Iron-catalyzed stereospecific olefin synthesis by direct coupling of alcohols and alkenes with alcohols

Article abstract of DOI:10.1021/ol200372y

Chemical equations presented. An efficient Fe(III)-catalyzed direct coupling of alkenes with alcohols and cross-coupling of alcohols with alcohols to give the corresponding substituted (E)-alkenes stereospecifically is demonstrated. Additionally, this reaction could be scaled up. The kinetic isotope effect (KIE) experiments indicated a typical secondary isotope effect in this process. Although benzylic alcohols were effective substrates, mild conditions, atom efficiency, environmental soundness, and stereospecificity are features that make this procedure very attractive.

Full text of DOI:10.1021/ol200372y

ORGANIC
LETTERS
2011
Vol. 13, No. 9
2208–2211
Iron-Catalyzed Stereospecific Olefin
Synthesis by Direct Coupling of Alcohols
and Alkenes with Alcohols
Zhong-Quan Liu,*,† Yuexia Zhang,† Lixing Zhao,‡ Zejiang Li,† Jiantao Wang,†
Huajie Li,† and Long-Min Wu†
State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou
Gansu 730000, P. R. China, and Gannan Normal University, Ganzhou, Jiangxi 341000,
P. R. China
liuzhq@lzu.edu.cn
Received February 18, 2011
ABSTRACT
An efficient Fe(III)-catalyzed direct coupling of alkenes with alcohols and cross-coupling of alcohols with alcohols to give the corresponding
substituted (E)-alkenes stereospecifically is demonstrated. Additionally, this reaction could be scaled up. The kinetic isotope effect (KIE)
experiments indicated a typical secondary isotope effect in this process. Although benzylic alcohols were effective substrates, mild conditions,
atom efficiency, environmental soundness, and stereospecificity are features that make this procedure very attractive.
CarbonÀcarbon bond formation by direct coupling of
alcohols with other partners might be very attractive since
it would be atom-efficient and environmentally benign
since water is the major byproduct.1 However, very few
successful systems to generate a CÀC bond by using
alcohols as alternatives to halides as coupling partners
have been achieved due to the poor leaving ability of the
hydroxyl group.2 Recently, some coupling reactions of
alcohols with allyl, aryl, and alkynyl partners have been
developed by us,3 Kabalka,4 Baba,5 and others. Of parti-
cular interest are the coupling of alcohols with alkenyl
reagents to prepare substituted olefins. Kabalka et al.4c
reported a coupling of alcohols with vinylboron dihalides
using a stoichiometric amount of nBuLi. In(III)- and Bi-
(III)-catalyzed couplings of alcohols with alkenylsilanes
have been explored by Baba et al.5e These two systems
prompted us to develop a direct coupling of alcohols with
olefins. Although an acid-catalyzed reaction of 9-fluorenol
with 9-alkylidene fluorenes has been reported 65 years ago,
this system suffered from seriously limited substrate
scopes.6 Recently, an efficient Pd(II)-catalyzed coupling
(2) For selected examples, see: (a) Dau-Schmidt, J. P.; Mayr, H. Chem.
Ber. 1994, 127, 205. (b) Rubin, M.; Gevorgyan, V. Org. Lett. 2001, 3, 2705.
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A.; Beller, M. Angew. Chem., Int. Ed. 2005, 44, 238. (i) Zhan, Z.; Yu, J.; Liu,
H.; Cui, Y.; Yang, R.; Yang, W.; Li, J. J. Org. Chem. 2006, 71, 8298. (j)
Tarlani, A.;Riahi, A.;Abedini, M.;Amini, M. M.;Muzart, J.J. Mol. Catal.
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A.; Beller, M. Adv. Synth. Catal. 2007, 349, 865. (l) Jana, U.; Biswas, S.;
Maiti, S. Eur. J. Org. Chem. 2008, 34, 5798. (m) Jiang, Y.-J.; Tu, Y.-Q.;
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Zhang, E. Chem.;Eur. J. 2008, 14, 10201. (o) Liu, Y.; Liu, L.; Wang, Y.;
Han, Y.; Wang, D.; Chen, Y. Green Chem. 2008, 10, 635. (p)Pridmore, S. J.;
Williams, J. M. J. Tetrahedron Lett. 2008, 49, 7413. (q) Zhang, S.-Y.; Tu,
Y.-Q.; Fan, C.-A.; Zhang, F.-M.; Shi, L. Angew. Chem., Int. Ed. 2009, 48,
8761. (r) He, J.; Kim, J. W.; Yamaguchi, K.; Mizuno, N. Angew. Chem., Int.
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Int. Ed. 2009, 48, 3982. (t) Diez, P. S.; Micalizio, G. C. J. Am. Chem. Soc.
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† Lanzhou University.
‡ Gannan Normal University.
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Chem. Res. 2002, 35, 695.
r
10.1021/ol200372y
Published on Web 03/31/2011
2011 American Chemical Society

of alcohols with olefins was developed by Yamamoto
et al.7 However, substituted alkenes as the desired products
were obtained in moderate yields by using a relatively high
(CF3CO)2O loading (3 equiv) and long reaction time
(Scheme 1). We wish to report herein the first example of
iron-catalyzedstereospecificsubstituted olefin synthesisby
direct coupling of alcohols with alkenes and alcohols.8
Inspired by the recent work of Jiao9 and Sanz,10 the
coupling reaction was designed to be catalyzed by Lewis
acids such as FeCl3, Fe(OTf)3, AlCl3, ZnCl2, etc. and
mediated by Brønsted acids such as TsOH, TfOH,
H2SO4, etc. It was found that the acids, catalysts, and
solvent critically affect the reaction efficiency. The desired
product was obtained in 66% isolated yield under the
typical conditions: 2.0 equiv of styrene, 1.0 equiv of
benzhydrol, 10 mol % FeCl3 6H2O, 1.0 equiv of TsOH,
3
CH2Cl2, 45 °C, 5 h (See Supporting Information). It is
worth noting that (E)-prop-2-ene-1,1,3-triyltribenzene was
obtained as the major product and the (Z)-isomer was not
observed in this system.
Scheme 1. Direct Coupling of Alcohols with Some Partners To
Give Substituted Olefins
To examine the scope of this system, the coupling
reactions of various olefins with different types of benzylic
alcohols were studied (Table 1). Styrene and its derivatives
gave the desired products in moderate to quantitative
yields. Neither aliphatic alkenes nor aliphatic alcohols
were reactive in this reaction. The 1H NMR spectra of all
products except for 1n (entry 14) indicated that only the E
isomers formed. Coupling of styrene with various benzylic
alcohols produced the corresponding substituted alkenes
in moderate to good yields (entries 1À6). Both p-methyl-
styrene and p-chlorostyrene gave good yields of the (E)-
aryl-substituted propenes (entries 7À10). Interestingly,
a different major product was obtained by a mix of
different ratios of R-methylstyrene and benzhydrol
(entries 11 and 12). The 1m was formed by coupling
of benzhydrol with 1,1-diphenylethylene in 92% iso-
lated yield (entry 13). Although it took place slowly, a
more steric olefin such as 1-phenyl-1-cyclohexene gave
the desired product in excellent yield (entry 14). 3-Benz-
hydryl-1, 2-dihydronaphthalene (1o) was isolated in
69% yield by the coupling of 1,2-dihydronaphthalene
with benzhydrol (entry 15).
It is well-known that alkenes could be formed by
dehydroxylation of the corresponding secondary and
tertiary alcohols promoted by a Brønsted acid and/or a
Lewis acid. Encouraged by these results, we began to
design a series of cross couplings of benzylic alcohols.
Fortunately, we successfully accomplished an efficient
cross coupling of two types of benzylic alcohols to
prepare various substituted alkenes with water as the
only byproduct (Table 2).
To the best of our knowledge, this is the first example of
the formation of olefins via cross coupling of two different
benzylic alcohols. As indicated in Table 2, various benzylic
alcohols (entries 1À5, 7À9) gave the desired products in
moderate to good yields except for 1-(2-naphthyl)ethanol
(entry 6). As expected, (3-(p-tolyl)but-1-ene-1,1-diyl)-
dibenzene was produced as the major product by coupling
of 1-(p-tolyl)ethanol with 1,1-diphenylethanol (entry 10).
Homocoupling of the benzylic alcohols also gave the
corresponding 1,3-diarylbut-1-ene derivatives in moderate
to high yields (entries 11À17). Since diarylcarbenium ions
are more stable than methylarylcarbenium ions, a selective
Initially, we chose styrene and benzhydrol as model
substrates to optimize suitable conditions for this reaction.
(3) (a) Liu, Z.-Q.; Sun, L.; Wang, J.-G.; Han, J.; Zhao, Y.-K.; Zhou,
B. Org. Lett. 2009, 11, 1437. (b) Liu, Z.-Q.; Wang, J.-G.; Han, J.; Zhao,
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Org. Lett., Vol. 13, No. 9, 2011
2209

Table 1. Direct Coupling of Alcohols with Olefinsa
Table 2. Cross-Coupling/Homocoupling of Benzylic Alcoholsa
a Reaction conditions: alcohol 1 (1.0 mmol), alcohol 2 (0.5 mmol),
FeCl3 6H2O (0.05 mmol), TsOH (0.5 mmol), CH2Cl2 (15 mL), 45 °C,
3
unless otherwise noted. b Isolated yields. c Reaction time, indicated by TLC.
alcohols were not effective, water as a side product and
exclusive E alkenes formation features make this system
very interesting.
Under the typical conditions, this coupling reaction
could be scaled up (Scheme 2). A mixture of (4-
chlorophenyl)(phenyl)methanol (1.015 g, 4.6 mmol), styr-
a Reaction conditions: benzylic alcohol (0.5 mmol), olefin (1.0 mmol),
FeCl3 6H2O (0.05 mmol), TsOH (0.5 mmol), CH2Cl2 (15 mL), 45 °C,
3
unless otherwise noted. b Reaction time, indicated by TLC. c Isolated yields.
d Reaction conditions: benzylic alcohol (1.0 mmol), olefin (0.5 mmol),
FeCl3 6H2O (0.05 mmol), TsOH (0.5 mmol), CH2Cl2 (15 mL), 45 °C.
3
ene (0.965 g, 9.2 mmol), FeCl3 6H2O (125 mg, 0.46mmol),
3
dehydration occurred in the cross-coupling reactions. The
stereoselectivity of the reaction of alcohol with alcohol is
the same as that of the reaction of alcohol with olefin, only
the E isomers were obtained as revealed by the NMR
spectra of all the products in Table 2. Although aliphatic
and TsOH (885 mg, 4.6 mmol) was dissolved in 30 mL of
CH2Cl2. The reaction was complete after stirring for 20 h
at 45 °C. The solvent was recovered, and the mixture was
purified by flash column chromatography (petroleum
ether) to afford the desired product in 61% yield.
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Org. Lett., Vol. 13, No. 9, 2011

Scheme 2. Coupling of Benzylic Alcohol with Olefin Could Be
Scaled up
Scheme 4. Proposed Mechanism for the Coupling of Alcohol
with Olefin
Scheme 3. Competing KIE Experiment
In conclusion, we developed a novel iron-catalyzed
stereospecific substituted olefin synthesis via direct cou-
pling of benzylic alcohols with alkenes. Additionally, the
C(sp3)ÀC(sp2) bond formation could also be achieved by
cross coupling of two different benzylic alcohols under the
reaction conditions. Furthermore, this reaction could be
scaled up. Although only benzylic alcohols were effective
substrates, mild conditions, atom efficiency, environmen-
tal soundness, and stereospecificity are features make this
procedure very attractive. Further investigation of this
system is underway in our laboratory.
To gain mechanistic insight, a competing kinetic isotope
effect (KIE) experiment was carried out (Scheme 3). As a
result, a typical secondary KIE was observed since the kH/
kD = 1.19 (see Supporting Information). It suggests that a
carbocation intermediate should be involved in this reac-
tion and the CÀH bond cleavage is not the rate-determin-
ing step.11 With these results in hand, a plausible
mechanism for this catalytic coupling reaction is depicted
in Scheme 4. A carbocation intermediate 2 would be
generated from the benzylic alcohol mediated by
Acknowledgment. This project is supported by Na-
tional Science Foundation of China (No. 21002045). We
also thank the State Key Laboratory of Applied Organic
Chemistry and Lanzhou University for financial support.
FeCl3 6H2O and TsOH.2l,9 Electrophilic addition of olefin
3
to 2 would form a new cationic intermediate 3; this would be
the rate-determine step which has been systematically studied
by Mayr et al.12 Then it would be followed by fast deproto-
nation to give the corresponding substituted alkenes 4.3
Supporting Information Available. Full experimental
details and characterization data for all products. This
material is available free of charge via the Internet at
http://pubs.acs.org.
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Org. Lett., Vol. 13, No. 9, 2011
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