First catalytic and green synthesis of aryl-(Z)-vinyl chlorides and its plausible addition-elimination mechanism

Article abstract of DOI:10.1021/ol062991c

(Chemical Equation Presented) Via a catalytic cycle in the presence of scandium triflate (2 mol %)/DMF (1 mol %)/benzoyl chloride (5 mol %), aromatic ketones were treated with bis(trichloromethyl) carbonate (BTC) to afford aryl-(Z)-vinyl chlorides. All metal triflates tested in the reaction showed highly catalytic activity. A plausible addition-elimination mechanism was proposed. The present work describes the first catalytic and green route to the synthesis of aryl-(Z)-vinyl chlorides.

Full text of DOI:10.1021/ol062991c

ORGANIC
LETTERS
2007
Vol. 9, No. 6
993-996
First Catalytic and Green Synthesis of
Aryl-(Z)-vinyl Chlorides and Its Plausible
Addition−Elimination Mechanism
Weike Su* and Can Jin
College of Pharmaceutical Sciences, Zhejiang UniVersity of Technology,
Zhejiang Key Laboratory of Pharmaceutical Engineering, Hangzhou 310014, PRC
suweike@zjut.edu.cn
Received December 11, 2006
ABSTRACT
Via a catalytic cycle in the presence of scandium triflate (2 mol %)/DMF (1 mol %)/benzoyl chloride (5 mol %), aromatic ketones were treated
with bis(trichloromethyl) carbonate (BTC) to afford aryl-(Z)-vinyl chlorides. All metal triflates tested in the reaction showed highly catalytic
activity. A plausible addition−elimination mechanism was proposed. The present work describes the first catalytic and green route to the
synthesis of aryl-(Z)-vinyl chlorides.
Vinyl chlorides are important intermediates in organic
synthesis for C-C and C-N formation in Pd-catalyzed
coupling reactions.1 They have been prepared in various
ways, among which the conversion of aromatic ketones to
vinyl chlorides has been well studied. However, toxic
phosphorus reagents such as PCl5,2 PCl3,3 and the Vilsmeier
reagent4 were involved in most cases where unpredictable
byproduct formation was frequently observed.
Recently, Rolando et al. developed a new method for the
direct synthesis of vinyl chlorides in strongly acidic solvents
such as trifluoroacetic acid or methanesulfonic acid.5 Besides
producing a large amount of acid waste, the method required
a lengthy reaction time (36 h) and the substrates were limited
only to aryl ketones with a methyl-substituted or a nonsub-
stituted phenyl ring and 2-nonanone. Modification of the
procedure exploited silica gel supported zinc halides to
perform this transformation, but stoichiometric amounts of
the catalyst and a large excess of acyl chloride have to be
involved.6 Obviously, the above methods are environmentally
unfriendly due to the large waste and pollution.
With the increase of environmental consciousness in
chemical research and industry, much attention has been paid
to green chemistry. The challenge for a sustainable environ-
ment calls for clean procedures that can avoid using toxic
organic reagents, large amounts of sensitive catalyst, and
unnecessary waste. In the course of our research aimed at
developing green organic processes, we have explored ionic
liquids7 as green solvents, metal triflate8 as a reusable new
type of Lewis acid catalyst, and BTC9 as a safe reagent,10
* To whom correspondence should be addressed. Fax: (+86)571-
88320752.
(1) (a) Corsico, E. F.; Rossi, R. A. J. Org. Chem. 2004, 69, 6427. (b)
Reddy, C. R. V.; Urgaonkar, S.; Verkade, J. G. Org. Lett. 2005, 7, 4427.
(2) (a) Kagan, J.; Arora, S. K.; Bryzgis, M.; Dhawan, S. N.; Reid, K.;
Singh, S. P.; Tow, L. J. Org. Chem. 1983, 48, 703. (b) Hirsl-Starcevic, S.;
Majerski, Z. J. Org. Chem. 1982, 47, 2520.
(3) Eszenyi, T.; Timar, T.; Sebok, P. Tetrahedron Lett. 1991, 32, 827.
(4) (a) Al-awar, R. S.; Joseph, S. P.; Comins, D. L. J. Org. Chem. 1993,
58, 7732. (b) Lilienkampf, A.; Johansson, M. P.; Wahala, K. Org. Lett.
2003, 5, 3387.
(6) Kodomari, M.; Nagaoka, T.; Furusawa, Y. Tetrahedron Lett. 2001,
42, 3105.
(7) Chen, J.; Wu, H.; Jin, C.; Zhang, X.; Xie, Y.; Su, W. Green Chem.
2006, 8, 330.
(8) (a) Chen, J.; Wu, H.; Zheng, Z.; Jin, C.; Zhang, X.; Su, W.
Tetrahedron Lett. 2006, 47, 5383. (b) Su, W.; Jin, C. J. Chem. Res. (S)
2003, 694. (c) Su, W.; Jin, C. J. Chem. Res. (S) 2005, 88. (d) Su, W.;
Hong, Z.; Shan, W.; Zhang, X. Eur. J. Org. Chem. 2006, 2, 723. (e) Su,
W.; Li, J.; Zheng, Z.; Shen, Y. Tetrahedron Lett. 2005, 46, 6037.
(9) Our review: Su, W.; Zhong, W.; Bian, G.; Shi, X.; Zhang, J. Org.
Prep. Proced. Int. 2004, 36, 499.
(5) Moughamir, K.; Mezgueldi, B.; Atmani, A.; Mestdagh, H.; Rolando,
C. Tetrahedron Lett. 1999, 40, 59.
10.1021/ol062991c CCC: $37.00
© 2007 American Chemical Society
Published on Web 02/23/2007

respectively. Herein, we wish to report an efficient and
catalytic method for the preparation of vinyl chlorides from
ketones.
The initial attempt to synthesize 2c from 1,2-diphenyl
ethanone using BTC or cyanuric trichloride in the presence
of Sc(OTf)3 (2 mol %) was unsuccessful (Scheme 1). Other
(5 mol %), which reacted with ketone in the presence of
Sc(OTf)3 to form the desired product 2c. The eliminated
benzoic acid reacted in situ with BTC to form benzoyl
chloride again, thus completing the cycle with CO2 and HCl
as the byproducts. The idea was environmentally friendly
compared to most previous reports. It should be mentioned
that DMF (1 mol %) was added as an activator so as to
accelerate the reaction.
Because the eliminated benzoic acid could be transformed
into benzoyl chloride in situ as demonstrated by the cycle,
it may be reasonable to test the possibility of using carboxylic
acid directly instead of benzoyl chloride to carry out the
reaction. Indeed, the protocol afforded 2c in moderate yield
(Table 1, entry 3). Because the use of benzoyl chloride
Scheme 1. Conversion of Phenylacetophenone (1c) to 2c
Table 1. Synthesis of (Z)-Vinyl Chlorides in Refluxing AcOEt
entry
R1
R2
CH3
product
yielda (%)
metal triflates were also tried but proved inefficient under
the reaction conditions. Even DMF (one of the most effective
activators of BTC) addition could not improve the result,
and only starting material was recovered. It is encouraging
to find acyl chlorides were very active for the transformation,
and a 95% yield of 2c could be isolated when 1,2-diphenyl
ethanone (1c) was treated with acetyl chloride or benzoyl
chloride (2.2 equiv) in the presence of Sc(OTf)3 (2 mol %).
An aliquot of 2.0 equiv of acyl chloride was necessary due
to the formation of carboxylic acids 3, thus resulting in an
equimolar amount of acid waste (Scheme 1).
BTC is an efficient chlorinating reagent in organic
synthesis,11 which can transform carboxylic acids easily into
acyl chlorides. Bearing this in mind, it occurred to us that a
reaction cycle may be established between carboxylic acids
and acyl chlorides in the above reaction. To our delight, when
the protocol was applied, 2c was successfully obtained
(Scheme 2), indicating the reaction cycle could proceed
1
2
3
4
5
6
7
8
9
10
11
12
13
Ph
Ph
Ph
2ab
2b
2cb
2db
2e
77
H
31d
83 (51c)
79
Ph
Ph
Ph
H
CH3
Ph
Ph
Ph
Ph
Ph
4-Me-Ph
4-Et-Ph
3-NO2-4-CN-Ph
3-Cl-Ph
â-C10H7
R-(â-MeO-C10H6)
2-C4H3S
2-(5-Cl-C4H2S)
2-(5-Br-C4H2S)
81
0d
76
64
65
82
80
79
2f
2gb
2h
2i
2jb
2k
2l
2m
74
14
15
16
17
18
19
20
21
Ph
CH2Cl
H
H
2n
2o
2p
2q
2r
2s
2t
0d
CH2dCH
n-C5H11
traced
27d,e
30d,e
33d,e
25d,e
traced
18d,e
cyclohexanone
CH3CH2
CH3CH2
cyclohexyl
cyclohexyl
CH3
CH3CH2
cyclohexyl
CH3
2u
Scheme 2. Lewis Acid/DMF-Catalyzed Reaction Cycle
Isolated yields based on ketones. b GC/MS analysis was performed to
a
c
ascertain the absence of the E isomer. Benzoic acid was used instead of
benzoyl chloride. d Reaction time: 24 h. e Conversion determined by GC-
MS.
afforded 2c in better yields, the conditions developed for 2c
were further applied to a variety of ketones, and the results
are summarized in Table 1.
Acetophenone afforded only 31% yield of 2b even after
24 h with the majority of the substrate unchanged (entry 2).
3-Nitro-4-cyano-acetophenone bearing two strong electron-
withdrawing groups did not undergo the transformation and
was recovered almost quantitatively (entry 6). A similar result
was obtained with ω-chloroacetophenone (entry 14). Other-
wise, m-chloropropiophenone gave the desired 2g in good
smoothly under the given conditions. It is worth noting that
only a very small amount of benzoyl chloride was required
(10) It was clear that BTC was an efficient substitution of toxic phosgene,
SOCl2, PCl3, POCl3, PCl5, etc.
(11) Previous review: Cotarca, L.; Delogu, P.; Nardelli, A.; Sunjic, V.
Synthesis 1995, 553.
994
Org. Lett., Vol. 9, No. 6, 2007

yield (entry 7). Reactions of phenylacetothiophene derivatives
with a catalytic amount of benzoyl chloride in the presence
of BTC/DMF could also proceed smoothly, and the corre-
sponding products were obtained with 82%, 80%, and 79%
yields, respectively (entries 10-12). Naphthyl-benzyl ketones
bearing a bulky group were also suitable substrates (entries
8 and 9). It could be concluded that electron-withdrawing
groups decrease the electronic density of keto-carbonyls and
therefore disfavor the carbonyl addition with acyl chloride.
mol %) was inefficient in the reactions and only gave trace
amounts of product. We supposed the strongly coordinate
oxygen-aluminum bond has lost the Lewis acid catalysis,
so conventional Lewis acid could not be recycled and reused
(eq 1).
1-Tetralone was efficiently converted into 2m under the
same conditions in 74% isolated yield (entry 13). However,
strong acid or other Lewis acid catalysts5 could not realize
the transformation with such efficiency, so the vinyl chloride
was contaminated with other byproducts. It should be noted
that product 2 did not react further under the present reaction
conditions, thus avoiding byproduct formation to a large
extent. Our protocol ensured a clean and facile route to the
synthesis of vinyl chloride.
When propiophenone was treated with BTC (0.4 mol) in
the presence of excess AlCl3 (1.2 mol) for 4 h, an unexpected
reaction occurred and chlorinated ketone 4 was obtained in
66% yield (Scheme 4).
Unfortunately, dienyl chloride was not obtained from
unsaturated ketone under the same conditions (entry 15).
Cholest-3,5-dien-7-one (5, Scheme 3) was easily formed
Scheme 4. AlCl3-Catalyzed Chlorination on the Aromatic Ring
Scheme 3. Lewis Acid Catalyzed Elimination Reaction
A very small amount of DMF was used as an activator in
the protocol, but when stoichiometric amounts or excess
DMF was used, the results were greatly different. Chloro-
formylation reaction occurred, and a â-chloro-R,â-unsatur-
ated aldehyde was formed.12
Obviously, the mechanism was different from Vilsmeier
halogenation or haloformylation. The reaction probably
proceeded with an acyl chloride mediated carbonyl addi-
tion, where 1-chloroalkylester was formed in the presence
when 7-oxocholesterol acetate was treated with a catalytic
amount of Yb(OTf)3. Aliphatic ketones were also converted
to vinyl chlorides though in lower yields (entries 16-21).
Effects of metal triflates were also examined with aliphatic
ketones (2u) in different solvents such as CHCl3, CH2Cl2,
THF, CH3CN, CH3NO2, etc., but the yield was not increased
obviously. It seems aromatic ketones should be more suitable
in the above reaction.
13
of Sc(OTf)3 followed by cis elimination6,14 of a carboxyl
acid to give (Z)-vinyl chloride (Scheme 5). The cis elimina-
tion may be performed via six-membered ring transition
states. The intermediate 6 (in Scheme 5) with the Cl, Ar,
and O group attached on the same R-carbon, and a â-H
should be unstable and could not be isolated under such
reaction conditions. But interestingly, previous literature
reported that aromatic aldehydes could react with acyl
chloride to give stable 1-chloroalkylesters via carbonyl
addition.8c,13
In addition, when catalytic Yb(OTf)3, Zn(OTf)2, Ga(OTf)3,
Bi(OTf)3, In(OTf)3, and Cu(OTf)2 were used instead of
Sc(OTf)3, the reaction of the aromatic ketone (1a) also
proceeded well (Table 2). However, conventional AlCl3 (5
Moreover, it is favorable when the phenyl group is oriented
at an equatorial position on this six-membered transition state.
Table 2. Effect of Different Metal Triflatesa
(12) Su, W. K.; Zhuang, Y. G.; Wu, D. Z.; Zhong, W. H. Org. Prep.
Proced. Int. 2007, accepted.
(13) (a) Neuenschwnder, M.; Bigler, P.; Christen, K.; Iseli, R.; Kyburz,
R. HelV. Chim. Acta 1978, 61, 2047. (b) Bigler, P.; Schonholzer, S.;
Neuenschwnder, M. HelV. Chim. Acta 1978, 61, 2059. (c) Bigler, P.; Muhle,
H.; Neuenschwnder, M. Synthesis 1978, 593. (d) Chou, T. S.; Knochel, P.
J. Org. Chem. 1990, 55, 4791. (e) Ishino, Y.; Mihara, M.; Takeuchia, T.;
Takemoto, M. Tetrahedron Lett. 2004, 45, 3503.
(14) (a) DePuy, C. H.; King, R. W. Chem. ReV. 1960, 60, 431. (b) March,
J. AdVanced Organic Chemistry, 4th ed.; John Wiley & Sons, Inc.: New
York, 1992; Chapter 17, pp 1006. (c) Bailey, W. J.; Baylouny, R. A. J.
Am. Chem. Soc. 1959, 81, 2126. (d) For AgOTf as the catalyst for the
elimination of phosphates and thiophosphates, see: Shimagaki, M.; Fujieda,
Y.; Kimura, T.; Nakata, T. Tetrahedron Lett. 1995, 36, 719.
entry
metal
yieldb (%)
entry
metal
yieldb (%)
1
2
3
Yb
Zn
Ga
76
64
69
4
5
6
Bi
In
Cu
74
73
70
a
b
Anhydrous metal triflates were used. Isolated yield based on
propiophenone.
Org. Lett., Vol. 9, No. 6, 2007
995

the absence of the E isomer, GC/MS analysis was performed
during the reaction (Table 1).
Scheme 5. Plausible Mechanism
In conclusion, we have developed a useful route to the
preparation of aryl-(Z)-vinyl chlorides, very useful materials
in transition metal promoted coupling reactions, with moder-
ate to good yields under mild conditions catalyzed by
scandium triflate.17 The confirmed stereochemical assign-
ments of the final products accorded with the mechanism
involved in the process. To the best of our knowledge, it is
the first catalytic and green synthesis of aryl-(Z)-vinyl
chloride. The advantages of this method include high
stereoselectivity, good atom economy, decreased waste
formation, the use of safer non-phosphorus reagents, and the
requirement of a very small amount of catalyst.
Acknowledgment. We thank the National Basic Research
Program of China [973 Program: 2003CB 114400] and the
National Natural Science Foundation of China [20476098
and 20676123] for financial support.
The stereochemistry of the double bond was exclusively (Z)-
configuration. Previous literature reported that 1H NMR shift
values of vinylic protons as well as methyl protons between
the (Z) and (E) configuration were obviously different.15 The
unambiguous stereochemical assignments of our results
agreed with the (Z)-configuration according to the literature.
The stereochemistry was also established by NOE experi-
ments and X-ray analysis16 (Figure 1). Further, to ascertain
Supporting Information Available: General procedure
for the synthesis of aryl-(Z)-vinyl chlorides and characteriza-
1
tion of the products, including copies of H and 13C NMR
spectra of all products, NOESY, and the X-ray crystal
structure of 2h. This material is available free of charge via
the Internet at http://pubs.acs.org.
OL062991C
(15) (a) Kropp, P. J.; Crawford, S. D. J. Org. Chem. 1994, 59, 3102. (b)
Fahey, R. C.; Schubert, C. J. Am. Chem. Soc. 1965, 87, 5172.
(16) CCDC-295191 contains the supplementary crystallographic data for
2h, which is available free of charge via www.ccdc.cam.ac.uk.
(17) General procedure: To a solution of ketone (5 mmol) and benzoyl
chloride (0.25 mmol, 0.035 g) in ethyl acetate (2 mL) was added Sc(OTf)3
(0.1 mmol, 0.049 g) successfully. The solution was heated to reflux for 10
min, and DMF (0.05 mmol) was added successively. Then, BTC (2 mmol,
0.594 g in 5 mL of ethyl acetate) was added dropwise very carefully over
8 h at reflux. After completion (monitored by TLC), the mixture was treated
with ammonia and extracted with ether. After dryness and condensation,
the products vinyl chlorides were obtained by preparative TLC.
Figure 1. X-ray structure of 2h.
996
Org. Lett., Vol. 9, No. 6, 2007