One-Pot Protocol for Synthesis of -Organosulfonyloxy Ketones from Secondary Alcohols Using Hypervalent Iodine(V)-Mediated Oxidations

Article abstract of DOI:10.1080/00397910902730952

Tosyloxy ketones and -mesyloxy ketones were directly prepared from alcohols in one pot by treatment with hypervalent iodine(V) reagents in combination with p-toluenesulfonic acid and methanesulfonic acid, respectively, in moderate to good yields. Reaction

Full text of DOI:10.1080/00397910902730952

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One-Pot Protocol for Synthesis
of α-Organosulfonyloxy
Ketones from Secondary
Alcohols Using Hypervalent
Iodine(V)–Mediated Oxidations
Swapnil S. Deshmukh a , Sameerana N. Huddar a &
Krishnacharya G. Akamanchi a
a Department of Pharmaceutical Sciences and
Technology , Institute of Chemical Technology ,
Mumbai, India
Published online: 03 Aug 2009.
To cite this article: Swapnil S. Deshmukh , Sameerana N. Huddar & Krishnacharya
G. Akamanchi (2009) One-Pot Protocol for Synthesis of α-Organosulfonyloxy Ketones
from Secondary Alcohols Using Hypervalent Iodine(V)–Mediated Oxidations, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic
Organic Chemistry, 39:17, 3101-3110, DOI: 10.1080/00397910902730952
To link to this article: http://dx.doi.org/10.1080/00397910902730952
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Synthetic Communications1, 39: 3101–3110, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902730952
One-Pot Protocol for Synthesis of
a-Organosulfonyloxy Ketones from
Secondary Alcohols Using Hypervalent
Iodine(V)–Mediated Oxidations
Swapnil S. Deshmukh, Sameerana N. Huddar, and
Krishnacharya G. Akamanchi
Department of Pharmaceutical Sciences and Technology,
Institute of Chemical Technology, Mumbai, India
Abstract: a-Tosyloxy ketones and a-mesyloxy ketones were directly prepared
from alcohols in one pot by treatment with hypervalent iodine(V) reagents in
combination with p-toluenesulfonic acid and methanesulfonic acid, respectively,
in moderate to good yields. Reactions were also feasible under solvent-free
conditions.
Keywords: Alcohols, Dess–Martin periodinane, hypervalent iodine(V) reagents,
organosulfonic acids, a-organosulfonyloxy ketones, solvent-free reaction condition
The a-organosulfonyloxy ketones are useful intermediates in the synthesis
of a variety of biologically important heterocyclic ring systems such as
thiazoles, imidazoles, oxazoles, pyrazines, pyrazoles, lactones, benzo-
furans, benzopyrazines, benzooxazines, benzothiazines, imidazo[2,1-b]
thiazoles, and thiazolo[3,2-a] benzimidazoles.[1–3] a-Organosulfonyloxy
ketones are also useful intermediates for a-azidation of ketones.[3d]
Hypervalent iodine reagents are extensively used in organic synthesis
because these reagents are mild, nonmetallic, and highly selective oxidants.
Development of new methodologies using these reagents is of current
Received November 8, 2008.
Address correspondence to Krishnacharya G. Akamanchi, Department of
Pharmaceutical Sciences and Technology, Institute of Chemical Technology,
Matunga, Mumbai 400019, India. E-mail: kgap@rediffmail.com
3101

3102
S. S. Deshmukh, S. N. Huddar, and K. G. Akamanchi
interest.[4] Our group has recently reported hypervalent iodine(V) reagents
for a-tosyloxylation of carbonyl compounds, including ketones.[5]
In continuation of our efforts to develop of useful synthetic meth-
odologies of hypervalent iodine(V) reagents, especially o-iodoxybenzoic
acid (IBX), Dess–Martin periodinane (DMP), and HIO3, we report here
a one-pot synthesis of a-organosulfonyloxy ketones starting from alco-
hols using DMP in combination with organosulfonic acids. One-pot
transformations offer a number of advantages, such as the time–cost
benefits gained by avoiding isolation, handling, and chromatography of
intermediates, as well as fewer workup steps.
Oxidation of alcohols to ketones is a fundamental organic trans-
formation for which a number of reagents and reagent systems are
available,[6] whereas only a few methods are available for direct a-
organosulfonyloxylation of ketones.[7] Combining these two steps in a
one-pot synthesis has great practical advantages, and we report one such
development using hypervalent iodine(V) reagents.
Some hypervalent iodine(III) reagents are known to promote direct
conversion of alcohols to a-tosyloxy ketones. Among them are poly
(4-hydroxytosyloxyiodo)styrenes,[8a] iodosylbenzene, 4-methyl-1-idosyl-
benzene, 3-(trifluromethyl)-1-idosylbenzene, (diacetoxyiodo)benzene,
4-methyl-1-(diacetoxyiodo)benzene, and 3-(trifluromethyl)-1-iodosylben-
zene in combination with p-toluenesulfonic acid monohydrate.[8b]
For developing the protocol, 1-(4-nitrophenyl)ethanol (1a) was
chosen as a model substrate, and studies were carried out using 3 equiv
Table 1. a-Tosyloxylation using hypervalent iodine(V) reagentsa
Yield (%)b
Entry
Reagent
Conditions
1b
1c
1
2
3
4
DMP
DMP
IBX
rt, 12 h
Nil
92
75
25
45
Nil
10
Reflux, 4 h
Reflux, 4.5 h
Reflux, 12 h
HIO3
35
aReactions were carried on a 5-mmol scale and with 3 equiv of reagents.
bIsolated yields using column chromatography.

a-Organosulfonyloxy Ketones
3103
Table 2. DMP-mediated direct conversion of secondary alcohols to
a-organosulfonyloxy ketonesa
Yield (%)b,c
Entry
1
Substrate
Product
R¼O-p-Ts
R¼OMs
92
88
2
3
82
80
80
77
4
73
71
5
76
73
(Continued )

3104
S. S. Deshmukh, S. N. Huddar, and K. G. Akamanchi
Table 2. Continued
Yield (%)b,c
Entry
6
Substrate
Product
R¼O-p-Ts
R¼OMs
77
74
7
8
89
75
86
72
9
68
64
10
11
82
81
77
71
aReactions were carried out on a 5-mmol scale in CH3CN at reflux temperature
with DMP (3 equiv) and organosulfonic acid (3 equiv).
1
bProducts were characterized by H NMR, IR, and physical constants.
cIsolated yields were determined using column chromatography.
of DMP and 3 equiv of p-toluenesulfonic acid monohydrate in acetoni-
trile. When the reaction was carried out at room temperature for 12 h,
only 1-(4-nitrophenyl)ethanone (1c) was obtained (Table 1, entry 1).
However, when the reaction was conducted at reflux temperature, it pro-
ceeded smoothly, and 2-(4-nitrophenyl)-2-oxo-ethyl-4-methanebenzene
sulfonate (1b) was obtained in 92% yield in 4 h (Table 1, entry 2). Other
hypervalent iodine(V) reagents such as IBX and HIO3 were also found to

a-Organosulfonyloxy Ketones
3105
be viable, and a-sulfonyloxylated compound (1b) was obtained in 75%
and 25% yields respectively with isolation of intermediate ketone in the
range of 10–35% yield (Table 1, entries 3 and 4).
For establishing general utility of this protocol, DMP was chosen as
oxidant, and the results are shown in Table 2.
As illustrated in Table 2, the reactivity profile of the substituted
alcohols was remarkable. The reaction was also facile with cyclohexanol,
isopropanol, and heterocyclic alcohol such as 1-(furan-2-yl)ethanol, and
in all cases corresponding a-organosulfonyloxy ketones were obtained in
moderate to good yields (Table 2, entries 9–11).
As solvent-free reactions are of current interest,[9] the reaction was
also carried out under solvent-free conditions, and results are summar-
ized in Table 3. The reaction is viable; however, yields were found to
be comparatively less.
In conclusion, a one-pot protocol has been developed for synthesis
of a-organosulfonyloxy ketones starting from corresponding alcohols
using hypervalent iodine(V) reagents, especially DMP, in combination
with organosulfonic acids. The reaction is also viable under solvent-free
conditions.
Table 3. DMP-mediated solvent-free a-organosulfonyloxylationa
Entry
1
Substrate
Product
Yieldb (%)
65
2
3
4
59
51
38
aReactions were carried out under solvent-free conditions on a 5-mmol scale
with DMP (3 equiv) and organosulfonic acid (3 equiv) at rt.
bCorresponding ketones were recovered in the range of 20–40%.

3106
S. S. Deshmukh, S. N. Huddar, and K. G. Akamanchi
a-ORGANOSULFONYLOXYLATION: GENERAL PROCEDURE
Alcohol (5 mmol) was added in one portion to a stirred suspension of
Dess–Martin periodinane (15 mmol) and organosulfonic acid (15 mmol)
in CH3CN (20 mL), and the reaction mixture was refluxed for 4 h. Sol-
vent was removed under reduced pressure, and the residue obtained
was diluted by adding CHCl3 (60 mL) and washed with saturated
solution of NaHCO3 (2 ꢀ 35 mL) and brine (60 mL). The organic layer
was dried over anhydrous Na2SO4 and concentrated under reduced pres-
sure to give crude a-organosulfonyloxylated product. Pure product was
obtained after column chromatography (SiO2, mesh size 60–120, eluent,
ethyl acetate–hexane, 15:85).
SOLVENT-FREE a-ORGANOSULFONYLOXYLATION:
GENERAL PROCEDURE
DMP (15 mmol) and p-toluenesulfonic acid monohydrate (15 mmol)
were gently ground for 15 min using pestle and mortar. The resulting
reaction mixture was washed with diethyl ether and dried under a strong
vacuum to afford solid reagent, which was slowly added in portions to
alcohol (5 mmol). An exotherm was observed. Stirring continued for
30 min, and CHCl3 (30 mL) was added. The slurry was filtered, and
the filtrate was washed with a saturated solution of NaHCO3
(2 ꢀ 35 mL) and brine (60 mL). The organic layer was dried over anhy-
drous Na2SO4 and concentrated under reduced pressure to give crude
a-organosulfonyloxylated product. Pure product was obtained after
column chromatography (SiO2, mesh size 60–120, eluent, ethyl acetate–
hexane, 15:85).
SPECTRAL DATA FOR SELECTED a-ORGANOSULFONYLOXY
KETONES FROM TABLE 2
2-(4-Nitrophenyl)-2-oxo-ethyl-4-methanebenzene-sulfonate (Entry 1)
Solid. Mp 130ꢁC (lit.[8b] 130–131ꢁC). IR (KBr): vmax ¼ 1180, 1340,
1
1710 cmꢂ1. H NMR (400 MHz, CDCl3): d 2.47 (s, 3 H), 5.25 (s, 2 H),
7.37 (d, J ¼ 8.3 Hz, 2 H), 7.83 (d, J ¼ 8.3 Hz, 2 H), 8.03 (d, J ¼ 8.9 Hz,
2 H), 8.32 (d, J ¼ 8.9 Hz, 2 H) ppm.

a-Organosulfonyloxy Ketones
3107
2-(4-Chlorophenyl)-2-oxo-ethyl-4-methanebenzene-sulfonate (Entry 2)
Solid. Mp 123ꢁC (lit.[7a] 125ꢁC). IR (KBr): vmax ¼ 1190, 1360, 1700 cmꢂ1
.
1H NMR (400 MHz, CDCl3): d 2.46 (s, 3 H), 5.21 (s, 2H), 7.35 (d,
J ¼ 8.4 Hz, 2 H), 7.45 (d, J ¼ 8.6 Hz, 2 H), 7.80 (d, J ¼ 8.6 Hz, 2 H),
7.84 (d, J ¼ 8.4 Hz, 2 H) ppm.
2-(2,4-Dichlorophenyl)-2-oxo-ethyl-methanesulfonate (Entry 3)
Solid. Mp 87ꢁC (lit.[5] 87ꢁC). IR (KBr): vmax ¼ 1710 cmꢂ1
.
1H NMR
(60 MHz,CDCl3): d 3.24 (s, 3H), 5.44 (s, 2H), 7.22–7.83 (m, 3H) ppm.
2-[2-Chloro-4(4-chlorophenoxy)phenyl]-2-oxo-ethyl-
methanesulfonate (Entry 4)
White solid. Mp 118ꢁC (lit.[5] 118–119ꢁC). IR (KBr): vmax ¼ 1715 cmꢂ1
.
1H NMR (60 MHz, CDCl3): d 3.20 (s, 3H), 5.44 (s, 2H), 7.20–7.89
(m, 7H) ppm.
2-(4-Methoxyphenyl)-2-oxo-ethyl-methanesulfonate (Entry 5)
[5]
1
Solid. Mp 98 C (lit. 98ꢁC). IR (KBr): vmax ¼ 1710 cmꢂ1. H NMR
(60 MHz, CDCl3): d 3.22 (s, 3H), 3.88 (s, 3H), 5.44 (s, 2H), 7.28
(d, J ¼ 7.8 Hz, 2H), 7.74 (d, J ¼ 7.8 Hz, 2H) ppm.
ꢁ
2-Oxo-2-p-tolylethyl-methanesulfonate (Entry 6)[5]
1
IR (KBr): vmax ¼ 1710 cmꢂ1. H NMR (60 MHz, CDCl3): d 2.44 (s, 3H),
3.28 (s, 3H), 5.48 (s, 2H), 7.28 (d, J ¼ 8.33 Hz, 2H), 7.77 (d, J ¼ 8.33 Hz,
2H) ppm.
2-Oxo-2-phenylethyl-methanesulfonate (Entry 7)
Solid. Mp 76–77ꢁC (lit.[3a] 76–78ꢁC). IR (KBr): vmax ¼ 1725 cmꢂ1
.
1H NMR (60 MHz, CDCl3): d 3.20 (s, 3H), 5.43 (s, 2H), 7.12–8.12
(m, 5H) ppm.

3108
S. S. Deshmukh, S. N. Huddar, and K. G. Akamanchi
1-Oxo-1-phenylpropan-2-yl-4-methanebenzene-sulfonate (Entry 8)
Solid. Mp 68ꢁC (lit.[7a] 68–69ꢁC). IR (KBr): vmax ¼ 1170, 1370, 1700 cmꢂ1
.
1H NMR (400 MHz, CDCl3): d 1.60 (d, J ¼ 7.0 Hz, 3H), 2.41 (s, 3H),
5.79 (q, J ¼ 7.0 Hz, 1H), 7.29 (d, J ¼ 8.1 Hz, 2H), 7.46 (t, J ¼ 7.2 Hz,
2H), 7.60 (t, J ¼ 7.2 Hz, 1H), 7.75 (d, J ¼ 7.2 Hz, 2H), 7.88 (d, J ¼ 8.1 Hz,
2H) ppm.
2-Oxo-cyclohexyl-4-methylbenzenesulfonate (Entry 9)
1
Solid. Mp 76ꢁC (lit.[8a] 74–76ꢁC) IR (KBr): vmax ¼ 1744 cmꢂ1. H NMR
(60 MHz, CDCl3): d 1.30–2.70 (m, 11H), 4.82 (s, 1H), 7.10 (d, 2H),
8.02 (d, 2H) ppm.
2-Oxo-propyl-methanesulfonate (Entry 10)
Oil.[3a] IR (neat): vmax ¼ 1738, 1367, 1187 cmꢂ1
.
1H NMR (60 MHz,
CDCl3): d 2.20 (s, 3H), 3.16 (s, 3H), 4.37 (s, 2H) ppm.
2-(Furan-2-yl)-2-oxo-ethyl-4-methanebenzenesulfonate (Entry 11)
1
Solid. Mp 65ꢁC (lit.[8a] 65–67ꢁC). IR (KBr): vmax ¼ 1670 cmꢂ1. H NMR
(60 MHz, CDCl3): d 3.27 (s, 3H), 5.53 (s, 2H), 7.28–8.05 (m, 7H) ppm.
ACKNOWLEDGMENTS
For financial assistance, S. S. D. thanks the World Bank for support
under the Technical Education Quality Improvement Program (TEQIP),
and S. N. H. thanks the Narotam Sekhsaria Foundation, Mumbai. We
are also thankful to M=S Omkar Chemicals in Badlapur, Thane, India,
for their generous gift of DMP.
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