A New Synthesis of β-Keto Sulfones from Olefins Utilizing Novel Xanthate Reagents

Full text of DOI:10.1002/bkcs.11302

Communication
DOI: 10.1002/bkcs.11302
BULLETIN OF THE
K. Lee
KOREAN CHEMICAL SOCIETY
A New Synthesis of β-Keto Sulfones from Olefins Utilizing Novel
Xanthate Reagents
*
Kieseung Lee
Department of Applied Chemistry, Woosuk University, Chonbuk 55338, Korea.
*E-mail: kslee@woosuk.ac.kr
Received August 25, 2017, Accepted September 17, 2017
Keywords: β-Keto sulfone, Group transfer, Radical reaction, Xanthate addition, Xanthate reduction
β-Keto sulfones1 have drawn considerable research interest
in recent decades due to their broad range of synthetic
utilities,1,2 and useful biological properties.3 For example,
β-keto sulfones have been used as important intermediates
in the synthesis of alkenes,2a ketones,2b arylamines,2c and
heterocycles.2d Certain β-keto sulfones exhibit antifungal,3a
antibacterial,3b and inhibitory activities against 11β-
hydroxysteroid dehydrogenase type I (11b-HSD1).3c
Consequently, a number of new synthetic approaches, e.g.,
AgNO3/K2S2O8 catalyzed aerobic oxysulfonylation of alkenes
in aqueous medium,4a oxysulfonylation of alkenes with sulfo-
nylhydrazides under transition metal-free conditions,4b and
catalyst-free radical reaction of ArN2BF4, DABCO.(SO2)2 and
silyl enol ethers4c have been recently reported. These methods,
however, may have some limitations such as strict reaction
conditions, limited substrate scope, or use of less readily avail-
able chemicals. Therefore, there is still a need to develop a
mild and general synthetic method for these compounds.
After the first report of Barton-McCombie reaction for
radical deoxygenation of secondary alcohols in 1975,5 xan-
thate radical chemistry has been extensively studied by
Zard’s group for a variety of organic synthesis.6 Based on
this xanthate chemistry, we have reported a new synthetic
approach to α-keto cyanophosphorane ylides from olefins
utilizing a novel xanthate reagent.7
Recently, we have reported one-pot synthesis of β-keto
sulfones via condensative decarboxylation of sulfonylacetic
acids with acid chlorides under mild reaction conditions.8
In continuation of our interest in developing a new syn-
thetic approach to β-keto sulfones from readily available
chemicals, we envisage that novel xanthate reagents 2 with
β-keto sulfonyl subunit could undergo xanthate transfer
addition to olefins 3 under radical conditions, and subse-
quent radical reduction of xanthate adducts 4 should pro-
vide β-keto sulfones 1 straightforwardly (Scheme 1).
The new synthetic approach began with the attempted
synthesis of requisite xanthate reagents 2, which was pre-
pared in 51–63% yields via one-pot, sequential treatment of
1,3-dichloroacetone 5 with sulfinates 6, and then O-ethyl
xanthate 8 in DMSO (Scheme 2).
Xanthate 2a and allylbenzene 3a (1.0 equiv) were heated to
reflux for 1 h in the presence of dilauroyl peroxide (DLP, 0.2
equiv) in 1,2-dichloroethane (DCE) under Ar affording xan-
thate adduct 4a in 79% yield along with reduced adduct
(β-keto sulfone) 1a in 3% yield, respectively (Run 1). The
similar concomitant formation of reduced adducts during xan-
thate addition process was also observed in our earlier
experiment,7 and this phenomenon continued as olefins
reacted in this reaction. When DLP (0.1 equiv) was added
every hour to the reaction mixture of (2a/3a), 2a was
completely consumed in 2 h, and the results were almost same
in terms of combined yields of (4a/1a). Therefore, the reaction
conditions of (Run 1) were adopted as the standard procedure
for operational simplicity. By following the procedures of
(Run 1), a range of olefins incorporating functional groups,
e.g., simple alkane, ether, ester, and ketone, were also reacted
with 2a to assess the stability of these functional groups, and
all the olefins tested have shown similar reactivity towards
xanthate 2a furnishing (4b–e/1b–e) in good combined yields
(75–83%) (Run 2–5). We also tested other xanthate reagents
2b–c for this conversion, and the results were good to excel-
lent in terms of combined yields of (4f–i/1f–i) (79–86%)
(Run 6–9).
Gratified with the promising results of xanthate addition
process, we undertook the radical reduction of 4 using
H3PO2/Et3N/AIBN,7,9 and the representative results are
summarized in Table 2.
For the radical reduction of 4, xanthate adducts 4 were
heated to reflux in 1,4-dioxane with H3PO2/Et3N/AIBN
(0.6 equiv) for 1 h under Ar. The reaction generally pro-
ceeded well for most xanthate adducts (4a–c, 4e–i) provid-
ing reduced adducts (1a–c, 1e–i) in 74-84% yields (Run
1–3, 5–9). Xanthate adduct 4d, however, gave lower yield
(67%) of 1d, presumably due to the instability of ester
group under basic conditions (Run 4).
In conclusion, a new synthetic approach to β-keto sul-
fones from olefins utilizing novel xanthate reagents 2 as the
key reagent has been developed. Considering several
advantages e.g., easy preparation of xanthate reagents 2 in
good yields as stable solids, mild reaction conditions, and
good to excellent overall yields, this synthetic route could
be a method of choice for the synthesis of β-keto sulfones.
The radical transfer addition of xanthates 2 to various
olefins was performed, and the representative results are
summarized in Table 1.
Bull. Korean Chem. Soc. 2017
© 2017 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Wiley Online Library
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Communication
ISSN (Print) 0253-2964 | (Online) 1229-5949
BULLETIN OF THE
KOREAN CHEMICAL SOCIETY
O
R2
1
O
O
O
O
O
O
O
O
R2(3)
S
S
Xa
S
R1
R1
R1
R2
Xa-redn
Xa-addition
Xa
2
4
Scheme 1. A new synthetic approach to β-keto sulfones 1 from olefines 3 utilizing new xanthate reagents 2 (where Xa = −SC(=S)OEt).
O
S
S
O
O
O
O
O
O
O
R1
ONa
(6)
KS
OEt
(8)
S
Xa
Cl
Cl
S
Cl
R1
R1
DMSO, rt, 10 h
DMSO, rt, 4 h
2
7
5
Scheme 2. Synthesis of novel xanthate reagents 2 (where R1 = ph-; p-Meph-; Me-; Xa = −SC(=S)OEt).
Table 1. Radical addition of xanthates 2 to olefins 3 affording
Table 2. Reduction of xanthate adducts 4 to reduced adducts
1 with H3PO2/Et3N/AIBN in 1,4-dioxane (where Xa = −S(C=S)
OEt).a
xanthate adducts 4 and concomitant partial reduction of 4 to
reduced adducts 1 (where Xa = −S(C=S)OEt).a
O
O
O
O
O
O
O
O
O
R2
O
O
(3)
O
O
O
O
S
S
+
S
Xa
R2
H3PO2, Et3N, AIBN
reflux, 1 h, Ar
R1
R1
R2
S
S
R1
DLP, DCE,
reflux,1 h, Ar
R1
R2
R1
R2
Xa
1
2
4
4
1
Xa
Run
R1=
R2=
–Ph (3a)
–(CH2)4Me (3b)
–OCH2Ph (3c)
–OAc (3d)
–CH2(C=O)Me (3e)
–Ph (3a)
–(CH2)4Me (3b)
–Ph (3a)
4/1 (Yields)b
Run
4
R1=
R2=
1 (Yield)b
1
2
3
4
5
6
7
8
9
a
Ph–(2a)
Ph–(2a)
Ph–(2a)
Ph–(2a)
4a/1a (77/3)
4b/1b (73/3)
4c/1c (71/4)
4d/1d (78/4)
4e/1e (80/3)
4f/1f (80/4)
4g/1g (82/4)
4h/1h (80/3)
4i/1i (75/4)
1
2
3
4
5
6
7
8
9
a
4a
4b
4c
4d
4e
4f
4g
4h
4i
Ph–
Ph–
Ph–
Ph–
–Ph
–(CH2)4Me
–OCH2Ph
–OAc
–CH2(C=O)Me
–Ph
–(CH2)4Me
–Ph
–(CH2)4Me
1a (80)
1b (82)
1c (74)
1d (67)
1e (77)
1f (79)
1g (78)
1h (77)
1i (84)
Ph–(2a)
Ph–
p-MePh–(2b)
p-MePh–(2b)
CH3–(2c)
CH3–(2c)
p-MePh–
p-MePh–
CH3–
CH3–
–(CH2)4Me (3b)
Xanthate 2 (0.5 mmol), DCE (3 mL), olefin 3 (1.0 eq), reflux,
10 min, DLP (0.2 eq), reflux, 1 h, Ar.
Xanthate adduct 4 (0.4 mmol), 1,4-dioxane (3 mL), H3PO2 (5.0 eq),
Et3N (5.5 eq), reflux, 10 min, AIBN (0.6 eq), reflux, 1 h, Ar.
Isolated yields by flash column chromatography on SiO2.
b
Isolated yields by flash column chromatography on SiO2.
b
Acknowledgments. Financial support from Woosuk Univ.
is gratefully acknowledged. The author deeply appreciates the
support and assistance of M. Y. Kim throughout this project.
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Supporting Information. Additional supporting informa-
tion is available in the online version of this article.
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Bull. Korean Chem. Soc. 2017
© 2017 Korean Chemical Society, Seoul & Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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