Table 1. Effect of Several Reaction Parameters on the
Iron-Catalyzed Arylation of 1 with PhMgBra
Scheme 1. Iron-Catalyzed Arylation of Cyclohexene (1) with
PhMgBr in the Presence of Mesityl Iodide (MesI)
modification to conditions
entry
in Scheme 1
2 (%)b
57
Ph2 (%)b,c
1
2
none
10
no Fe(acac)3
0
trace
10
3
FeCl3 instead of Fe(acac)3
Fe(acac)2 instead of Fe(acac)3
no xantphos
42
4
28
14
5
14
46
6
no MesI
0
trace
36
7
p-Tol-I instead of MesI
c-C6H11I instead of MesI
no THF
39d(þ8)e
8
0
32
9
trace
tracef
trace
44
coordination site as well as to prevent cross-coupling with
PhMgBr.10 As shown in a deuterium labeling experiment
discussed later, both the aryl Grignard reagent and the
mesityl iodide participate in the hydrogen abstraction in an
olefin complex B, probably to generate two π-allylic iron
species11 C and D. Thus, this hydrogen-abstraction process
appears to be insensitive to the steric effects of the mesityl
group. However, the subsequent reductive elimination is
subject to the steric effects of the mesityl group, as judged
by the complete absence of mesitylated cyclohexene via D
as opposed to the competitive formation of a p-tolylated
product when p-tolyl iodide was used (cf. Table 1, entry 7).
The typical conditions that convert cyclohexene (1) to
3-phenylcyclohex-1-ene (2) are described first. A solution
of PhMgBr in THF (1.08 M, 18.5 mL, 20.0 mmol) was
added over 10 min to a solution of Fe(acac)3 (353 mg,
1.00 mmol, 5.0 mol %,), xantphos12 (579 mg, 1.00 mmol,
5.0 mol %), and mesityl iodide (4.92 g, 20.0 mmol, 1 equiv)
in degassed cyclohexene (1, 40.0 mL, 20 equiv), and the
resulting mixture was stirred for 20 min at 0 °C. After
aqueous workup, GC analysis indicated the formation of 2
in 52% yield based on PhMgBr, together with a small
amount of biphenyl (15%) that was formed by iron-cata-
lyzed homocoupling of the organometallic reagent.13 Ana-
lytically pure 2 was obtained in 42% yield after column
chromatography and distillation. When the reaction was
performed on a 0.3 mmol scale, 2 was isolated in 57% yield.
While the reaction in the presence of 20 equiv of cyclohexene
was homogeneous, the use of 3ꢀ5 equiv resulted in black
precipitates and a lower yield. Neither here nor for the other
examples of olefin arylation illustrated in Table 2 did we
observe products from other potentially competing side
reactions, such as mesitylation (from D, vide supra), cross-
coupling between PhMgBr and mesityl iodide,10 addition of
10
Et2O instead of THF
a Reaction conditions: A solution of PhMgBr in THF (1.0 M, 0.3 mmol)
was slowly added over 5 min to a mixture of cyclohexene (6 mmol), MesI
(0.3 mmol), Fe(acac)3 (0.015 mmol), and xantphos (0.015 mmol), and the
reaction mixture was stirred for 30 min at 0 °C. b Yield based on PhMgBr,
determined by GC in the presence of undecane as an internal standard.
d
c Yield based on the consumption of PhMgBr. 4-Methyl-1,10-biphenyl
and 1-cyclohexyl-4-methylbenzene were also obtained. e The amount of
1-(cyclohex-2-enyl)-4-methylbenzene in parentheses. f 1,10-Bis(cyclohex-2-
ene) was mainly obtained.
a phenyl or mesityl group across the double bond, and
arylation of THF,9,14 and polyarylated products.
The effect of the key reaction parameters on the reaction
of cyclohexene is summarized in Table 1 and detailed in the
Supporting Information (SI). In the absence of the iron
catalyst (entry 2), the reaction did not proceed at all. Both
Fe(III) (entry 3) and Fe(II) (entry 4) salts gave similar
results. The absence of the ligand (entry 5) resulted in a
lower yield and the formation of black precipitates, sug-
gesting that the phosphine ligand stabilized the catalytic
system. To obtain the bestyield of 57% (entry 6), 1 equiv of
mesityl iodide was essential. While a fraction of the mesityl
iodide (30ꢀ40%) was recovered at the end of the reaction,
the use of 0.5 equiv resulted in a decrease in the yield by 5 to
10%. The use of tolyl iodide instead of mesityl iodide
resulted in a comparable combined yield of 47% (entry 7)
including partial tolylation of cyclohexene, aswell ascross-
coupling between PhMgBr and tolyl iodide. The use of an
aliphatic halide gave neither the desired product nor any
cyclohexene derivatives (entry 8). Removal of THF as
much as possible at the beginning of the reaction sup-
pressed both the formation of 2 and the homocoupling
(entry 9). The use of diethyl ether instead of THF resulted
in the formation of a cyclohexene dimer (1,10-bis(cyclohex-
2-ene)) instead of the arylated product 2 (entry 10).
(10) (a) Hatakeyama, T.; Nakamura, M. J. Am. Chem. Soc. 2007,
129, 9844. (b) Hatakeyama, T.; Hashimoto, S.; Ishizuka, K.; Nakamura,
M. J. Am. Chem. Soc. 2009, 131, 11949.
The reaction of 1 equiv of an aryl Grignard reagent with
10ꢀ20 equiv of an alkene in the presence of 5 mol % of
Fe(acac)3 took place in a synthetically acceptable yield
with a TON of 5ꢀ10 for cycloalkenes, allylbenzenes and
trans-β-methylstyrene (Table 2). In no case did we observe
any diarylated products. The Grignard reagent was con-
sumed partly for hydrogen abstraction (eq 2) and for
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€
Angew. Chem., Int. Ed. 2009, 48, 7251. (b) Furstner, A.; Martin, R.;
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Leeuwen, P. W. N. M.; Goubitz, K.; Fraanje, J. Organometallics 1995,
14, 3081.
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Org. Lett. 2005, 7, 1943–1946. (b) Nagano, T.; Hayashi, T. Org. Lett.
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