Vicinal dichlorination of olefins using NH4Cl and oxone

Article abstract of DOI:10.1055/s-0033-1340298

A mild and efficient protocol for the preparation of 1,2-dichloroalkane derivatives from olefins using NH₄Cl and Oxone at room temperature is described. A variety of terminal, internal, and cyclic alkenes reacted smoothly to give the corresponding dichlorinated products in good to excellent yields. Moreover, 1,2-disubstituted symmetrical and unsymmetrical olefins dichlorinated with moderate to excellent diastereoselectivity. This method precludes the use of acidic additives and transition metals in the synthesis of vicinal dichlorides.

Full text of DOI:10.1055/s-0033-1340298

PAPER
▌251
®
paper
Vicinal Dichlorination of Olefins Using NH4Cl and Oxone
Vicinal Dichlorination of Olefins Using NH4Cl and Oxone®
Peraka Swamy, Marri Mahender Reddy, Macharla Arun Kumar, Mameda Naresh, Nama Narender*
Inorganic and Physical Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India
Fax +91(40)27160387; E-mail: narendern33@yahoo.co.in
Received: 28.08.2013; Accepted after revision: 29.10.2013
as targets of synthesis and inspired methods for stereose-
lective chlorination.7
Abstract: A mild and efficient protocol for the preparation of 1,2-
dichloroalkane derivatives from olefins using NH4Cl and Oxone® at
room temperature is described. A variety of terminal, internal, and
cyclic alkenes reacted smoothly to give the corresponding dichlori-
nated products in good to excellent yields. Moreover, 1,2-disubsti-
tuted symmetrical and unsymmetrical olefins dichlorinated with
moderate to excellent diastereoselectivity. This method precludes
the use of acidic additives and transition metals in the synthesis of
vicinal dichlorides.
Stereoselective vicinal dichlorination of olefins is both
relevant and valuable, which enables the construction of
key motifs common to chlorosulfolipids.8 The most
straightforward approach for olefin dichlorination is the
direct addition of molecular chlorine across the double
bond. The potential safety problems, toxic nature, and
hazardous HCl by-products circumvented its routine syn-
thetic utility as chlorinating agent. Alternatively, a few re-
agent combinations have been developed for the
dichlorination of alkenes.9 Among them, the Markó–
Maguire reagent (BnEt3NCl/KMnO4/TMSCl)10 and the
Mioskowski reagent (Et4NCl3)11 have found successful
applications in stereoselective vicinal dichlorination of al-
kenes. More recently, Yoshimitsu and co-workers12a and
Tong and Ren12b developed the methods by employing
NCS/Ph3P and NaCl/Oxone®, respectively, for the dichlo-
rination of olefins. However, most of the existing methods
usually have the disadvantages of using expensive re-
agents, stoichiometric amounts of transition metals, acidic
additives, excess amount of molecular chlorine for re-
agent preparation prior to use, strong acids as chlorinating
agents, and limited applicability to olefinic substrates. In
view of the shortcomings of the above-mentioned meth-
ods and widespread interest in chlorine-containing com-
pounds, research in viable synthetic strategy development
Key words: vicinal dichlorination, olefins, NH4Cl, Oxone®, diaste-
reoselectivity
Halogenated organic compounds are essential building
blocks for chemical synthesis1 and play an important role
in industrial, agricultural, and pharmaceutical applica-
tions.2 More than 2000 chlorine-containing natural prod-
ucts are currently known,3 and many of which display
interesting biological activity of various kinds.4 In many
cases, the natural and non-natural compounds of biologi-
cal importance possess halogens within their structures
for enhancing either the biological activity or chemical
stability and intrinsic potency.5 For instance, the naturally
occurring bioactive polychlorides, such as chlorosulfolip-
ids, have chlorine-substituted multiple stereogenic centers
as their structural feature (Figure 1).6 These chlorosulfoli-
pids, which constitute an intriguing subclass of naturally
occurring organochlorines, have recently gained interest
–
SO3
Cl
O
Cl
Cl
Cl
Cl
Cl
Cl
hexachlorosulfolipid (I)
Me
Cl
–
SO3
O
O
O
Cl
OH Cl
OH
R
Cl
OH
Me
Cl
Cl
Cl
Cl
Cl
Cl
OH
R = OH, undecachlorosulfolipid A (II)
R = H, undecachlorosulfolipid B (III)
Figure 1 Natural bioactive chlorosulfolipids I–III
SYNTHESIS 2014, 46, 0251–0257
Advanced online publication: 28.11.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0033-1340298; Art ID: SS-2013-Z0594-OP
© Georg Thieme Verlag Stuttgart · New York

252
P. Swamy et al.
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for installation of sp3C–Cl (sp3 carbon–chlorine) bond re-
mains an important topic.
Table 1 Effect of Solvent on the Vicinal Dichlorination of Styrenea
Cl
NH4Cl
Oxone®
In continuation of our research program to develop envi-
ronmentally friendly and viable protocols for halogena-
tion,13 earlier we have explored the aromatic
chlorination13b and α-chlorination of carbonyl
compounds13c using NH4Cl as chlorine source and Ox-
one® as an oxidant. We disclose herein the vicinal dichlo-
rination of olefins using NH4Cl and Oxone® under mild
conditions.
Oxone® (2KHSO5·KHSO4·K2SO4), a potassium triple salt
containing potassium peroxy monosulfate, is an inexpen-
sive and effective oxidant. As a result of its stability, non-
toxic ‘green’ nature, affordability and safety profile,
Oxone® is becoming an increasingly popular reagent for
several oxidative transformations.14
Cl
solvent, r.t.
1a
2a
Entry
Solvent
Time (h)
Yield (%)b
1
acetone
24
24
24
24
24
24
24
24
24
0.08
24
24
24
24
24
24
24
24
24
24
0
2
MeCN
0
3
CHCl3
5
4
CH2Cl2
7
5
DCE
16
7
6
CCl4
7
DME
37
47
13
46
33
56
27
58
37
49
30
39
56
53
66
45
70
63
62
76
74
75
75
74
74
72
We envisioned the synthesis of vicinal dichloro deriva-
tives from olefins following our experience with previ-
ously developed methods for the chlorination (Scheme
1).13b,c In this context, our preliminary investigations com-
menced with the model reaction of styrene (1a) with
NH4Cl and Oxone® in a single or mixture of solvents in
order to evaluate the effect of solvent on the vicinal di-
chlorination (Table 1). The results summarized in Table 1
revealed that the sole solvent system could not provide
good results (Table 1, entries 1–10) and the two-phase sol-
vent system consisting of H2O and a chlorinated solvent is
crucial to achieve high yields of the desired products (Ta-
ble 1, entries 23–32). In particular, the best results were
obtained when a 1:4 mixture of dichloromethane and wa-
ter was used as the solvent system (Table 1, entry 26).
8
1,4-dioxane
THF
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
H2O
DCE–MeCN (4:1)
DCE–DME (4:1)
DCE–THF (4:1)
DCE–acetone (4:1)
CH2Cl2–MeCN (4:1)
CH2Cl2–DME (4:1)
CH2Cl2–THF (4:1)
CH2Cl2–acetone (4:1)
CHCl3–acetone (4:1)
CHCl3–DME (4:1)
R
R
NH4Cl, Oxone®
a)
b)
MeCN, r.t.
up to 99% yield
H2O–1,4-dioxane (4:1) 0.58
Cl
O
O
H2O–DME (4:1)
H2O/CHCl3 (4:1)
H2O/CCl4 (4:1)
0.58
0.58
0.58
0.58
0.58
0.58
0.58
0.58
0.58
0.58
0.58
NH4Cl, Oxone®
R2
R2
R1
R1
MeOH, r.t.
up to 97% yield
Cl
Scheme 1 Our previous work on chlorination using NH4Cl and
H2O/DCE (4:1)
Oxone®
H2O/CH2Cl2 (4:1)
H2O/CH2Cl2 (1:1)
H2O/CH2Cl2 (2:1)
H2O/CH2Cl2 (3:1)
H2O/CH2Cl2 (1:2)
H2O/CH2Cl2 (1:3)
H2O/CH2Cl2 (1:4)
With the optimized conditions in hand, the generality of
the reaction was investigated with a variety of olefins (Ta-
ble 2 and Table 3). All the substrates were treated with 2.2
equivalents of NH4Cl and 1.1 equivalent of Oxone® in a
1:4 mixture of dichloromethane and water at room tem-
perature (Scheme 2). As shown in Table 2, all the terminal
aromatic, heteroaromatic, and aliphatic alkenes resulted 31
in the formation of the corresponding vicinal dichlorina-
tion products 2a–i in good to excellent yields. Aromatic
terminal alkenes with activated phenyl ring including 4-
methylstyrene (1b) and 2,4-dimethylstyrene (1c) reacted
smoothly to afford the dichlorinated products 2b and 2c in
83% and 84% yield, respectively (Table 2, entries 2 and
32
a Reaction conditions: substrate 1a (2 mmol), NH4Cl (4.4 mmol), Ox-
one® (2.2 mmol), solvent (10 mL), r.t.
b The product was characterized by NMR spectroscopy and the yield
was based on GC.
Synthesis 2014, 46, 251–257
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Vicinal Dichlorination of Olefins Using NH4Cl and Oxone®
253
3), while those with deactivated phenyl ring comprising 4-
chlorostyrene (1d), 4-bromostyrene (1e), and 4-vinylben-
zoic acid (1f) generated the corresponding products 2d,
2e, and 2f in relatively lower yields (Table 2, entries 4–6).
Polyaromatic alkene, 2-vinylnaphthalene (1g), and het-
eroaromatic alkene 1h were observed to be excellent sub-
strates for the reaction and the corresponding products 2g
and 2h were obtained in 77% and 86% yield, respectively
(Table 2, entries 7 and 8). Aliphatic terminal alkene 1i
also gave the corresponding vicinal dichloro product 2i
smoothly in 85% yield (Table 2, entry 9).
Cl
R2
R1
Cl
2
NH4Cl, Oxone®
R2 = H
R2
R1
1 or 3
1 = alkyl, aryl
CH2Cl2/H2O (1:4)
r.t., 20–120 min
Cl
R2
R
R1
Cl
4
R
2 = alkyl, aryl, acid, ester
Scheme 2 Vicinal dichlorination of olefins using NH4Cl and
Oxone®
Table 2 Vicinal Dichlorination of Terminal Olefins Using NH4Cl and Oxone®a
Entry
Substrate
Time (min)
Product
Yield (%)b
76
Cl
Cl
1
1a
35
2a
Cl
Cl
Cl
2
3
4
1b
1c
1d
35
40
45
2b
2c
2d
83
84
76
Cl
Cl
Cl
Cl
Cl
Cl
Cl
5
6
7
1e
1f
45
2e
2f
77
69
77
Br
Br
Cl
Cl
120
50
HOOC
HOOC
Cl
Cl
1g
2g
Cl
Cl
8
9
1h
1i
30
35
2h
2i
86
85
N
N
Cl
n-C10H21
Cl
n-C10H21
a Reaction conditions: substrate (2 mmol), NH4Cl (4.4 mmol), Oxone® (2.2 mmol), CH2Cl2/H2O (1:4) (10 mL), r.t.
b The products were characterized by NMR spectroscopy and yields were based on GC.
© Georg Thieme Verlag Stuttgart · New York
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254
P. Swamy et al.
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Subsequently, 1,2-disubstituted unsymmetrical and sym- 4c in 71% (dr 3.4:1), 87% (dr 5.2:1), and 86% (dr 4.3:1)
metrical olefins were submitted to the vicinal dichlorina- yield, respectively (Table 3, entries 1–3). The deactivated
tion and the products 4a–j were obtained in good to olefins containing acid and ester functionalities with aryl
excellent yields (Table 3). Unsymmetrical acyclic olefins substituents 3d and 3e reacted incompletely even after
with aryl/alkyl and alkyl substituents 3a, 3b, and 3c af- 120 minutes and gave the desired products 4d and 4e in
forded the respective dichlorinated products 4a, 4b, and 58% (dr 4.9:1) and 63% (dr 5:1) yield, respectively (Table
Table 3 Vicinal Dichlorination of 1,2-Disubstituted Alkenes Using NH4Cl and Oxone®a
NH4Cl
Cl
Oxone®
R2
R2
R1
R1
CH2Cl2/H2O (1:4)
r.t.
3a–j
R1 = aryl, alkyl
2 = aryl, alkyl, acid, ester
Cl
4a–j
R
Entry
Substrate 3
Time (min)
20
Product 4
Yield (%)b
71
drc
Cl
Cl
OH
OH
1
3a
4a
3.4:1
Ph
Ph
Ph
Cl
Cl
2
3
4
5
6
3b
3c
3d
3e
3f
35
4b
87
86
58
63
94
5.2:1
4.3:1
4.9:1
5:1
Ph
Cl
n-C5H11
20
4c
4d
4e
4f
n-C5H11
Cl
Cl
COOH
COOH
120
120
20
Ph
Ph
Ph
Cl
Cl
COOMe
COOMe
Ph
Cl
Cl
>33:1
Cl
Cl
Cl
7
3g
20
4g
80
10:1
Cl
8
9
3h
3i
20
20
4h
4i
63
90
20:1
Cl
Cl
Cl
>6.4:1
Cl
2.1:1
Ph
Ph
84
10
3j
35
4j
Ph
Ph
(92)d
(>2.8:1)d
Cl
a Reaction conditions: substrate 3 (2 mmol), NH4Cl (4.4 mmol), Oxone® (2.2 mmol),
CH2Cl2/H2O (1:4) (10 mL), r.t.
b The products were characterized by NMR spectroscopy and yields were based on GC.
c Determined on the crude by 1H NMR spectroscopy.
d The values shown in parentheses were obtained when cis-stilbene was used as the substrate.
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Vicinal Dichlorination of Olefins Using NH4Cl and Oxone®
255
1
internal standard for H NMR and CDCl3 for 13C NMR spectra.
Coupling constants (J) are reported in hertz (Hz) and standard ab-
breviations were used to denote signal multiplicities. Column chro-
matography was carried out using silica gel (100–200 mesh).
3, entries 4 and 5). Unsymmetrical cyclic olefins includ-
ing indene (3f) and 1,2-dihydronaphthalene (3g) reacted
smoothly and furnished the corresponding dichlorinated
products 4f and 4g in excellent yields and diastereoselec-
tivities within 20 minutes (Table 3, entries 6 and 7). Sim- Vicinal Dichlorination of Olefins 1 and 3; General Procedure
Oxone® (1.35 g, 2.2 mmol) was slowly added to a well stirred solu-
tion of NH4Cl (4.4 mmol) and olefin 1 or 3 (2 mmol) in CH2Cl2/H2O
(1:4; 10 mL) and the reaction mixture was allowed to stir at r.t., until
the olefin had completely disappeared (monitored by TLC, eluent:
ilarly, symmetrical cyclic olefins, such as cyclohexene
(3h) and cis-cyclooctene (3i), were used in this reaction
and the respective vicinal dichlorinated products 4h and 4i
were obtained in 63% (dr 20:1) and 90% (dr >6.4:1) yield,
respectively (Table 3, entries 8 and 9). Both the trans- and
cis-stilbenes provided the corresponding product 4j in
84% (dr 2.1:1) and 92% (dr >2.8:1) yield, respectively.
n-hexane or n-hexane–EtOAc). The organic layer was separated,
and the aqueous phase was extracted with CH2Cl2 (2 × 15 mL). The
combined organic layers were dried (Na2SO4), filtered, and concen-
trated. The residue was purified by column chromatography on sil-
ica gel (100–200 mesh) using n-hexane or n-hexane–EtOAc as
eluent to give the desired products.
As can be seen from Table 3, it is evident that the dichlo-
rination of 1,2-disubstituted olefins provided the corre-
sponding dichlorinated products with predominant anti-
stereoselectivity. The stereochemistry of the isolated vic-
inal dichloro products was established based on 1H NMR
spectroscopy by comparing chemical shift (δ) and cou-
pling constant (J) values of protons attached to the car-
bons bearing Cl atoms with the previously reported data
(see Supporting Information).
1-(1,2-Dichloroethyl)benzene (2a)9g
Yield: 266 mg (1.52 mmol, 76%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 7.46–7.34 (m, 5 H), 5.04–4.96 (m,
1 H), 4.05–3.88 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 137.89, 129.07, 128.73, 127.31,
61.69, 48.27.
HRMS-EI: m/z [M]+ calcd for C8H8Cl2: 174.00031; found:
174.00008.
A plausible reaction mechanism for the vicinal dichlorina-
tion of olefins is depicted in Scheme 3. The reaction of
Oxone® with NH4Cl in a CH2Cl2/H2O solvent system gen-
erates trichloramine12b (NCl3) in situ, which further
reacts15 with olefin A to form a three-membered cyclic
chloronium ion intermediate B. The cyclic intermediate B
1-(1,2-Dichloroethyl)-4-methylbenzene (2b)
Yield: 313 mg (1.66 mmol, 83%); colorless oil.
1H NMR (500 MHz, CDCl3): δ = 7.29 (d, J = 8.24 Hz, 2 H), 7.20 (d,
J = 7.93 Hz, 2 H), 4.99–4.95 (m, 1 H), 4.01–3.89 (m, 2 H), 2.36 (s,
3 H).
13C NMR (125 MHz, CDCl3): δ = 139.05, 134.98, 129.41, 127.20,
61.66, 48.26, 21.16.
HRMS-EI: m/z [M]+ calcd for C9H10Cl2: 188.01596; found:
188.01544.
undergoes ring opening by the nucleophile Cl– (NCl2 ) via
–
2
an SN pathway to yield the corresponding dichlorinated
product C.
1-(1,2-Dichloroethyl)-2,4-dimethylbenzene (2c)
Cl
Cl R2
Yield: 341 mg (1.68 mmol, 84%); colorless oil.
–
NCl2
R2
R2
R1
1H NMR (500 MHz, CDCl3): δ = 7.33 (d, J = 7.93 Hz, 1 H), 7.08 (d,
J = 7.93 Hz, 1 H), 7.01 (s, 1 H), 5.30–5.25 (m, 1 H), 4.06–3.96 (m,
2 H), 2.38 (s, 3 H), 2.31 (s, 3 H).
NCl3
R1
+
_ NCl
–
– NCl2
R1
Cl
(A)
(B)
(C)
13C NMR (125 MHz, CDCl3): δ = 138.82, 136.01, 133.07, 131.50,
Scheme 3 Plausible reaction mechanism
127.43, 126.21, 57.71, 47.48, 21.07, 19.11.
HRMS-EI: m/z [M]+ calcd for C10H13Cl2: 203.03943; found:
203.03943.
In conclusion, we have developed an efficient, mild, and
economically acceptable method for the vicinal dichlori-
nation of olefins. Simple reaction conditions, short reac-
tion times, and use of nonhazardous, easy to handle, and
commercially available reagents render this dichlorina-
tion method as an extremely practical and safe for the syn-
1-Chloro-4-(1,2-dichloroethyl)benzene (2d)
Yield: 318 mg (1.52 mmol, 76%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 7.42–7.30 (m, 4 H), 5.00–4.92 (m,
1 H), 4.02–3.82 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 136.43, 135.00, 128.99, 128.79,
60.63, 48.00.
thesis of 1,2-dichloroalkane derivatives.
A broad
substrate scope was demonstrated; thus both 1,2-disubsti-
tuted unsymmetrical (cyclic and acyclic) and symmetrical
(cyclic and acyclic), and terminal aromatic and aliphatic
alkenes are good substrates for the vicinal dichlorination
reaction in the presence of NH4Cl/Oxone®. Internal ole-
fins were dichlorinated with moderate to high diastereose-
lectivities.
HRMS-EI: m/z [M]+ calcd for C8H9Cl3: 209.97698; found:
209.97686.
1-Bromo-4-(1,2-dichloroethyl)benzene (2e)
Yield: 391 mg (1.54 mmol, 77%); colorless oil.
1H NMR (500 MHz, CDCl3): δ = 7.53 (d, J = 8.39 Hz, 2 H), 7.29 (d,
J = 8.39 Hz, 2 H), 4.98–4.92 (m, 1 H), 4.01–3.95 (m, 1 H), 3.91–
3.85 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 136.89, 131.91, 129.06, 123.14,
60.63, 47.91.
HRMS-EI: m/z [M]+ calcd for C8H9BrCl2: 253.92647; found:
253.92631.
All chemicals used were reagent grade and used as received without
further purification. 1H NMR spectra were recorded at 300 and 500
MHz and 13C NMR spectra at 75 and 125 MHz in CDCl3. The
chemical shifts (δ) are reported in ppm units relative to TMS as an
© Georg Thieme Verlag Stuttgart · New York
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256
P. Swamy et al.
PAPER
4-(1,2-Dichloroethyl)benzoic Acid (2f)
1H NMR (300 MHz, CDCl3): δ = 4.16–4.05 (m, 1 H), 3.99–3.89 (m,
1 H), 2.03–1.88 (m, 1 H), 1.82–1.67 (m, 1 H), 1.62 (d, J = 6.61 Hz,
3 H), 1.43–1.21 (m, 6 H), 0.90 (t, J = 6.61 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 67.40, 60.19, 34.98, 31.15, 25.78,
22.45, 21.83, 13.96.
Yield: 302 mg (1.38 mmol, 69%); white solid.
1H NMR (500 MHz, CDCl3): δ = 8.15 (d, J = 8.24 Hz, 2 H), 7.54 (d,
J = 8.24 Hz, 2 H), 5.07–5.03 (m, 1 H), 4.05–4.00 (m, 1 H), 3.96–
3.91 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 171.61, 143.62, 130.68, 130.29,
128.84, 60.51, 47.82.
HRMS-EI: m/z [M]+ calcd for C8H16Cl2: 182.06291; found:
182.06279.
HRMS-EI: m/z [M]+ calcd for C9H8Cl2O2: 218.99796; found:
218.99714.
erythro-2,3-Dichloro-3-phenylpropanoic Acid (4d)
Yield: 254 mg (1.16 mmol, 58%); white solid.
2-(1,2-Dichloroethyl)naphthalene (2g)
Yield: 346 mg (1.54 mmol, 77%); white solid.
1H NMR (500 MHz, CDCl3): δ = 7.48–7.36 (m, 5 H), 6.63 (br s, 1
H), 5.19 (d, J = 10.68 Hz, 1 H), 4.65 (d, J = 10.52 Hz, 1 H).
1H NMR (500 MHz, CDCl3): δ = 7.77–7.68 (m, 4 H), 7.42–7.35 (m,
3 H), 5.07–5.00 (m, 1 H), 3.98–3.86 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 172.07, 135.98, 129.57, 128.84,
128.08, 60.62, 58.70.
13C NMR (125 MHz, CDCl3): δ = 135.08, 133.45, 132.87, 128.92,
128.12, 127.72, 127.22, 126.80, 126.63, 124.09, 61.99, 48.11.
HRMS-EI: m/z [M]+ calcd for C9H8Cl2O2: 218.99796; found:
218.99715.
HRMS-EI: m/z [M]+ calcd for C12H11Cl2: 225.02378; found:
225.02370.
Methyl erythro-2,3-Dichloro-3-phenylpropanoate (4e)9e
Yield: 293 mg (1.26 mmol, 63%); a 5:1 diastereomeric mixture;
white solid (major isomer).
1H NMR (300 MHz, CDCl3): δ = 7.45–7.38 (m, 5 H), 5.15 (d,
J = 10.68 Hz, 1 H), 4.61 (d, J = 10.68 Hz, 1 H), 3.89 (s, 3 H).
13C NMR (75 MHz, CDCl3): δ = 167.95, 136.26, 130.26, 129.43,
128.02, 60.97, 58.74, 53.36.
2-(1,2-Dichloroethyl)pyridine (2h)
Yield: 302 mg (1.72 mmol, 86%); yellow oil.
1H NMR (300 MHz, CDCl3): δ = 8.67–8.60 (m, 1 H), 7.74 (dt,
J = 7.7, 1.1 Hz, 1 H), 7.45 (d, J = 7.7 Hz, 1 H), 7.33–7.25 (m, 1 H),
5.15–5.07 (m, 1 H), 4.33–4.22 (m, 1 H), 4.10–4.01 (m, 1 H).
13C NMR (75 MHz, CDCl3): δ = 156.14, 149.67, 136.97, 123.67,
123.00, 61.08, 46.71.
HRMS-EI: m/z [M]+ calcd for C10H10Cl2O2: 233.01361; found:
233.01361.
HRMS-ESI: m/z [M]+ calcd for C7H7Cl2N: 176.0028; found:
176.0028.
trans-1,2-Dichloro-2,3-dihydro-1H-indene (4f)9g
Yield: 351 mg 1.88 mmol (94%); a >33:1 diastereomeric mixture;
yellow oil (major isomer).
1H NMR (300 MHz, CDCl3): δ = 7.49–7.40 (m, 1 H), 7.37–7.25 (m,
3 H), 5.34 (d, J = 3.0 Hz, 1 H), 4.68–4.61 (m, 1 H), 3.69 (dd,
J = 16.8, 6.0 Hz, 1 H), 3.17 (dd, J = 16.8, 3.3 Hz, 1 H).
1,2-Dichlorododecane (2i)16
Yield: 406 mg (1.70 mmol, 85%); colorless oil.
1H NMR (300 MHz, CDCl3): δ = 4.09–4.00 (m, 1 H), 3.76 (dd,
J = 11.2, 5.1 Hz, 1 H), 3.65 (dd, J = 11.2, 7.4 Hz, 1 H), 2.07–1.91
(m, 1 H), 1.77–1.65 (m, 1 H), 1.60–1.50 (m, 1 H), 1.44–1.20 (m, 15
H), 0.88 (t, J = 6.7 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 139.75, 129.63, 127.86, 125.42,
125.03, 67.54, 64.43, 40.67.
13C NMR (75 MHz, CDCl3): δ = 61.20, 48.21, 35.02, 31.88, 29.55,
29.52, 29.39, 29.30, 28.97, 25.79, 22.66, 14.09.
HRMS-EI: m/z [M]+ calcd for C9H8Cl2: 187.00813; found:
187.00850.
HRMS-EI: m/z [M]+ calcd for C12H24Cl2: 238.12551; found:
238.12560.
trans-1,2-Dichloro-1,2,3,4-tetrahydronaphthalene (4g)19
Yield: 321 mg (1.6 mmol, 80%); a 10:1 diastereomeric mixture;
colorless oil (major isomer).
1H NMR (500 MHz, CDCl3): δ = 7.37–7.32 (m, 1 H), 7.28–7.19 (m,
2 H), 7.14 (d, J = 7.3 Hz, 1 H), 5.23 (d, J = 2.7 Hz, 1 H), 4.67–4.63
(m, 1 H), 3.19–3.10 (m, 1 H), 2.89–2.83 (m, 1 H), 2.70–2.62 (m, 1
H), 2.17–2.10 (m, 1 H).
erythro-2,3-Dichloro-3-phenylpropan-1-ol (4a)17
Yield: 291 mg (1.42 mmol, 71%); a 3.4:1 diastereomeric mixture;
white solid (major isomer).
1H NMR (300 MHz, CDCl3): δ = 7.40–7.23 (m, 5 H), 5.02 (d,
J = 9.0 Hz, 1 H), 4.38–4.29 (m, 1 H), 4.14–3.94 (m, 2 H), 2.30 (br
s, 1 H).
13C NMR (75 MHz, CDCl3): δ = 134.76, 132.23, 130.95, 128.97,
13C NMR (75 MHz, CDCl3): δ = 138.07, 128.92, 128.57, 127.79,
65.93, 64.10, 61.29.
128.71, 126.59, 59.63, 59.35, 24.86, 23.74.
HRMS-EI: m/z [M]+ calcd for C10H10Cl2: 200.01596; found:
HRMS-EI: m/z [M]+ calcd for C9H10Cl2O: 205.01870; found:
200.01645.
205.01810.
trans-1,2-Dichlorocyclohexane (4h)20
Yield: 192 mg (1.26 mmol, 63%); a 20:1 diastereomeric mixture;
yellow oil (major isomer).
1H NMR (300 MHz, CDCl3): δ = 4.14–3.88 (m, 2 H), 2.41–2.24 (m,
erythro-1,2-Dichloro-1-phenylpropane (4b)18
Yield: 328 mg (1.74 mmol, 87%); a 5.2:1 diastereomeric mixture;
yellow oil (major isomer).
1H NMR (300 MHz, CDCl3): δ = 7.46–7.30 (m, 5 H), 4.91 (d,
J = 7.9 Hz, 1 H), 4.44–4.33 (m, 1 H), 1.71 (d, J = 6.4 Hz, 3 H).
2 H), 1.85–1.63 (m, 4 H), 1.51–1.33 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 63.13, 33.36, 23.04.
13C NMR (125 MHz, CDCl3): δ = 138.60, 128.73, 128.47, 127.71,
67.38, 60.16, 22.12.
HRMS-EI: m/z [M]+ calcd for C6H10Cl2: 152.01596; found:
152.01550.
HRMS-EI: m/z [M]+ calcd for C9H10Cl2: 189.02378; found:
189.02370.
trans-1,2-Dichlorocyclooctane (4i)12
Yield: 325 mg (1.8 mmol, 90%); a >6.4:1 diastereomeric mixture;
colorless oil (major isomer).
erythro-2,3-Dichlorooctane (4c)
Yield: 314 mg (1.72 mmol, 86%); a 4.3:1 diastereomeric mixture;
colorless oil (major isomer).
Synthesis 2014, 46, 251–257
© Georg Thieme Verlag Stuttgart · New York

PAPER
Vicinal Dichlorination of Olefins Using NH4Cl and Oxone®
257
1H NMR (300 MHz, CDCl3): δ = 4.33–4.24 (m, 2 H), 2.35–2.21 (m,
2 H), 2.13–1.96 (m, 2 H), 1.93–1.78 (m, 2 H), 1.77–1.65 (m, 2 H),
1.64–1.49 (m, 2 H), 1.48–1.32 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 68.08, 33.23, 25.37, 25.00.
HRMS-EI: m/z [M]+ calcd for C8H14Cl2: 181.05508; found:
(7) (a) Kawahara, T.; Okino, T. Stud. Nat. Prod. Chem. 2012,
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W.; Carreira, E. M. Nature 2009, 457, 573. (c) Kanady, J. S.;
Nguyen, J. D.; Ziller, J. W.; Vanderwal, C. D. J. Org. Chem.
2009, 74, 2175. (d) Nilewski, C.; Geisser, R. W.; Ebert, M.-
O.; Carreira, E. M. J. Am. Chem. Soc. 2009, 131, 15866.
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181.05501.
erythro-1,2-Dichloro-1,2-diphenylethane (4j)21
Yield: 421 mg (1.68 mmol, 84%; a 2.1:1 diastereomeric mixture)
from cis-stilbene and 462 mg (1.84 mmol, 92%; a >2.8:1 diastereo-
meric mixture) from trans-stilbene; white crystals (major isomer).
1H NMR (300 MHz, CDCl3): δ = 7.7–7.13 (m, 10 H), 5.21 (s, 2 H).
13C NMR (75 MHz, CDCl3): δ = 138.28, 128.95, 128.50, 127.99,
65.68.
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Peterson, J. R.; Selle, B. J. Tetrahedron Lett. 1984, 25, 607.
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1197. (c) Yakabe, S.; Hirano, M.; Morimoto, T. Synth.
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A. S.; Wakharkar, R. D.; Bedekar, A. V. Tetrahedron 1999,
55, 11127. (f) He, Y.; Goldsmith, C. R. Synlett 2010, 1377.
(g) Kitamura, T.; Tazawa, Y.; Morshed, M. H.; Kobayashi,
S. Synthesis 2012, 44, 1159.
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(b) Markó, I. E.; Richardson, P. R.; Bailey, M.; Magure, A.
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HRMS-EI: m/z [M]+ calcd for C14H12Cl2: 250.03161; found:
250.03199.
Acknowledgment
We thank the CSIR Network project CSC-0125 for financial sup-
port. P.S acknowledges the financial support from UGC, India in
the form of a fellowship. M.M.R, M.A.K and M.N acknowledge the
financial support from CSIR, India in the form of fellowships.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SunIfoigop
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© Georg Thieme Verlag Stuttgart · New York
Synthesis 2014, 46, 251–257