A mild and efficient iron-catalyzed synthesis of alkenyl halides via direct addition of benzyl halides to arylalkynes

Article abstract of DOI:10.1002/adsc.200800708

An efficient and mild iron-catalyzed synthesis of alkenyl halides has been developed via direct carbon-carbon bond formation by using benzyl halides and arylalkynes.

Full text of DOI:10.1002/adsc.200800708

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DOI: 10.1002/adsc.200800708
A Mild and Efficient Iron-Catalyzed Synthesis of Alkenyl Halides
via Direct Addition of Benzyl Halides to Arylalkynes
Zhongquan Liu,a,* Jianguo Wang,a Yankai Zhao,a and Bo Zhoua
a
Institute of Organic Chemistry, Gannan Normal University, 341000, Ganzhou, Jiangxi, State Key Laboratory of Applied
Organic Chemistry and Department of Chemistry, Lanzhou University, Lanzhou 730000, Peopleꢀs Republic of China
Fax : (+86)-931-862-5657; phone: (+86)-931-891-2280; e-mail: liuzhongquan@yahoo.cn
Received: November 15, 2008; Revised: January 16, 2009; Published online: February 2, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800708.
Abstract: An efficient and mild iron-catalyzed syn-
thesis of alkenyl halides has been developed via
direct carbon-carbon bond formation by using
benzyl halides and arylalkynes.
À
Keywords: alkenyl halides; C C bond formation;
electrophilic addition; homogeneous catalysis; iron
Scheme 1. Iron-catalyzed addition of benzyl halides to aryl
alkynes.
À
The development of direct C C bond formation pro- to arylalkynes by using 5 mol% of FeCl3·6H2O as the
cesses that use sustainable, environmentally benign active catalyst (Scheme 1). To the best of our knowl-
and low-cost catalysts is a critical challenge for organ- edge, this is the first example of an iron-catalyzed for-
ic synthetic chemists. First row transition metals, espe- mation of alkenyl halides via direct addition of benzyl
cially iron, may become the possible alternatives of halides to arylalkynes.
precious metals such as palladium, rhodium, iridium,
For the initial test reaction, we selected 1-phenyl-
and ruthenium. Recently, some efficient iron-cata- ethyl bromide (1a) and phenylacetylene (2a) as stan-
lyzed systems have been explored for carbon-carbon dard substrates to optimize suitable conditions for
couplings.[1] We wish to report herein an efficient and this addition reaction (Table 1). The desired alkenyl
mild iron-catalyzed synthesis of various substituted al- bromide (3a) was obtained in 84% yield using 5
kenyl halides via addition of benzyl halides to arylal- mol% of anhydrous FeCl3 at 508C in CH2Cl2 (Table 1,
kynes.
entry 1). Surprisingly, the isolated yield of the product
À
In the past decades, Lewis acid-promoted C C increased to 97% by using 5 mol% of FeCl3·6H2O as
bond formation reactions by addition of carbenium catalyst (Table 1, entry 2). However, other iron salts
ions to alkenes have been extensively explored.[2] and copper salts were inactive to this reaction
However, compared with alkenes, the use of alkynes (Table 1, entries 3–6). A decrease or increase of the
as electron-rich substrates to be attacked by carbeni- catalyst dosage was less efficient than 5 mol% also
um ions seems limited. In addition, most of these pro- (Table 1, entries 7 and 8). A low yield of 3a was iso-
cedures were catalyzed by anhydrous zinc chloride lated at room temperature (Table 1, entry 9). Further
and bromide.[3] The main drawbacks of these systems investigation of the solvent effect showed that CH2Cl2
are the difficulties in handling the moisture-sensitive is a more effective solvent (Table 1, entries 10–18). A
catalyst as well as the need for anhydrous conditions 61% isolated yield of 3a was obtained catalyzed by 5
and long reaction times.[3] Therefore, the development mol% of FeCl3 in a mixed solvent (CH3OH/CH2Cl2)
of more efficient and mild catalysts to promote the involving the proton source (Table 1, entry 19).
generation of alkenyl halides by direct addition of
It is seen from Table 2 that arylalkynes with elec-
various halides to alkynes remains attractive. We have tron-withdrawing groups such as fluorine gave excel-
successfully accomplished an efficient and mild syn- lent yields of the desired product (Table 2, entry 1)
thesis of alkenyl halides via addition of benzyl halides while arylalkynes bearing electron-donating groups
Adv. Synth. Catal. 2009, 351, 371 – 374
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371

Zhongquan Liu et al.
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Table 1. Optimization of the typical reaction conditions.[a]
Table 2. Addition of different alkynes to 1-phenylethyl bro-
mide 1a.[a]
Entry Alkynes
Main product
Yield [%][b]
(E/Z)
1
2
3
3b
3c
3d
98 (5:1)
93 (5:1)
77 (2:1)
Entry Catalyst [mol%]
Solvent
T
Yield
[8C] [%][b]
1
FeCl3 (5)
FeCl3·6H2O (5)
Fe2ACHTUNGTRENNUNG(SO4)3 (5)
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
50
50
50
50
50
50
50
50
r.t.
50
50
50
50
50
50
50
50
50
84
97
0
0
0
2[c]
3
4
FeCl2 (5)
4
3e
50 (3:1)
5
CuBr2 (5)
6
CuBr (5)
0
7
FeCl3·6H2O (1)
82
76
31
53
35
0
0
0
0
0
8
FeCl3·6H2O (10) CH2Cl2
5
6
3f
81 (1:1)
0
9
FeCl3·6H2O (5)
FeCl3·6H2O (5)
FeCl3·6H2O (5)
FeCl3·6H2O (5)
FeCl3·6H2O (5)
FeCl3·6H2O (5)
FeCl3·6H2O (5)
FeCl3·6H2O (5)
FeCl3·6H2O (5)
FeCl3·6H2O (5)
FeCl3 (5)
CH2Cl2
DCE
CHCl3
CCl4
H2O
CH3OH
THF
benzene
cyclohexane
CH3NO2
10
11
12
13
14
15
16
17
18
19[d]
–
7
8
–
–
0
0
[a]
0
0
61
Reaction
conditions:
1-phenylethyl
bromide
1a
(0.5 mmol), alkyne (0.6 mmol), 5 mol% FeCl3·6H2O,
CH3OH/CH2Cl2 50
CH2Cl2, 508C, 12 h.
[b]
Isolated yield of the E/Z mixture; the E/Z ratios were
determined by 1H NMR.
[a]
Reaction conditions: 1-phenylethyl bromide (0.5 mmol),
phenylacetylene (0.6 mmol), 12 h.
Isolated yield of the E/Z mixture.
E/Z=3:1 (determined by H NMR).
Conditions: 1a (0.5 mmol), 2a (0.6 mmol), CH3OH
[b]
[c]
[d]
1
ides are activated by the Lewis acid to form a carbo-
cation intermediate 1, which attacks the electron-rich
arylalkynes to generate a vinyl cation 2. The sp-hy-
bridized vinyl cation can be attacked by an XFeCl3
(0.6 mmol), CH2Cl2 (2 mL), 12 h.
gave appreciably lower yields (Table 2, entries 2 and ion to give the E/Z mixture of product and the Lewis
3). Alkenyl halides can be also generated smoothly acid which will be reused as catalyst in the next cata-
using 1,2-substituted ethynes such as 1-phenyl-1-pro- lytic cycle.
pyne (Table 2, entry 4) and diphenylethyne (Table 2,
In conclusion, this work demonstrates an efficient
entry 5). Propargyl alcohols, heteroarylalkynes and al- and mild iron-catalyzed synthesis of alkenyl halides
kylalkynes were inactive in this reaction (Table 2, en- via direct addition of benzyl halides to arylalkynes.
tries 6–8).
Compared with the traditional system for preparing
Various benzyl halides were investigated as sub- alkenyl halides by using anhydrous ZnCl2 or ZnBr2
strates for addition to phenylacetylene under the typi- which has long suffered from difficulties in handling
cal conditions (Table 3). Benzyl chlorides gave moder- the catalyst and moisture sensitive conditions, the
ate yields of the corresponding alkenyl chlorides, elec- present method would provide a better alternative
tronic and steric effects were not obvious (Table 3, en- due to its atom efficiency, sustainable catalyst and
tries 1–8). Benzyl bromides also gave moderate yields mild conditions. Extension of this system to other sub-
of the desired products without distinct inductive and strates is underway in our laboratory.
steric effects besides p-nitrobenzyl bromide (Table 3,
entries 9–14). Diphenylmethyl bromides gave excel-
lent yields of the corresponding product (Table 3,
entry 15). However, alkenyl bromide proved to be in-
Experimental Section
1H and 13C NMR spectra were recorded on a Varian Mercu-
ry Plus-400 spectrometer in CDCl3 with TMS as internal
standard. Mass spectra were determined on a Hewlett Pack-
active in this system (Table 3, entry 16).
À
A plausible mechanism for the iron-catalyzed C C
bond formation is depicted in Scheme 2 that is similar
to that of the zinc-catalyzed procedure.[4] Benzyl hal- ard 5988A spectrometer by direct inlet at 70 eV. GC-MS
372
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Adv. Synth. Catal. 2009, 351, 371 – 374

A Mild and Efficient Iron-Catalyzed Synthesis of Alkenyl Halides
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Table 3. Addition of different benzyl halides to phenylacetylene.[a]
Entry Benzyl alcohols Major product
Yield [%][b] Entry Benzyl alcohols Major product
Yield [%][b]
(E/Z)
(E/Z)
1
2
3
4
3g
3h
3i
59 (4:1)
9
3o
3p
3q
3r
61 (10:1)
64 (7:1)
60 (3:1)
60 (5:1)
61 (3:1)
69 (5:1)
61 (3:1)
10
11
12
3j
5
6
7
8
3k
3l
58 (4:1)
66 (3:1)
52 (2:1)
48 (2:1)
13
14
15
16
–
0
3s
3t
52 (4:1)
98 (7:1)
0
3m
3n
–
[a]
[b]
Reaction conditions: benzyl halide (0.5 mmol), phenylacetylene (0.6 mmol), 5 mol% FeCl3·6H2O, CH2Cl2, 508C, 12 h.
Isolated yield of the E/Z mixture; the E/Z ratios were determined by H NMR.
1
Typical Procedure
1-Phenylethyl bromide (0.5 mmol, 92.5 mg) was added to a
mixture of phenylacetylene (0.6 mmol, 61.2 mg) and
FeCl3·6H2O (0.025 mmol, 6.8 mg) in 2 mL of CH2Cl2, then
the system was heated at 508C for 12 h. The solvent was re-
moved under reduced pressure and column chromatographic
separation gave the E/Z mixture of the product 3a; yield:
139.2 mg (97%).
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