Highly Selective Approach to α-Iodoketones from Aminoalkynols with Iodine Monochloride

Article abstract of DOI:10.1055/s-0036-1590897

A protocol has been developed to achieve selective and direct synthesis of α-iodoketones under mild condition, from the reaction of aminoalkynols with iodine monochloride. The scope of the reaction was investigated using various aminoalkynols with iodine

Full text of DOI:10.1055/s-0036-1590897

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–G
paper
A
en
V. V. Rao et al.
Paper
Synthesis
Highly Selective Approach to α-Iodoketones from Aminoalkynols
with Iodine Monochloride
Vijay V. Raoa,b
OH
O
Na2CO3 (3 equiv)
Nedaossadat Mirzadeha
Suresh Bhargava*a
Pravin R. Likhar*c
OH
ICl (3 equiv)
R2
R2
R1
THF, 0 °C
I
N
NH
R1
H
R1 = CO2Et, CO2Ph, Ac, Bz
10 examples
up to 82% yield
a Center for Advanced Materials and Industrial Chemistry,
School of Applied Sciences, RMIT University, 124 LaTrobe
Street, Melbourne VIC 3000, Australia
R2 = H, Cl, F, NO2, Me, OMe
• Mild reaction
conditions
• Metal free
activation
• Fast and
suresh.bhargava@rmit.edu.au
regioselective
b IICT-RMIT Joint Research Center, CSIR-IICT, Uppal Road,
Tarnaka, Hyderabad 500007, India
c Organometallic Gp., I & P C Division, CSIR-IICT, Uppal
Road, Tarnaka, Hyderabad 500007, India
plikhar@iict.res.in
Received: 22.07.2017
Accepted after revision: 04.08.2017
Published online: 31.08.2017
In our previous study, we have reported the selective
formation of pyrrole nucleus over indole in the electrophilic
cyclization of alkynes7 and the synthesis of iodo-dihydrofu-
ran by electrophilic cyclization of amino alkynols mediated
by molecular iodine.8 While optimizing the reaction condi-
tions for the synthesis of iodo-substituted dihydrofurans
from aminoalkynols, various electrophilic I+ sources were
examined to enhance the product yield. Surprisingly, when
iodine monochloride was tested in place of molecular io-
dine, the reaction failed to give the desired iodo-substituted
dihydrofuran product, instead a different product was ob-
served within 30 minutes (Scheme 2). The isolated product
2a was characterized by 1H and 13C NMR spectroscopy,
HRMS, and X-ray diffraction (Figure 1), and surprisingly
proved to be α-iodoketone rather than an iodocyclized
product.
Contrary to previous observations, this finding on the
formation of α-iodoketone from iodine monochloride and
aminoalkynols, is first to be reported. As far as our knowl-
edge is concerned such conversion has never been observed
with iodine monochloride, which usually gives the cyclized
product or addition of iodine and chlorine across the triple
bond.10
DOI: 10.1055/s-0036-1590897; Art ID: ss-2017-t0415-op
Abstract A protocol has been developed to achieve selective and di-
rect synthesis of α-iodoketones under mild condition, from the reaction
of aminoalkynols with iodine monochloride. The scope of the reaction
was investigated using various aminoalkynols with iodine monochloride
and the corresponding α-iodoketones were obtained selectively with-
out forming iodocyclized and/or addition products.
Key words iodine monochloride, regioselective, iodonium activation,
α-iodoketones, iodocyclization
α-Haloketones are often found in natural products and
biologically active molecules1 and are one of the versatile
synthetic intermediates, finding wide applications in or-
ganic synthesis owing to their various reactive sites.2 Con-
ventionally, they are synthesized by halogenation of the ke-
tones in the presence of oxidants3 or by converting one α-
haloketone into the other by halogen exchange reaction.4
Olefins are converted into α-haloketones by oxidative halo-
genation using reagents like, Ag2CrO4-I2, IBX, NBS, NIS, and
even by photoirradiation.5 There have been comparatively
less reports for the conversion of alkynes into α-haloke-
tones. The reaction of terminal alkynes with molecular io-
dine in the presence of silver nitrate gives α,α-diiodoke-
tones along with few other side products like di-iodo-
alkenes and iodoalkynes.2 Haloalkynes have also been used
to generate α-haloketones, aided by metal catalysts such as
gold and silver.6 Though there exists a plethora of reactions
to make α-haloketones (Scheme 1), they sometimes suffer
from undesirable multiple halogenation on the α-carbon,
and the need for expensive catalysts when alkynes are used
as substrates. Moreover, there is a lack of reports to synthe-
size them directly from internal alkynes.
O
X
R'
R
R
O
R'/H
X/H
R
X
O
R'
R
R
X'
Scheme 1 Established procedures for the formation of α-haloketones
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

B
V. V. Rao et al.
Paper
Synthesis
a) Previous Study8
I
OH
K2CO3 (3 equiv)
I2 (3 equiv)
O
O
MeCN, r.t.
NH
NH
O
O
O
1a
47%
(iodo-dihydrofuran)
b) This study
I
OH
O
K2CO3 (3 equiv)
ICl (3 equiv)
OH
O
O
I
MeCN, r.t.
NH
NH
NH
O
O
O
O
O
2a
+
I
1a
62%
(α-iodoketone)
OH
Cl
NH
O
O
not observed
Scheme 2 Synthesis of α-iodoketones from aminoalkynols mediated by ICl
Table 1 Optimization for the Reaction of Aminoalkynol with ICla
Having discovered this unique reaction with respect to
iodine monochloride, we aimed to optimize the reaction
conditions to enhance the yield of the reaction by varying
solvent, base and temperature. The results are summarized
in Table 1.
OH
O
OH
base, ICl
I
solvent
NH
NH
O
O
The initial reaction of alkynol 1a was performed with
K2CO3 (3 equiv) and ICl (3 equiv) in MeCN at room tempera-
ture and the yield of α-iodoketone obtained was about 62%
(Table 1, entry 1). There was a slight increase in the yield
when Na2CO3 was used as a base (entry 2) and further in-
crease when THF was used as the solvent (entry 3). In the
O
O
1a
2a
Entry
Reactant
Solvent
Temp
(°C)
Base
Yield of
2a (%)b
1
2
3
4
5
6
1a
1a
1a
1a
1a
1a
MeCN
MeCN
THF
r.t.
r.t.
r.t.
r.t.
0
K2CO3
62
65
71
Na2CO3
Na2CO3
NaHCO3
Na2CO3
NaHCO3
c
THF
–
THF
76
c
CH2Cl2
0
–
a Reaction conditions: Alkynol 1a (0.08 mmol), base (3 equiv), ICl (3 equiv),
solvent (2 mL) at the mentioned temperature for 30 min under N2.
b Isolated yield.
c Inseparable mixture of products.
presence of NaHCO3, the desired product was formed along
with the by-products, which were inseparable from the
crude mixture of products (entry 4). When the reaction was
carried out in the presence of Na2CO3 at 0 °C, the yield in-
creased to 76% (entry 5). Similarly, when the reaction was
performed at low temperature (0 °C) using NaHCO3, again
inseparable mixture of products were obtained (entry 6).
Figure 1 X-ray crystal structure of 2a (C13H16INO4).9 Pale yellow nee-
dles obtained from EtOAc/pentane. Ellipsoids show 50% probability lev-
els. The hydrogen atoms bonded to N1 and O4 were located in the
difference Fourier map but refined to unusually short distances. In this
case, bond length and displacement restraints were used to achieve a
stable refinement.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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V. V. Rao et al.
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Synthesis
Thus, the optimal conditions used in entry 5 were extended
further to examine the scope of the reaction.
except the benzoyl group, for which no desired product was
observed (2d, entry 6). The effect of various substituents on
the aromatic ring was also examined. Presence of fluoro,
chloro, and nitro groups on the aromatic ring decreased the
yield of reaction (2e–h, entries 7–10), the lowest yield was
observed for the nitro substituent (2h, entry 10). The elec-
tronically rich substituents like methyl (2i) and methoxy
groups (2j) afforded a high yield of α-iodoketones (entries
11 and 12). Overall, the reaction seemed to tolerate both
electron-withdrawing and electron-donating groups and
amine protecting groups as mentioned above.
Various aminoalkynols with different amine protective
groups and substituents on the aromatic ring were pre-
pared using previously reported methods.8 These substrates
were subjected to optimized reaction conditions and tested
for the synthesis of α-iodoketones. The results are summa-
rized in Table 2.
The presence of amine protective groups such as ethyl
formate, benzyl formate, acetyl, and benzoyl were investi-
gated; they all led to good yields (2a–c, Table 2, entries 3–5)
Table 2 Scope of the Reaction Using Various Aminoalkynols with ICla
OH
O
Na2CO3 (3 equiv)
ICl (3 equiv)
OH
R2
R2
R1
THF, 0 °C
I
N
NH
R1
H
1a–j
2a–j
Entry
Reactant
I+ Source
Conditions
Product
Yield (%)b
1a
I
O
O
OH
1
I2
K2CO3, MeCN, r.t.
47
NH
NH
O
O
I
O
1a
O
OH
2
3
I2
KOt-Bu, MeCN, r.t.
78
NH
NH
O
O
O
O
2a
2b
2c
1a
O
ICl
Na2CO3, THF, 0 °C
76 (69)c
OH
I
OH
NH
NH
O
O
O
O
O
O
1b
O
OH
Ph
4
ICl
Na2CO3, THF, 0 °C
71
I
OH
Ph
NH
NH
O
O
O
1c
O
OH
5
ICl
Na2CO3, THF, 0 °C
63
I
OH
NH
NH
O
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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V. V. Rao et al.
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Synthesis
Table 2 (continued)
Entry
Reactant
I+ Source
Conditions
Product
Yield (%)b
2d
1d
O
OH
d
6
ICl
Na2CO3, THF, 0 °C
–
I
OH
NH
NH
O
O
2e
1e
O
F
F
OH
7
ICl
ICl
ICl
ICl
ICl
ICl
Na2CO3, THF, 0 °C
Na2CO3, THF, 0 °C
Na2CO3, THF, 0 °C
Na2CO3, THF, 0 °C
Na2CO3, THF, 0 °C
Na2CO3, THF, 0 °C
64 (54)c
I
OH
NH
NH
O
O
O
O
O
O
O
O
2f
1f
O
Cl
Cl
OH
8
55
I
OH
NH
O
NH
O
2g
1g
O
OH
9
60e
I
OH
Cl
NH
O
Cl
NH
O
O
2h
1h
O2N
O2N
OH
10
11
12
53e
I
OH
NH
NH
O
O
O
O
2i
1i
O
OH
75
I
OH
NH
NH
O
O
O
O
2j
1j
O
OH
82
I
OH
O
NH
O
NH
O
O
O
O
a Reaction conditions: alkynol (0.2 mmol), base (3 equiv), I+ source (3 equiv), solvent (5 mL) for 30–60 min under N2.
b Isolated yield.
c Isolated yield for gram scale (5 mmol) synthesis in parentheses.
d No desired product observed.
e Iodo-dihydrofuran product was also observed in 5–10% yield.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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Synthesis
The scalability of the reaction was demonstrated by
testing the two substrates 1a and 1e in 5 mmol scale. The
scale-up reaction proceeded well in both cases though with
a slight decrease in the reaction yield (entry 3 and 7).
The same reaction conditions optimized for α-iodoke-
tone synthesis were applied to 4-phenylbut-3-yn-1-ol (3a;
0.2 mmol) and the α-iodoketone product 4a was obtained
in 45% yield (Scheme 3). But when homopropargyl amine-
substituted aniline 5a was tested for the formation of α-io-
doketone, surprisingly only iodocyclized product was ob-
served in 68% yield (Scheme 4). The product 6a was the
same as reported in our previous iodocyclization study
with molecular iodine7 and no α-iodoketone product was
observed.
served in the Berliner’s and Rossi’s study.11 All the previous
reports employ molecular iodine as the electrophilic re-
agent and there have been no reports of such reaction with
respect to iodine monochloride. The attack of hydroxyl nu-
cleophile generating from the residual water in the solvent,
on the activated intermediate over other favorably placed
intramolecular nucleophiles (forming iodocyclized product)
or chloride ion, is seldom observed. Even in cases where
water is used as a solvent for iodocyclization, such reactions
are not observed.12 We believe that the mechanism of the
reaction involves alkyne activation by coordination of I+ to
the C–C triple bond. This activated intermediate can either
exist in symmetrical iodonium form I1 or vinyl cation form
I2. In the next step, the addition of the hydroxyl group from
the water molecule gives iodo-enol, which tautomerises,
giving the α-iodoketone 2a (Scheme 5).
To summarize, we were successfully able to discover
and identify an unusual reactivity of the aminoalkynol sub-
strate with iodine monochloride, which is a surprising devi-
ation from our previously reported study. The newly devel-
oped reaction conditions were applied to synthesize vari-
ous α-iodoketone derivatives from aminoalkynols. The
reaction is regioselective and can accommodate a wide
range of substituted amino alkynols both on the aromatic
ring and on the amine group. We were also able to success-
fully apply the optimized reactions condition for 4-phenyl-
but-3-yn-1-ol and synthesize the respective α-iodoketone.
O
Na2CO3 (3 equiv)
OH
ICl (3 equiv)
I
OH
THF, 0 °C
3a
4a
(45%)
α-iodoketone
Scheme 3 ICl-mediated conversion of 4-phenylbut-3-yn-1-ol into α-io-
doketone
Though there are few reports of alkynes being convert-
ed into α-iodoketones due to the hydration of the activated
alkyne-iodonium ion intermediate, they are often encoun-
tered as a minor product, usually below 10% yield as ob-
I
O
Na2CO3 (3 equiv)
NHTs
N
Ts
ICl (3 equiv)
+
I
NHTs
NH
NH
THF, 0 °C
NH
O
O
O
O
O
O
(not observed)
5a
6a
(68%)
Iodo-pyrrole
Scheme 4 ICl-mediated iodocyclization of homopropargyl amine-substituted aniline giving iodopyrrole
I
OH
NH
ICl
OH
H2O
– H+
OH
OH
I
NH
NH
I1
CO2Et
CO2Et
CO2Et
(or)
1a
OH
keto–enol
tautomerism
OH
I
O
I2
NH
CO2Et
I
NH
CO2Et
2a
Scheme 5 Plausible mechanism for the formation of α-iodoketone from aminoalkynol
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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V. V. Rao et al.
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The chemistry and drastic change in the reactivity of the
same substrates toward two similar yet different electro-
philic source is interesting to observe, especially the selec-
tivity towards hydration rather than iodocyclization by the
internal potential nucleophiles. More investigations into
such conversions will be done in the future.
HRMS (ESI): m/z [M + Na]+ calcd for C18H18INO4Na+: 462.0173; found:
462.0194.
N-[2-(4-Hydroxy-2-iodobutanoyl)phenyl]acetamide (2c)
Yield: 43.7 mg (63%, 0.126 mmol); yellow solid; mp 124–126 °C.
1H NMR (400 MHz, CDCl3): δ = 11.41 (s, 1 H), 8.76 (d, J = 8.5 Hz, 1 H),
7.93 (dd, J = 8.1, 1.3 Hz, 1 H), 7.62–7.54 (m, 1 H), 7.15–7.08 (m, 1 H),
5.76 (t, J = 7.1 Hz, 1 H), 3.88–3.74 (m, 2 H), 2.39–2.31 (m, 2 H), 2.25 (s,
3 H).
All reactions were performed using oven dried glassware under N2 at-
mosphere. Chemicals were purchased from Sigma Aldrich and used as
received, unless otherwise mentioned. The products were purified by
column chromatography on silica gel 60–120 mesh. Technical grade
solvents were used for chromatography and distilled prior to use.
NMR spectra were recorded in Fourier transform mode. The 1H NMR,
13C NMR, and 19F NMR spectra were recorded on a 300 MHz, 400 MHz,
and 500 MHz spectrophotometer using CDCl3 and TMS as the internal
standard. Standard abbreviations were used to describe the multiplic-
ities in the 1H NMR spectra; coupling constants are reported in Hz.
Low- and high-resolution mass spectra were recorded by an ion-trap
method and mass/charge (m/z) ratios are reported as values in atomic
mass units. All melting points are uncorrected.
13C NMR (126 MHz, CDCl3): δ = 198.75, 169.50, 142.07, 135.70,
130.21, 122.43, 121.29, 118.89, 61.42, 37.43, 25.65, 23.48.
HRMS (ESI): m/z [M + H – H2O]+ calcd for C12H13INO2+: 329.9985;
found: 329.9997.
Ethyl [4-Fluoro-2-(4-hydroxy-2-iodobutanoyl)phenyl]carbamate
(2e)
Yield: 50.6 mg (64%, 0.128 mmol); gram-scale yield: 1.077 g (54%, 2.7
mmol); yellow solid; mp 98–100 °C.
1H NMR (400 MHz, CDCl3): δ = 10.64 (s, 1 H), 8.54–8.46 (m, 1 H), 7.57
(dd, J = 9.4, 2.9 Hz, 1 H), 7.33–7.27 (m, 1 H), 5.63 (t, J = 7.1 Hz, 1 H),
4.23 (q, J = 7.1 Hz, 2 H), 3.87–3.72 (m, 2 H), 2.39–2.30 (m, 2 H), 1.33 (t,
J = 7.1 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 197.22 (s), 156.48 (d, J = 242.8 Hz),
153.88 (s), 138.74 (s), 122.70 (d, J = 22.1 Hz), 121.63 (d, J = 7.0 Hz),
119.48 (d, J = 5.6 Hz), 115.99 (d, J = 23.6 Hz), 61.50 (s), 61.35 (s), 37.32
(s), 23.16 (s), 14.49 (s).
α-Iodoketones 2a–j and 4a from Aminoalkynols 1a–j and Alkynol
3a; General Procedure
Aminoalkynol 1a–j or alkynol 3a (0.2 mmol) and Na2CO3 (64 mg, 0.6
mmol, 3 equiv) were added to THF maintained at 0 °C under N2. To the
above stirred solution, a 1 M solution of ICl in CH2Cl2 (97.5 mg, 0.6
mL, 0.6 mmol, 3 equiv) was slowly added dropwise and the reaction
was allowed to proceed till the starting material was consumed (30–
60 min). Once the reaction was complete, EtOAc was added to the re-
action mixture and the organic phase was washed with sat. aq
Na2S2O3 and then washed with H2O. The organic layer was separated
and dried (anhyd Na2SO4). The solvent was evaporated under vacuum
and the crude product was purified by silica gel column chromatogra-
phy using PE/EtOAc (7:3) mixture as eluent.
19F NMR (376 MHz, CDCl3): δ = –120.12.
HRMS (ESI): m/z [M + Na]+ calcd for C13H15INO4Na+: 417.9922; found:
417.9952.
Ethyl [4-Chloro-2-(4-hydroxy-2-iodobutanoyl)phenyl]carbamate
(2f)
Yield: 45.3 mg (55%, 0.11 mmol); yellow solid; mp 92–95 °C.
1H NMR (400 MHz, CDCl3): δ = 10.74 (s, 1 H), 8.51 (d, J = 9.1 Hz, 1 H),
7.84 (d, J = 2.3 Hz, 1 H), 7.51 (dd, J = 9.1, 2.3 Hz, 1 H), 5.65 (t, J = 7.1 Hz,
1 H), 4.23 (q, J = 7.1 Hz, 2 H), 3.89–3.73 (m, 2 H), 2.40–2.31 (m, 2 H),
1.33 (t, J = 7.1 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 197.23, 153.67, 141.07, 135.27,
129.60, 126.45, 121.23, 119.67, 61.59, 61.39, 37.30, 23.13, 14.48.
Ethyl [2-(4-Hydroxy-2-iodobutanoyl)phenyl]carbamate (2a)
Yield: 57.3 mg (76%, 0.152 mmol); gram-scale yield: 1.30 g (69%, 3.45
mmol); yellow solid; mp 82–84 °C.
1H NMR (500 MHz, CDCl3): δ = 10.90 (s, 1 H), 8.52 (dd, J = 8.6, 0.9 Hz, 1
H), 7.92 (dd, J = 8.1, 1.4 Hz, 1 H), 7.59–7.54 (m, 1 H), 7.08–7.03 (m, 1
H), 5.74 (t, J = 7.1 Hz, 1 H), 4.23 (q, J = 7.1 Hz, 2 H), 3.87–3.75 (m, 2 H),
2.38–2.32 (m, 2 H), 1.33 (t, J = 7.1 Hz, 3 H).
HRMS (ESI): m/z [M + Na]+ calcd for C13H15ClINO4Na+: 433.9626;
found: 433.9716.
13C NMR (126 MHz, CDCl3): δ = 198.21, 153.82, 142.62, 135.60,
130.32, 121.37, 119.71, 118.45, 61.48, 61.37, 37.46, 23.44, 14.51.
HRMS (ESI): m/z [M + Na]+ calcd for C13H16INO4Na+: 400.0016; found:
400.0056.
Ethyl [5-Chloro-2-(4-hydroxy-2-iodobutanoyl)phenyl]carbamate
(2g)
Yield: 49.4 mg (60%, 0.12 mmol); yellow oil.
1H NMR (400 MHz, CDCl3): δ = 10.99 (s, 1 H), 8.62 (d, J = 2.1 Hz, 1 H),
7.84 (d, J = 8.7 Hz, 1 H), 7.02 (dd, J = 8.7, 2.1 Hz, 1 H), 5.67 (t, J = 7.1 Hz,
1 H), 4.24 (q, J = 7.1 Hz, 2 H), 3.87–3.72 (m, 2 H), 2.38–2.30 (m, 2 H),
1.34 (t, J = 7.1 Hz, 3 H).
13C NMR (101 MHz, CDCl3): δ = 197.41, 153.55, 143.69, 142.01,
131.46, 121.64, 119.59, 116.55, 61.66, 61.39, 37.33, 23.25, 14.46.
Benzyl [2-(4-Hydroxy-2-iodobutanoyl)phenyl]carbamate (2b)
Yield: 62.4 mg (71%, 0.142 mmol); yellow solid; mp 78–80 °C.
1H NMR (500 MHz, CDCl3): δ = 11.00 (s, 1 H), 8.53 (d, J = 8.5 Hz, 1 H),
7.91 (dd, J = 8.1, 1.2 Hz, 1 H), 7.59–7.54 (m, 1 H), 7.45–7.30 (m, 5 H),
7.09–7.04 (m, 1 H), 5.73 (t, J = 7.1 Hz, 1 H), 5.22 (s, 2 H), 3.84–3.73 (m,
2 H), 2.36–2.30 (m, 2 H).
HRMS (ESI): m/z [M + Na]+ calcd for C13H15ClINO4Na+: 433.9626;
found: 433.9653.
13C NMR (126 MHz, CDCl3): δ = 198.20, 153.58, 142.41, 136.00,
135.60, 130.35, 128.60, 128.33, 121.57, 119.78, 118.56, 67.08, 61.47,
37.43, 23.39.
Ethyl [2-(4-Hydroxy-2-iodobutanoyl)-4-nitrophenyl]carbamate
(2h)
Yield: 44.8 mg (53%, 0.106 mmol); yellow solid; mp 116–118 °C.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G

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V. V. Rao et al.
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1H NMR (400 MHz, CDCl3): δ = 11.19 (s, 1 H), 8.82 (d, J = 2.5 Hz, 1 H),
8.75 (d, J = 9.5 Hz, 1 H), 8.41–8.35 (m, 1 H), 5.79 (t, J = 7.0 Hz, 1 H),
4.29 (q, J = 7.1 Hz, 2 H), 3.91–3.77 (m, 2 H), 2.44–2.35 (m, 2 H), 1.36 (t,
J = 7.1 Hz, 3 H).
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1590897.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
13C NMR (101 MHz, CDCl3): δ = 197.22, 153.22, 147.77, 140.75,
129.86, 126.21, 119.78, 117.62, 62.25, 61.25, 37.21, 22.82, 14.39.
HRMS (ESI): m/z [M + H – H2O]+ calcd for C13H14IN2O5+: 404.9942;
References
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Ethyl [2-(4-Hydroxy-2-iodobutanoyl)-4-methylphenyl]carbamate
(2i)
Yield: 58.7 mg (75%, 0.15 mmol); yellow solid; mp 100–103 °C.
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(9) CCDC number 1554465 contains the supplementary crystallo-
graphic data for this paper. The data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/getstructures.
1H NMR (400 MHz, CDCl3): δ = 10.75 (s, 1 H), 8.39 (dd, J = 8.7, 1.6 Hz, 1
H), 7.68 (s, 1 H), 7.38 (d, J = 8.7 Hz, 1 H), 5.73 (t, J = 7.1 Hz, 1 H), 4.22
(q, J = 7.1 Hz, 2 H), 3.88–3.74 (m, 2 H), 2.39–2.31 (m, 5 H), 1.32 (t, J =
7.1 Hz, 3 H).
13C NMR (75 MHz, CDCl3): δ = 198.14, 153.87, 140.23, 136.50, 130.78,
130.19, 119.73, 118.49, 61.56, 61.23, 37.46, 23.51, 20.77, 14.50.
HRMS (ESI): m/z [M + Na]+ calcd for C14H18INO4Na+: 414.0173; found:
414.0045.
Ethyl [2-(4-Hydroxy-2-iodobutanoyl)-5-methoxyphenyl]carba-
mate (2j)
Yield: 66.8 mg (82%, 0.164 mmol); yellow solid; mp 107–110 °C.
1H NMR (400 MHz, CDCl3): δ = 11.39 (s, 1 H), 8.16 (d, J = 2.6 Hz, 1 H),
7.85 (d, J = 9.1 Hz, 1 H), 6.58 (dd, J = 9.1, 2.6 Hz, 1 H), 5.68 (t, J = 7.1 Hz,
1 H), 4.23 (q, J = 7.1 Hz, 2 H), 3.90 (s, 3 H), 3.85–3.72 (m, 2 H), 2.38–
2.29 (m, 2 H), 1.33 (t, J = 7.1 Hz, 3 H).
13C NMR (126 MHz, CDCl3): δ = 196.63, 165.39, 153.92, 145.70,
132.55, 111.37, 109.13, 102.73, 61.59, 61.36, 55.66, 37.62, 23.44,
14.50.
HRMS (ESI): m/z [M + Na]+ calcd for C14H18INO5Na+: 430.0122; found:
430.0105.
4-Hydroxy-2-iodo-1-phenylbutan-1-one (4a)
Yield: 26.1 mg (45%, 0.09 mmol); light yellow oil.
1H NMR (300 MHz, CDCl3): δ = 8.02 (d, J = 7.2 Hz, 2 H), 7.62–7.54 (m, 1
H), 7.52–7.43 (m, 2 H), 5.68 (t, J = 7.1 Hz, 1 H), 3.89–3.74 (m, 2 H),
2.42–2.32 (m, 2 H).
13C NMR (75 MHz, CDCl3): δ = 194.75, 133.93, 133.64, 128.78, 128.74,
61.67, 37.17, 22.71.
(10) (a) Bellina, F.; Colzi, F.; Mannina, L.; Rossi, R.; Viel, S. J. Org.
Chem. 2003, 68, 10175. (b) Godoi, B.; Schumacher, R. F.; Zeni, G.
Chem. Rev. 2011, 111, 2937.
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(b) Rossi, R.; Carpita, A.; Bellina, F.; Stabile, P.; Mannina, L. Tetra-
hedron 2003, 59, 2067.
HRMS (ESI): m/z [M + H]+ calcd for C10H12IO2+: 290.9876; found:
290.9869.
(12) (a) Han, J.-S.; Chen, S.-Q.; Zhong, P.; Zhang, X.-H. Synth.
Commun. 2014, 44, 3148. (b) Batistatos, M.; Fousteris, M. A.;
Nikolaropoulos, S. S.; Le Bras, J.; Muzart, J. Lett. Org. Chem. 2010,
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Chem. 2006, 8, 522.
Acknowledgment
The authors thank Dr. Steven Priver for single crystal XRD analysis.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–G