Sodium sulfinate-mediated trans-stilbene formation from benzylic halides

Article abstract of DOI:10.1002/adsc.201200167

A convenient and efficient method for the synthesis of various symmetrical and non-symmetrical trans-stilbene derivatives from benzylic halides in the absence of any transition metals is described. Sodium sulfinates played an important role in this transformation. Various functional groups were well tolerated under the optimized reaction conditions. Copyright

Full text of DOI:10.1002/adsc.201200167

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DOI: 10.1002/adsc.201200167
Sodium Sulfinate-Mediated trans-Stilbene Formation from
Benzylic Halides
Feng Zhao,a Jiaying Luo,a Qi Tan,a Yunfeng Liao,a Shengming Peng,a,*
and Guo-Jun Denga,*
a
Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education, College of Chemistry,
Xiangtan University, Xiangtan 411105, Peopleꢀs Republic of China
Fax : (+86)-731-5829-2251; e-mail: shengmingpeng@xtu.edu.cn or gjdeng@xtu.edu.cn
Received: February 28, 2012; Published online: && &&, 0000
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200167.
Abstract: A convenient and efficient method for
the synthesis of various symmetrical and non-sym-
metrical trans-stilbene derivatives from benzylic
halides in the absence of any transition metals is de-
scribed. Sodium sulfinates played an important role
in this transformation. Various functional groups
were well tolerated under the optimized reaction
conditions.
Keywords: benzylic halides; elimination; sodium
sulfinates; stilbenes
Stilbene derivatives are widely used in the manufac-
ture of industrial dyes, dye lasers, optical brighteners,
phosphors, scintillators and other materials.[1] Many
synthetic routes to stilbene derivatives have been re-
ported,[2] such as aldol-type condensation,[3] Wittig–
Horner reaction,[4] Heck reaction,[5] McMurry reac-
tion and Perkin reaction.[6] Among them, the Wittig–
Horner reaction has proved to be very selective and
versatile in the preparation of different substituted
Scheme 1. Different routes for C=C bond formation.
stilbenes from benzylic halides and carbonyl com-
pounds.[7] In this reaction, the benzylic halide was
firstly converted into a phosphorus ylide or other re-
lated sulfur[8] or silicon ylide[9] to generate a carbanion. anhydrous reaction conditions severely limited appli-
The subsequent addition and elimination of the carb- cations of this method in stilbene synthesis. The de-
anion with the carbonyl compound afforded the final velopment of stilbene formation from two (or even
alkene product (Scheme 1, 1).[10] The direct use of two different) benzylic halides under mild reaction condi-
benzylic halides for stilbene formation would afford tions would be highly desirable. It is well known that
a convenient and straightforward route via intermo- benzylic halides are readily converted into the corre-
lecular elimination. However, this kind of transforma- sponding benzylic sulfones with sodium sulfinates.[12]
tion is rarely used for the synthesis of stilbenes. The The treatment of benzylic sulfones with strong base
research groups of Kharasch and Hauser observed the or transition metal catalyst generates symmetrical stil-
direct formation of symmetric stilbenes when they benes. However, the reaction required anhydrous re-
treated benzylic halides with sodium amide or lithium action conditions and is not suitable for non-symmet-
amide in liquid ammonia.[11] However, the absolute rical stilbene analogues (Scheme 1, 2).[13]
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Table 1. Optimization of the reaction conditions.[a]
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Recently, we and others developed various palladi-
um-catalyzed desulfitative reactions with alkenes, ni-
triles and azoles using sodium sulfinates as aryl sour-
ces.[14] During our studies on desulfitative cross-cou-
pling of sodium sulfinates with benzylic halides, we
observed that stilbenes were formed in certain yields.
We speculated that the reaction of benzylic halide
with sodium sulfinate generated a benzylic sulfone in-
termediate which subsequently reacted with another
equivalent of benzylic halide to give the final product.
This method could afford an alternative route for
non-symmetrical stilbene directly from two benzylic
halides. This result prompted us to systematically in-
vestigate the reaction conditions. Herein, we report
a sodium sulfinate-mediated trans-stilbene formation
directly from two benzylic halides in the absence of
any transition metal catalyst (Scheme 1, 3).
To begin our study, the commercially available and
inexpensive benzylic chloride (1a) was used as
a model substrate. Since the screening of transition
metal catalysts did not improve the reaction yield sig-
nificantly, we focused our investigation on transition
metal-free conditions and the results are summarized
in Table 1. When K2CO3 and NaOH were used, no
desired product was observed as determined by GC
and 1H NMR methods (Table 1, entries 1 and 2).
Then various bases were tested in the presence of
sodium p-toluenesulfinate (entries 3–10). Weak bases
KHCO3 and KF were ineffective (entries 3 and 4).
The desired product was obtained in low yields when
K2CO3 and Cs2CO3 were employed (entries 5 and 6).
Strong bases NaOH and KOH improved the reaction
significantly, and the desired trans-stilbene was ob-
tained in 82% and 90% yields, respectively (entries 8
and 9). It was found that the base and sodium sulfi-
nate were both necessary for this transformation. No
product formed in the absence of KOH (entry 10).[15]
Other sodium sulfinates were also effective. Sodium
benzenesulfinate and sodium 4-chlorobenzenesulfi-
nate were efficient additives and gave the desired
product in 78% and 77% yield, respectively (en-
tries 11 and 12). Sodium methanesulfinate and sodium
benzenesulfonate proved to be ineffective (entries 13
and 14). The solvent also played an important role for
this kind of reaction. The use of other solvents de-
[a]
Conditions: 1a (0.4 mmol), additive (0.2 mmol), base
(0.6 mmol), solvent (0.5 mL), 1008C, 16 h under air
unless otherwise noted.
GC yield.
5 mmol water was added.
[b]
[c]
[d]
0.1 mmol additive was used.
creased the reaction yields significantly (entries 15– stituent at the para position significantly decreased
18). To our delight, a good yield was obtained when the reaction yield to 30%, and a large amount of
the reaction was carried out in an aqueous media starting material was left under the given reaction
(entry 19). Decreasing the amount of sodium p-tolu- conditions (entry 3). Halogen substituents such as
A
fluoride, chloride and bromide were all well tolerated
With the optimized reaction conditions in hand, we and gave the desired products in good yields (en-
then explored the scope and generality of this trans- tries 4–6). A nitro substituent at the para position of
formation. Various benzylic chlorides bearing elec- benzyl chloride also significantly decreased the reac-
tron-withdrawing and electron-donating substituents tion yield (entry 7). The position of the substituents
were investigated (Table 2). 4-Methylbenzyl chloride did not affect the reaction yields and ortho- or meta-
1b underwent smooth elimination to give the desired substituted benzyl chlorides all gave the desired prod-
product 3b in 72% yield (entry 2). A methoxy sub- uct in good yields (entries 8–11). Notably, more steric
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Sodium Sulfinate-Mediated trans-Stilbene Formation from Benzylic Halides
Table 2. Symmetrical stilbene formation from benzylic hali-
Table 3. Non-symmetrical stilbene formation from benzyl
des.[a]
halides.[a]
[a]
Conditions: substrate
(0.2 mmol), 4-CH3-C6H4SO2Na
I
(0.2 mmol), substrate II
(0.2 mmol), KOH
(0.6 mmol), DMSO (0.5 mL), 808C, 24 h under air.
Isolated yield.
1c (0.4 mmol), 4-CH3-C6H4SO2Na (0.4 mmol), KOH
[b]
[c]
(0.8 mmol).
challenging task than that of the symmetrical ones
since three potential products can be formed. The re-
action of 4-methoxybenzyl chloride (1c) with 4-fluoro-
benzyl bromide (2c) was chosen as a model since me-
thoxy is an electron-donating group and fluoro is an
electron-withdrawing group (Table 3, entry 1). The re-
action did not afford the desired non-symmetrical
product in satisfactory yield under the optimized reac-
tion conditions, partially due to the low reactivity of
[a]
Conditions:
1
or
2
(0.4 mmol), 4-CH3-C6H4SO2Na
(0.2 mmol), KOH (0.6 mmol), DMSO (0.5 mL), 1008C,
16 h under air.
Isolated yield.
GC yield.
[b]
[c]
substrates such as 1-(chloromethyl)naphthalene (1l) 1c. However, this could be solved by increasing the
successfully afforded the product in 80% yield amount of 1c to 2 equiv along with the use of more
(entry 12). Under the optimized conditions, various base and additive. The reaction of 1c with various
benzyl bromides were also tested for this reaction. In benzylic halides (bromides or chlorides) resulted the
general, the reactions of benzyl bromides gave better desired non-symmetrical trans-stilbenes in moderate
yields than those of benzyl chlorides (entries 13–16). to good yields (entries 1–6). Other benzylic chlorides
It should be noted that these reactions all selectively such as 1a and 1b could also react smoothly with an
formed the trans-stilbene derivatives and only trace equal amount of 2c and 1a, and afforded the desired
amounts of cis-stilbene derivatives were observed as product in 76%, 69% and 75% yields, respectively
1
determined by GC and H NMR methods.[16]
(entries 7–9). In general, these reactions showed very
The formation of non-symmetrical stilbene deriva- good selectivity and less than 10% homo-coupling by-
tives from two different benzylic halides is a more products were observed in most cases.
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Scheme 2. Control experiments.
Scheme 3. Proposed mechanism.
Several control experiments were set up to further Various symmetrical and non-symmetrical stilbene de-
understand the reaction mechanism. The reaction of rivatives were selectively obtained from benzylic hal-
an equal amount of benzyl chloride with sodium p- ides in good yields. The sodium sulfinate played an
toluenesufinate resulted in a yield of 73% [Scheme 2, important role in this transformation. Functional
Eq. (1)]. The reaction of benzyl p-tolyl sulfone with groups such as methyl, methoxy, fluoro, chloro,
benzyl chloride afforded the desired product in 76% bromo and trifluoromethyl were well tolerated under
yield [Eq. (2)]. The reaction yield significantly de- the optimized reaction conditions. Further investiga-
creased when benzyl p-tolyl sulfone was used solely tion including the scope, mechanism, and application
[Eq. (3)]. Based on these observations, a tentative re- of carbon-carbon double bond formation from benzyl-
action mechanism is illustrated in Scheme 3. Taking ic halides are in progress in our laboratory.
the elimination of benzyl chloride 1a as an example:
first, the reaction of 1a with sodium p-toluenesufinate
generates a benzyl p-tolyl sulfone intermediate A,
which is subsequently deprotoned by KOH to yield
Experimental Section
a carbanion intermediate B. The intermolecular sub-
stitution of B with 1a generates an intermediate C.
Again, the deprotonation of C generates D which can
afford E by H-migration. A reductive elimination of
E affords the final desired product 3a.
Typical Procedure
An oven-dried pressure tube (10 mL) was charged with
benzyl chloride (1a, 50.4 mg, 0.4 mmol), KOH (33.6 mg,
0.6 mmol), sodium p-toluenesulfinate (35.8 mg, 0.2 mmol),
and DMSO (0.5 mL). The reaction vessel was closed under
air and the resulting solution was stirred at 1008C for 16 h.
After cooling to room temperature, the volatiles were re-
In summary, we have demonstrated a novel sodium
sulfinate-mediated intermolecular elimination of ben-
zylic halides under transition metal-free conditions. moved under vacuum and the residue was purified by
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Sodium Sulfinate-Mediated trans-Stilbene Formation from Benzylic Halides
column chromatography (silica gel, petroleum ether) to give
3a (CAS: 103-30-0) as a white solid; yield: 82%.
For non-symmetrical stilbene formation, all starting mate-
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Acknowledgements
This work was supported by the National Natural Science
Foundation of China (21172185), the Hunan Provincial Nat-
ural Science Foundation of China (11JJ1003), the New Cen-
tury Excellent Talents in University from Ministry of Educa-
tion of China (NCET-11-0974), and the Scientific Research
Foundation for Returned Scholars, Ministry of Education of
China (2011-1568).
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6 Sodium Sulfinate-Mediated trans-Stilbene Formation from
Benzylic Halides
Adv. Synth. Catal. 2012, 354, 1 – 6
Feng Zhao, Jiaying Luo, Qi Tan, Yunfeng Liao,
Shengming Peng,* Guo-Jun Deng*
6
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