Synthesis of arylethyl (E)-styrylsulfones and arylsulfones by one-pot DIBAL-H/NaH-mediated reaction of β-ketosulfones

Article abstract of DOI:10.1055/s-0033-1339117

A facile one-pot synthetic route for preparing a series of arylethyl (E)-styrylsulfones or arylethyl arylsulfones is developed. The efficient one-pot DIBAL-H/NaH-mediated route includes reduction of α-benzyl-β- arylketosulfones and retroaldol/aldol or retro aldol reaction of the resulting intermediate. The DIBAL-H/NaH-mediated reaction mechanism has been discussed. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0033-1339117

LETTER
▌1739
lSetyternthesis of Arylethyl (E)-Styrylsulfones and Arylsulfones by One-Pot
DIBAL-H/NaH-Mediated Reaction of β-Ketosulfones
Synthesis of Arylethyl (E)-Styrylsulfones and Arylsulfones
Meng-Yang Chang,* Yi-Chia Chen, Chieh-Kai Chan
Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan
Fax +886(7)3125339; E-mail: mychang@kmu.edu.tw
Received: 25.03.2014; Accepted: 18.04.2014
β-ketosulfone 1a or 2a with benzyl bromide in the pres-
ence of K2CO3 in boiling acetone for eight hours. Treat-
ment of α-bromo acetophenone with MeSO2Na or
TolSO2Na afforded the starting material 1a or 2a in quan-
Abstract: A facile one-pot synthetic route for preparing a series of
arylethyl (E)-styrylsulfones or arylethyl arylsulfones is developed.
The efficient one-pot DIBAL-H/NaH-mediated route includes re-
duction of α-benzyl-β-arylketosulfones and retroaldol/aldol or retro-
aldol reaction of the resulting intermediate. The DIBAL-H/NaH- titative yield under refluxing cosolvent of 1,4-dioxane
mediated reaction mechanism has been discussed.
conditions.
Key words: aldol reaction, aluminum, condensation, sulfones, tan-
MeO
P
dem reaction
OMe
O
O
S
β-Ketosulfone constitutes a diverse structural class asso-
ciated with important synthetic and medicinal applica-
tions.1,2 The skeleton is a versatile intermediate as it is a
useful precursor for functional-group transformations
(e.g., vinyl, β-hydroxy, or β-halosulfones).3 Amongst
these sulfonyl derivatives, substituted aryl sulfones are in-
creasingly drawing interest due to their potential biologi-
cal activities. Furthermore, benzyl styryl sulfones (e.g.,
ON013105, ON013100, ON01910.Na), belongs to the
class of non-ATP competitive molecules and it is under
evaluation as an anticancer agent.4 The antimigraine med-
icine eletriptan (Relpax) possesses the arylethyl sulfonyl
substituent (Figure 1).5 Generally, sulfones are prepared
by a variety of methods. Thiol or sulfide building blocks
are typically employed, and the desired oxidation state is
subsequently achieved via redox chemistry.6,7 In recent
years, many efforts have been expanded on developing a
transition-metal- or metal-free-catalyzed cross-coupling
reaction of substituted sulfinates (or sulfonyl halides) with
substituted halides, especially for preparing unsymmetri-
cal diaryl sulfones.8–10
MeO
OMe
ON013105, P = OP(=O)O2Na2
ON013100, P = OH
ON01910.Na, P = NHCH2CO2Na
O
O
S
N
Me
N
H
eletriptan (Relpax)
Figure 1 Representative biologically active sulfones
O
O
S
Ph
Ph
K2CO3,
PhCH2Br
O
O
DIBAL-H
THF
O
O
O
O
5a (84%, for 3a)
S
S
Ph
X
Ph
X
O
O
acetone
then NaH
S
1a, X= Me
2a, X = Tol
Tol
Ph
3a, X = Me (95%)
4a, X = Tol (97%)
Ph
6a (90%, for 4a)
Herein, we describe a tandem reduction–retroaldol–aldol
or reduction–retroaldol reaction of α-substituted β-keto-
sulfones under mild reaction conditions, affording aryl-
ethyl (E)-styrylsulfones 5 and arylsulfones 6 in good
yields. To achieve the best reaction conditions, the one-
pot reaction of α-benzyl-α-benzoylsulfone 3a (X = Me)
and 4a (X = Tol) was selected as the model reaction using
DIBAL-H (1.0 M in hexane, 1.0 equiv) as a reductant in
THF at room temperature, followed by the sequential ad-
dition of excess NaH (60% in oil) as the base. The reaction
process was traced by TLC until the reactant was con-
sumed. As shown in Scheme 1, compounds 3a or 4a were
prepared with excellent yields via monobenzylation of
Scheme 1 Synthetic route of compounds 5a and 6a
As shown in Table 1, entries 1–4, we found that three
equivalents of base, room temperature, and eight hours of
reaction time should be the optimal one-pot conditions for
increasing the yields of 5a or 6a. With the results in hand,
four aluminum- or boron-containing reductants and three
bases were investigated at room or reflux temperature in
the absence of a Lewis acid or transition-metal catalyst.
Two products, 5a and 6a, were obtained in moderate
yields when LiAlH(Ot-Bu)3/NaH, L-Selectride/NaH, or
LiBHEt3/NaH were employed under the above reaction
conditions (Table 1, entries 5–7). For a one-pot reaction of
compound 3a with KOt-Bu or DBU, Table 1, entries 8 and
9 show that a nearly 1:1 product ratio of an unknown
mixture and 5a were observed. For the formation of 6a,
SYNLETT 2014, 25, 1739–1744
Advanced online publication: 02.06.2014
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
DOI: 10.1055/s-0033-1339117; Art ID: st-2014-w0256-l
© Georg Thieme Verlag Stuttgart · New York

1740
M.-Y. Chang et al.
LETTER
Table 1 Optimization of Reaction Conditionsa
O
O
O
O
DIBAL-H
THF
DIBAL-H
THF
O
O
O
S
S
S
Tol
Ph
X
then NaH
(X = Tol)
then NaH
(X = Me)
Ph
Ph
Ph
Ph
5a
6a
3a, X= Me
4a, X = Tol
Entry
Reductant (equiv)b
Base (equiv)
Temp (°C)
Time (h)
Yield of 5a (%)c Yield of 6a (%)c
1
DIBAL-H (1)
DIBAL-H (1)
DIBAL-H (1)
DIBAL-H (1)
LiAlH(Ot-Bu)3 (1)
L-Selectride (1)
LiBEt3 (1)
NaH (3)
NaH (6)
NaH (3)
NaH (3)
NaH (3)
NaH (3)
NaH (3)
KOt-Bu (3)
DBU (3)
NaH (3)
25
25
67
25
25
25
25
25
67
25
8
84
80
79
83
80
73
74
37d
45d
90
88
80
83
80
77
82
78
76
85
2
8
3
8
4
20
8
5
6
8
7
8
8
DIBAL-H (1)
DIBAL-H (1)
DIBAL-H (3)
8
9
8
e
10
8
–
a The one-pot reaction was run on a 0.5 mmol scale with starting materials 3a or 4a in THF (10 mL).
b 1.0 M of reductant solution was used.
c The product was >95% pure as determined by 1H NMR analysis.
d An unknown mixture (for entry 8, 40%; entry 9, 38%) was isolated.
e Phenylethyl methylsulfone was isolated.
KOt-Bu or DBU did not cause byproducts. When three ates A1 and A2 caused intermediates B1 and B2 with the
equivalents of DIBAL-H were employed, phenylethyl aluminum-chelated complex of sulfone and benzalde-
methylsulfone was isolated at a 76% yield instead of the hyde. After the chelated Al–O bond rotation and intra-
desired product 5a (Table 1, entry 10). No influence on molecular proton exchange (or intermolecular
the formation of product 6a was observed for the addition deprotonation), the occurrence of the carbanion equilibri-
of excess amounts of DIBAL-H. According to the above um between intermediates B1 and C should be preferred
phenomenon, we envision that DIBAL-H and NaH make to be formed. Furthermore, in situ intramolecular aldol
up the optimal combination controlling the formation of condensation of the primary carbanion of intermediate C
5a and 6a. The structure of 5a was determined by single- with benzaldehyde motif, followed by the removal of alu-
crystal X-ray crystallography.11,12
minum complex, produced a sole phenylethyl (E)-styryl-
sulfone 5a via the proposed six-membered ring of
intermediate C. Because there was no proton exchange of
intermediate B2, phenylethyl tosylsulfone 6a was formed
from intermediate B. For the formation of product 5a, one
equivalent of DIBAL-H was a key factor in the presence
For the possible DIBAL-H/NaH-mediated reaction mech-
anism, the formation of intermediate A was first proposed
via the DIBAL-H-mediated reduction of β-ketosulfone 3a
(X = Me) or 4a (X = Tol), as shown in Scheme 2. With the
involvement of NaH, the retroaldol reaction of intermedi-
reduction
retroaldol
bond rotation/
proton exchange
aldol
condensation
L
L
–
Al
L
L
L
L
–
Al
O+
–
Al
O
for B1
5a
+
O+
S
O
O
S
O
3a
or
NaH
DIBAL-H
Ph
O
S
4a
Ph
X
Ph
X
C
Ph
O
O
L = i-Bu
Ph
Ph
for B2
A1, X = Me
A2, X = Tol
B1, X = Me
B2, X = Tol
6a
Scheme 2 Possible reaction mechanism
Synlett 2014, 25, 1739–1744
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Arylethyl (E)-Styrylsulfones and Arylsulfones
1741
of the base. Excess amounts of DIBAL-H promoted the substituents (R, Ar), with diversified aromatic or aliphatic
rapid overreduction (conversion from benzaldehyde into groups, were well-performed. For a DIBAL-H/NaH-
benzyl alcohol) such that intermediate C could not react mediated reaction, products 5a–t were isolated at 60–84%
with the resulting benzaldehyde to yield the desired 5a. yields. Table 2, entry 6 shows that 5f, with the 2-pyridinyl
Therefore, the equivalent of DIBAL-H was not apparently group, was only separated at a 60% yield. A reasonable
important for the generation of 6a.
Table 2 Synthesis of Skeletons 3 and 5a–c
reason could be that DIBAL-H chelated the nitrogen atom
of the 2-pyridinyl group to decrease the isolated yield of
5f. For the 2,6-difluorobenzyl group, the given yield of 5b
was lower (68%, Table 2, entry 13) due to the effect of ste-
ric hindrance. Table 2, entry 20 shows that 80% of 5t with
the cyclopentenyl group was isolated.
O
O
O
O
O
S
R
S
Ar
Me
O
R
Ar
O
O
K2CO3
3a–s
DIBAL-H
5a–s
According to the above experimental procedure, synthesis
of phenylethyl tosylsulfones 6 was further examined (Ta-
ble 3). Treatment of 2a or 4a with bromides afforded 4a–
j in the presence of K2CO3 at 80–97% yields. Next, the
yields of 6a–j were achieved in the range of 72–87% by
the one-pot reaction. For Table 3, entry 6, lower yields of
6f with the 2-pyridinyl group were also observed. After
benzylation of 2a and cinnamylation of the resulting 4a,
4i with the disubstituted group was generated (Table 3,
entry 9). By a one-pot reaction of 4i, 82% of 6i with the
α,α′-bisalkylated group was easily synthesized. Further-
more, β-ketosulfones 4k–l were chosen as the materials to
examine the one-pot reaction. Cyclic vinyl sulfones 6k–l
were accomplished at 73% and 70% yields via the intra-
molecular aldol reaction and dehydration. Under the
CDCl3 solution, compound 4k was easily converted into
2-sulfonylnaphthalene at room temperature within one
day. The structure of 6k was determined by single-crystal
X-ray crystallography.11
S
Ar
Me
O
O
RCH2Br
O
O
O
O then NaH
Me
1a–d
S
S
Ph
Me
Ph
3t
5t
Entry 1 Ar
3 R
Yield of 3 Yield of 5
(%)
(%)
1
2
3
4
5
6
7
8
9
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
1a Ph
3a Ph
95
90
92
94
86
82
90
92
88
85
92
90
84
94
88
81
93
86
82
5a 84
5b 70
5c 78
5d 83
5e 70
5f 60
5g 80
5h 76
5i 72
3b 2,6-F2C6H3
3c 3,5-(MeO)2C6H3
3d (E)-styrene
3e C7H15
3f 2-pyridine
3g 1-naphthalene
3h 4-PhC6H4
3i 4-O2NC6H4
3j 9-anthracene
3k Ph
To extend this one-pot protocol, 7a,b were chosen as the
starting materials (Scheme 3). Changing the α-substituent
of skeleton 3 or 4 to a phenyl group, the formation of ben-
zyl sulfones 8a,b was found at 83% and 81% yields. But
attempts to prepare the skeleton of benzyl styryl sulfones
failed, and no side arm of an (E)-styryl group was deter-
mined on the skeleton of 8b. The possible reason could be
that the secondary delocalized carbanion I was more sta-
ble than primary carbanion II such that sequential aldol
condensation of intermediate II with benzaldehyde did
not occur. In another way, by changing the X group of
skeleton 3 or 4 to a phenyl or n-butyl group, the formation
of phenylethyl sulfones 8c,d was found at 84% and 86%
yields. The results are similar to a one-pot reaction of
compounds 7a,b. After replacing the X group from tolu-
ene with benzene group of 7c, 8c still yielded (84%). For
conversion from 7d into 8d, proton exchange equilibrium
between intermediates B1 and C (X = n-Bu) should not be
generated based on the same secondary carbanions. Direct
protonation of the initial formed intermediate B1 should
be preferred to proceed. These examples demonstrate that
the above one-pot plausible reaction mechanism is a rea-
sonable pathway via the highly regiospecificity. On the
basis of the established protocol, a reaction of skeleton 9
(Ar = 4-nitrophenyl) with the combination of DIBAL-
H/NaH produced skeleton 10. The 4-nitrophenyl electron-
withdrawing group should inhibit the formation of inter-
10 1a Ph
5j 73
5k 78
5l 74
11 1b, 4-PhC6H4
12 1b, 4-PhC6H4
13 1b 4-PhC6H4
3l 3,5-(MeO)2C6H3
3m 2,6-F2C6H3
5m 68
5n 80
5o 83
5p 77
5q 83
5r 78
5s 74
5t 80
14 1c 4-MeOC6H4 3n Ph
15 1c 4-MeOC6H4 3o 3,5-(MeO)2C6H3
16 1c 4-MeOC6H4 3p 2,6-F2C6H3
17 1d 4-MeC6H4
18 1d 4-MeC6H4
19 1d 4-MeC6H4
3q Ph
3r 3,5-(MeO)2C6H3
3s 2,6-F2C6H3
3t cyclopentenyl
20
–
a The reaction was run on a 1.0 mmol scale with 1a–d, K2CO3 (2.9
equiv), and bromides (1.05 equiv) in acetone (10 mL) at reflux.
b The one-pot reaction was run on a 0.5 mmol scale with 3a–t,
DIBAL-H (1.0 equiv), and NaH (3.0 equiv) in THF (10 mL) at r.t.
c The product was >95% pure as determined by 1H NMR analysis.
As shown in Table 2, 3a–t were efficiently constructed in
good yields (80–95%) by the monoalkylation of β-keto-
sulfones 1a–d and 3t with different bromides. Different
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1739–1744

1742
M.-Y. Chang et al.
LETTER
Table 3 Synthesis of Skeletons 4 and 6a–c
O
O
O
O
O
O
O
S
R1
R
S
S
Tol
Tol
Tol
R1
O
O
O
R
S
R
K2CO3
4a–j
6a–h,j
6i
DIBAL-H
then NaH
Tol
R1
+
RCH2Br
O
O
O
2a or 4a
O
O
S
Tol
S
Tol
( )n
( )n
4k–l
6k, n = 1
6l, n = 2
Entry
2 or 4a R1
4 R
Yield of 4 (%)
Yield of 6 (%)
1
2a H
2a H
2a H
2a H
2a H
2a H
2a H
2a H
4a Bn
2a H
4a Ph
97
82
90
88
86
80
88
93
80
83
6a 84
6b 87
6c 84
6d 82
6e 80
6f 72
6g 81
6h 86
6i 82
6j 78
2
4b 2,6-F2C6H3
3
4c 3,5-(MeO)2C6H3
4d (E)-styrene
4e C7H15
4
5
6
4f 2-pyridine
7
4g 1-naphthalene
4h CH=CH2
8
9
4i (E)-cinnamyl
10
4j 9-anthracene
O
O
O
S
S
Tol
11
12
–
–
6k 73
6l 70
4k
O
O
O
Tol
4l
a The reaction was run on a 1.0 mmol scale with 2a or 4a, K2CO3 (2.9 equiv), and bromides (1.05 equiv) in acetone (10 mL) at reflux.
b The one-pot reaction was run on a 0.5 mmol scale with 4a–l, DIBAL-H (1.0 equiv) and NaH (3.0 equiv) in THF (10 mL) at r.t.
c The product was >95% pure as determined by 1H NMR analysis.
O
for X = Me
+ PhCHO
O
O
O
O
O
O
O
O
DIBAL-H
then NaH
S
S
S
S
–
–
Ph
X
X
Ph
Ph
Ph
Ph
I
II
8a (83%)
8b (81%)
7a, X = Tol
7b, X = Me
O
O
O
O
O
O
O
O
O
O
S
S
DIBAL-H
then NaH
DIBAL-H
then NaH
S
S
X
Me
Ph
X
Me
Ph
R
Ph
7c, X = Ph
7d, X = n-Bu
O2N
9a, R = Ph
9b, R = (E)-styryl
9c, R = 1-naphthalene
R
8c (84%)
8d (86%)
10a (81%)
10b (80%)
10c (74%)
Scheme 3 Synthesis of compounds 8a–d and 10a–c
Synlett 2014, 25, 1739–1744
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Arylethyl (E)-Styrylsulfones and Arylsulfones
1743
O
O
O
O
O
O
O
DIBAL-H
NaH
S
S
S
+
Ph
Me
CHO
Ph
Ph
Ph
Ph
3a
MeO
OMe
5a (74%)
5n (14%)
(1 equiv)
Scheme 4 Control experiment
Tetrahedron Lett. 2004, 45, 4021. (c) Nishimura, T.;
mediate B, and the expected styryl motif was not involved
in skeleton 10.
Takiguchi, Y.; Hayashi, T. J. Am. Chem. Soc. 2012, 134,
9086. For β-hydroxysulfones, see: (d) Gotor, V.; Rebolledo,
F.; Liz, R. Tetrahedron: Asymmetry 2001, 12, 513. (e) Wan,
X.; Meng, Q.; Zhang, H.; Sun, Y.; Fan, W.; Zhang, Z. Org.
Lett. 2007, 9, 5613. For β-halosulfones, see: (f) Suryakiran,
N.; Reddy, T. S.; Suresh, V.; Lakshman, M.; Venkateswarlu,
Y. Tetrahedron Lett. 2006, 47, 4319. (g) Suryakiran, N.;
Prabhakar, P.; Reddy, T. S.; Mahesh, K. C.; Rajesh, K.;
Venkateswarlu, Y. Tetrahedron Lett. 2007, 48, 877. (h) Ni,
C.; Zhang, L.; Hu, J. J. Org. Chem. 2009, 74, 3767. For other
sulfonyl derivatives, see: (i) Marco, J.-L.; Fernandez, I.;
Khiar, N.; Fernandez, P.; Romero, A. J. Org. Chem. 1995,
60, 6678. (j) Kumar, D.; Sundaree, M. S.; Patel, G.; Rao, V.
S.; Varma, R. S. Tetrahedron Lett. 2006, 47, 8239. (k) Curti,
C.; Crozet, M. D.; Vanelle, P. Tetrahedron 2009, 65, 200.
To gather more information, a control experiment was set
up under standard conditions. Competition reactions be-
tween in situ generated benzaldehyde and the addition of
one equivalent of 4-methoxybenzaldehyde were carried
out following the above protocol (Scheme 4). The ratio of
products 5a (74%) and 5n (14%) could be obtained as
nearly as 5:1 as determined by the separated products.
Based on this, we believe that the exchange rate of aryl al-
dehyde controls this product ratio. This means that an in-
tramolecular benzaldehyde exchange is easier than
intermolecular involvement of 4-methoxybenzaldehyde
for the aluminum-chelated intermediate B1. In summary,
we have successfully described the one-pot DIBAL-
H/NaH-mediated synthesis of β-ketosulfones 3 or 4 for
preparing a series of substituted arylethyl (E)-styrylsul-
fones 5 or arylsulfones 6. The facile synthetic route begins
with simple starting materials and reagents and provides a
potential methodology for chemical biology research.
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Kahraman, M.; Adenu, G.; Barnes, C. L. Heterocycles 2004,
The authors would like to thank the National Science Council of the
Republic of China for its financial support (NSC 102-2113-M-037-
005-MY2).
References and Notes
(1) (a) Simpkins, N. S. In Sulfones in Organic Synthesis;
Baldwin, J. E., Ed.; Pergamon Press: Oxford, 1993.
(b) Trost, B. M. Comprehensive Organic Chemistry;
Pergamon Press: Oxford, 1991. (c) El-Awa, A.; Noshi, M.
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(2) For recent synthesis of β-ketosulfones, see: (a) Pospisil, J.;
Sato, H. J. Org. Chem. 2011, 76, 2269. (b) Sreedhar, B.;
Rawat, V. S. Synlett 2012, 23, 413. (c) Kumar, A.; Muthyala,
M. K. Tetrahedron Lett. 2011, 52, 5368. (d) Suryakiran, N.;
Reddy, T. S.; Ashalatha, K.; Lakshman, M.; Venkateswarlu,
Y. Tetrahedron Lett. 2006, 47, 3853. (e) Lu, Q.; Zhang, J.;
Zhao, G.; Qi, Y.; Wang, H.; Lei, W. J. Am. Chem. Soc. 2013,
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A. O.; Gellis, A.; Vanelle, P. Eur. J. Med. Chem. 2007, 42,
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(3) For vinyl sulfones, see: (a) Reddy, D. B.; Reddy, N. S.;
Reddy, M. V. R.; Balasubramanyam, S. Org. Prep. Proced.
Int. 1998, 20, 205. (b) Kabalka, G. W.; Guchhait, S. K.
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1739–1744

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M.-Y. Chang et al.
LETTER
www.ccdc.cam.ac.uk/conts/retrieving.html [or from the
62, 583. (g) Denmark, S. E.; Harmata, M. A.; White, K. S.
J. Org. Chem. 1987, 52, 4031.
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
+44(1223)336033; e-mail: deposit@ccdc.cam.ac.uk].
(12) Representative Procedure for the Synthesis of Skeleton
5DIBAL-H (1.0 M in hexane, 0.5 mL, 0.5 mmol) was added
to a solution of substituted β-ketosulfones 3 (0.5 mmol) in
THF (10 mL) at r.t. The reaction mixture was stirred at r.t.
for 10 min. NaH (60% in oil, 60 mg, 1.5 mmol) was added
to the stirred solution at r.t. The reaction mixture was stirred
at r.t. for 8 h. NH4Cl aq (15%, 1 mL) was added to the
reaction mixture, and the solvent was concentrated. The
residue was diluted with H2O (10 mL), and the mixture was
extracted with CH2Cl2 (3 × 20 mL). The combined organic
layers were washed with brine, dried, filtered, and
(8) For metal-mediated synthesis of disubstituted sulfones for
Pd, see: (a) Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Panrisi,
L. M. Org. Lett. 2002, 4, 4719. (b) Cacchi, S.; Fabrizi, G.;
Goggiamani, A.; Panrisi, L. M. Synlett 2003, 361.
(c) Cacchi, S.; Fabrizi, G.; Goggiamani, A.; Panrisi, L. M.
Berning R. J. Org. Chem. 2004, 69, 5608. (d) Bandgar, B. P.;
Bettigeri, S. V.; Phopase, J. Org. Lett. 2004, 6, 2105. For Cu,
see: (e) Baskin, J. M.; Wang, Z. Y. Org. Lett. 2002, 4, 4423.
(f) Feng, X. W.; Wang, J.; Zhang, J.; Yang, J.; Wang, N.;
Yu, X. Q. Org. Lett. 2010, 12, 4408. (g) Kar, A.; Sayyed, I.
A.; Lo, W. F.; Kaiser, H. M.; Beller, M.; Tse, M. K. Org.
Lett. 2007, 9, 3405. (h) Zhu, W.; Ma, D. J. Org. Chem. 2005,
70, 2696. For Fe, see: (i) Redddy, M.; Reddy, P.; Sreedhar,
B. Adv. Synth. Catal. 2010, 352, 1861. For Ir, see: (j) Ueda,
M.; Hartwig, J. F. Org. Lett. 2010, 12, 92.
(9) For very recent examples for the synthesis of disubstituted
sulfones from halides and sulfinates that were prepared in
situ from organomatals and SO2, see for Zn: (a) Rocke, B.;
Bahnck, K. B.; Herr, M.; Lavergne, S.; Mascitti, V.;
Perreault, C.; Polivkova, J.; Shavnya, A. Org. Lett. 2014, 16,
154. For Mg, see: (b) Deeming, A. S.; Russell, C. J.;
Hennessy, A. J.; Willis, M. C. Org. Lett. 2014, 16, 150. For
Li, see: (c) Umierski, N.; Manolikakes, G. Org. Lett. 2013,
15, 4972.
evaporated to afford the crude product. Purification on silica
gel (hexanes–EtOAc = 10:1 to 6:1) afforded skeleton
5.Compound 5a: yield 84% (114 mg); colorless solid; mp
63–65 °C (recrystallized from hexanes and EtOAc). ESI-
HRMS: m/z calcd for C16H17O2S [M+ + 1]: 273.0949; found:
273.0952. 1H NMR (400 MHz, CDCl3): δ = 7.60 (d, J = 15.6
Hz, 1 H), 7.48–7.39 (m, 5 H), 7.33–7.21 (m, 5 H), 6.72 (d,
J = 15.2 Hz, 1 H), 3.39–3.35 (m, 2 H), 3.18–3.14 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 144.97, 137.52, 132.12,
131.36, 129.08 (2×), 128.85 (2×), 128.55 (2×), 128.40 (2×),
126.95, 124.68, 56.50, 28.78. Anal. Calcd for C16H16O2S: C,
70.56; H, 5.92. Found: C, 70.75; H, 6.30. Single-crystal X-
ray crystallography: crystal of compound 5a was grown by
slow diffusion of EtOAc into a solution of compound 5a in
CH2Cl2 to yield colorless prisms. The compound crystallizes
in the orthorhombic crystal system, space group Pna21,
a = 26.9302(15) Å, b = 9.6456(5) Å, c = 5.2760(5) Å, V =
1372.01(17) Å3, Z = 4, δcalcd = 1.318 g cm–3, F(000) = 576,
2θ range 1.511–25.057°, R indices (all data) R1 = 0.0419,
wR2 = 0.1113.
(10) For recent metal-free synthetic examples, see: (a) Umierski,
N.; Manolikakes, G. Org. Lett. 2013, 15, 188. (b) Qin, Q.;
Mague, J. T.; Pascal, R. A. Org. Lett. 2010, 12, 928.
(c) Maloney, K.; Kuethe, J.; Linn, K. Org. Lett. 2011, 13,
102. (d) Li, Y.; Cheng, K.; Lu, X.; Sun, J. Adv. Synth. Catal.
2010, 352, 1876.
(11) CCDC 979312 (5a), 982010 (5r), and 979313 (6k) contain
the supplementary crystallographic data for this paper. This
data can be obtained free of charge via
Synlett 2014, 25, 1739–1744
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