One-pot synthesis of β-keto sulfones by the condensative decarboxylation of sulfonylacetic acids with acid chlorides under mild conditions

Full text of DOI:10.1002/bkcs.10591

Note
DOI: 10.1002/bkcs.10591
BULLETIN OF THE
K. Lee
KOREAN CHEMICAL SOCIETY
One-Pot Synthesis of β-Keto Sulfones by the Condensative
Decarboxylation of Sulfonylacetic Acids with Acid Chlorides under Mild
Conditions
*
Kieseung Lee
Department of Applied Chemistry, Woosuk University, Chonbuk 565-701, Korea.
E-mail:kslee@woosuk.ac.kr
*
Received June 15, 2015, Accepted August 28, 2015, Published online November 24, 2015
Keywords: β-Keto sulfones, Sulfonylacetic acids, Acid chlorides, Condensation, Decarboxylation
β-Ketosulfonesareimportant compoundsinorganic synthesis
O
OLi
O
O
O
O
O
O+
O
O
n-BuLi (2 eq)
R
2
COCl (2)
H
3
1
S
S
S
due to their broad range of synthetic versatility. For example,
R1
OH
R1
OLi
R1
R2
-CO
2
H
β-keto sulfones have been utilized as important intermediates
1
3
2
a
2b
2c
in the synthesis of alkenes, alkynes, ketone derivatives,
Scheme 1. A new approach to β-keto sulfones (3) from sulfonylacetic
acids (1) using acid chlorides (2).
2d
andheterocycles, andalsousedastheprecursorstoothersul-
fonyl derivatives such as β-hydroxy sulfones and α-diazo-
3
a
3b
β-keto sulfones.
Therefore, there have been strenuous efforts to develop new
approaches to these highly versatile compounds, and the rep-
resentative synthetic routes include oxidation of β-oxo sul-
Results and Discussion
4
a
fides/sulfoxides to sulfones,
acylation of lithium
Various types of sulfonylacetic acids and acid chlorides were
reacted using n-BuLi as the base, and the representative results
are summarized in Table 1 (vide infra). When phenylsulfony-
lacetic acid was treated sequentially with n-BuLi (2.1 equiv)
4
b
(
methylsulfonyl)methylide with 1-acylimidazole, SnCl2-
4
c
catalyzed addition of diazo sulfones to aldehydes, P O -
2
5
mediated dehydrative condensation of benzylsulfonylacetic
4
d
acids with benzene or halobenzene, acid-catalyzed reaction
ꢀ
and benzoyl chloride (0.6 equiv) at −78 C, 3a was obtained
4
e
of sulfonyl chlorides with acetylenes and water, condensa-
in 84% yield (Entry 1). It is important to note that, theoreti-
cally, two equivalents of dilithium dianion of phenylsulfony-
lacetic acid are required for the high conversion to β-keto
sulfone 3a since the initial coupling product formed is going
to be deprotonated immediately by any unreacted dilithium
dianion of phenylsulfonylacetic acid. Increasing the amount
of benzoyl chloride added over 0.6 equiv or altering the reac-
tion temperature/time, however, did not bring forth any signif-
icant improvements in the yield of 3a. Under these standard
conditions, other acid chlorides e.g., hexanoyl chloride, cyclo-
propanecarboxylic chloride, 2-furoyl chloride, and thiophene-
tion of ketones with sodium sulfinates using Koser’s
4f
reagent, rhodium(I)-catalyzed addition of arylboronic acids
4
g
to sulfonylacetonitrile, and AgNO /K S O catalyzed aero-
3
2 2 8
4h
bic oxysulfonylation of alkenes in aqueous medium. These
synthetic routes, however, may have some limitations such as
strict reaction conditions, limited substrate scope, and use of
expensive or less readily available chemicals.
Methyl phenyl sulfone has been utilized as the starting
5
material for the synthesis of β-keto sulfones. The scope, how-
ever, was very limited, and the reported yields were moderate
to good. It is well-known that carboxylic acids with electron-
2
-carbonyl chloride were also examined, and each acyl chlo-
withdrawing groups such as CN, NO2, C O, CX or
3
ride was found to couple smoothly with dilithium dianion of
phenylsulfonyaceticacidstoprovidethecorrespondingβ-keto
sulfones 3b–e in 75–87% yields (Entry 2–5).
double or triple bonds in the α-position do undergo successful
6
decarboxylationeitherasthefreeacidorinthesaltform. With
the above fact in mind, we envision that if the carboxylic acid
functionality is introduced to the methyl subunit of sulfonyl
compounds as an activator and a regiodirector toward base,
the resulting sulfonylacetic acids can be used as valuable start-
ing chemicals for the synthesis of β-keto sulfones 3 via con-
densative decarboxylation of sulfonylacetic acids 1 with
acid chlorides 2 as depicted in Scheme 1.
To determine the scope of this one-pot procedure, other sul-
fonylacetic acids such as (p-methoxyphenyl, n-butyl, benzyl)
sulfonylacetic acid were also reacted with benzoyl chloride
and hexanoyl chloride, respectively, under standard condi-
tions and the results (64–86% yields) were found satisfactory
(Entry 6–11).
The reaction presumably proceeds through condensation
Herein we wish to report for the first time a direct synthesis
of β-keto sulfones from sulfonylacetic acids and acid chlorides
under mild conditions.
between dilithium dianion of sulfonylacetic acid and acid
chloride to afford the acylated anion intermediate of dilithium
dianion of sulfonylacetic acid, which is smoothly
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KOREAN CHEMICAL SOCIETY
Table 1. One-pot synthesis of β-ketosulfones (3) by the condensative
decarboxylation of sulfonylacetic acids (1) with acid chlorides (2)
under mild conditions.
(10 mL) was added n-BuLi (840 μL, 2.1 equiv, 2.5 M in hex-
anes) by syringe until a red color persisted. The solution was
a
ꢀ
stirred at −78 C for 15 min under Ar, and then benzoyl chlo-
ride (69.6 μL, 0.6 equiv) was added by syringe. The red color
OLi
O
n-BuLib
O
O
c
O
O
O
(i) R COCl (2)
O
O
2
of the solution was immediately changed to pale-yellow. The
S
S
O+
S
R
1
OLi
ꢀ
R
1
OH THF
(ii) H
3
R1
R2
resulting mixture was stirred at −78 C for 30 min, and
H
1
3
allowed to warm up to room temperature for 1 h. The reaction
was quenched with aq. HCl (10 mL, 0.1 N) and then extracted
d,e
Entry
R
1
R
2
3 (Yield, %)
with Et O (20 mL). The organic layer was separated, and the
2
aqueous layer was extracted with Et O (10 mL × 2). The com-
bined organic layers were washed with saturated brine, dried
2
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
p-MeOPh
p-MeOPh
CH
CH
PhCH2
PhCH
Ph
CH
3a (84)
3b (87)
3c (80)
3d (82)
3e (75)
3f (86)
3g (76)
3h (83)
3i (75)
3j (74)
3k (64)
3
2 4
(CH )
over MgSO , filtered, and concentrated. Flash chromatogra-
4
Cyclopropanyl
2-Furanyl
2-Thiophenyl
Ph
CH (CH )
Ph
CH
Ph
CH
phy of the residue on SiO (CH Cl /hexane, 10/1) afforded
2
2
2
ꢀ
−1
3
9
a (109.3 mg, 84%) as a white solid. Mp 93–94 C (Ref. 4e
2–93 C); IR (KBr) 1674, 1318, 1158 cm ; H-NMR
ꢀ
1
(
(
CDCl ) δ 4.74 (s, 2H), 7.47–7.67 (m, 6H), 7.89–7.95
3
3
3
3
2 4
m, 4H).
3
3
(CH
(CH
2
)
)
3
3
1
-(Phenylsulfonyl)heptan-2-one (3b): A white solid; mp
2
(CH
(CH
2
2
)
4
4
ꢀ ꢀ
3–44 C (Ref. 9a 45–46 C); IR (KBr) 1716, 1301, 1153
4
1
1
0
1
−
1
1
cm ; H NMR (CDCl ) δ 0.88 (t, 3H, J = 6.8 Hz),
3
2
)
1
.20–1.34 (m, 4H), 1.52–1.59 (m, 2H), 2.69 (t, 2H, J = 7.3
Reaction conditions and agents:
Hz), 4.15 (s, 2H), 7.58 (bt, 2H, J = 7.8 Hz), 7.69 (bt, 1H, J
= 7.6 Hz), 7.89 (bd, 2H, J = 7.3 Hz).
a
b
c
0
2
,2 -Bipyridine (ca. 2–3 mg) was added as an indicator.
n-BuLi (2.1 equiv), –78 C, 15 min, Ar.
(0.6 equiv), –78 C, 30 min then warm up to room temperature, 1
ꢀ
ꢀ
1-Cyclopropyl-2-(phenylsulfonyl)ethanone (3c):
A
2
ꢀ ꢀ
white solid; mp 57–58 C (Ref. 5 58 C); IR (KBr) 1695,
h, Ar.
d
e
−1 1
Isolated yield after flash column chromatography on SiO
2
.
1311, 1151 cm ; H NMR (CDCl ) δ 1.02−1.06 (m, 2H),
3
Isolated yield calculated based on the theoretical amount (0.5 equiv) of
needed.
1
.08−1.12 (m, 2H), 2.27 (m, 1H), 4.30 (s, 2H), 7.57 (bt, 2H,
J = 7.8 Hz), 7.68 (bt, 1H, J = 7.6 Hz), 7.92 (bd, 2H, J =
.3 Hz).
-(Furan-2-yl)-2-(phenylsulfonyl)ethanone (3d): An off-
2
7
decarboxylated either in the salt stage or upon addition of
aqueous HCl solution to yield β-keto sulfone.
1
7
ꢀ
−1
white solid; mp 75–76 C; IR (KBr) 1649, 1316, 1156 cm ;
1
In conclusion, a simple synthetic protocol for β-keto sul-
fones from sulfonylacetic acids has been developed via react-
ing the dilithium salt of sulfonylacetic acids with acid
chlorides under mild conditions. Considering several advan-
tages of this new route e.g., easy availability of the starting
materials, mild conditions, good yields, and wide scope of
applicability, this one-pot protocol could be the method of
choice for the synthesis of β-keto sulfones.
H NMR (CDCl ) δ 4.60 (s, 2H), 6.57 (dd, 1H, J = 3.8 Hz, J
3
1
2
=
(
(
1.7 Hz), 7.32 (d, 1H, J = 3.8 Hz), 7.52–7.59 (m, 3H), 7.66
13
bt, 1H, J = 7.3 Hz), 7.89 (bd, 2H, J = 7.3 Hz); C NMR
CDCl ) δ 63.4, 113.2, 120.3, 128.5, 129.2, 134.2, 138.7,
3
1
48.0, 151.8, 175.7; Anal. calcd. for C H O S : C,
12 10 4 1
5
7.59; H, 4.03, found: C, 57.68; H, 4.02.
-(Phenylsulfonyl)-1-(thiophen-2-yl)ethanone (3e): A
2
ꢀ
1 1
ꢀ
brown solid; mp 86–88 C (Ref. 4a 79–80 C); IR (KBr)
−
1
649, 1306, 1146 cm ; H NMR (CDCl ) δ 4.64 (s, 2H),
3
Experimental
7.15 (bt, 1H, J = 4.4 Hz), 7.55 (bt, 2H, J = 7.6 Hz), 7.66 (bt,
H, J = 7.6 Hz), 7.75 (bd, 1H, J = 3.9 Hz), 7.79 (bd, 1H, J =
1
General. All reactions were carried out in an oven-dried
4.9 Hz), 7.90 (bd, 2H, J = 7.3 Hz).
1
13
glassware under Ar. H NMR (400 MHz) and C NMR
100 MHz) spectra were obtained in CDCl on a Jeol FT
2-(4-Methoxylphenylsulfonyl)-1-phenylethanone (3f ):
ꢀ ꢀ
A white solid; mp 107–108 C (Ref. 9b 105–106 C); IR
(
3
−1 1
NMR spectrometer (Akishima, Japan). LR/HR mass spectra
were measured in EI (70 eV) mode. CHN analyses were done
with Vario EL elemental analyzer (Hanau, Hessen, Germany).
All commercially available reagents were purchased from
commercial sources, and used directly. Sulfonylacetic acids
(KBr) 1676, 1319, 1151 cm ; H NMR (CDCl ) δ 3.87 (s,
3
3H), 4.71 (s, 2H), 6.98 (d, 2H, J = 9.0 Hz), 7.48 (bt, 1H, J =
7.8 Hz), 7.79 (bt, 1H, J = 7.6 Hz), 7.80 (d, 2H, J = 9.0 Hz),
7.95 (bd, 2H, J = 7.3 Hz).
1-(4-Methoxyphenylsulfonyl)heptan-2-one (3g): Color-
less liquid; IR (neat) 1719, 1323, 1146 cm ; H NMR
−
1
1
(
R = p-MeO , n-Bu , PhCH ) were prepared according
1
2
8
to the reported procedures.
(CDCl ) δ 0.88 (t, 3H, J = 6.8 Hz), 1.24–1.33 (m, 4H),
3
Representative Experimental Procedures: Synthesis of 1-
1.52–1.60 (m, 2H), 2.69 (t, 2H, J = 7.3 Hz), 3.89 (s, 3H),
Phenyl-2-(phenylsulfonyl)ethanone (3a). To a stirred, pre-
4.11 (s, 2H), 7.02 (d, 2H, J = 8.8 Hz), 7.80 (d, 2H, J = 8.8
ꢀ
13
cooled (−78 C) solution of phenylsulfonylacetic acid (200.2
Hz); C NMR (CDCl ) δ 13.8, 22.3, 22.8, 30.9, 44.3, 55.7,
3
0
mg, 1.0 mmol) and 2,2 -bipyridine (ca. 2–3 mg) in dry THF
67.1, 114.5, 130.2, 130.5, 164.1, 198.6; HRMS (EI) calcd.
Bull. Korean Chem. Soc. 2015, Vol. 36, 2956–2958
© 2015 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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BULLETIN OF THE
Note
KOREAN CHEMICAL SOCIETY
for C H O S 284.1082, found 284.1081; Anal. calcd. for
References
1
4 20 4 1
C H O S : C, 59.13; H, 7.09, found: C, 59.23; H, 7.17.
1
4 20 4 1
2
-(Butylsulfonyl)-1-phenylethanone (3h): A white solid;
1. (a) N. S. Simpkins, In Sulfones in Organic Synthesis, Vol. 10,
J. E. Baldwin Ed., Pergamon Press, Oxford, 1993, p. 58;
(b) Y. M. Markitanov, V. M. Timoshenko, Y. G. Shermolovich,
J. Sulfur Chem. 2014, 35, 188.
ꢀ
ꢀ
mp 79–80 C(Ref. 3b71–73 C); IR (KBr) 1688, 1321, 1133
−
1 1
cm ; H NMR (CDCl ) δ 0.98 (t, 1H, J = 7.3 Hz), 1.46–1.55
3
(
2
(
m, 2H), 1.84–1.92 (m, 2H), 3.26 (t, 2H, J = 8.2 Hz), 4.57 (s,
H), 7.52 (bt, 2H, J = 7.8 Hz), 7.65 (bt, 1H, J = 7.6 Hz), 8.02
bd, 2H, J = 7.3 Hz).
-(Butylsulfonyl)heptan-2-one (3i): A white solid; mp
2
. (a) M. Ihara, S. Suzuki, T. Taniguchi, Y. Tokunaga, K. Fukumoto,
Tetrahedron 1995, 51, 9873; (b) T. Mandai, T. Yanagi,
K. Araki, Y. Morisaki, M. Kawada, J. Otera, J. Am. Chem. Soc.
2
1
984, 106, 3670; (c) H. Guo, Y. Zhang, Synth. Commun. 2000,
30, 2559; (d) N. Monteiro, G. Balme, J. Org. Chem. 2000,
5, 3223.
ꢀ
8 C; IR (KBr) 1719, 1314, 1141 cm ; H NMR (CDCl )
3
−1 1
5
δ 0.89 (t, 1H, J = 6.8 Hz), 0.97 (t, 1H, J = 7.3 Hz),
6
1
1
8
2
.27–1.35 (m, 4H), 1.44–1.53 (m, 2H), 1.58–1.65 (m, 2H),
3. (a) V. Gotor, F. Rebolledo, R. Liz, Tetrahedron: Asymmetry
2001, 12, 513;(b) H. J. Monteiro, Synth. Commun. 1987,
17, 983.
.84–1.92 (m, 2H), 2.71 (t, 2H, J = 7.3 Hz), 3.13 (t, 2H, J =
1
3
.0 Hz), 3.99 (s, 2H); C NMR (CDCl ) δ 13.4, 13.8, 21.5,
3
4
. (a) B. M. Trost, D. P. Curran, Tetrahedron Lett. 1981, 22, 1287;
b) C. A. Ibarra, R. C. Rodriguez, M. C. F. Monreal,
F. C. G. Navarro, J. M. Tesorero, J. Org. Chem. 1989, 54,
2.3, 22.7, 23.8, 30.9, 44.8, 53.2, 62.8, 199.8; HRMS
(
(
EI) calcd. for C H O S 234.1290, found 234.1293; Anal.
11 22 3 1
calcd. for C H O S : C, 56.37; H, 9.46, found: C,
11 22 3 1
5
1
620; (c) C. R. Holmquist, E. J. Roskamp, Tetrahedron Lett.
992, 33, 1131; (d) N. S. Reddy, E. P. Reddy, M. V. R. Reddy,
56.50; H, 9.52.
2
-(Benzylsulfonyl)-1-phenylethanone (3j): A white solid;
Synth. Commun. 2004, 34, 2691; (e) C. Lai, C. Xi, Y. Jiang,
R. Hua, Tetrahedron Lett. 2005, 46, 513; (f ) D. Kumar,
S. Sundaree, V. S. Rao, R. S. Varma, Tetrahedron Lett. 2006,
ꢀ
ꢀ
mp 110–111 C (Ref. 9c 110–112 C); IR (KBr) 1689, 1320,
146 cm ; H NMR (CDCl ) δ 4.39 (s, 2H), 4.55 (s, 2H),
.39–7.40 (m, 3H), 7.49–7.55 (m, 4H), 7.65 (bt, 1H, J =
.3 Hz), 7.96 (bd, 2H, J = 7.3 Hz).
−
1 1
1
7
7
3
4
7, 4197; (g) G. C. Tsui, Q. Glenadel, C. Lau, M. Lautens,
Org. Lett. 2011, 13, 208; (h) A. K. Singh, R. Chawla,
L. D. S. Yadav, Tetrahedron Lett. 2014, 55, 4742.
2
-(Benzylsulfonyl)heptan-2-one (3k): A white solid; mp
ꢀ
−1
1
8
0–81 C; IR (KBr) 1713, 1317, 1135 cm ; H NMR
5. M. W. Thomsen, B. M. Handwerker, S. A. Katz, R. B. Belser,
J. Org. Chem. 1988, 53, 906.
(
CDCl ) δ 0.90 (t, 3H, J = 7.1 Hz), 1.26–1.33 (m, 4H),
3
6
. M. B. Smith, J. March, March’s Advanced Organic Chemistry.
Reactions, Mechanisms, and Structures, 5th ed., Wiley Inter-
science, New York, 2001, p. 808.
1
4
2
1
.57–1.64 (m, 2H), 2.64 (t, 2H, J = 7.3 Hz), 3.83 (s, 2H),
1
3
.40 (s, 2H), 7.39–7.48 (m, 5H); C NMR (CDCl ) δ 13.8,
3
2.3, 22.6, 30.9, 45.0, 59.5, 60.0, 127.6, 129.0, 129.1,
31.0, 200.0; HRMS (EI) calcd. for C H O S 268.1133,
7
8
. D. C. Forbes, M.S. South, R. Rengasamy, A. J. Obiako, J. Adirika,
D. R. Battiste, J. Sulfur Chem. 2015, 36, 413.
. (a) D. J. Pasto, D. McMillan, T. Murphy, J. Org. Chem. 1965, 30,
1
4 20 3 1
found 268.1133; Anal. calcd. for C H O S : C, 62.66; H,
1
4 20 3 1
7.51, found: C, 62.57; H, 7.40.
2
688;(b)W.E. Parham, R. F.Motter, G. L. O. Mayo, J. Am. Chem.
Soc. 1959, 81, 3386; (c) M. V. R. Reddy, S. Reddy, Acta Chim.
Hung. 1985, 120, 275.
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Acknowledgments. This work was financially supported by
the Woosuk University Research Fund in 2015. The author
deeply appreciates the support and the encouragement of
M.-Y. Kim throughout this project.
9
(
(
b) R. T. Amel, P. J. Marek, J. Org. Chem. 1973, 38, 3513;
c) Y. C. Kuo, T. Aoyama, T. Shioiri, Chem. Pharm. Bull.
1
982, 30, 526.
SupportingInformation. Additionalsupportinginformation
is available in the online version of this article.
Bull. Korean Chem. Soc. 2015, Vol. 36, 2956–2958
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