Entry 3). 2-Bromobutane, a secondary alkyl halide, afforded the
product in 48% yield. The yield was not improved by elongation
of the reaction time (Entry 4). In the case of 2-bromo-
2-methylpropane, a tertiary alkyl halide, the desired product,
was not obtained (Entry 5).
As the desired iron complex 1 was obtained and charac-
terized, we evaluated the iron complex 1 in the cross-coupling
reaction and optimized the reaction conditions using the reaction
of phenylmagnesium bromide (3a) with bromocyclohexane (4a)
(Table 1). To begin with, the reaction was conducted in some
ethereal solvents (Entries 1-4). Diethyl ether (Et2O) gave the
best result, and phenylcyclohexane (5a) was obtained in a good
yield (88%) along with the formation of biphenyl (6a) in 11%
yield. CPME (cyclopentyl methyl ether) was also a suitable
solvent, whereas the yield of the desired product decreased in
THF or DME (1,2-dimethoxyethane) probably due to the strong
coordination ability of THF and DME to iron and/or magne-
sium. In iron-catalyzed cross-coupling reactions, Nakamura and
co-workers reported that the slow addition of Grignard reagent
to the reaction mixture is effective for the formation of the
desired compound.3a We investigated the influence of addition
rate of 3a on the formation of 5a. The yield of 5a decreased and
increase of the formation of 6a was observed by decreasing the
rate of addition (Entries 5 and 6). Therefore, the fast addition
resulted in the effective formation of the desired product 5a in
our system (Entry 1). The reaction was also examined at several
temperatures. The yield of 5a decreased slightly when the
reaction was conducted at 35 °C (Entries 1, 7, and 8). Regarding
amounts of the catalyst 1 and the Grignard reagent 3a,
employments of 1.0 mol % of the catalyst and 1.2 equivalent
of the magnesium reagent lead to a good result (Entries 7 and
9-15). Furthermore, the reaction was found to be complete
within 5 min (Entry 16).13
Chem. Lett. 2011, 40, 983-985
© 2011 The Chemical Society of Japan