Synthesis of Vinyl Chlorides via Triphosgene-Pyridine Activation of Ketones

Article abstract of DOI:10.1021/acs.joc.5b01137

Herein, we describe a mild method to prepare aliphatic and aromatic vinyl chlorides from their corresponding ketones via triphosgene-pyridine activation in dichloromethane at reflux. The mechanism of this reaction is proposed to involve formation of a put

Full text of DOI:10.1021/acs.joc.5b01137

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Synthesis of Vinyl Chlorides via Triphosgene-Pyridine Activation of Ketones
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Mirza A. Saputra, Ly Ngo,§ and Rendy Kartika*
Department of Chemistry
232 Choppin Hall
Louisiana State University
Baton Rouge, LA 70803, USA
rkartika@lsu.edu
ABSTRACT
Herein we describe a mild method to prepare aliphatic and aromatic vinyl chlorides from their
corresponding ketones via triphosgeneꢀpyridine activation in dichloromethane at reflux. The
mechanism of this reaction is proposed to involve formation of a putative αꢀchloro pyridinium
carbamate intermediate, which appeared to readily undergo an E2 elimination in the presence of
pyridine.
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Vinyl chlorides are a ubiquitous functional group. They are readily found in numerous
chlorineꢀcontaining natural products.1 Furthermore, vinyl chlorides play a significant role in
organic synthesis, as they serve as a convenient intermediate for transition metalꢀcatalyzed
carbonꢀcarbon and carbonꢀheteroatom bond forming processes.2 Naturally, syntheses of vinyl
chlorides have been subjected to multiple studies because of their broad applications. In fact,
there are abundant precedents on the production of vinyl chlorides from a variety of starting
materials, including α,βꢀunsaturated carbonyl compounds,3 vinyl trifluoroborates,4 vinyl
triflates,5 alkynes,6 and cyclopropenes.7 Preparation of vinyl chlorides could be also expediently
carried out from ketones. Nevertheless, there are many challenges often associated with this
approach. For example, many of the established protocols often used strongly acidic conditions8
or harsh halogenating reagents, such as thionyl chloride and other chlorinated phosphorousꢀbased
reagents (PCl3, PCl5, POCl3).9 These sets of reaction conditions thereby limited the scope of
substrates.10 There are also reports on methods that generated byproducts, including
contamination of geminalꢀdichloride adducts that were often inseparable by chromatography
from the desired vinyl chlorides.11
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Driven by our synthetic interests in chlorosulfolipid natural products,12 we recently
developed a series of new reactions that enabled robust conversion of unreactive aliphatic
alcohols to the corresponding alkyl chlorides under exceedingly mild conditions.13 For instance,
as shown in Scheme 1, we discovered that treatment of secondary alcohols with triphosgene and
pyridine in dichloromethane at reflux cleanly produced the corresponding alkyl chlorides with
excellent stereospecificity.13a Our chemistry was operationally simple; the existence of
triphosgene as a stable nonꢀhygroscopic crystalline material at room temperature permitted easy
and safe handling of the chlorinating reagent.14 In fact, this reaction did not require scrupulously
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inert nor anhydrous conditions. More importantly, our chlorination method was high yielding
and advantageously tolerated by a variety of sensitive functionalities that otherwise would be
problematic under classical chlorination conditions.13b The mechanism of this reaction was
proposed to involve conversion of the starting alcohol to pyridinium carbamate 2 via
chloroformate 1, upon treatment with triphosgene and pyridine. This novel mode of nucleophilic
activation subsequently enhanced the electrophilicity of intermediate 2 at the carboxyl position,
specifically towards an SN2 nucleophilic substitution by chloride ions, which ultimately led to an
inversion of stereochemistry. This process also regenerated the nucleophilic promoter, i.e.
pyridine, and carbon dioxide as the sole byproduct.
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Scheme 1. TriphosgeneꢀPyridine Promoted Stereospecific Chlorination of Alcohols
These studies naturally inspired us to investigate the applicability of our chlorination
conditions to convert ketones to their corresponding chlorinated products, such as vinyl
chlorides. Literature examples on the utility of triphosgene to activate ketones are quite rare.
One such example was reported by Su and a coꢀworker, in which they synthesized vinyl
chlorides by subjecting ketones to a mixture of catalytic Sc(OTf)3ꢀDMFꢀbenzoyl chloride in the
presence of triphosgene.11a Herein, we wish to report our metalꢀfree variant to this chemistry,
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highlighted by a convenient and practical use of triphosgene and pyridine under mild conditions
to achieve this useful functional group interconversion.
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Our preliminary studies are depicted in Figure 1, in which 4ꢀtertꢀbutyl cyclohexanone 3
was employed as the starting material. As shown in Graph 1A, these studies were initially
carried out by varying the amount of pyridine by 1.0 equivalent increments while employing a
constant 0.5 equivalent of triphosgene. These reactions were performed at room temperature as a
100 mM solution in dichloromethane based on starting ketone 3. The progress of reaction was
then periodically monitored by GC analyses. Gratifyingly, these pilot conditions readily
generated the corresponding vinyl chloride 4. We observed that the extent of product formation
appeared to be directly correlated to the amount of pyridine introduced to the solution, but the
starting ketone was not fully consumed under these conditions even after 48 hours of stirring.
Interestingly, an attempt to activate ketone 3 with triphosgene and pyridine in nonꢀchlorinated
solvents failed to yield the desired vinyl chloride. In addition, the use of other chlorinated
solvents, such as chloroform and dichloroethane, only resulted in lower conversion yields.
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Figure 1. Reaction Optimization(a,b)
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Graph 1A.
Conditions: triphosgene (0.5 equiv), pyridine
Graph 1B.
Conditions: triphosgene (0.5 equiv), pyridine
(n equiv), reflux
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(n equiv), room temperature
100
75
100
75
6 hours
6 hours
50
25
0
50
25
0
24 hours
48 hours
24 hours
48 hours
1
2
3
4
1
2
3
4
Pyridine (equiv)
Pyridine (equiv)
Graph 1C.
Graph 1D.
Conditions: triphosgene (1.0 equiv), pyridine
Conditions: triphosgene (1.0 equiv), pyridine
(n equiv), room temperature
(n equiv), reflux
100
75
100
75
6 hours
6 hours
50
25
0
50
25
0
24 hours
48 hours
24 hours
48 hours
1
2
3
4
1
2
3
4
Pyridine (equiv)
Pyridine (equiv)
(a) Yields were determined by GC analyses of the crude mixtures assuming that the starting
material and product elicited identical GC responses.
(b) The remaining material in the crude mixture was unreacted starting ketone 3.
To help push the reaction to reach completion, the above experiments were repeated at
reflux (Graph 1B). Similarly, the reaction appeared to plateau at 80% conversion with 4.0
equivalents of pyridine. As shown in Graphs 1C and 1D, we then increased the amount of
triphosgene to 1.0 equivalent while steadily modulating the amount of pyridine from 1.0 to 4.0
equivalents. This new set of reactions were also conducted both at room temperature and reflux.
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Eventually, the use of 4.0 equivalents of pyridine at reflux was found to yield the highest
production of vinyl chloride 4 (up to 97% GC conversion) after 48 hours of reaction.
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Overall, the optimal reaction conditions were established to involve the use of 1.0
equivalent of triphosgene and 4.0 equivalents of pyridine in dichloromethane at reflux. We then
evaluated the compatibility of various ketones in this methodology. To expedite the rate of
reaction, the scope of substrate study was performed in preparative scales at 200 mM
concentration for aliphatic ketones or 500 mM for aromatic ketones. As shown in Table 1,
entries 1ꢀ5, various cyclohexanoneꢀderived substrates were initially subjected to the chlorination
conditions. Simple cyclohexanone cleanly produced the corresponding vinyl chloride 6a in
100% GC conversion. However, an attempt to purify this product only led to 20% isolation yield
presumably due to its rapid decomposition during column chromatography. The use of 4ꢀtertꢀ
butylcyclohexanone and 4ꢀphenylcyclohexanone generated vinyl chlorides 6b and 6c,
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respectively, in quantitative GC yields and good isolation yields.
Exposure of 2ꢀ
phenylcyclohexanone and 2ꢀsecꢀbutylcyclohexanones to these chlorination conditions furnished
vinyl chlorides 6d and 6e as a mixture of regioisomers, favoring the fully substituted double
bond. Interestingly, starting materials 5d and 5e was not fully consumed after 24 hours of
stirring. Similarly, the apparent instability of vinyl chlorides 6d and 6e towards chromatographic
purification resulted in reduced isolation yields.
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Table 1. Scope of Substrates
triphosgene (1.0 equiv),
pyridine (4.0 equiv)
O
Cl
R
R
R'
R'
CH2Cl2, reflux
Isolation
Yield(c)
Isolation
Yield(c)
entry
substrate
product(s)
GC Yield(a,b)
time (h)
16
entry
substrate
product(s)
GC Yield(a,b)
time (h)
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11
Cl
O
12
1(d)
13
14
Cl
Cl
Cl
O
O
O
100%
20%
80%
93%
Me
8(e)
89%
22%
48
6a
6b
6c
5a
5b
5c
MeO
O2N
MeO
O2N
6h
6i
5h
5i
15
tBu
Ph
tBu
2(d)
100%
15
Cl
O
16
17
18
Me
9(e)
51%(g)
54%(h)
72
24
3(d) Ph
100%
24
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Cl
O
Cl
O
10(e)
98%
54%
4(d)
85%
(3:1 rr)
42%
34%
24
Ph
Cl
Ph
O
6j
5j
6d
5d
Cl
Cl
O
O
5(d)
66%
(6:1 rr)
24
72
11(d)
79%
41%
25%
24
24
sBu
sBu
6e
5e
6k
6l
5k
5l
Cl
O
Cl
O
6(e)
43%
(5:1 Z:E)
23%
(5:1 Z:E)(f)
12(e)
100%
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Me
Me
6f
5f
Cl
O
Cl
O
13(e)
trace(i)
--
24
7(e)
71%
33%
48
Ph
Ph
Me
6m
6g
5m
5g
(a) Yields were determined by GCꢀMS analyses of the crude mixtures assuming that the starting
material and product elicited identical GC responses.
(b) The remaining material in the crude mixture was unreacted starting ketone.
(c) Low isolation yields were presumably due to decomposition of vinyl chlorides during
chromatography. We screened a variety of chromatographic conditions, including the use of
neutralized silica and alumina.
(d) Reactions were performed at 200 mM concentration based on starting ketones.
(e) Reactions were performed at 500 mM concentration based on starting ketones.
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(f) The olefin isomers were inseparable by chromatography. The E:Z ratio was determined by
1H NMR. The major olefin geometry was determined by an NOE experiment.
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(g) The GCꢀMS analysis of the crude material indicated 10% of geminalꢀdichloride byproduct 7.
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(h) The combined yield for an inseparable 5:1 mixture of vinyl chloride 6i and
Cl Cl
geminalꢀdichloride byproduct 7.
Me
O2N
7
(i) Decomposition of starting material was observed.
While cyclic ketones appeared to be more readily tolerated in this methodology, acyclic
aliphatic ketone, such as dibenzylketone 5f, was surprisingly rather problematic. Treatment of
this compound to the established triphosgeneꢀpyridine activation led to formation of vinyl
chloride 6f in modest 43% conversion even though the reaction was performed at an increased
concentration for an extended period of time. In addition, the GC analysis of the crude material
revealed a 5:1 mixture of olefin isomers, favoring the Z geometry. As demonstrated in entries 7ꢀ
9, the compatibility of various aromatic ketones was also investigated through the use of
substituted acetophenones 5gꢀ5i. Similarly, the corresponding vinyl chlorides 6gꢀ6i were
produced in a varying degree of conversion and isolation yields, depending upon the stability of
the products during chromatography. Unexpectedly, paraꢀnitroacetophenone generated geminalꢀ
dichloride adduct 7 in 10% yield. This byproduct was inseparable by chromatography from the
desired vinyl chloride 6i. We also subjected 1ꢀtetralone 5j to this reaction, and this compound
furnished the corresponding product 6j in good conversion and isolation yields. As shown in
entries 11ꢀ13, the use of more elaborate substrates, such as cyclohexaneꢀ1,3ꢀdione 5k, readily
produced the corresponding bis(vinyl chloride) 6k in a decent yield. Furthermore, exposure of
α,βꢀunsaturated ketone 5l to these chlorination conditions afforded the desired divinyl chloride
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6l in 100% conversion, but the apparent instability of this compound under chromatography
again rendered a low isolation yield. Interestingly, α,βꢀunsaturated ketone 5m was not reactive
under identical chlorination conditions. In fact, this starting material only produced a trace
amount of divinyl chloride 6m, along with other unidentifiable decomposition materials.
The mechanism for our vinyl chloride formation is proposed in Scheme 2. We believed
that activation of ketones with triphosgene and pyridine in dichloromethane initially produced αꢀ
chloro chloroformate 8. Although this presumed intermediate was not observed in any of our
GCꢀMS and NMR studies, the potential participation of this species was supported by Coghlan’s
report, which described the conversion of aldehydes to analogous αꢀchloro chloroformate
functionality under similar reaction conditions.15 As depicted in Figure 1, the extent of vinyl
chloride formation appeared to be dependent on the concentration of pyridine. This could
hypothetically suggest the involvement of pyridine as a nucleophilic activator, which
transformed αꢀchloro chloroformate 8 to the corresponding αꢀchloro pyridinium carbamate
intermediate 9.13a Such a putative reactive intermediate then proceeded to undergo an E2
elimination of the pyridinium carbamate moiety upon deprotonation of the adjacent αꢀhydrogen,
presumably by pyridine. This process would eventually produce the corresponding vinyl
chloride while regenerating pyridine and releasing carbon dioxide as a byproduct. Nevertheless,
at this point, we could not rule out an alternative pathway, which involved the possibility of αꢀ
chloro chloroformate 8 to undergo direct E2 elimination induced by pyridine.
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Scheme 2. Proposed Reaction Mechanism
CONCLUSION
We have demonstrated that ketones could be conveniently transformed to vinyl chlorides,
using a simple protocol with a mixture of triphosgene and pyridine in dichloromethane at reflux.
Although our method is proven to be mild and applicable for various types of ketones, the
presumed instability of the desired vinyl chloride products under chromatography rendered their
isolation rather difficult. Nonetheless, our investigations have shed a new insight into a novel
activation of αꢀchloro chloroformates by pyridine to αꢀchloro pyridinium carbamate
intermediates.
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EXPERIMENTAL SECTION
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All materials, unless otherwise stated, were purchased from commercial sources and
utilized without further purification. Anhydrous reactions were conducted in ovenꢀdried
glassware, which was then cooled under vacuum and purged with nitrogen gas. Anhydrous
solvents (dichloromethane, toluene, acetonitrile, diethyl ether, and tetrahydrofuran) were filtered
through activated 3Å molecular sieves under nitrogen in a solvent purification system. Reactions
were either monitored by analytical thin layer chromatography (TLC Silica Gel 60 F254, Glass
Plates) and analyzed using 254 nm UV light and anisaldehyde – sulfuric acid or potassium
permanganate stains, or via Gas Chromatography – Mass Spectrometry (GCꢀMS). The column
for the GCꢀMS system was 5% phenyl methyl siloxane, measuring 30 meters in length with an
internal diameter of 250 ꢀm and film thickness of 0.25 ꢀm. Low and high mass readings were
set to 40 to 800 m/z, respectively. Oven, inlet, and detector temperatures were set to 250ºC, and
helium was used as the inert carrier gas. Column chromatography was completed using silica gel
or neutral alumina. Unless otherwise noted, all 1H and 13C NMR spectra were recorded in CDCl3
using a spectrometer operating at 400 MHz for 1H and 100 MHz for 13C. Chemical shifts (δ) are
reported in ppm relative to residual CHCl3 as an internal reference (1H: 7.26 ppm, 13C: 77.00
ppm). Coupling constants (J) are reported in Hertz (Hz). Peak multiplicity is indicate as follows:
s (singlet), d (doublet), t (triplet), q (quartet), p (pentet), x (septet), h (heptet), b (broad), and m
(multiplet). FTꢀIR spectra were recorded using thin film, and absorption frequencies were
reported in reciprocal centimeters (cmꢀ1). High Resolution Mass Spectrometry (HRMS) analyses
were performed using Electron Spray Ionization – Time of Flight (ESIꢀTOF) method.
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General Procedure. Into an ovenꢀdried pressure vessel, ketone (1.0 equiv) was
dissolved in anhydrous CH2Cl2 (200 mM or 500 mM concentration). Triphosgene (1.0 equiv)
was added in one portion, followed by pyridine (4.0 equiv). The mixture was then warmed to a
gentle reflux at 35°C bath, and the progress of reaction was monitored by GCꢀMS analyses.
Upon completion, unless otherwise noted, the crude mixture was partition with 1M HCl and
CH2Cl2 (1:1 ratio, 20 mL). The aqueous layer was further extracted with CH2Cl2 (3x10 mL).
The combined organic layers were then dried over Na2SO4 and concentrated under vacuum. The
resulting residue was then purified by flash column chromatography.
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1-chloro-cyclohexene (6a).16 Ketone 5a (208 ꢁL, 2.00 mmol) was dissolved in CH2Cl2
(10.0 mL) along with triphosgene (593 mg, 2.00 mmol) and pyridine (647 ꢁL, 8.00 mmol).
Without aqueous workup, the crude mixture was directly purified with column chromatography
on neutral alumina using 100% pentane to afford vinyl chloride 6a (47 mg, 0.40 mmol) as
1
colorless oil. H NMR (400 MHz, CDCl3); δ (ppm) = 5.79ꢀ5.78 (m, 1H), 2.30ꢀ2.25 (m, 2H),
2.10ꢀ2.05 (m, 2H), 1.75ꢀ1.69 (m, 2H), 1.60ꢀ1.54 (m, 2H). 13C NMR (100 MHz, CDCl3); δ (ppm)
= 131.9, 124.5, 32.8, 26.1, 23.7, 21.3. IR (cmꢀ1) = 2917, 2849, 2045, 1463, 995, 700. GCꢀMS: Rt
= 7.55 min; M+ = 116.0 calculated for C6H9Cl, experimental = 116.1.
4-tert-butyl-1-chloro-cyclohexene (6b).11b Ketone 5b (309 mg, 2.00 mmol) was
dissolved in CH2Cl2 (10.0 mL) along with triphosgene (593 mg, 2.00 mmol) and pyridine (647
ꢁL, 8.00 mmol). After aqueous workup, the crude mixture was purified with column
chromatography on silica gel using 100% hexanes to afford vinyl chloride 6b (276 mg, 1.60
1
mmol) as colorless oil. H NMR (400 MHz, CDCl3); δ (ppm) = 5.77 (t, J = 3.1 Hz, 1H), 2.40ꢀ
2.26 (m, 2H), 2.10 (m, 1H), 1.90ꢀ1.82 (m, 2H), 1.39ꢀ1.24 (m, 2H), 0.87 (s, 9H). 13C NMR (100
MHz, CDCl3); δ (ppm) = 131.6, 124.6, 43.0, 34.0, 32.1, 27.6, 27.2, 25.1. IR (cmꢀ1) =2959, 2868,
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1366, 1025, 982, 719. GCꢀMS: Rt = 13.00 min; M+ = 172.1 calculated for C10H17Cl,
experimental = 172.1.
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4-phenyl-1-chloro-cyclohexene (6c).17 Ketone 5c (261 mg, 1.50 mmol) was dissolved
in CH2Cl2 (7.5 mL) along with triphosgene (445 mg, 1.50 mmol) and pyridine (485 ꢁL, 6.00
mmol). After aqueous workup, the crude mixture was purified with column chromatography on
silica gel using 100:0 → 98:2 → 96:4 hexanes : EtOAc to afford vinyl chloride 6c (267 mg, 1.39
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mmol) as white crystals. H NMR (400 MHz, CDCl3); δ (ppm) = 7.38 (t, J = 7.6 Hz, 2H), 7.28
(d, J = 7.6 Hz, 3H), 5.95 (t, J = 3.0 Hz, 1H), 2.88 (m, 1H), 2.59 (m, 1H), 2.45 (dd, J = 5.5 Hz,
2H), 2.32 (m, 1H), 2.10ꢀ1.97 (m, 2H). 13C NMR (100 MHz, CDCl3); δ (ppm) = 145.6, 131.8,
128.6, 126.8, 126.4, 124.1, 39.0, 34.0, 33.3, 30.8. IR (cmꢀ1) = 3027, 2920, 2839, 978, 755, 698.
GCꢀMS: Rt = 17.37 min; M+ = 192.1 calculated for C12H13Cl, experimental = 192.1.
2-phenyl-1-chloro-cyclohexene (6d).18 Ketone 5d (261 mg, 1.50 mmol) was dissolved
in CH2Cl2 (7.5 mL) along with triphosgene (445 mg, 1.50 mmol) and pyridine (485 ꢁL, 6.00
mmol). After aqueous workup, the crude mixture was purified with column chromatography on
silica gel, buffered with 1% Et3N, using 100% hexanes to afford vinyl chloride 6d (121 mg, 0.63
1
mmol) as colorless oil. H NMR (400 MHz, CDCl3); δ (ppm) = 7.40ꢀ7.36 (m, 2H), 7.31ꢀ7.28
(m, 3H), 2.53ꢀ2.50 (m, 2H), 2.44ꢀ2.39 (m, 2H), 1.87ꢀ1.77 (m, 4H). 13C NMR (100 MHz, CDCl3);
δ (ppm) = 141.6, 134.4, 128.1, 128.1, 127.8, 126.9, 34.1, 33.0, 23.9, 22.7. IR (cmꢀ1) = 3055,
3022, 2932, 2860, 1003, 756, 698. GCꢀMS: Rt = 16.90 min; M+ = 192.1 calculated for C12H13Cl,
experimental = 192.1. The minor regioisomer was not isolable presumably due to its instability
to column chromatography.
2-sec-butyl-1-chloro-cyclohexene (6e). Ketone 5e (338 ꢁL, 2.00 mmol) was dissolved
in CH2Cl2 (10.0 mL) along with triphosgene (593 mg, 2.00 mmol) and pyridine (647 ꢁL, 8.00
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mmol). After aqueous workup, the crude mixture was purified with column chromatography on
silica gel, buffered with 1% Et3N, using 100% hexanes to afford vinyl chloride 6e (118 mg, 0.68
mmol) as yellow oil. 1H NMR (400 MHz, CDCl3); δ (ppm) = 2.58ꢀ2.49 (h, J = 7.2 Hz, 1H),
2.30ꢀ2.16 (m, 2H), 2.07ꢀ1.90 (m, 2H), 1.75ꢀ1.69 (m, 2H), 1,63ꢀ1.57 (m, 2H), 1.31 (p, J = 7.4 Hz,
2H), 0.95 (d, J = 6.9 Hz, 3H), 0.81 (t, J = 7.4 Hz, 3H). 13C NMR (100 MHz, CDCl3); δ (ppm) =
148.7, 144.1, 129.7, 34.4, 27.1, 26.4, 22.8, 22.4, 22.1, 18.2, 12.2. IR (cmꢀ1) = 2962, 2934, 2874,
1782, 1129, 1061, 847. GCꢀMS: Rt = 12.61 min; M+ = 172.1 calculated for C10H17Cl,
experimental = 172.1. HRꢀMS: (MꢀH+O)•+ = 187.0885 calculated for C10H16ClO, experimental
= 187.0880. The minor regioisomer was not isolable presumably due to its instability to column
chromatography.
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1,1’-[(1E/Z)-2-chloro-1-propene-1,3-diyl]bis-benzene (6f).19 Ketone 6f (210 mg, 2.00
mmol) was dissolved in CH2Cl2 (4.0 mL) along with triphosgene (593 mg, 2.00 mmol) and
pyridine (647 ꢁL, 8.00 mmol). Without aqueous workup, the crude mixture was directly purified
with column chromatography on neutral alumina using 100% pentane to afford vinyl chloride 6f
(104 mg, 0.46 mmol) as colorless oil in a mixture of 5:1 Z:E olefin isomers. 1H NMR (400
MHz, CDCl3, *denoted the minor isomer); δ (ppm) = 7.64 (d, J = 7.4 Hz, 2H), 7.41ꢀ7.28 (m,
13
10H), 6.99 (s, 0.2H)*, 6.57 (s, 1H), 3.96 (s, 0.4H)*, 3.83 (s, 2H). C NMR (100 MHz, CDCl3,
*denoted the minor isomer); δ (ppm) = 137.4, 135.0, 133.5, 130.1*, 129.1, 129.1, 128.7*, 128.6,
128.5*, 128.2, 127.7, 127.6*, 127.0, 126.8*, 125.9, 47.4, 40.6*. IR (cmꢀ1) = 2916, 2849, 2067,
2046, 1493, 1453, 750, 695. GCꢀMS for major isomer: Rt = 20.02 min; M+ = 228.7 calculated
for C15H13Cl, experimental = 228.1. GCꢀMS for minor isomer: Rt = 20.43 min; M+ = 228.7
calculated for C15H13Cl, experimental = 228.1. Major olefin isomer was determined by NOESY
experiment (see supporting information).
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1-chloro-vinylbenzene (6g).11b Ketone 5g (233 ꢁL, 2.00 mmol) was dissolved in
CH2Cl2 (4.0 mL) along with triphosgene (593 mg, 2.00 mmol) and pyridine (647 ꢁL, 8.00
mmol). Without aqueous workup, the crude mixture was directly purified with column
chromatography on silica gel, buffered with 1% Et3N, using 100:0 → 98:2 → 96:4 hexanes :
EtOAc to afford vinyl chloride 6g (90 mg, 0.65 mmol) as yellow oil. 1H NMR (400 MHz,
CDCl3); δ (ppm) = 7.66 (dd, J = 2.1 and 7.7 Hz, 2H), 7.40ꢀ7.38 (m, 3H), 5.80 (d, J = 1.9 Hz,
1H), 5.56 (d, J = 1.9 Hz, 1H). 13C NMR (100 MHz, CDCl3); δ (ppm) = 140.0, 136.9, 129.1,
128.3, 126.4, 112.7. IR (cmꢀ1) = 2925, 1774, 1446, 1220, 879, 768, 670. GCꢀMS: Rt = 10.66
min; M+ = 138.0 calculated for C8H7Cl, experimental = 138.1.
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1-(1-chloroethenyl)-4-methoxy-benzene (6h).20 Ketone 5h (300 mg, 2.00 mmol) was
dissolved in CH2Cl2 (4.0 mL) along with triphosgene (593 mg, 2.00 mmol) and pyridine (647
ꢁL, 8.00 mmol). Without aqueous workup, the crude mixture was directly purified with column
chromatography on neutral alumina using 100:0 → 98:2 → 92:8 pentane : EtOAc to afford vinyl
1
chloride 6h (74 mg, 0.44 mmol) as white crystals. H NMR (400 MHz, CDCl3); δ (ppm) = 7.57
(d, J = 8.8 Hz, 2H), 6.88 (d, J = 8.8 Hz, 2H), 5.65 (d, J = 1.8 Hz, 1H), 5.41 (d, J = 1.8 Hz, 1H),
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3.83 (s, 3H). C NMR (100 MHz, CDCl3); δ (ppm) = 160.3, 139.6, 129.6, 127.8, 113.6, 110.8,
55.4. IR (cmꢀ1) = 2916, 2849, 2068, 2045, 1605, 1487, 1254, 834, 676. GCꢀMS: Rt = 14.62 min;
M+ = 168.0 calculated for C9H9ClO, experimental = 168.0.
1-(1-chloroethenyl)-4-nitro-benzene (6i). Ketone 5i (330 mg, 2.00 mmol) was
dissolved in CH2Cl2 (4.0 mL) along with triphosgene (593 mg, 2.00 mmol) and pyridine (647
ꢁL, 8.00 mmol). After aqueous workup, the crude mixture was purified with column
chromatography on silica gel, buffered with 1% Et3N, using 100:0 → 95:5 → 85:5 hexanes :
EtOAc to afford vinyl chloride 6i (198 mg, 1.08 mmol) as yellow crystals in a 5:1 mixture with
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geminalꢀdichloride product 7. 1H NMR (400 MHz, CDCl3, *denoted the minor product); δ
(ppm) = 8.24 (d, J = 8.9 Hz)*, 8.21 (d, J = 8.8 Hz, 2H), 7.93 (d, J = 8.9 Hz)*, 7.78 (d, J = 8.8
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Hz, 2H), 5.94 (d, J = 2.1 Hz, 1H), 5.73 (d, J = 2.1 Hz, 1H), 2.56 (s, 3H)*. C NMR (100 MHz,
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CDCl3, *denoted the minor product); δ (ppm) = 147.9,* 142.7, 137.8,* 127.2, 126.8,* 123.6,
123.6,* 116.5, 38.6.* IR (cmꢀ1) = 2916, 2849, 2066, 2046, 1523, 1344, 859, 700. GCꢀMS of the
major product: Rt = 16.56 min; M+ = 183.0 calculated for C8H6ClNO2, experimental = 183.0.
GCꢀMS for the minor product: Rt = 17.83 min; M+ = 219.0 calculated for C8H7Cl2NO2,
experimental = 219.0. HRꢀMS: (M+H)+ 184.0163 calculated for C8H7ClNO2, experimental
184.0160.
1-chloro-3,4-dihydronaphtalene (6j).11b Ketone 5j (266 ꢁL, 2.00 mmol) was dissolved
in CH2Cl2 (4.0 mL) along with triphosgene (593 mg, 2.00 mmol) and pyridine (647 ꢁL, 8.00
mmol). After aqueous workup, the crude mixture was purified with column chromatography on
1
silica gel using 100% hexanes to afford vinyl chloride 6j (177 mg, 1.08 mmol) as orange oil. H
NMR (400 MHz, CDCl3); δ (ppm) = 7.72 (1H, d, J = 7.5 Hz), 7.39ꢀ7.31 (2H, m), 7.24 (1H, d, J
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= 7.4 Hz), 6.29 (1H, t, J = 4.6 Hz), 2.94 (2H, t, J = 8.0 Hz), 2.52ꢀ2,47 (2H, m). C NMR (100
MHz, CDCl3); δ (ppm) = 136.4, 132.5, 130.6, 128.3, 127.4, 126.8, 126.1, 124.2, 27.7, 24.3. IR
(cmꢀ1) = 2934, 2888, 2833, 1161, 812, 758. GCꢀMS: Rt = 15.28 min; M+ = 164.0 calculated for
C10H9Cl, experimental = 164.1.
1,3-dichloro-1,3-cyclohexadiene (6k).21 Diketone 5k (224 mg, 2.00 mmol) was
dissolved in CH2Cl2 (10.0 mL) along with triphosgene (593 mg, 2.00 mmol) and pyridine (647
ꢁL, 8.00 mmol). Without aqueous workup, the crude mixture was directly purified with column
chromatography on silica gel, buffered with 1% Et3N, using 100% hexanes to afford bis(vinyl
1
chloride) 6k (120 mg, 0.81 mmol) as yellow oil. H NMR (400 MHz, CDCl3); δ (ppm) = 5.99
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(q, J = 1.6 Hz, 1H), 5.75 (td, J = 4.5 and 1.6 Hz, 1H), 2.56ꢀ2.50 (m, 2H), 2.47ꢀ2.40 (m, 2H). 13C
NMR (100 MHz, CDCl3); δ (ppm) = 134.7, 126.7, 123.9, 119.7, 29.9, 24.4. IR (cmꢀ1) = 2949,
2886, 2832, 1632, 1591, 1351, 1059, 805, 766, 731. GCꢀMS: Rt = 10.31 min; M+ = 148.0
calculated for C6H6Cl2, experimental = 148.0.
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3-chloro-1-phenylbutadiene (6l).11b Ketone 5l (292 mg, 2.00 mmol) was dissolved in
CH2Cl2 (4.0 mL) along with triphosgene (593 mg, 2.00 mmol) and pyridine (647 ꢁL, 8.00
mmol). After aqueous workup, the crude mixture was purified with column chromatography on
silica gel using 100% hexanes to afford divinyl chloride 6l (81 mg, 0.49 mmol) as orange oil,
which appeared to rapidly decompose upon isolation. GCꢀMS: Rt = 14.87 min; M+ = 164.0
calculated for C10H9Cl, experimental = 164.1.
ACKNOWLEDGMENT
This material is based upon work supported by the National Science Foundation under CHEꢀ
1464788. Generous financial support from Louisiana State University is greatly appreciated.
We thank Professor George Stanley for kindly allowing us to use the GCꢀMS instrument in his
laboratories. We also thank Ms. Caitlan Ayala for her assistance in the preparation of this
manuscript.
SUPPORTING INFORMATION
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GCꢀMS chromatograms for Figure 1 and Table 1, as well as H and 13C NMR spectra for
characterized compounds. This material is available free of charge via the Internet at
http://pubs.acs.org.
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