Regioselective C-H alkylation of anisoles with olefins catalyzed by cationic half-sandwich rare earth alkyl complexes

Article abstract of DOI:10.1002/anie.201206233

A half sandwich helping: Cationic rare-earth alkyl species generated from half-sandwich rare-earth dialkyl complexes and [Ph₃C][B(C ₆F₅)₄] can serve as unique catalysts for the C-H regioselective alkylation of anisoles with alkenes. The reaction affords either ortho-monoalkylated derivatives or products substituted at the benzylic position, depending on the substrate chosen. Copyright

Full text of DOI:10.1002/anie.201206233

.
Angewandte
Communications
DOI: 10.1002/anie.201206233
À
C H Alkylation
À
Regioselective C H Alkylation of Anisoles with Olefins Catalyzed by
Cationic Half-Sandwich Rare Earth Alkyl Complexes**
Juzo Oyamada and Zhaomin Hou*
Anisole derivatives are important aromatic compounds, their
structural motifs are observed in many useful materials, such
as pharmaceuticals, natural products, and fluorescent dyes.[1]
The development of efficient, selective processes for the
synthesis of anisole derivatives is therefore of much interest
and importance. Among the most straightforward and atom-
À
economical routes to anisole derivatives is the C H alkylation
Figure 1. Half-sandwich rare-earth mono- and dialkyl complexes.
À
of anisoles with alkenes. However, such C H bond alkylation
approaches for the synthesis of anisole derivatives have met
with limited success to date. The Friedel–Crafts reaction of
À
anisoles with alkenes is a well-known route to alkylated
anisole derivatives, but such Lewis acid catalyzed alkylation
reactions generally suffer from poor regioselectivity and often
give a mixture of ortho- and para-regioisomers with the para-
regioisomer as the main product, owing to steric and
electronic influences.[2–4] Recently, the late-transition-metal-
direct the C H activation to selectively take place at the
ortho-position.[9] At first, we chose complex 1 as a catalyst to
examine the reaction of anisole with styrene and ethylene, but
no alkylation product was observed (See Table 1, entry 1). To
Table 1: ortho-Alkylation of anisole with styrene catalyzed by rare-earth
À
catalyzed ortho-C H alkylations of various aromatic com-
complexes.[a]
pounds possessing a directing group have been reported.[5–7]
However, these late-transition-metal catalysts seemed unsuit-
À
able for the ortho-selective C H alkylation of anisoles,
because the interaction between an ether group and the
À
metal center is too weak to regioselectively direct the C H
bond activation. To the best of our knowledge, the catalytic
Entry
[M]
Yield of 5aa [%][b]
Yield of 6aa [%][b]
À
1[c]
2
3
4
5
1
0
60
58
94 (91)
91
0
15
12
2
1
0
ortho-selective C H alkylation of anisoles with an alkene has
not been previously reported.
2-Sc
2-Sc[d]
2-Y
2-Gd
2-Sm
2-Lu
In view of the strong oxophilicity of rare-earth metal
ions[8,9] and the high activity of rare-earth alkyl species toward
[10–12]
À
unsaturated C C bonds,
earth alkyl complexes might serve as unique catalysts for the
we envisioned that the rare-
6
7
1
17
0
À
ortho-selective C H alkylation of anisoles with alkenes.
[a] Reaction conditions: [M] (0.025 mmol), [Ph3C][B(C6F5)4]
(0.025 mmol), 3a (1 mmol), 4a (1.5 mmol), toluene (3 mL), 708C, 24 h,
unless otherwise noted. [b] Yield (based on 3a) measured by GC
analysis. Yield of isolated product is given in parentheses. [c] With or
without [Ph3C][B(C6F5)4]. [d] 4a (1 mmol).
À
Herein, we report the rare-earth catalyzed C H bond
addition of anisoles to various olefins, which constitutes the
first example of catalytic ortho-selective alkylation of an
anisole compound with an alkene.
We have recently found that the silylene-linked half-
sandwich rare-earth alkyl complexes such as 1 (Figure 1)
À
=
could serve as unique catalysts for the ortho-selective C H
facilitate the insertion of a C C double bond into a possible
silylation of anisoles with hydrosilanes, because the coordi-
nation of the methoxy group to the rare-earth metal ion can
metal–anisyl active species,[9] we then turned to the cationic
rare-earth alkyl complexes, which have shown high activity
for olefin polymerization.[10,11] To our delight, the cationic
half-sandwich scandium alkyl species, generated by the
reaction of the half-sandwich scandium dialkyl complex
2-Sc[11f] with an equivalent of [Ph3C][B(C6F5)4],[13] showed
[*] Dr. J. Oyamada, Prof. Dr. Z. Hou
Organometallic Chemistry Laboratory and Advanced Catalyst
Research Team, RIKEN Advanced Science Institute
2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)
E-mail: houz@riken.jp
À
high catalytic activity and selectivity for the ortho-C H
alkylation of anisole with styrene, which afforded the 1:1
addition product 5aa as a major product (60%) and a small
amount (15%) of the 1:2 addition product 6aa formed by
insertion of two molecules of styrene into an ortho-C H bond
of anisole (entry 2). When the yttrium (2-Y) or gadolinium (2-
Gd) analogue was used instead of 2-Sc, the yield of the mono-
[**] This work was partly supported by a Grant-in-Aid for Young
Scientists (B; No. 24750046, to J.O.) and a Grant-in-Aid for
Scientific Research (S; No. 21225004, to Z.H.) from JSPS.
À
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201206233.
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Chemie
Table 2: ortho-Alkylation of various substituted anisoles with styrenes.[a]
insertion) of styrene.[11a] In all of these reactions, the
À
alkylation took place at only one of the two ortho-C H
positions of anisole; meta, para, and di-ortho-alkylation were
all not observed. The lutetium and samarium complexes 2-Lu
and 2-Sm were less effective under the same conditions
(entries 6 and 7). Neither the neutral rare-earth dialkyl
complexes nor [Ph3C][B(C6F5)4] alone afforded the alkylation
product, which shows that a cationic rare-earth alkyl species is
essential in the present reaction.
Entry Substrate
4 (R2)
Product
Yield [%][b]
92
1
4b (tBu)
Complex 2-Y was then utilized to examine the reactions of
various substituted anisoles and styrenes. Some representa-
tive results are summarized in Table 2. As with styrene, 4-tert-
butylstyrene (4b) and 4-methylstyrene (4c) also reacted
3a
5ab
5ac
2
3
3a
4c (Me)
4d (F)
93
51
À
selectively with the ortho-C H bond of anisole to give in high
yields the linear alkylation products 5ab and 5ac, respec-
tively, in the presence of 2.5 mol% of 2-Y/[Ph3C][B(C6F5)4]
(Table 2, entries 1 and 2). 4-Fluorostyrene (4d) seemed less
reactive and needed a higher catalyst loading (5%) and
a higher feed (3 equiv to anisole) to give a higher yield of the
alkylation product 5ad (entries 3 and 4). The reaction of
styrene with various substituted anisole derivatives also took
place exclusively at the ortho position of the methoxy group.
3a
3a
5ad
5ad
4
5
4d (F)
4a (H)
79[c]
90
3b
3c
3d
3e
3 f
5ba
5ca
5da
5ea
5 fa
5ga
5ha
6[d]
4a (H)
4a (H)
4a (H)
4a (H)
4a (H)
4a (H)
88
À
À
À
The aromatic C I, C Cl and C F bonds survived the catalytic
reaction conditions to selectively give the corresponding
halogen-containing alkylated products (entries 6–8). Allyl
and propenyl groups are also compatible with this catalyst
(entries 9 and 10). In the case of 1,4-dimethoxybenzene (3h),
the reaction took place at one of the two ortho positions of
each MeO group to selectively give the para-dialkylated
product 5ha (entry 11). In the case of 2-methoxynaphthalene
7
87
8
77 (86)[e]
À
(3i), which has two different ortho-C H bonds, the alkylation
9
84
À
at the 3-C H bond predominated over that at the more active
Table 3: ortho-Alkylation of anisole with various olefins.[a]
10
11
86
3g
3h
93[f]
Entry
2-M
Olefin (equiv)
Product
Yield [%][b]
12
4a (H)
3i
5ia
5ia’
92 (6:1)[g]
1
2
3
2-Sc
2-Y
82
(21)
80
4e (2)
4e (2)
5ae
5ae
13
4a (H)
90
3j
5ja
2-Sc
[a] Reaction conditions: 2-Y (0.025 mmol), [Ph3C][B(C6F5)4] (0.025 mmol),
3 (1 mmol), 4 (1.5 mmol), toluene (3 mL), 708C, 24 h, unless otherwise
noted. [b] Yield of isolated product (based on 3). [c] 3a (0.5 mmol), 4d
(1.5 mmol). Yield determined by GC analysis. [d] 2-Y (0.04 mmol), [Ph3C]
[B(C6F5)4] (0.04 mmol) and 4a (2 mmol) were used. [e] Yield determined by
1H NMR spectroscopy is given in parentheses. [f] 3h (0.5 mmol) was used.
[g] The product ratio (5ia/5ia’) determined by 1H NMR spectroscopy is
given in parentheses.
4 f (4)
5af
4
5
2-Sc
2-Sc
64
95
4g (1.4)
5ag
4h (2)
5ah
[a] Reaction conditions: 2-M (0.025 mmol), [Ph3C][B(C6F5)4]
(0.025 mmol), 3a (1 mmol), 4 (1.4–4 mmol), toluene (3 mL), 708C, 24 h.
[b] Yield of isolated product (based on 3a). Yield measured by GC
analysis is given in parentheses.
insertion product 5aa was increased to 91–94% under the
same conditions (entries 4 and 5), probably because 2-Y and
2-Gd are less effective for the polymerization (or continuous
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Table 4: Alkylation of ortho-methylanisoles.[a]
À
(acidic) 1-C H bond, to give two regioisomers (5ia and 5ia’)
in a 6:1 molar ratio (entry 12). This is probably due to the
steric influence of the hydrogen atom at the 8 position. The
steric factor became further dominant in the reaction of 3-
methylanisole (3j), which led to the alkylation taking place
À
only at the less sterically demanding 6-C H bond to give 5ja
Entry
1[c,d]
3
4
Product (yield [%])[b]
exclusively (entry 13). In the case of 2-methylanisole, only
a trace amount of the alkylation product was observed,
whereas 1,2-dimethoxybenzene did not react with styrene
under the same conditions.
4e
3k
3k
3k
7ke (30)
2[d]
3
4e 7ke (50)
4e 7ke (69)
In the reaction of anisole with 1-octene (4e), complex 2-Sc
showed a higher activity than 2-Y to selectively give the
branched alkylation product 5ae (Table 3, entries 1 and 2).
Allyltrimethylsilane (4 f) could also serve as an alkylation
agent for anisole to give the corresponding alkylation product
5af in a similar fashion (entry 3). In the case of vinyltrime-
thylsilane (4g), the linear alkylation product 5ag was
exclusively obtained (entry 4). The reaction of norbornene
(4h) with anisole gave the norbornyl-substituted product 5ah
in almost quantitative yield (entry 5). The reaction of
ethylene (1 atm) with anisole gave an oligomer product,
probably because of the tendency (relatively high activity) of
ethylene towards polymerization (successive insertion).
Although 2-methylanisole (3k) did not react with styrene,
its reaction with 1-octene (4e) proceeded under similar
conditions. However, the alkylation took place selectively at
4
3k
4 f
7kf (57)
5[e]
3k
4h
7kh (83)
6
7
4e
3l
7le (77)
8le (5)
4e
3
2
À
À
the sp benzylic C H bond rather than at the aromatic sp C
3m
7me (77)
8me (5)
H bond.[8b,14] Complex 2-Y seemed more effective than 2-Sc
À
for this benzylic C H alkylation reaction (Table 4, entries 1–
3). The reactions of 2-methylanisole (3k) with allyltrimethyl-
silane (4 f) and norbornene (4h) also exclusively gave the
8
4e
3n
3n
5ne (17)
À
benzylic C H alkylation products when 2-Y/[Ph3C][B(C6F5)4]
was used as the catalyst (entries 4 and 5). In the reactions of
2,6-dimethylanisole (3l) and 2,4,6-trimethylanisole (3m) with
1-octene, the alkylation took place predominantly at one of
the two ortho-methyl groups to give the monoalkylated
products 7le and 7me, respectively, as the major products
(77%). A small amount (5%) of dialkylated products (8le
and 8me) resulting from alkylation at both ortho-methyl
groups was also obtained in these cases (entries 6 and 7). No
alkylation at the para-methyl group was observed in the case
of 2,4,6-trimethylanisole, which suggests that the interaction
between the methoxy group and the catalyst metal center is
essential in the present alkylation reactions. For 2,5-dime-
thoxytoluene (3n) with 1-octene, the alkylation took place
only at the 5 position of the phenyl ring to give 5ne, albeit
9[f]
4e
5ne (77)
5ne’ (9)
[a] Reaction conditions: 2-Y (0.025 mmol), [Ph3C][B(C6F5)4]
(0.025 mmol), 3 (1 mmol), 4 (4 mmol), toluene (3 mL), 708C, 24 h.
[b] Yield of isolated product (based on 3). [c] 2-Sc was used instead of 2-Y.
[d] 4e (2 mmol). [e] 4h (1.1 mmol). [f] 4e (2 mmol). 2-Sc was used
instead of 2-Y.
À
than at the benzylic C H) to give 5oh in almost quantitative
yield (Scheme 1). Similarly, the reaction of 1,4-benzodioxane
(3p) with norbornene selectively gave the 2,5-dialkyalted
product 5ph, whereas no reaction between 1,2-dimethoxy-
benzene and norbornene was observed under the same
conditions.
A possible mechanism for the present catalytic alkylation
of anisoles is shown in Scheme 2. The coordination of the
oxygen atom of anisole compound 3 to the metal center of the
cationic alkyl species A, which is generated from the neutral
dialkyl precursor 2-M and [Ph3C][B(C6F5)4], would give B. In
the case of an anisole compound without substituents at the
with a low conversion (17%; entry 8), which suggests that, if
sterically allowed, the C H activation at an ortho-sp C H
bond is preferred to that at an sp C H bond. When 2-Sc was
used instead of 2-Y in this reaction, a much higher conversion
2
À
À
3
À
2
À
was obtained to give the sp C H alkylation product 5ne in
77% yield with a small amount of the benzylic sp3 C H
À
alkylation product 5ne’ (9%; entry 9). 2-Ethylanisole did not
react with 1-octene at either the benzylic or the ortho-sp C
H position under same conditions.
In contrast to the benzylic C H alkylation of 2-methyl-
anisole (Table 4, entry 5), the reaction of the less sterically
2
À
À
ortho positions (R’ = H), the ortho-C H bond could be
activated to give the anisyl species E.[9,15,16] The 2,1-insertion
of a 1-alkene into the metal–anisyl bond in E to afford F
would be sterically favored, which, upon deprotonation of
another molecule of anisole 3, should yield the branched
alkylation product 5 and regenerate E. In the case of styrene,
À
demanding 2,3-dihydrobenzofuran (3o) with norbornene
selectively took place at the ortho sp2 C H bond (rather
À
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the case of 2-methyl-substituted anisole derivatives, the
3
À
alkylation occurs exclusively at the benzylic sp C H bond.
Functional groups such as halogens, allyl groups, and pro-
penyl groups are compatible with this catalyst system. Studies
À
on the further application of this catalytic C H activation/
insertion process are in progress.[17]
Received: August 3, 2012
Published online: November 7, 2012
Scheme 1. Alkylation of cyclic aromatic ethers 3o and 3p with norbor-
nene (4h).
Keywords: alkenes · alkylation · anisoles · C-H activation ·
rare-earth complexes
.
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À
Scheme 2. A possible mechanism for the catalytic C H alkylation of
anisoles with olefins.
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1,2-insertion would be preferred, because a stable benzallylic
species such as G could possibly be formed, which, after
deprotonation with 3, should give the linear alkylation
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of the silyl group, thus affording the linear product (Table 3,
entry 4).
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À
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À
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In summary, we have demonstrated that the cationic rare-
earth alkyl species generated from half-sandwich rare-earth
dialkyl complexes (such as 2-M) and [Ph3C][B(C6F5)4] can
À
serve as a unique catalyst for the C H alkylation of anisoles
with alkenes. The reaction of anisole derivatives without
a substituent at the ortho position with various olefins takes
2
À
place regioselectively at the ortho-sp C H bond to afford the
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[13] [PhNMe2H][B(C6F5)4] was also effective as an activator.
3
À
[14] For the benzylic sp C H functionalization of 2-methylanisoles,
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[15] An intramolecular kinetic isotope effect was not observed (kH/
kD = 1.0) in the reaction of 4-methyl[2-D]anisole with styrene,
À
which suggests that C H bond cleavage is not involved in the
rate-determining step (see the Supporting Information).
[16] The formation of a Sc–anisyl species in the reaction of 2-Sc/
[C6H5NMe2H][B(C6F5)4] with anisole was confirmed by
1H NMR analysis. See the Supporting Information for details.
[17] N,N-Dimethylaniline could also react with 1-octene and norbor-
nene under similar conditions to give the corresponding ortho-
alkylation products in 81% and 86% yields, respectively.
Further studies are in progress and will be reported in due
course.
[12] a) C. G. J. Tazelaar, S. Bambirra, D. van Leusen, A. Meetsma, B.
Hessen, J. H. Teuben, Organometallics 2004, 23, 936; b) F.
Lauterwasser, P. G. Hayes, S. Brꢀse, W. E. Piers, L. L. Schafer,
12832 www.angewandte.org
ꢀ 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2012, 51, 12828 –12832