Iron-Catalyzed π-Activated C-O Ether Bond Cleavage with C-C and C-H Bond Formation

Article abstract of DOI:10.1002/ejoc.201301372

A novel and efficient allylic alkylation reaction between π-activated ethers and allylsilane was realized under mild conditions through iron(III)-catalyzed C sp 3-O ether bond cleavage. The present protocol provides an attractive approach for the construction of sp³-sp³ C-C bonds and can be potentially applied for the selective reduction of benzyl and allyl ethers to their corresponding hydrocarbon compounds by using triethylsilane as a hydride-transfer reagent.

Full text of DOI:10.1002/ejoc.201301372

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201301372
Iron-Catalyzed π-Activated C–O Ether Bond Cleavage with C–C and C–H
Bond Formation
Xiaohui Fan,*[a,b] Xiao-Meng Cui,[a] Yong-Hong Guan,[a] Lin-An Fu,[a] Hao Lv,[a]
Kun Guo,[a] and Hong-Bo Zhu[a]
Keywords: Synthetic methods / Allylation / C–O activation / C–C coupling / Hydrogen transfer / Iron
A novel and efficient allylic alkylation reaction between π-
activated ethers and allylsilane was realized under mild con-
ditions through iron(III)-catalyzed Csp3–O ether bond cleav-
age. The present protocol provides an attractive approach for
the construction of sp3–sp3 C–C bonds and can be potentially
applied for the selective reduction of benzyl and allyl ethers
to their corresponding hydrocarbon compounds by using tri-
ethylsilane as a hydride-transfer reagent.
particular interest, as it not only provides efficient access to
Introduction
C
sp3–Csp3 bonds but it also introduces a C=C bond at the
same time for further synthetic transformations. Strikingly,
only 9-BBN-derived allylborane (BBN 9-borabicy-
Carbon–carbon bond formation by using oxygen-based
electrophiles as coupling partners is an attractive strategy
in terms of both the accessibility of the starting materials
and environmental concerns.[1] Ethers are readily available
and green compounds that have garnered much attention
over the past decade as novel electrophiles in transition-
metal-catalyzed cross-coupling reactions, such as using aryl
and vinyl ethers instead of halides in Suzuki and Kumada
couplings.[2] In contrast to the considerable efforts devoted
to exploring Csp2–O type ethers (e.g., phenol- and enol-de-
rived ethers) as coupling partners to construct Csp3–Csp2
bonds, very few reaction systems have been developed for
the catalytic activation of Csp3–O ether bonds for the con-
struction of Csp3–Csp3 bonds,[3] because of the high bond
dissociation energy of these bonds and the poor leaving
ability of the OR group in alkyl ethers.[1,4] The direct and
selective activation of the Csp3–O bond in unactivated ethers
still remains particularly challenging to chemists. Recently,
several Ni-complex-catalyzed coupling reactions between
=
clo[3.3.1]nonane; Scheme 1) can be used as a nucleophile in
this main-group-metal-catalyzed alkyl–allyl cross-coupling
reaction; cheaper and conventional allylsilane reagents were
shown to be thoroughly incompetent in this transforma-
tion.[8–10] Very recently, we reported a novel procedure for
the construction of carbon–nitrogen bonds through an
iron-catalyzed ether Csp3–O cleavage protocol.[11] In contin-
uation of our study on the application of ethers as electro-
philes in organic synthesis, we are eager to extend this strat-
egy to the assembly of carbon–carbon bonds. A careful lit-
erature survey revealed that no precedent for the use of the
ecologically benign Lewis acid FeCl3 in combination with
readily available ethers and an allylsilane for the construc-
tion of Csp3–Csp3 bonds has been reported; herein, we wish
to report our preliminary results on this reaction.
benzylic ethers and Grignard reagents to construct Csp3
–
Csp3 bonds have been developed by Shi,[5] Jarvo,[6] and
others. Nevertheless, the application of soft nucleophiles as
coupling partners to such transformations is rare. In 2011,
the Kobayashi group uncovered an efficient method for the
construction of Csp3–Csp3 bonds by coupling benzyl and
allyl ethers with allyl boron reagents under the catalysis of
InOTf (Tf = trifluoromethylsulfonyl).[7] This protocol is of
Scheme 1. Methods for the allylation of benzyl ethers.
[a] School of Chemical and Biological Engineering, Lanzhou
Jiaotong University,
Results and Discussion
Lanzhou 730070, China
E-mail: fanxh@mail.lzjtu.cn
www.lzjtu.edu.cn
Our work started by testing the allylic alkylation of ether
1a with allyltrimethylsilane (2a, 1.5 equiv.) in 1,2-dichloro-
ethane in the presence of FeCl3 (10 mol-%) in air. The reac-
tion proceeded smoothly at room temperature; the substrate
[b] Beijing National Laboratory for Molecular Sciences (BNLMS),
Beijing, 100190, China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301372.
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Iron-Catalyzed π-Activated C–O Ether Bond Cleavage
was completely consumed within 2.5 h to give desired allyl- summarized in Table 2. A wide range of secondary benzylic
ation product 3a in 69% yield (Table 1, entry 1). Encour- and allylic ethers including those bearing aromatic chloro
aged by this result, a range of solvents were explored or methoxy groups, C=C bonds, cyclopropyl, and acetal
(Table 1, entries 1–10). Among the solvents used, the reac- groups were compatible with the optimal reaction condi-
tion performed in CH2Cl2 was significantly better than tions, and all of these substrates furnished the correspond-
those performed in other solvents, which led to the isolation ing products in good to excellent yields within a short
of allylated product 3a in almost quantitative yield (Table 1, period of time at room temperature (Table 2, entries 1–16).
entry 10). Unfortunately, lowering the amount of 2a from Primary benzylic ether 1q was unable to undergo this con-
1.5 to 1.3 equiv. (relative to 1a) or the amount of FeCl3 version even under harsh reaction conditions (Table 2, en-
from 10 to 5 mol-% was clearly unfavorable for the reaction, try 17), presumably because of its higher bond dissociation
as the yields of desired product 3a decreased considerably energy. In contrast, effective transformation was observed
to 83 and 75%, respectively (Table 1, entries 11 and 12). in the reaction of primary allylic methyl ether 1r with 2a to
The reaction showed strong catalyst dependence; no con- give corresponding product 3r in 62% yield (Table 2, en-
version was observed in the absence of FeCl3 (Table 1, en- try 18). Upon subjecting tertiary benzylic ethers 1s, 1t, and
try 13). Ether 1a could not undergo this transformation un- 1u to this reaction, the results were rather different. Tri-
der the catalysis of other Lewis acids such as FeCl2, Fe- phenylmethyl methyl ether (1s) smoothly underwent this
(acac)3, Fe(acac)2, BF3·OEt2, CuI, Cu(acac)2, Cu(OAc)2, allylation reaction with a prolonged reaction time to pro-
and ZnCl2 (Table 1, entries 15–22; acac = acetylacetonate), vide desired product 3s in 98% yield (Table 2, entry 19).
whereas only 46% yield of the product was formed in the However, 1t and 1u were hampered by a competing elimi-
case of FeCl3·6H2O (Table 1, entry 14). Furthermore, nation reaction, which resulted in the isolation of elimi-
among the examined Brønsted acids (e.g., TfOH and HCl), nation products 3t and 3u exclusively without the observa-
only triflic acid exhibited catalytic activity in this transfor- tion of the desired allylated products (Table 2, entries 20
mation, and a moderate yield of 3a was obtained (Table 1, and 21). These results reveal that the steric properties of the
entry 23), which reveals that FeCl3 acts as the true catalyst benzylic ethers have a clear influence on the outcome of the
for the allylation of ether 1a.
reaction. More sterically hindered tertiary benzylic methyl
ethers that have hydrogen atoms in the β position tend to
undergo rapid β-hydride elimination to give olefins rather
than substituted products. With respect to electronic effects,
the reaction was facilitated by electron-rich benzylic methyl
ethers bearing an electron-donating group on the phenyl
ring. Ethers containing electron-withdrawing groups under-
went a slower allylation reaction to give the corresponding
products in relatively lower yields (Table 2, entries 6 and 9;
8 and 10). Acid-sensitive groups such as the acetal and cy-
clopropyl groups tolerated the reaction conditions. Further-
more, the reaction was not sensitive to water and air, which
clearly confirms the advantage of this reaction system. In
addition, upon submitting (E)-1-methoxy-1-phenylbut-2-
ene (1p) to this allylation reaction, thermodynamically fa-
vored C–C double-bond isomeric product 3pЈ together with
un-rearranged product 3p were obtained in 70% yield as a
2.4:1 mixture of unseparated regioisomers (Table 2, en-
try 16; see Supporting Information for details); this suggests
that the reaction most likely proceeds through a carbo-
cation pathway. This hypothesis is consistent with our pre-
vious mechanistic studies.[11] Notably, non-π-activated
ethers, such as 2-phenylethyl methyl ether, were found to
be unsuitable substrates for this transformation even under
harsh reaction conditions.[12]
Table 1. Optimization of the reaction conditions.[a]
Subsequently, triethylsilane (2b) was tested as a nucleo-
phile for this transformation under typical reaction condi-
tions for the reduction of the selected ethers to hydro-
carbons (Table 3). To our delight, hydride transfer from
Et3SiH to benzylic and allylic C–O ether bonds was success-
ful under the mild conditions, and the reaction even took
[a] Reaction conditions: 1a (0.35 mmol), solvent (4 mL), r.t., in air.
[b] Yield of isolated product. [c] 40 °C.
With the optimized reaction conditions in hand, the place in the presence of other groups such as an aromatic
scope of this FeCl3-catalyzed allylic alkylation reaction was methoxy group, a C=C bond, and a cyclopropyl group.
further expanded to a variety of ethers, and the results are Given that methyl ethers could serve as useful protecting
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X. Fan et al.
SHORT COMMUNICATION
Table 2. Allylation of ethers with allyltrimethylsilane.[a]
groups for alcohols in organic synthesis,[13] this catalytic
system can be potentially used as an efficient method for
the reduction of benzylic and allylic alcohols and ethers to
their corresponding hydrocarbon compounds.
Table 3. Catalytic reduction of ethers with triethylsilane.[a]
[a] Reaction conditions: benzylic ether (0.35 mmol), 2b
(0.53 mmol), CH2Cl2 (4 mL), FeCl3 (10 mol-%), r.t., in air. [b] Yield
of isolated product.
Finally, with the aim of investigating the reactivity of
ethers and aldehydes,[8] the reaction of equimolar amounts
of 3-methoxy-1,3-diphenylprop-1-ene (1o) and cinnam-
aldehyde (1x) with allyltrimethylsilane (2a) was studied
(Scheme 2). Under the optimized reaction conditions, only
ether 1o underwent this transformation to afford desired
allylation product 3o in 93% yield, whereas aldehyde 1x
was completely recovered. This demonstrates that ethers are
more suitable electrophiles in this catalytic system.
Scheme 2. Selective allylation of ether against aldehyde.
Conclusions
In summary, we have demonstrated a convenient and
economical method for the cross-coupling of benzyl/allyl
ethers with allylsilane through iron-catalyzed Csp3–O ether
bond cleavage under mild conditions. The present protocol
provides an attractive approach to construct sp3–sp3 C–C
bonds together with the introduction of a C=C bond in
high efficiency, and it can be used for the selective reduction
of benzylic and allylic ethers to their corresponding hydro-
carbon compounds by employing triethylsilane as
a
hydride-transfer reagent. Further exploration of ethers as
electrophiles in organic synthesis through Lewis acid cata-
lyzed C–O bond activation is in progress in our laboratory.
[a] Reaction conditions: benzylic ether (0.35 mmol), 2a
(0.53 mmol), CH2Cl2 (4 mL), FeCl3 (10 mol-%), r.t., in air. [b] Yield
of isolated product. [c] Mixture of C–C double-bond regioisomers,
2.4:1 (see Supporting Information).
Experimental Section
General Information: Reactions were monitored by analytical thin-
layer chromatography (TLC) by using ultraviolet light, phos-
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Iron-Catalyzed π-Activated C–O Ether Bond Cleavage
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by analytical TLC. 1H NMR and 13C NMR spectra were recorded
at 400 and 100 MHz, respectively, by using CDCl3 as the solvent
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mass spectra (HRMS) were performed with an ICP-MS or ITCI-
Orbitrap Elite spectrometer. Melting points were measured with a
micromelting apparatus.
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Typical Procedure for Iron-Catalyzed Allylation: Allyltrimethylsil-
ane (2a) (60.6 mg, 0.53 mmol, 1.5 equiv.), ether 1a–u (0.35 mmol,
1.0 equiv.), and FeCl3 (5.7 mg, 0.035 mmol, 10 mol-%) were added
successively under ambient temperature to CH2Cl2 (4 mL) in air.
After stirring at room temperature for the appropriate time (moni-
tored by TLC), the reaction was quenched by the addition of H2O
(3 mL) and then the mixture was extracted with ethyl acetate (3ϫ
3 mL). The combined organic layer was washed with brine, dried
with Na2SO4, and concentrated. The crude product was purified
by column chromatography on silica gel (petroleum ether or petro-
leum ether/ethyl acetate) to afford corresponding product 3a–u.
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lytical data for all compounds.
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[12] Besides 2-phenylethyl methyl ether, other unactivated ethers
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tested in this transformation. However, these substrates re-
mained intact under high temperatures and prolonged reaction
times.
Acknowledgments
The authors thank the National Natural Science Foundation of
China (NSFC) (grant number 21162013) and Beijing National Lab-
oratory for Molecular Sciences (BNLMS) for financial support and
Prof. Zhi-Xiang Yu and Dr. Yong Liang for helpful discussions.
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Received: September 10, 2013
Published Online: December 6, 2013
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