Difunctionalization of Alkenes Using 1-Chloro-1,2-benziodoxol-3-(1H)-one

Article abstract of DOI:10.1021/acs.joc.6b00295

Difunctionalization of alkenes with 1-chloro-1,2-benziodoxol-3-(1H)-one (1) was investigated. Various additional nucleophiles were tested, and oxychlorination, dichlorination, azidochlorination, chlorothiocyanation, and iodoesterfication were demonstrated. The oxychlorination product was obtained efficiently when the reaction was operated in water. Dichlorination occurred in the presence of a Lewis basic promoter, such as 4-phenylpyridine N-oxide, as an additive. The reaction with in situ-generated azido anion afforded azidochlorinated compounds with a chlorine atom at the terminal position, while the reaction with trimethylsilyl isothiocyanate produced chlorothiocyanation adducts with a chlorine atom at the benzylic position. On the other hand, when 1 was treated with tetra-n-butylammonium iodide prior to the addition of alkenes, only iodoesterification occurred selectively. These mild reactions enable convenient site-selective difunctionalizations of substrates having two alkene moieties. NMR experiments suggested that the electrophilic reactive species in each reaction varied depending on the nature of the added nucleophile.

Full text of DOI:10.1021/acs.joc.6b00295

Article
pubs.acs.org/joc
Difunctionalization of Alkenes Using 1‑Chloro-1,2-benziodoxol-3-
(1H)‑one
Hiromichi Egami,* Takahiro Yoneda, Minako Uku, Takafumi Ide, Yuji Kawato,
and Yoshitaka Hamashima*
School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka 422-8526, Japan
S
* Supporting Information
ABSTRACT: Difunctionalization of alkenes with 1-chloro-1,2-benziodoxol-3-(1H)-one (1)
was investigated. Various additional nucleophiles were tested, and oxychlorination,
dichlorination, azidochlorination, chlorothiocyanation, and iodoesterfication were demon-
strated. The oxychlorination product was obtained efficiently when the reaction was operated
in water. Dichlorination occurred in the presence of a Lewis basic promoter, such as 4-
phenylpyridine N-oxide, as an additive. The reaction with in situ-generated azido anion afforded
azidochlorinated compounds with a chlorine atom at the terminal position, while the reaction
with trimethylsilyl isothiocyanate produced chlorothiocyanation adducts with a chlorine atom
at the benzylic position. On the other hand, when 1 was treated with tetra-n-butylammonium
iodide prior to the addition of alkenes, only iodoesterification occurred selectively. These mild
reactions enable convenient site-selective difunctionalizations of substrates having two alkene
moieties. NMR experiments suggested that the electrophilic reactive species in each reaction
varied depending on the nature of the added nucleophile.
1,2,4,5-tetramethylbenzene (durene) in acetic acid11a and α-
INTRODUCTION
■
chlorination of β-dicarbonyl compounds (Scheme 1b).11b Since
1 would undergo rapid ligand exchange reaction with added
nucleophile X, we expected that various types of reactive
species could be formed (Scheme 1c).12 For example,
substitution by an electronically neutral Lewis base would
give a more Lewis-acidic hypervalent iodine(III), and ligand
exchange reaction followed by reductive elimination would give
Cl−X species. Thus, the nature of the added nucleophile may
influence the reaction pathway, opening up the possibility of
obtaining unique difunctionalization products. To investigate
differences in reactivity and synthetic utility compared to other
chlorinating reagents, we examined the use of 1 for
difunctionalization of alkenes with various nucleophiles. In
this report, we present various reactions of styrene derivatives
with 1-chloro-1,2-benziodoxol-3-(1H)-one 1, including oxy-
chlorination,13 dichlorination,14 azidochlorination,15 chlorothio-
cyanation,16 as well as iodoesterification17 (Scheme 1d).
Difunctionalization of alkenes is a powerful tool for the
synthesis of complex molecules, because two functional groups
can be introduced into an organic framework at once.1 Among
various functional groups, chlorine is often found in natural
products and bioactive compounds, and organochlorine
compounds have also been utilized as useful building blocks.
Although many methodologies are available to prepare
organochlorine compounds,2 difunctionalization-type chlorina-
tion of alkenes is one of the most attractive.3
We have previously reported several trifluoromethylation
reactions of C−C multiple bonds with Togni reagent in the
presence of copper catalyst,4 and in the preparation of the
Togni reagent, 1-chloro-1,2-benziodoxol-3-(1H)-one (1)5,6 is
synthesized as a precursor for ligand exchange reaction with a
trifluoromethyl anion (Scheme 1a).7 During the course of our
investigation, we became interested in the reactivity of 1.
Among chlorine-containing hypervalent iodine reagents,
iodobenzene dichloride is a representative reagent for chloro-
functionalization of alkenes. For example, Nicolaou et al.
achieved asymmetric dichlorination of allylic alcohols using a
dimeric cinchona alkaloid derivative as a catalyst,8 and Du and
Zhao et al. recently reported oxychlorination of alkenes using
iodobenzene dichloride in DMF.9 However, the utility of such
reagents in difunctionalization of alkenes has not been
thoroughly examined. Furthermore, the reactivity of 1 toward
organo-functional groups has not been studied, except in a few
cases. For example, 1 was used as a terminal oxidant in alcohol
oxidation with 2,2,6,6-tetramethylpyrrolidine N-oxide
(TEMPO).10 As for the use of 1 as an electrophilic chlorination
reagent, there are only two reports describing chlorination of
RESULTS AND DISCUSSION
■
Development of Difunctionalization of Alkenes with
1. 1. Reaction with Water. Initially, oxychlorination of alkenes
was selected as a test reaction for investigating the reactivity of
the chlorination reagent 1, because the corresponding product,
chlorohydrin, represents an important class of substructures in
organic synthesis.13 With reference to previous reports on
oxychlorination,18 we carried out the reaction in a mixture of
acetone/H2O as a solvent. Although the reaction proceeded
Received: February 9, 2016
© XXXX American Chemical Society
A
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good to high yields were generally obtained (3c−3e). In
addition, ortho-substituted styrenes were applicable to provide
corresponding products 3f and 3g in high yields, while the
substrate having an strongly electron-withdrawing group, such
as a nitro group, was transformed in only 48% yield (3h). The
reaction of geminally and vicinally disubstituted alkenes
proceeded smoothly to give 3i and 3j in 76% and 85% yields,
respectively. Reactions of aliphatic alkene 2k afforded 3k in
40% yield, though dichlorination also proceeded as an
undesired reaction.
Scheme 1. Use of 1-Chloro-1,2-benziodoxol-3-(1H)-one (1)
2. Reaction with Pyridine N-Oxide. We next attempted to
use pyridine N-oxide as an oxygen-based nucleophile, expecting
that the corresponding N-oxide adduct would undergo
elimination of pyridine to give α-chloroketones. However, no
N-oxide adduct was formed. Instead, the dichlorination product
was formed cleanly in nonprotic solvent (Table 2).19 Addition
Table 2. Dichlorination with 4-Ph-pyridine N-oxide (4-Ph-
PNO)
slowly at room temperature, chlorohydrins were cleanly formed
at 40 °C (Table 1). The reactions with electron-rich 2a and 2b
provided the corresponding chlorohydrins in 76% and 69%
isolated yields, respectively. This reaction could also be applied
to styrene derivatives having no electron-donating groups, and
a
Table 1. Oxychlorination in Acetone/Water
a
The reactions were carried out with 1 (2.2 equiv) and 4-
phenylpyridine-N-oxide (1 equiv) at 40 °C in 1,2-dichloroethane on
a 0.2 mmol scale.
of 4-phenylpyridine N-oxide gave better results for all the
substrates examined. It is considered that the N-oxide acted as a
Lewis basic promoter for 1, and not as an actual nucleophile;
the second chloride ion would come from substitution reaction
of a chloride ion within 1 by pyridine N-oxide. Thus, we also
examined the reaction with tetrabutylammonium chloride
(TBAC) in place of the combination of pyridine N-oxide and
1, but this reaction afforded a lower yield (∼50% yield).
All dichlorination products were isolated by a recycle gel
permeation chromatography (GPC) system with polystyrene/
divinylbenzene porous polymer, because of the instability of
some products in the presence of silica gel. In dichloroethane
(DCE), the reaction of styrene derivatives bearing electron-
donating groups proceeded smoothly at 40 °C, affording the
corresponding products (4a,b,l,m) in good yields. Although 4-
chlorostyrene 2d reacted slowly, the desired product 4d was
obtained in 34% yield, together with the 2-chlorostyrene
derivative (20% yield) as a byproduct. A more electron-
deficient one did not provide the corresponding dichlorination
product. For example, no reaction occurred in the reaction of
a
The reactions were carried out with 1 (1.1 equiv) at 40 °C in
acetone/water on a 0.2 mmol scale, unless otherwise mentioned.
b
1
Determined by H NMR analysis by using 1,1,2,2-tetrachloroethane
c
as an internal standard. Run with 1.5 equiv of 1.
B
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2h. An ortho-substituted substrate 2f provided dichlorination
product 4f (50%) and the corresponding 2-chlorostyrene
derivative (34%). This reaction was also applicable to
benzopyran 2i, giving the corresponding dichloride 4i in 70%
yield. Although some unidentified byproducts were detected by
NMR analysis of the crude mixture, aliphatic product 4k was
isolated in 35% yield.
chlorosuccinimide (NCS), a commonly used chlorinating
reagent, for azidochlorination of alkenes is quite rare, to our
knowledge.15c To compare the utility of this reagent, the
reaction with NCS instead of 1 was examined under the similar
reaction conditions (eq 1). As a result, azidochlorination
proceeded to give 5a in 78% yield after 24 h, suggesting that the
reaction with 1 is faster than that with NCS.
3. Reaction with Trimethylsilyl Azide (TMSN3). Having
confirmed that 1 can act as a mild electrophilic chlorinating
reagent, we turned our attention to the introduction of a
nitrogen functional group. Thus, trimethylsilyl azide (TMSN3)
was added as an external nucleophile to the reaction mixture of
1 and the substrates in nonprotic solvent. Although the reaction
without an additive was sluggish, the addition of fluoride ion to
generate azide anion was effective to accelerate the desired
azidochlorination reaction. Screening of the reaction conditions
revealed that CsF was the fluoride ion source of choice.19
Furthermore, the reaction temperature was crucial to control
the regioselectivity; a significant amount of the regioisomer was
formed as a byproduct when the reaction was run at 40 °C.
Similarly to the other reactions, electron-donating groups on
the aryl ring facilitated the reaction, and the products (5a,l,m)
were obtained in good to high yields (Table 3). In the case of
4. Reaction with (Trimethylsilyl)isothiocyanate (TMSNCS).
Following the azidochlorination with TMSN3, chlorothiocya-
nation of alkenes, which has rarely been reported,16 was next
examined with TMSNCS (Table 4). Unlike the azidochlorina-
a
Table 4. Chlorothiocyanation Using 1 with TMSNCS
a
Table 3. Azidochlorination Using 1 with TMSN3
a
a
The reactions were carried out with 1 (2 equiv) and TMSNCS (2
The reactions were carried out with 1 (2 equiv), TMSN3 (2.5 equiv),
b
equiv) in CH2Cl2 on a 0.2 mmol scale. Isolated using a GPC system.
CsF (2 equiv) at 0 °C in CH2Cl2 on a 0.2 mmol scale, unless otherwise
c
d
b
c
d
Run for 1 h. Determined by NMR analysis using 1,1,2,2-
mentioned. Run for 24 h. Run at −15 °C. Isolated yield of trans-
isomer. Determined by H NMR analysis using 1,1,2,2-tetrachloro-
ethane as an internal standard.
e
e
1
tetrachloroethane as an internal standard. These compounds could
not be isolated due to their instability. Isolated by chromatography on
f
silica gel.
2i, signals of the corresponding regioisomer were detected in
the 1H NMR spectrum of the crude mixture when the reaction
was performed at 0 °C. However, when the reaction was
performed at −15 °C, no regioisomer was detected, and 5i was
obtained in 48% NMR yield (trans/cis = 34%/14%). An ortho-
substituent on the aryl ring retarded the formation of desired
product 5f, and dichlorination product 4f, 2-chlorostyrene
derivative, and 2-chloro-2′-methoxyacetophenone were ob-
served as byproducts. Again, the disubstituted substrate 2j
could be used, and the product 5j was isolated in 46% yield. In
these reactions, incorporation of a fluorine atom was not
observed. When the reaction of 3-nitrostyrene 2h was carried
out under the standard conditions, a trace amount of the
azidochlorination product was detected in the 1H NMR
spectrum of the crude mixture. Incidentally, the use of N-
tion, the reaction did not require the addition of a fluoride ion
source. The ratio between 1 and TMSNCS was important for
this reaction, because when the reaction was conducted with an
excess of TMSNCS, dithiocyanation occurred as a side reaction.
The structure of the resulting product was unambiguously
determined from the HMBC and HSQC spectra.19 It is
noteworthy that the chlorine atom was introduced at the
benzylic position, which is distinct from other reactions (vide
supra). The reaction was completed within only 15 min, and
good to high yields were obtained with not only electron-rich
but also electron-poor substrates. Since most of the products
were not stable on silica gel, purification was performed using a
recycle GPC system. In the case of substrates having an
electron-withdrawing group, the corresponding products could
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tolerate silica gel chromatography (6d and 6o). Since partial
decomposition of 6i and 6m occurred even during purification
by GPC, the thiocyanation products were isolated after
transformation of 6. Thus, treatment of the crude reaction
products with acetone/H2O at room temperature gave more
stable oxythiocyanation compounds 7i and 7m in 62% and 76%
isolated yield, respectively (Scheme 2). Additionally, the high
reactions, some functional groups were tolerant of these
reaction conditions. The regioselectivity was the same as that
observed in preceding oxyiodination reactions, including the
reaction using the combination of iodobenzene dichloride and
iodine in MeOH, which was reported by Yusubov and co-
workers.20 The reactions of electron-rich substrates proceeded
smoothly, and the corresponding products were obtained in
good to high yields, irrespective of the position of substituents.
In contrast, a trace amount of product 8h was observed in the
reaction of 2h having a nitro group. In the case of 4-phenyl-1-
butene 2k, an inseparable mixture of some unidentified
products was obtained.
Scheme 2. Transformation of Chlorothiocyanation Products
6. Site-Selective Difunctionalization. As described above, 1
seems to show mild reactivity compared with other
halogenation reagents. Taking advantage of this feature, we
expected that site-selective functionalization of substrates
having multiple olefins would be possible. Thus, we
investigated the difunctionalization reactions of substrates
bearing two olefin moieties (2q and 2r) (Scheme 3). To our
a
b
Scheme 3. Site-Selective Difunctionalization
Isolated yield. Determined by NMR analysis using 1,1,2,2-
tetrachloroethane as an internal standard.
reactivity of this reaction enabled difunctionalization of
cyclohexene.16b It should be noted that a complex mixture
was formed when NCS was used instead of 1, indicating the
mild reactivity of the present reagent combination.
5. Reaction with Tetra-n-butylammonium Iodide (TBAI).
During further screening of the reaction conditions, we found
that the combination of 1 and TBAI selectively afforded the
corresponding iodoesterification products 8 in good to high
yields (Table 5). As in the case of the chloro-difunctionalization
a
Table 5. Iodoesterification Using 1 with TBAI
delight, site-selective reactions occurred: In the case of 2q, only
the styrene moiety reacted to give the corresponding products
3q, 4q, and 8q, due to the higher reactivity of the conjugated
alkene compared with the allylic ether moiety. In addition, 3r,
4r, and 8r were selectively obtained in the reaction of 2r. These
results suggest that the reaction of 1 would be sensitive to steric
hindrance at the reaction site.
Mechanistic Discussion. In general, difunctionalization of
alkenes using a hypervalent iodine reagent is thought to
proceed through the coordination of alkenes to the hypervalent
iodine atom to generate an iodonium cation and/or the
a
The reactions were carried out with 1 (1.5 equiv) and TBAI (1.5
equiv) in CH2Cl2 at 40 °C on a 0.2 mmol scale, unless otherwise
mentioned. Run with 3 equiv of TBAI. Run at 60 °C.
b
c
D
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corresponding carbocation.1a,12,21 In the light of the proposed
reaction mechanism of dioxy-functionalization of alkenes,21 the
oxychlorination and the dichlorination could be explained by a
similar mechanism, as shown in Scheme 4. Thus, the first
nucleophile in each reaction attacks at the benzylic position,
and substitution reaction by a chloride ion occurs at the
terminal position.
Scheme 4. Typical Mechanism of Alkene Difunctionalization
Using a Hypervalent Iodine Reagent
Although a similar reaction mechanism might be applicable
to other difunctionalization reactions, the following results let
us to probe the actual reactive species in aziochlorination and
chlorothiocyanation: (1) The combination of TMSCl, CsF, and
azido-type hypervalent iodine reagent 922 provided the same
product 5, and not the regioisomer (eq 2 and Table 3),
1
Figure 1. H NMR study of azidochlorination.
suggesting that the same chemical species is operative in both
reactions. (2) The regioselectivity of azidochlorination and that
of chlorothiocyanation are complementary to each other.
First, we measured the 1H NMR spectrum of a 1:1:1 mixture
of 1, TMSN3, and CsF (Figure 1). At the initial stage, in
addition to 1 and 9, trimethylsilyl 2-iodobenzoate was detected
(Figure 1a). The amount of 1 continued to decrease over the
initial 2.5 h (Figure 1b), while that of 9 gradually increased.
The reaction of 9 with TMSCl and CsF after 30 min gave a
mixture similar to that shown in Figure 1a, in which the
formation of a larger amount of trimethylsilyl 2-iodobenzoate
was observed (Figure 2a). After 2.5 h, both 1 and 9 were clearly
observed, while trimethylsilyl 2-iodobenzoate was no longer
detected, as was seen in Figure 1b (Figure 2b). The formation
of trimethylsilyl 2-iodobenzoate at the initial stage suggested
the generation of chlorine azide (ClN3) in the reaction mixture,
and the disappearance of trimethylsilyl 2-iodobenzoate after 2.5
h might be associated with reoxidation of 2-iodobenzoate by
ClN3 to regenerate hypervalent iodine reagents. When styrene
derivative 2a was added to the reaction mixture of 1, TMSN3,
and CsF after 2.5 h (Figure 1b), no reaction occurred,
indicating that neither 1 nor 9 could react with olefins.
However, upon further addition of TMSCl to this reaction
mixture, which might allow regeneration of ClN3, the
azidochlorination proceeded at 0 °C together with formation
of the regioisomer and dichlorination products. Based on these
results, we speculate that ClN3 is the actual reactive species in
this azidochlorination, although intermediate 10 generated in
1
Figure 2. H NMR spectra of the mixture of 9, TMSCl, and CsF.
situ cannot be ruled out at present (Scheme 5).15b In the
reaction with 9 (eq 2), the yield was decreased to 65%
compared with the reaction with 1 (Table 3), and some
1
unidentified byproducts were detected by H NMR analysis of
the crude mixture. We think that this might be due to the
higher concentration of highly reactive ClN3 at the initial stage
of the reaction starting from 9.
To examine chlorothiocyanation, we also conducted NMR
experiments using a mixture of 1 and TMSNCS in CDCl3. In
this case, most of compound 1 disappeared quickly, and peaks
of trimethylsilyl 2-iodobenzoate were observed clearly (Figure
3a). Thus, we considered that thiocyanogen chloride (Cl−
SCN) would be an active species in this reaction (Scheme 6).23
The involvement of Cl−SCN can explain the observed
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regioselectivity of the product can be understood in terms of
the inherent reactivity of putative intermediate 11 (Scheme 6).
Scheme 5. Proposed Mechanism of Azidochlorination
CONCLUSION
■
The reactivity of 1 toward alkenes was investigated. Oxy-
chlorination, dichlorination, azidochlorination, chlorothiocya-
nation, and iodoesterification were achieved with appropriate
nucleophiles and reaction conditions. In addition, chemo-
selective difunctionalizations were successfully achieved,
reflecting the mild reactivity of these reactions. The nature of
the reactive intermediates in each reaction was investigated by
means of NMR experiments, which indicated that hypervalent
iodine reagent 1 can generate various active species in the
presence of appropriate additives. Further applications of 1
toward other functional groups are ongoing in our laboratory.
EXPERIMENTAL SECTION
■
General Experimental. Chemical shifts are reported downfield
1
from TMS (= 0) or CDCl3 for H NMR. For 13C NMR, chemical
shifts are reported in the scale relative to CDCl3. Infrared spectra were
measured with KBr plate, and only diagnostic absorptions of infrared
spectra are listed below. Column chromatography was performed with
silica gel N-60 (40−100 mm). As described in the Results and
Discussion section, purification was carried out using a recycling
preparative HPLC system, if necessary. TLC analysis was performed
on Silica gel 60 F254-coated glass plates. Visualization was
accomplished by means of ultraviolet (UV) irradiation at 254 nm or
by spraying 12-molybdo(VI)phosphoric acid ethanol solution as the
developing agent. Dehydrated dichloromethane (CH2Cl2), dichloro-
ethane (DCE), acetone, TMSN3, TMSNCS, 4-phenylpyridine N-oxide
(4-Ph-PNO), CsF, and TMSCl were obtained from commercial
sources, and used as received. 1-Chloro-1,2-benziodoxol-3-(1H)-one 1
was prepared according to the literature.7
Figure 3. 1H NMR studies of chlorothiocyanation and iodoester-
ification.
Typical Procedure for Oxychlorination. To a solution of 1 (62
mg, 0.22 mmol) in acetone/H2O (2 mL/2 mL) was added 4-
methoxystyrene 2a (26 μL, 0.2 mmol) at 40 °C. The mixture was
stirred for 24 h at the same temperature, then quenched with sat.
NaHCO3, and diluted with ethyl acetate and H2O. The organic phase
was dried over MgSO4, filtered, and concentrated under reduced
pressure. The residue was purified by column chromatography on
silica gel (n-hexane/ethyl acetate = 10/1) to provide 3a (28.2 mg,
76%).
Scheme 6. Proposed Mechanism of Chlorothiocyanation and
Iodoesterfication
2-Chloro-1-(4-methoxyphenyl)ethan-1-ol (3a). Colorless oil; 28.2
mg, 76%; 1H NMR (500 MHz, CDCl3): δ = 7.31 (d, J = 8.8 Hz, 2H),
6.90 (d, J = 8.8 Hz, 2H), 4.85 (dd, J = 3.6, 8.7 Hz, 1H), 3.81 (s, 3H),
3.70 (dd, J = 3.6, 11.1 Hz, 1H), 3.63 (dd, J = 8.7, 11.1 Hz, 1H), 2.66
ppm (brs, 1H); 13C NMR (125 MHz, CDCl3): δ = 159.7, 132.1, 127.3,
114.0, 73.7, 55.3, 50.9 ppm; IR (CHCl3): 3599, 3009, 1613, 1513,
1249 cm−1; HRMS (ESI+-TOF): Calcd for [C9H11ClO2 + H]+: m/z =
187.0520, Found: 187.0518.
1-(Benzo[d][1,3]dioxol-5-yl)-2-chloroethan-1-ol (3b). Colorless
1
solid; 27.6 mg, 69%; Mp 94−95 °C; H NMR (500 MHz, CDCl3):
δ = 6.88 (d, J = 1.3 Hz, 1H), 6.83 (dd, J = 1.3, 7.9 Hz, 1H), 6.79 (d, J =
7.9 Hz, 1H), 5.96 (s, 2H) 4.80 (dd, J = 3.4, 8.6 Hz, 1H), 3.68 (dd, J =
3.4, 11.3 Hz, 1H), 3.60 (dd, J = 8.6, 11.3 Hz, 1H), 2.66 ppm (brs, 1H);
13C NMR (125 MHz, CDCl3): δ = 147.9, 147.6, 133.9, 119.7, 108.3,
106.5, 101.2, 73.9, 50.8 ppm; IR (CHCl3): 3595, 3032, 1489, 1446,
1246 cm−1; HRMS (ESI+-TOF): Calcd for [C9H9ClO3 + Na]+: m/z =
223.0132, Found: 223.0142.
regioselectivity (Table 4). The σ* orbital of the S−Cl bond
would interact with alkene to give a three-membered thionium
ion, which is opened by attack of the remaining chloride ion
(Scheme 6). It should be noted that Cl−SCN can be formed
readily from easy-to-handle reagent 1, while the previous
procedures required gaseous chlorine (Cl2).16,23
2-Chloro-1-phenylethan-1-ol (3c). Colorless oil; 23.6 mg, 76%; 1H
NMR (500 MHz, CDCl3): δ = 7.40−7.32 (m 5H), 4.91−4.90 (m,
1H), 3.75 (dd, J = 3.4, 11.2 Hz, 1H), 3.65 (dd, J = 9.1, 11.2 Hz, 1H),
2.69 ppm (d, J = 2.3 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ =
139.9, 128.7, 128.4, 126.0, 74.1, 50.9 ppm; IR (CHCl3): 3595, 3035,
3009, 1454, 1238, 1192 cm−1; HRMS (ESI+-TOF): Calcd for
[C8H9ClO + H]+: m/z = 157.0415, Found: 157.0416.
1
The reaction of 1 with TBAI was also monitored by H
NMR analysis. Although the signals were broad, the pattern was
quite similar to that of 2-iodobenzoic acid, except that the
signals were shifted to higher magnetic field. According to the
literature, these peaks are not due to the tetra-n-butylammo-
nium salt of 2-iodobenzoate.24 Thus, it seems likely that
hypoiodous compound 11 is generated.25 The structure and
2-Chloro-1-(4-chlorophenyl)ethan-1-ol (3d). Colorless solid; 28.3
mg, 74%; Mp 33−34 °C; 1H NMR (500 MHz, CDCl3): δ = 7.37−7.32
F
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(m, 4H), 4.89 (ddd, J = 3.4, 3.4, 8.6 Hz, 1H), 3.72 (dd, J = 3.4, 11.0
Hz, 1H), 3.61 (dd, J = 8.6, 11.0 Hz, 1H), 2.65 ppm (d, J = 3.4 Hz,
1H); 13C NMR (125 MHz, CDCl3): δ = 138.3, 134.2, 128.8, 127.4,
73.3, 50.7 ppm; IR (CHCl3): 3595, 3007, 1597, 1492 cm−1; HRMS
(ESI+-TOF): Calcd for [C8H8Cl2O + Na]+: m/z = 212.9844, Found:
212.9842.
1-(4-Bromophenyl)-2-chloroethan-1-ol (3e). Colorless oil; 35.1
mg, 75%; 1H NMR (500 MHz, CDCl3): δ = 7.51 (d, J = 8.2 Hz, 2H),
7.27 (d, J = 8.2 Hz, 2H), 4.87 (ddd, J = 3.4, 3.4, 8.6 Hz, 1H), 3.72 (dd,
J = 3.4, 11.3 Hz, 1H), 3.60 (dd, J = 8.5, 11.3 Hz, 1H), 2.69 ppm (d, J =
3.4 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 138.8, 131.8, 127.7,
122.4, 73.4, 50.6 ppm; IR (CHCl3): 3595, 1593, 1489, 1072 cm−1;
HRMS (ESI+-TOF): Calcd for [C8H8BrClO + Na]+: m/z = 256.9339,
Found: 256.9350.
2-Chloro-1-(2-methoxyphenyl)ethan-1-ol (3f). Colorless oil; 34.8
mg, 93%; 1H NMR (500 MHz, CDCl3): δ = 7.44 (d, J = 7.5 Hz, 1H),
7.32−7.28 (m, 1H), 7.00 (dd, J = 7.5, 7.5 Hz, 1H), 6.89 (d, J = 8.6 Hz,
1H), 5.15−5.12 (m, 1H), 3.87−3.84 (m, 4H), 3.64 (dd, J = 8.6, 10.9
Hz, 1H), 2.92 ppm (d, J = 5.2 Hz, 1H); 13C NMR (125 MHz,
CDCl3): δ = 156.2, 129.2, 127.8, 127.2, 120.8, 110.4, 70.4, 55.3, 49.5
ppm; IR (CHCl3): 3586, 2962, 1603, 1492, 1287 cm−1; HRMS (ESI+-
TOF): Calcd for [C9H11ClO2 − HCl + H]+: m/z = 151.0754, Found:
151.0754.
2-Chloro-1-(2-bromophenyl)ethan-1-ol (3g). Colorless oil; 36.0
mg, 76%; 1H NMR (500 MHz, CDCl3): δ = 7.63 (dd, J = 1.7, 7.7 Hz,
1H), 7.55 (dd, J = 1.2, 8.0 Hz, 1H), 7.39−7.36 (m, 1H), 7.21−7.18
(m, 1H), 5.27 (ddd, J = 2.9, 3.4, 8.9 Hz, 1H), 3.92 (dd, J = 2.9, 11.5
Hz, 1H), 3.54 (dd, J = 8.9, 11.5 Hz, 1H), 2.74 ppm (d, J = 3.4 Hz,
1H); 13C NMR (125 MHz, CDCl3): δ = 138.8, 132.8, 129.8, 127.8,
127.7, 121.9, 72.9, 49.5 ppm; IR (CHCl3): 3587, 3065, 1570, 1497,
1029 cm−1; HRMS (ESI+-TOF): Calcd for [C8H8BrClO − HCl +
H]+: m/z = 198.9753, Found: 198.9753.
silica gel was washed with CH2Cl2. The organic solvent was
concentrated under reduced pressure. The residue was purified by a
recycle GPC system (CHCl3) to provide 4a (32.7 mg, 80%).
1-(1,2-Dichloroethyl)-4-methoxybenzene (4a). Yellowish viscous
1
oil; 32.7 mg, 80%; H NMR (500 MHz, CDCl3): δ = 7.33 (d, J = 9.1
Hz, 2H), 6.91 (d, J = 9.1 Hz, 2H), 4.98 (dd, J = 6.2, 8.4 Hz, 1H), 3.99
(dd, J = 6.2, 11.3 Hz, 1H), 3.91 (dd, J = 8.4, 11.3 Hz, 1H), 3.82 ppm
(s, 3H); 13C NMR (125 MHz, CDCl3): δ = 160.1, 130.1, 128.7, 114.2,
61.6, 55.3, 48.3 ppm; IR (CHCl3): 3005, 1612, 1516, 1254 cm−1;
HRMS (ESI+-TOF): Calcd for [C9H10Cl2O + Na]+: m/z = 227.0006,
Found: 226.9988.
5-(1,2-Dichloroethyl)benzo[d][1,3]dioxole (4b). Colorless oil; 30.3
mg, 69%; 1H NMR (500 MHz, CDCl3): δ = 6.90 (d, J = 1.7, 1H), 6.86
(dd, J = 1.7, 7.9 Hz, 1H), 6.79 (d, J = 7.9, 1H), 5.99 (s, 2H) 4.30 (dd, J
= 6.5, 8.4 Hz, 1H), 3.96 (dd, J = 6.5, 11.2 Hz, 1H), 3.87 ppm (dd, J =
8.4, 11.2 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 148.3, 148.1,
131.7, 121.6, 108.2, 107.3, 101.5, 61.8, 48.3 ppm; IR (CHCl3): 3036,
3009, 1492, 1446, 1238 cm−1; HRMS (ESI+-TOF): Calcd for
[C9H8Cl2O2 + H]+: m/z = 218.9974, Found: 218.9976.
1-Chloro-4-(1,2-dichloroethyl)benzene (4d). Colorless oil; 14.2
mg, 34%; 1H NMR (500 MHz, CDCl3): δ = 7.39−7.34 (m, 4H), 4.97
(dd, J = 6.3, 8.3 Hz, 1H), 3.99 (dd, J = 6.3, 11.3 Hz, 1H), 3.88 ppm
(dd, J = 8.3, 11.3 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 136.5,
135.0, 129.0, 128.8, 60.6, 48.0 ppm; IR (CHCl3): 3036, 2953, 1495,
1094, 833 cm−1; HRMS (ESI+-TOF): Calcd for [C8H7Cl3 + H]+: m/z
= 208.9686, Found: 208.9688.
1-(1,2-Dichloroethyl)-2-methoxybenzene (4f). Colorless oil; 20.5
mg, 50%; 1H NMR (500 MHz, CDCl3): δ = 7.47 (dd, J = 1.7, 7.5 Hz,
1H), 7.35−7.31 (m, 1H), 7.01 (ddd, J = 1.2, 7.5, 7.5 Hz, 1H), 6.19 (d,
J = 8.0 Hz, 1H), 5.55 (dd, J = 6.7, 7.2 Hz, 1H), 4.03 (dd, J = 6.7, 11.3
Hz, 1H), 3.94 (dd, J = 7.2, 11.3 Hz, 1H), 3.88 ppm (s, 3H); 13C NMR
(125 MHz, CDCl3): δ = 156.5, 130.2, 128.3, 126.0, 120.8, 110.9, 56.5,
55.6, 47.9 ppm; IR (CHCl3): 3007, 2960, 1603, 1493, 1265 cm−1;
HRMS (ESI+-TOF): Calcd for [C9H10Cl2O − HCl + H]+: m/z =
169.0415, Found: 169.0415.
2-Chloro-1-(3-nitrophenyl)ethan-1-ol (3h). Colorless oil; 19.5 mg,
48%; 1H NMR (500 MHz, CDCl3): δ = 8.30 (s, 1H), 8.20 (d, J = 8.0
Hz, 1H), 7.75 (d, J = 8.0 Hz, 1H), 7.58 (dd, J = 8.0, 8.0 Hz, 1H), 5.04
(ddd, J = 3.4, 4.0, 8.3 Hz, 1H), 3.81 (dd, J = 3.4, 11.5 Hz, 1H), 3.67
(dd, J = 8.3, 11.5 Hz, 1H), 2.80 ppm (d, J = 4.0 Hz, 1H); 13C NMR
(125 MHz, CDCl3): δ = 148.4, 142.0, 132.2, 129.6, 123.3, 121.2, 72.9,
50.4 ppm; IR (CHCl3): 3034, 1703, 1533, 1265 cm−1; HRMS (ESI+-
TOF): Calcd for [C8H8ClNO3 + H]+: m/z = 202.0265, Found:
202.0266.
3,4-Dichloro-2,2-dimethylchromane (4i). Yellow solid; 32.2 mg,
1
70%; Mp 57−58 °C; H NMR (500 MHz, CDCl3): δ = 7.49 (d, J =
7.5 Hz, 1H), 7.22 (dd, J = 1.7, 7.5 Hz, 1H), 7.01−6.98 (m, 1H), 6.83−
6.82 (m, 1H), 5.17 (d, J = 8.6 Hz, 1H), 4.23 (d, J = 8.6 Hz, 1H), 1.61
(s, 3H), 1.36 ppm (s, 3H); 13C NMR (125 MHz, CDCl3): δ = 151.9,
130.2, 129.9, 121.5, 120.6, 117.5, 79.0, 67.3, 59.4, 27.6, 19.5 ppm; IR
(CHCl3): 3688, 3001, 1605, 1485, 1195 cm−1; HRMS (ESI+-TOF):
Calcd for [C11H12Cl2O + H]+: m/z = 231.0338, Found: 231.0344.
3-Chloro-2,2-dimethylchroman-4-ol (3i). Colorless solid; 32.2 mg,
1
76%; Mp 77−78 °C; H NMR (500 MHz, CDCl3): δ = 7.48 (d, J =
7.9 Hz, 1H), 7.23−7.20 (m, 1H), 7.00−6.97 (m, 1H), 6.81 (dd, J =
1.1, 8.5 Hz, 1H), 4.79 (d, J = 9.1 Hz, 1H), 3.99 (d, J = 9.1 Hz, 1H),
2.55 (brs 1H), 1.57 (s, 3H), 1.34 ppm (s, 3H); 13C NMR (125 MHz,
CDCl3): δ = 151.8, 129.7, 127.5, 122.4, 121.1, 116.9, 78.9, 70.1, 68.4,
27.7, 19.1 ppm; IR (CHCl3): 3588, 3009, 1586, 1485, 1196 cm−1;
HRMS (ESI+-TOF): Calcd for [C11H13ClO2 + Na]+: m/z = 235.0496,
Found: 235.0495.
1
(3,4-Dichlorobutyl)benzene (4k). Colorless oil; 14.4 mg, 35%; H
NMR (500 MHz, CDCl3): δ = 7.33−7.30 (m, 2H), 7.24−7.21 (m,
3H), 4.03−3.98 (m, 1H), 3.78 (dd, J = 5.1, 11.3 Hz, 1H), 3.67 (dd, J =
7.3, 11.3 Hz, 1H), 2.95−2.90 (m, 1H), 2.80−2.74 (m, 1H), 2.35−2.28
(m, 1H), 2.07−2.00 ppm (m, 1H); 13C NMR (125 MHz, CDCl3): δ =
140.4, 128.6, 128.5, 126.3, 60.2, 48.2, 36.7, 32.0 ppm; IR (CHCl3):
3083, 2955, 1603, 1496, 1292 cm−1; HRMS (ESI+-TOF): Calcd for
[C10H12Cl2 − HCl + H]+: m/z = 167.0622, Found: 167.0623.
1-(4-(tert-Butyl)dimethylsiloxyphenyl)-1,2-dichloroethane (4l).
Yellowish oil; 44.7 mg, 73%; 1H NMR (500 MHz, CDCl3): δ =
7.27 (d, J = 8.5 Hz, 2H), 6.84 (d, J = 8.5 Hz, 2H), 4.97 (dd, J = 6.8, 7.4
Hz, 1H), 3.97 (dd, J = 6.8, 11.3 Hz, 1H), 3.90 (dd, J = 7.4, 11.3 Hz,
1H), 0.99 (s, 9H), 0.22 ppm (s, 6H); 13C NMR (125 MHz, CDCl3): δ
= 156.4, 130.7, 128.6, 120.2, 61.8, 48.5, 25.6, 18.2, − 4.4 ppm; IR
(CHCl3): 2958, 2932, 2858, 1605, 1512, 1265 cm−1; HRMS (ESI+-
TOF): Calcd for [C14H22Cl2OSi + H]+: m/z = 305.0890, Found:
305.0896.
1-Chloro-2-(4-methoxyphenyl)propan-2-ol (3j). Colorless oil; 34.3
mg, 85%; 1H NMR (500 MHz, CDCl3): δ = 7.39 (d, J = 9.1 Hz, 2H),
6.90 (d, J = 9.1 Hz, 2H), 3.81−3.79 (m, 4H), 3.72 (d, J = 10.5 Hz,
1H), 2.56 (brs, 1H), 1.63 ppm (s, 3H); 13C NMR (125 MHz, CDCl3):
δ = 158.9, 136.3, 126.2, 113.7, 73.5, 55.5, 55.2, 27.2 ppm; IR (CHCl3):
3568, 3035, 3005, 1612, 1512, 1246, 1180 cm−1; HRMS (ESI+-TOF):
Calcd for [C10H13ClO2 + Na]+: m/z = 223.0496, Found: 223.0488.
1-Chloro-4-phenylbutan-2-ol (3k). Colorless oil; 14.8 mg, 40%; 1H
NMR (500 MHz, CDCl3): δ = 7.31−7.28 (m, 2H), 7.22−7.21 (m,
3H), 3.84−3.80 (m, 1H), 3.63 (dd, J = 3.2, 11.2 Hz, 1H), 3.50 (dd, J =
7.2, 11.2 Hz, 1H), 2.87−2.81 (m, 1H), 2.75−2.69 (m, 1H), 2.20 (d, J
= 2.9 Hz, 1H), 1.90−1.82 ppm (m, 2H); 13C NMR (125 MHz,
CDCl3): δ = 141.3, 128.5, 128.4, 126.0, 70.6, 50.5, 35.8, 31.7 ppm; IR
(CHCl3): 3586, 3064, 1603, 1497, 1265 cm−1; HRMS (ESI+-TOF):
Calcd for [C10H13ClO + H]+: m/z = 185.0728, Found: 185.0727.
Typical Procedure for Dichlorination. To a solution of 1 (124
mg, 0.44 mmol) and 4-phenylpyridine N-oxide (34 mg, 0.2 mmol) in
1,2-dichloroethane (4 mL) was added 4-methoxystyrene 2a (26 μL,
0.2 mmol) at 40 °C. The mixture was stirred for 24 h at the same
temperature, then passed through a short pad of silica gel, and the
tert-Butyl (4-(1,2-dichloroethyl)phenyl)carbamate (4m). Color-
1
less solid; 57.4 mg, 99%; Mp = 123−124 °C; H NMR (500 MHz,
CDCl3): δ = 7.39 (d, J = 8.8 Hz, 2H), 7.32 (d, J = 8.8 Hz, 2H), 6.52
(bs, 1H), 4.96 (dd, J = 6.8, 7.9 Hz, 1H), 3.97 (dd, J = 6.8, 11.2 Hz,
1H), 3.89 (dd, J = 7.9, 11.2 Hz, 1H), 1.52 ppm (s, 9H); 13C NMR
(125 MHz, CDCl3): δ = 152.5, 139.1, 132.3, 128.2, 118.5, 80.9, 61.5,
48.3, 28.3 ppm; IR (CHCl3): 3687, 3437, 1728, 1523, 1157 cm−1;
HRMS (ESI+-TOF): Calcd for [C13H17Cl2NO2 + Na]+: m/z =
312.0529, Found: 312.0531.
G
DOI: 10.1021/acs.joc.6b00295
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
Typical Procedure for Azidochlorination. To a solution of 1
(112 mg, 0.4 mmol) and TMSN3 (66 μL, 0.5 mmol) in CH2Cl2 (2
mL) was added CsF (60 mg, 0.4 mmol) at 0 °C. Then, 4-
methoxystyrene 2a (26 μL, 0.2 mmol) was added. The mixture was
stirred for 12 h at the same temperature and then diluted with ethyl
acetate and H2O. The organic phase was dried over Na2SO4, filtered,
and concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (n-hexane/ethyl acetate = 10/1)
to provide 5a (42.4 mg, quant.).
2158, 1610, 1250 cm−1; Anal. calcd for C10H10ClNOS: C, 52.75; H,
4.43; N, 6.15%. Found: C, 52.72; H, 4.36; N, 6.21%.
(1-Chloro-2-thiocyanatoethyl)benzene (6c). Colorless oil; 26.7
mg, 68%; 1H NMR (500 MHz, CDCl3): δ = 7.43−7.40 (m, 5H), 5.11
(dd, J = 7.5, 7.5 Hz, 1H), 3.61 (dd, J = 7.5, 13.8 Hz, 1H), 3.48 ppm
(dd, J = 7.5, 13.8 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 137.6,
129.6, 129.1, 127.2, 111.0, 60.3, 42.0 ppm; IR (CHCl3): 3036, 3007,
2158, 1492, 1454, 1238, 1196 cm−1; HRMS (ESI+-TOF): Calcd for
[C9H8ClNS + H]+: m/z = 198.0139, Found: 198.0131.
1-(1-Azido-2-chloroethyl)-4-methoxybenzene (5a). Yellowish oil;
42.4 mg, quant.; H NMR (500 MHz, CDCl3): δ = 7.26−7.25 (m,
1-Chloro-4-(1-chloro-2-thiocyanatoethyl)benzene (6d). Colorless
oil; 27.8 mg, 60%; H NMR (500 MHz, CDCl3): δ = 7.41−7.36 (m,
1
1
2H), 6.93 (d, J = 8.6 Hz, 2H), 4.68 (dd, J = 6.9, 6.9 Hz, 1H), 3.82 (s,
3H), 3.67−3.65 ppm (m, 2H); 13C NMR (125 MHz, CDCl3): δ =
160.1, 128.5, 128.3, 114.4, 66.6, 55.3, 47.5 ppm; IR (CHCl3): 3036,
3007, 2110,1611, 1514, 1252 cm−1; HRMS (ESI+-TOF): Calcd for
[C9H10ClN3O + H]+: m/z = 212.0585, Found: 212.0589.
4H), 5.08 (dd, J = 7.2, 7.5 Hz, 1H), 3.60 (dd, J = 7.2, 13.5 Hz, 1H),
3.43 ppm (dd, J = 7.5, 13.5 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ
= 136.1, 135.6, 129.4, 128.6, 110.7, 59.4, 41.8 ppm; IR (CHCl3): 3036,
3007, 2160, 1599, 1493, 1238, 1196 cm−1; HRMS (ESI+-TOF): Calcd
for [C9H7Cl2NS + H]+: m/z = 231.9747, Found: 231.9750.
1-(1-Azido-2-chloroethyl)-2-methoxybenzene (5f). Yellowish oil;
8.7 mg, 21%; H NMR (500 MHz, CDCl3): δ = 7.35−7.32 (m, 2H),
1-Bromo-4-(1-chloro-2-thiocyanatoethyl)benzene (6e). Yellowish
oil; 30.7 mg, 56%; H NMR (500 MHz, CDCl3): δ = 7.56 (d, J = 8.6
1
1
7.02−6.99 (m, 1H), 6.92 (d, J = 8.0 Hz, 1H), 5.17 (dd, J = 4.0, 8.9 Hz,
1H), 3.87 (s, 3H), 3.79 (dd, J = 4.0, 11.5 Hz, 1H), 3.64 (dd, J = 8.9,
11.5 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 156.4, 130.0, 127.5,
124.7, 120.9, 110.7, 61.7, 55.5, 46.8 ppm; IR (CHCl3): 3036, 2116,
1493, 1265, 1032 cm−1; HRMS (ESI+-TOF): Calcd for [C9H10ClN3O
+ Na]+: m/z = 234.0405, Found: 234.0399.
Hz, 2H), 7.31 (d, J = 8.6 Hz, 2H), 5.06 (dd, J = 7.5, 7.5 Hz, 1H), 3.59
(dd, J = 7.5, 13.8 Hz, 1H), 3.42 ppm (dd, J = 7.5, 13.8 Hz, 1H); 13C
NMR (125 MHz, CDCl3): δ = 136.6, 132.3, 128.8, 123.7, 110.7, 59.5,
41.7 ppm; IR (CHCl3): 3036, 3007, 2160, 1593, 1489, 1196 cm−1;
HRMS (ESI+-TOF): Calcd for [C9H7BrClNS + H]+: m/z = 275.9244,
Found: 275.9257.
4-Azido-3-chloro-2,2-dimethylchromane (5i). Colorless oil; 14.3
mg, 30%; trans-isomer: 1H NMR (500 MHz, CDCl3): δ = 7.38 (d, J =
7.4 Hz, 1H), 7.25−7.21 (m, 1H), 7.01−6.98 (m, 1H), 6.82 (d, J = 8.5
Hz, 1H), 4.61 (d, J = 9.4 Hz, 1H), 4.08 (d, J = 9.4 Hz, 1H), 1.58 (s,
3H), 1.36 ppm (s, 3H); 13C NMR (125 MHz, CDCl3): δ = 152.2,
130.2, 128.2, 121.4, 119.3, 117.5, 78.6, 65.6, 62.8, 27.4, 19.1 ppm; IR
(CHCl3): 2986, 2930, 2106, 1585, 1486, 1240 cm−1; HRMS (ESI+-
TOF): Calcd for [C11H12ClN3O + H]+: m/z = 238.0742, Found:
238.0745.
4-Chloro-2,2-dimethyl-3-thiocyanatochromane (6i). Yellow solid;
99% (NMR yield); 1H NMR (500 MHz, CDCl3): δ = 7.51 (d, J = 8.0
Hz, 1H), 7.27−7.23 (m, 1H), 7.05−7.02 (m, 1H), 6.84−6.82 (dd, J =
1.2, 8.6 Hz, 1H), 5.33 (d, J = 8.0 Hz, 1H), 3.71 (d, J = 8.0 Hz, 1H),
1.68 (s, 3H), 1.42 ppm (s, 3H); 13C NMR (125 MHz, CDCl3): δ =
151.6, 130.6, 130.4, 122.0, 119.8, 117.7, 110.1, 78.4, 60.0, 55.9, 27.9,
21.9 ppm. This compound could not be purified in benzyl chloride
form. Thus, isolation was carried out after hydroxylation.
1-(tert-Butyl)dimethylsiloxyphenyl-1-chloro-2-thiocyanato-
ethane (6l). Yellowish oil; 50.1 mg, 76%; 1H NMR (500 MHz,
CDCl3): δ = 7.27 (d, J = 8.3 Hz, 2H), 6.86 (d, J = 8.3 Hz, 2H), 5.06
(dd, J = 7.5, 7.5 Hz, 1H), 3.59 (dd, J = 7.5, 13.6 Hz, 1H), 3.46 (dd, J =
7.5, 13.6 Hz, 1H), 0.98 (s, 9H), 0.21 ppm (s, 6H); 13C NMR (125
MHz, CDCl3): δ = 156.8, 130.3, 128.4, 120.6, 111.1, 60.3, 42.2, 25.6,
18.2, − 4.5 ppm; IR (CHCl3): 3036, 29532, 2858, 1258, 1607, 1173
cm−1; HRMS (ESI+-TOF): Calcd for [C15H22ClNOSSi + H]+: m/z =
328.0953, Found: 328.0952.
1-(2-Azido-1-chloropropan-2-yl)-4-methoxybenzene (5j). Yellow-
1
ish oil; 20.9 mg, 46%; H NMR (500 MHz, CDCl3): δ = 7.37 (d, J =
8.6 Hz, 2H), 6.92 (d, J = 8.6 Hz, 2H), 3.82 (s, 3H), 3.70 (d, J = 11.5
Hz, 1H), 3.64 (d, J = 11.5 Hz 1H), 1.82 ppm (s, 3H); 13C NMR (125
MHz, CDCl3): δ = 159.4, 132.5, 127.2, 114.0, 66.0, 55.3, 53.2, 22.4
ppm; IR (CHCl3): 3007, 2114, 1610, 1514, 1253 cm−1; HRMS (ESI+-
TOF): Calcd for [C10H12ClN3O + Na]+: m/z = 248.0561, Found:
248.0558.
tert-Butyl (4-(1-Chloro-2-thiocyanatoethyl)phenyl)carbamate
(6m). Yellow solid; quant. (NMR yield); 1H NMR (500 MHz,
CDCl3): δ = 7.41 (d, J = 8.5, 2H), 7.33 (d, J = 8.5 Hz, 2H), 6.56 (bs,
1H), 5.06 (dd, J = 7.4, 7.4 Hz, 1H), 3.60 (dd, J = 7.4, 13.6 Hz, 1H),
3.45 (dd, J = 7.4, 13.6 Hz, 1H), 1.52 ppm (s, 9H); 13C NMR (125
MHz, CDCl3): δ = 152.2, 139.1, 131.5, 128.0, 118.7, 111.0, 81.0, 60.1,
42.0, 28.3 ppm. This compound could not be purified in benzyl
chloride form. Thus, isolation was carried out after hydroxylation.
1-(1-Chloro-2-thiocyanatoethyl)-4-methylbenzene (6n). Yellow-
1-(4-(tert-Butyl)dimethylsiloxyphenyl)-1-azido-2-chloroethane
(5l). Yellow viscous oil; 55.8 mg, 89%; 1H NMR (500 MHz, CDCl3): δ
= 7.19 (d, J = 8.6 Hz, 2H), 6.86 (d, J = 8.6 Hz, 2H), 4.67 (t, J = 7.2 Hz,
1H), 3.66 (d, J = 7.2 Hz, 2H), 0.98 (s, 9H), 0.21 ppm (s, 6H); 13C
NMR (125 MHz, CDCl3): δ = 156.3, 129.1, 128.1, 120.5, 66.7, 47.6,
25.6, 18.2, −4.4 ppm; IR (CHCl3): 2957, 2930, 2115, 1607, 1521
cm−1; Anal. calcd for C14H22ClN3OSi: C, 53.92; H, 7.11; N, 13.47%.
Found: C, 53.54; H, 6.70; N, 13.38%.
tert-Butyl (4-(1-Azido-2-chloroethyl)phenyl)carbamate (5m). Yel-
low viscous oil; 37.6 mg, 63%; 1H NMR (500 MHz, CDCl3): δ = 7.41
(d, J = 8.6 Hz, 2H), 7.25 (d, J = 8.6 Hz, 2H), 6.57 (brs, 1H), 4.68 (t, J
= 6.9 Hz, 1H), 3.65 (d, J = 6.9 Hz, 2H), 1.52 ppm (s, 9H); 13C NMR
(125 MHz, CDCl3): δ = 152.5, 139.1, 130.8, 127.7, 118.7, 80. 9, 66.5,
47.4, 28.3 ppm; IR (CHCl3): 3435, 3036, 2158, 2113, 1728, 1521,
1238 cm−1; HRMS (ESI+-TOF): Calcd for [C13H17ClN4O2 + Na]+:
m/z = 319.0932, Found: 319.0932.
1
ish oil; 34.1 mg, 81%; H NMR (500 MHz, CDCl3): δ = 7.30 (d, J =
8.0 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 5.08 (dd, J = 7.5, 7.5 Hz, 1H),
3.61 (ddd, J = 7.5, 13.6 Hz, 1H), 3.47 (ddd, J = 7.5, 13.6 Hz, 1H), 2.37
ppm (s, 3H); 13C NMR (125 MHz, CDCl3): δ = 139.7, 134.7, 129.8,
127.0, 111.1, 60.3, 42.0, 21.2 ppm; IR (CHCl3): 3036, 3007, 2158,
1603, 1238, 1196 cm−1; HRMS (ESI+-TOF): Calcd for [C10H10ClNS
+ H]+: m/z = 212.0295, Found: 212.0305.
1-(1-Chloro-2-thiocyanatoethyl)-4-fluorobenzene (6o). Colorless
oil; 32.2 mg, 75%; H NMR (500 MHz, CDCl3): δ = 7.44−7.40 (m,
Typical Procedure for Chlorothiocyanation. To a solution of 1
(112 mg, 0.4 mmol) in CH2Cl2 (2 mL) was added TMSNCS (56 μL,
0.4 mmol) at 0 °C. Then, 2l (47 mg, 0.2 mmol) was added. The
mixture was stirred for 15 min at 0 °C, then diluted with CH2Cl2, and
the solution was passed through a short pad of silica gel. The solvent
was evaporated under reduced pressure. The residue was purified by a
recycle GPC system to provide 6l (50.1 mg, 76%).
1
2H), 7.14−7.09 (m, 2H), 5.09 (dd, J = 6.9, 8.7 Hz, 1H), 3.60 (dd, J =
6.9, 13.8 Hz, 1H), 3.44 ppm (dd, J = 8.0, 13.8 Hz, 1H); 13C NMR
(125 MHz, CDCl3): δ = 163.2 (d, J = 249.5 Hz), 133.5 (d, J = 3.6 Hz),
129.1 (d, J = 9.6 Hz), 116.2 (d, J = 21.6 Hz), 110.8, 59.5, 42.0 ppm; IR
(CHCl3): 3036, 3007, 2160, 1607, 1512 cm−1; HRMS (ESI+-TOF):
Calcd for [C9H7ClFNS + H]+: m/z = 216.0045, Found: 216.0044.
2-(1-Chloro-2-thiocyanatoethyl)naphthalene (6p). Colorless
solid; 35.5 mg, 72%; Mp 64.6−65.4 °C; 1H NMR (500 MHz,
CDCl3): δ = 7.92−9.86 (m, 4H), 7.57−7.50 (m, 3H), 5.28 (dd, J =
7.2, 7.7 Hz, 1H), 3.71 (dd, J = 7.2, 13.5 Hz, 1H), 3.57 ppm (dd, J =
7.7, 13.5 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 134.7, 133.6,
1-(1-Chloro-2-thiocyanatoethyl)-4-methoxybenzene (6a). Yellow
1
oil; 40.3 mg, 88%; H NMR (500 MHz, CDCl3): δ = 7.34 (d, J = 8.6
Hz, 2H), 6.93 (d, J = 8.6 Hz, 2H), 5.08 (dd, J = 7.2, 7.7 Hz, 1H), 3.83
(s, 3H), 3.61 (dd, J = 7.2, 13.4 Hz, 1H), 3.46 ppm (dd, J = 7.7, 13.4
Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 160.4, 129.6, 128.5,
114.4, 111.1, 60.2, 56.4, 42.0 ppm; IR (CHCl3): 3036, 3007, 2839,
H
DOI: 10.1021/acs.joc.6b00295
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The Journal of Organic Chemistry
Article
132.9, 129.4, 128.2, 127.8, 127.2, 127.1, 127.0, 123.6, 110.0, 60.6, 41.8
ppm; IR (CHCl3): 3036, 3007, 2158, 1601, 1510, 1238, 1196 cm−1;
HRMS (ESI+-TOF): Calcd for [C13H10ClNS − HCl + H]+: m/z =
212.0528, Found: 212.0527.
2-Iodo-1-(2-methoxyphenyl)ethyl 2-Iodobenzoate (8f). Colorless
oil; 94.5 mg, 93%; 1H NMR (500 MHz, CDCl3): δ = 8.05 (dd, J = 1.7,
7.9 Hz, 1H), 8.02 (d, J = 7.9 Hz, 1H), 7.46 (ddd, J = 1.1, 7.4, 7.9 Hz,
1H), 7.41 (dd, J = 1.1, 7.7 Hz, 1H), 7.34−7.30 (m, 1H), 7.19 (ddd, J =
1.7, 7.4, 7.9 Hz, 1H), 6.98−6.95 (m, 1H), 6.91 (d, J = 8.5 Hz, 1H),
6.44 (dd, J = 4.0, 7.4 Hz, 1H), 3.89 (s, 3H), 3.73 (dd, J = 4.0, 10.5 Hz,
1H), 3.58 ppm (dd, J = 7.4, 10.5 Hz, 1H); 13C NMR (125 MHz,
CDCl3): δ = 164.8, 156.1, 141.5, 134.4, 132.9, 131.4, 129.6, 128.0,
126.6, 120.6, 110.6, 94.4, 71.3, 55.5, 7.8 ppm; IR (CHCl3): 3009, 1732,
1493, 1242, 1103 cm−1; HRMS (ESI+-TOF): Calcd for [C16H14I2O3 +
Na]+: m/z = 530.8925, Found: 530.8926.
Typical Procedure for Oxythiocyanation. To a solution of 1
(112 mg, 0.4 mmol) in CH2Cl2 (2 mL) was added TMSNCS (56 μL,
0.4 mmol) at 0 °C. Then, 2m (44 mg, 0.2 mmol) was added. The
mixture was stirred for 15 min at 0 °C, then diluted with CH2Cl2, and
the solution was passed through a short pad of silica gel. The solvent
was evaporated under reduced pressure. The residue was dissolved in
acetone/H2O. The solution was stirred for 15 min at room
temperature and then extracted with CH2Cl2. The organic layer was
dried over Na2SO4, filtered, and concentrated in vacuo. The residue
was purified by chromatography on silica gel (n-hexane/ethyl acetate =
10/1) to give 7m (44.7 mg, 76%).
2,2-Dimethyl-3-thiocyanatochroman-4-ol (7i). Yellow solid; 29.1
mg, 62%; Mp 62−65 °C; 1H NMR (500 MHz, CDCl3): δ = 7.49 (d, J
= 7.5 Hz, 1H), 7.26−7.23 (m, 1H), 7.20 (dd, J = 7.5, 7.5 Hz, 1H), 6.28
(d, J = 9.2 Hz, 1H), 4.92 (d, J = 9.2 Hz, 1H), 3.42 (d, J = 9.2 Hz, 1H),
1.64 (s, 3H), 1.39 ppm (s, 3H); 13C NMR (125 MHz, CDCl3): δ =
151.6, 130.1, 128.0, 122.4, 121.6, 117.2, 110.9, 78.7, 67.4, 59.7, 28.0,
21.0 ppm; IR (CHCl3): 3595, 3036, 2990, 2156, 1610, 1585, 1485,
1456 cm−1; HRMS (ESI+-TOF): Calcd for [C12H13NO2S + H]+: m/z
= 236.0740, Found: 236.0738.
3-Iodo-2,2-dimethylchroman-4-yl 2-Iodobenzoate (8i). Yellow
1
solid; 59.8 mg, 56%; Mp 94−96 °C; H NMR (500 MHz, CDCl3):
δ = 8.04 (d, J = 7.9 Hz, 1H), 7.87 (dd, J = 1.7, 7.9 Hz, 1H), 7.43−7.39
(m, 1H), 7.29−7.24 (m, 2H), 7.19 (ddd, J = 1.7, 7.4, 7.9 Hz, 1H), 6.94
(dd, J = 7.4, 7.4 Hz, 1H), 6.87 (d, J = 7.9 Hz, 1H), 6.66 (d, J = 7.7 Hz,
1H), 4.61 (d, J = 7.7 Hz, 1H), 1.70 (s, 3H), 1.60 ppm (s, 3H); 13C
NMR (125 MHz, CDCl3): δ = 166.0, 152.9, 141.5, 134.3, 133.0, 131.1,
130.3, 128.6, 128.0, 121.2, 118.6, 117.5, 94.6, 78.3, 73.9, 36.6, 28.4,
24.3 ppm; IR (CHCl3): 3035, 3007, 1730, 1585, 1246, 1196 cm−1;
HRMS (ESI+-TOF): Calcd for [C18H16I2O3 + Na]+: m/z = 556.9081,
Found: 556.9091.
1-Iodo-2-(4-methoxyphenyl)propan-2-yl 2-Iodobenzoate (8j).
1
Colorless oil; 103.4 mg, 99%; H NMR (500 MHz, CDCl3): δ =
tert-Butyl (4-(1-Hydroxy-2-thiocyanatoethyl)phenyl)carbamate
8.00−7.95 (m, 2H), 7.46−7.42 (m, 1H), 7.37 (d, J = 8.9 Hz, 2H), 7.17
(ddd, J = 1.7, 7.5, 7.5 Hz, 1H), 6.90 (d, J = 8.9 Hz, 2H), 3.93 (d, J =
10.3 Hz, 1H), 3.84 (d, J = 10.3 Hz, 1H), 3.81 (s, 3H), 2.14 ppm (s,
3H); 13C NMR (125 MHz, CDCl3): δ = 164.7, 159.1, 141.3, 135.6,
133.3, 132.6, 131.2, 128.0, 126.2, 113.9, 93.9, 82.5, 55.3, 25.8, 17.5
ppm; IR (CHCl3): 3007, 1730, 1514, 1292, 1252 cm−1; HRMS (ESI+-
TOF): Calcd for [C17H16I2O3 + Na]+: m/z = 544.9081, Found:
544.9089.
1
(7m). Yellow solid; 44.7 mg, 76%; Mp 102−106 °C; H NMR (500
MHz, CDCl3): δ = 7.38 (d, J = 8.6 Hz, 2H), 7.30 (d, J = 8.6 Hz, 2H),
6.55 (brs, 1H), 4.97 (dd, J = 4.0, 8.6 Hz, 1H), 3.22 (dd, J = 4.0, 13.2
Hz, 1H), 3.15 (dd, J = 8.6, 13.2 Hz, 1H) 1.52 ppm (s, 9H); 13C NMR
(125 MHz, CDCl3): δ = 152.6, 138.8, 135.1, 126.6, 118.8, 112.3, 80.9,
72.3, 41.9, 28.3 ppm; IR (CHCl3): 3036, 3007, 1726, 1521, 1238
cm−1; HRMS (ESI+-TOF): Calcd for [C14H18N2O3S + Na]+: m/z =
317.0930, Found: 317.0937.
2-(4-(tert-Butyl)dimethylsiloxyphenyl)-1-iodoethyl-2-yl 2-Iodo-
Typical Procedure for Iodoesterification. To a solution of 1
(85 mg, 0.3 mmol) in CH2Cl2 (1 mL) was added TBIA (111 mg, 0.3
mmol) at room temperature. Then, 4-methoxystyrene 2a (26 μL, 0.2
mmol) was added. The mixture was warmed up to 40 °C, stirred for 6
h, and then diluted with ethyl acetate and H2O. The organic phase was
dried over Na2SO4, filtered, and concentrated under reduced pressure.
The residue was purified by column chromatography on silica gel (n-
hexane/ethyl acetate = 10/1) to provide 8a (84.3 mg, 83%).
2-Iodo-1-(4-methoxyphenyl)ethyl 2-Iodobenzoate (8a). Yellowish
oil; 84.3 mg, 83%; 1H NMR (500 MHz, CDCl3): δ = 8.00 (dd, J = 1.1,
7.9 Hz, 1H), 7.92 (dd, J = 1.7, 7.9 Hz, 1H), 7.44−7.41 (m, 1H), 7.38
(d, J = 8.8 Hz, 2H), 7.16 (ddd, J = 1.7, 7.9, 7.9 Hz, 1H), 6.91 (d, J =
8.8 Hz, 2H), 6.09 (dd, J = 5.7, 7.9 Hz, 1H), 3.81 (s, 3H), 3.66 (dd, J =
7.9, 10.6 Hz, 1H), 3.56 ppm (dd, J = 5.7, 10.6 Hz, 1H); 13C NMR
(125 MHz, CDCl3): δ = 165.0, 160.0, 141.4, 134.5, 132.8, 131.3,
130.0, 128.1, 127.9, 114.1, 94.3, 76.4, 55.3, 7.6 ppm; IR (CHCl3):
3007, 1730, 1514, 1254 cm−1; HRMS (ESI+-TOF): Calcd for
[C16H14I2O3 + Na]+: m/z = 530.8925, Found: 530.8932.
1
benzoate (8l). Colorless oil; 56.9 mg, 47%; H NMR (500 MHz,
CDCl3): δ = 8.00 (dd, J = 7.9 Hz, 1H), 7.93 (dd, J = 1.7, 7.9 Hz, 1H),
7.44−7.41 (m, 1H), 7.32 (d, J = 8.5 Hz, 2H), 7.16 (ddd, J = 1.7, 7.4,
7.9 Hz, 1H), 6.84 (d, J = 8.5 Hz, 2H), 6.09 (dd, J = 5.1, 7.9, 1H), 3.65
(dd, J = 7.9, 10.6 Hz, 1H), 3.56 (dd, J = 5.1, 10.6 Hz, 1H), 0.98 (s,
9H), 0.20 ppm (s, 6H); 13C NMR (125 MHz, CDCl3): δ = 165.0,
156.2, 141.4, 134.5, 132.8, 131.2, 130.6, 128.0, 127.9, 120.2, 94.3, 76.4,
25.6, 18.2, 7.7, − 4.4 ppm; IR (CHCl3): 3007, 2957, 2932, 1730, 1510,
1265 cm−1; HRMS (ESI+-TOF): Calcd for [C21H26I2O3Si + Na]+: m/
z = 630.9633, Found: 630.9632.
1-(4-((tert-Butoxycarbonyl)amino)phenyl)-2-iodoethyl 2-Iodo-
benzoate (8m). Yellowish solid; 63.2 mg, 53%; Mp 116−117 °C;
1H NMR (500 MHz, CDCl3): δ = 7.99 (d, J = 7.9 Hz, 1H), 7.92 (dd, J
= 1.7, 7.4 Hz, 1H), 7.44−7.36 (m, 5H), 7.18−7.15 (m, 1H), 6.54 (bs,
1H), 6.07 (dd, J = 5.7, 7.9, 1H), 3.64 (dd, J = 7.9, 10.8 Hz, 1H), 3.55
(dd, J = 5.7, 10.8 Hz, 1H), 1.51 ppm (s, 9H); 13C NMR (125 MHz,
CDCl3): δ = 165.0, 152.6, 141.5, 139.0, 134.4, 132.9, 132.4, 131.3,
128.0, 127.5, 118.5, 94.3, 80.8, 76.3, 28.3, 7.4 ppm; IR (CHCl3): 3437,
3035, 3007, 1728, 1517, 1254, 1159 cm−1; HRMS (ESI+-TOF): Calcd
for [C20H21I2NO4 + Na]+: m/z = 615.9452, Found: 615.9442.
Typical Procedure for Site-Selective Oxychlorination. To a
solution of 1 (62 mg, 0.22 mmol) in acetone/H2O (2 mL/2 mL) was
added 2q (32 mg, 0.2 mmol) at 40 °C. The solution was stirred for 24
h at the same temperature, then quenched with sat. NaHCO3, and
diluted with ethyl acetate and H2O. The organic phase was dried over
MgSO4, filtered, and concentrated under reduced pressure. The
residue was purified by column chromatography on silica gel (n-
hexane/ethyl acetate = 10/1) to provide 3q (23.1 mg, 54%).
1-(Benzo[d][1,3]dioxol-5-yl)-2-iodoethyl 2-Iodobenzoate (8b).
1
Colorless oil; 103.4 mg, 99%; H NMR (500 MHz, CDCl3): δ =
8.01 (d, J = 8.6 Hz, 1H), 7.93 (dd, J = 1.7, 8.0 Hz, 1H), 7.45−7.42 (m,
1H), 7.19−7.16 (m, 1H), 6.94−6.92 (m, 2H), 6.81 (d, J = 8.0 Hz,
1H), 6.03 (dd, J = 5.7, 7.5 Hz, 1H), 5.98 (s, 2H), 3.63 (dd, J = 7.5,
10.6 Hz, 1H), 3.54 ppm (dd, J = 5.7, 10.6 Hz, 1H); 13C NMR (125
MHz, CDCl3): δ = 164.9, 148.0, 147.9, 141.5, 134.2, 133.0, 131.8,
131.3, 128.0, 120.8, 108.4, 106.9, 101.3, 94.4, 76.5, 7.5 ppm; IR
(CHCl3): 3007, 1732, 1489, 1250, 810 cm−1; HRMS (ESI+-TOF):
Calcd for [C16H12I2O4 + Na]+: m/z = 544.8717, Found: 544.8728.
2-Iodo-1-phenylethyl 2-Iodobenzoate (8c). Colorless oil; 47.6 mg,
50%; 1H NMR (500 MHz, CDCl3): δ = 8.01 (d, J = 8.0 Hz, 1H), 7.96
(dd, J = 1.7, 7.5 Hz, 1H), 7.46−7.35 (m, 6H), 7.19−7.16 (m, 1H),
6.12 (dd, J = 5.2, 7.5 Hz, 1H), 3.66, (dd, J = 7.5, 10.6 Hz, 1H), 3.60
ppm (dd, J = 5.2, 10.6 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ =
165.0, 141.5, 138.0, 134.3, 132.9, 131.3, 128.9, 128.7, 128.0, 126.6,
94.4, 76.5, 7.5 ppm; IR (CHCl3): 3022, 1732, 1242, 1132, 1099 cm−1;
HRMS (ESI+-TOF): Calcd for [C15H12I2O2 + Na]+: m/z = 500.8819,
Found: 500.8833.
1-(4-(Allyloxy)phenyl)-2-chloroethan-1-ol (3q). Colorless solid;
1
23.1 mg, 54%; Mp 49−51 °C; H NMR (500 MHz, CDCl3): δ =
7.30 (d, J = 8.8 Hz, 2H), 6.92 (d, J = 8.8 Hz, 2H), 6.09−6.01 (m, 1H),
5.41 (dd, J = 1.7, 17.6 Hz, 1H), 5.29 (dd, J = 1.7, 10.5 Hz, 1H), 4.86−
4.84 (m, 1H), 4.55−4.53, (m, 2H), 3.71 (dd, J = 3.7, 11.2 Hz, 1H),
3.63 (dd, J = 8.5, 11.2 Hz, 1H), 2.59 ppm (d, J = 2.8 Hz, 1H); 13C
NMR (125 MHz, CDCl3): δ = 158.7, 133.1, 132.2, 127.3, 117.8, 114.9,
73.7, 68.8, 50.9 ppm; IR (CHCl3): 3036, 3007, 1610, 1512, 1238, 1196
I
DOI: 10.1021/acs.joc.6b00295
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
cm−1; HRMS (ESI+-TOF): Calcd for [C11H13ClO2 + Na]+: m/z =
235.0496, Found: 235.0495.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b00295.
2-Chloro-1-(2,2-dimethyl-2H-chromen-6-yl)ethan-1-ol (3r). Col-
orless oil; 28.5 mg, 60%; 1H NMR (500 MHz, CDCl3): δ = 7.10 (dd, J
= 1.7, 8.0 Hz, 1H), 7.01 (d, J = 1.7 Hz, 1H), 6.76 (d, J = 8.0 Hz, 1H),
6.31 (d, J = 10.0 Hz, 1H), 5.63 (d, J = 10.0 Hz, 1H), 4.81−4.79 (m,
1H), 3.70 (dd, J = 3.4, 11.3 Hz, 1H), 3.62 (dd, J = 9.4, 11.3 Hz, 1H),
2.56 (d, J = 2.3 Hz, 1H), 1.43 ppm (s, 6H); 13C NMR (125 MHz,
CDCl3): δ = 153.1, 132.0, 131.2, 126.8, 124.0, 122.0, 121.4, 116.4,
76.5, 73.8, 51.0, 28.0, 28.0 ppm; IR (CHCl3): 3595, 3007, 1639, 1491,
1263 cm−1; HRMS (ESI+-TOF): Calcd for [C13H15ClO2 + Na]+: m/z
= 261.0653, Found: 261.0641.
Optimization of the reaction conditions and NMR
spectra of isolated products (PDF)
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: hamashima@u-shizuoka-ken.ac.jp.
*E-mail: hegami@u-shizuoka-ken.ac.jp.
Typical Procedure for Site-Selective Dichlorination. To a
solution of 1 (124 mg, 0.44 mmol) and 4-phenylpyridine N-oxide (34
mg, 0.2 mmol) in 1,2-dichloroethane (4 mL) was added 2q (32 mg,
0.2 mmol) at 40 °C. The mixture was stirred for 24 h at the same
temperature, then passed through a short pad of silica gel, and the
silica gel was washed with CH2Cl2. The organic solvent was evaporated
under reduced pressure. The residue was purified by recycle GPC
system (CHCl3) to provide 4q (31.7 mg, 69%).
1-(Allyloxy)-4-(1,2-dichloroethyl)benzene (4q). Colorless oil; 31.7
mg, 69%; 1H NMR (500 MHz, CDCl3): δ = 7.32 (d, J = 8.6 Hz, 2H),
6.92 (d, J = 8.6 Hz, 2H), 6.09−6.01 (m, 1H), 5.42 (dd, J = 1.7, 17.2,
1H), 5.30 (dd, J = 1.7, 10.3 Hz, 1H), 4.98 (dd, J = 6.3, 8.0 Hz, 1H),
4.55 (d, J = 5.2 Hz, 2H), 3.99 (dd, J = 6.3, 11.5 Hz, 1H), 3.91 ppm
(dd, J = 8.0, 11.5 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ = 159.1,
132.9, 130.2, 128.7, 117.9, 114.9, 68.8, 61.6, 48.3 ppm; IR (CHCl3):
1611, 1512, 1242, 1178, 835 cm−1; HRMS (ESI+-TOF): Calcd for
[C11H12Cl2O + H]+: m/z = 231.0338, Found: 231.0344.
6-(1,2-Dichloroethyl)-2,2-dimethyl-2H-chromene (4r). Yellowish
oil; 32.5 mg, 63%; 1H NMR (500 MHz, CDCl3): δ = 7.12 (dd, J = 2.3,
8.2 Hz, 1H), 7.00 (d, J = 2.3 Hz, 1H), 6.76 (d, J = 8.2 Hz, 1H), 6.30
(d, J = 9.9 Hz, 1H), 5.64 (d, J = 9.9 Hz, 1H), 4.92 (dd, J = 6.8, 7.9 Hz,
1H), 3.96 (dd, J = 6.8, 11.2 Hz, 1H), 3.89 (dd, J = 7.9, 11.2 Hz, 1H),
1.44 ppm (s, 6H); 13C NMR (125 MHz, CDCl3): δ = 153.6, 131.3,
130.1, 128.1, 125.3, 121.8, 121.3, 116.5, 61.9, 48.4, 28.2 ppm; IR
(CHCl3): 3035, 2978, 1730, 1610, 1491, 1238, 1195 cm−1; HRMS
(ESI+-TOF): Calcd for [C13H14Cl2O + Na]+: m/z = 279.0314, Found:
279.0320.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by a grant for the Platform for Drug
Discovery, Informatics and Structural Life Science from The
Ministry of Education, Culture, Sports, Science and Technol-
ogy-Japan (MEXT) and Japan Agency for Medical Research
and Development (AMED).
REFERENCES
■
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2012, 51, 10938. (b) Chemler, S. R.; Bovino, M. T. ACS Catal. 2013,
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Typical Procedure for Site-Selective Iodoesterification. To a
solution of 1 (85 mg, 0.3 mmol) in CHCl3 (1 mL) was added TBIA
(111 mg, 0.3 mmol) at room temperature. Then, 2q (32 mg, 0.2
mmol) was added. The mixture was warmed up to 40 °C, stirred for 3
h, and diluted with ethyl acetate and H2O. The organic phase was
dried over Na2SO4, filtered, and concentrated under reduced pressure.
The residue was purified by column chromatography on silica gel (n-
hexane/ethyl acetate = 10/1) to provide 8q (69.1 mg, 65%).
1-(4-(Allyloxy)phenyl)-2-iodoethyl 2-Iodobenzoate (8q). Yellow-
(4) (a) Shimizu, R.; Egami, H.; Nagi, T.; Chae, J.; Hamashima, Y.;
Sodeoka, M. Tetrahedron Lett. 2010, 51, 5947. (b) Shimizu, R.; Egami,
H.; Hamashima, Y.; Sodeoka, M. Angew. Chem., Int. Ed. 2012, 51,
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1
ish oil; 69.1 mg, 65%; H NMR (500 MHz, CDCl3): δ = 8.00 (d, J =
7.5 Hz, 1H), 7.92 (dd, J = 1.7, 8.0 Hz, 1H), 7.44−7.36 (m, 3H), 7.17
(ddd, J = 1.7, 7.5, 7.5 Hz, 1H), 6.92 (d, J = 8.6 Hz, 2H), 6.10−6.01 (m,
2H), 5.41 (dd, J = 1.7, 17.2 Hz, 1H), 5.29 (dd, J = 1.7, 10.6 Hz, 1H),
3.65 (dd, J = 7.7, 10.6 Hz, 1H), 3.56 ppm (dd, J = 5.4, 10.6 Hz, 1H);
13C NMR (125 MHz, CDCl3): δ = 165.0, 159.0, 141.5, 134.4, 133.0,
132.9, 131.3, 130.2, 128.1, 127.9, 117.9, 114.8, 94.3, 76.4, 68.8, 7.6
ppm; IR (CHCl3): 3035, 1730, 1611, 1512, 1240 cm−1; HRMS (ESI+-
TOF): Calcd for [C18H16I2O3 + Na]+: m/z = 556.9081, Found:
556.9087.
(6) Recently, 1 was utilized as an intermediate for the synthesis of
other hypervalent iodine reagents, see: (a) Kiyokawa, K.; Kosaka, T.;
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756.
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1-(Benzo[d][1,3]dioxol-5-yl)-2-iodoethyl 2-Iodobenzoate (8r).
Colorless oil; 59.5 mg, 58%; 1H NMR (500 MHz, CDCl3): δ =
8.00 (d, J = 7.5 Hz, 1H), 7.93 (dd, J = 1.7, 8.0 Hz, 1H), 7.43 (dd, J =
7.5, 7.5 Hz, 1H), 7.19−7.15 (m, 2H), 7.05 (d, J = 2.3 Hz, 1H), 6.77 (d,
J = 8.0 Hz, 1H), 6.31 (d, J = 10.0 Hz, 1H), 6.04 (dd, J = 5.2, 8.0 Hz,
1H), 5.63 (d, J = 10.0 Hz, 1H), 3.64 (dd, J = 8.0, 10.7 Hz, 1H), 3.54
ppm (dd, J = 5.2, 10.7 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ =
165.0, 153.4, 141.5, 134.4, 132.8, 131.3, 131.2, 130.1, 127.9, 127.4,
124.9, 121.9, 121.2, 116.5, 94.3, 76.6, 76.5, 28.1, 7.6 ppm; IR (CHCl3):
2797, 1730, 1491, 1250, 1126, 909 cm−1; HRMS (ESI+-TOF): Calcd
for [C20H18I2O3 + Na]+: m/z = 582.9238, Found: 582.9219.
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DOI: 10.1021/acs.joc.6b00295
J. Org. Chem. XXXX, XXX, XXX−XXX