Copper Acetate Mediated α-Oxysulfonylation of α-Diazo β-Ketosulfones

Article abstract of DOI:10.1055/s-0036-1588162

Copper acetate mediated α-oxysulfonylation of α-diazo β-ketosulfones in wet nitromethane under nitrogen provides α-oxysulfonyl β-ketosulfones. The use of different copper salts is investigated for the development of a facile and efficient transformation.

Full text of DOI:10.1055/s-0036-1588162

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2017, 49, A–L
paper
A
en
C.-K. Chan et al.
Paper
Synthesis
Copper Acetate Mediated α-Oxysulfonylation of α-Diazo β-Keto-
sulfones
Chieh-Kai Chana
Heui-Sin Wanga
a-oxysulfonylation
O
O
S
Ru-Ting Hsu*b
Meng-Yang Chang*a
O
O
S
Cu(OAc)2
Ar
R
· 25 examples
· 8–82% yields
O
Ar
R
2
O
S
R
wet MeNO2
O
N2
O
O
a Department of Medicinal and Applied Chemistry, Kaohsiung
Medical University Hospital, Kaohsiung Medical University,
Kaohsiung 80708, Taiwan
b Department of Medical Imaging and Radiology, Shu-Zen
Junior College of Medicine and Management, Kaohsiung,
82144, Taiwan
ruting@ms.szmc.edu.tw
mychang@kmu.edu.tw
Received: 28.12.2016
Accepted after revision: 07.03.2017
Published online: 30.03.2017
α-oxysulfonylation
O
S
R1
OH
O
O
O
O
S
DOI: 10.1055/s-0036-1588162; Art ID: ss-2016-h0888-op
R
R
α
O
Cu(OAc)2
this work
R1
2
O
previous work
O
N2
Abstract Copper acetate mediated α-oxysulfonylation of α-diazo β-ke-
tosulfones in wet nitromethane under nitrogen provides α-oxysulfonyl
β-ketosulfones. The use of different copper salts is investigated for the
development of a facile and efficient transformation. A plausible mech-
anism is proposed herein.
(R = SO2R1)
O
O
S
R1
1
2
Other5
Koser2
Togo4
PhI(OTs)OH
(i) I2/Oxone
(i) i-PrI/mCPBA
(ii) DMP or IBX
(iii) NH4I/mCPBA
(ii) I2/mCPBA
Key words diazo compounds, β-ketosulfones, oxysulfonylation, cop-
per acetate, bond formation
Wirth3
(iii) PS-PEG-ArI/mCPBA
chiral iodoarenes/mCPBA
(iv) ArI/Oxone
Scheme 1 Synthesis of α-oxysulfonyl ketones
α-Functionalization of carbonyl synthons has attracted
considerable interest among synthetic organic researchers
because the method leads to the formation of carbon–car-
bon or carbon–heteroatom bonds, and the resulting prod-
ucts can be transformed into diversified molecules under a
variety of reaction conditions.1 Among a number of α-func-
tionalized hetero substituents, such as halo (C–X bond for-
mation),1a alkoxy or hydroxy (C–O bond formation),1b ami-
no, diazo or azido (C–N bond formation),1c,d mercapto (C–S
bond formation),1e or boron (C–B bond formation),1f the de-
velopment of new synthetic strategies for α-functionaliza-
tion of carbonyl synthons is still in high demand. Therefore,
compared to reported work on the establishment of an oxy
substituent (e.g., hydroxy, alkyloxy, aryloxy, aminooxy, or
carbonyloxy) on the α-position of carbonyl compounds, we
found that the introduction of an α-oxysulfonyl group is
less documented.2–5 Furthermore, we observed that the α-
oxysulfonylation of carbonyl synthons has almost been ex-
clusively focused on the use of the Koser-type indane (a hy-
pervalent iodine reagent), as shown in Scheme 1.
catalytic chiral-iodoarene-mediated enantioselective
α-oxysulfonylation of ketones 1.3 The Togo group investi-
gated non-metallic oxidants (Oxone or mCPBA) for the α-
oxysulfonylation of ketones 1 with iodo-containing re-
agents (e.g., iodoarenes or iodine) under acidic (p-TsOH or
AcOH) conditions.4 Similarly, the efficient utilization of dif-
ferent iodoarene derivatives has been successfully reported
for synthesizing α-sulfonyloxy ketones 2.5
In our ongoing research program on the formation of
sulfonyl skeletons by α-functionalization of β-ketosul-
fones,6 we modified our synthetic aim to introducing the
diazo group on the α-position of β-ketosulfones. α-Diazo β-
ketosulfones are of great interest because of the ambiphilic
intermediates. Accordingly, many synthetic applications of
α-diazo β-ketosulfones exist for the preparation of func-
tionalized sulfonyl skeletons.7 Herein, we wanted to de-
scribe the synthetic route for substituted α-oxysulfonyl β-
ketosulfones 5 via the Cu(OAc)2-mediated self-dimerizative
debenzoylation of α-diazo β-ketosulfones 4 (2 equiv), as
shown in Scheme 2. This two-step procedure for the α-di-
azotization of β-ketosulfones 3 with benzenesulfonyl azide
In 1982, α-oxysulfonylation with [hydroxy(tosyloxy)io-
do]benzene [HTIB, PhI(OTs)OH] was first demonstrated by
the Koser group.2 Subsequently, Wirth et al. developed a
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

B
C.-K. Chan et al.
Paper
Synthesis
and Cu(OAc)2 promoted the α-oxysulfonylation of α-diazo
β-ketosulfones 4, and established carbon–nitrogen (C–N)
and carbon–oxygen (C–O) bond formation.
Table 1 Reaction Conditionsa
O
O
S
O
O
O
O
S
S
Tol
O
Ph
Tol
Ph
2
copper salt
conditions
O
diazotization
α-oxysulfonylation
2
Ph
Tol
O
O
S
O
X
O
O
O
S
O
O
S
N2
O
S
O
6a, X = Cl
6b, X = Br
6c, X = I
Cu(OAc)2
PhSO2N3, DBU
THF
Ar
R
O
Tol
5a
Ar
R
Ar
R
O
S
R
O
O
wet MeNO2
(for 2 equiv of 4)
4a
N2
O
O
3
4
5
Entry Cu salt (equiv)
Solvent (mL)
Time (h) Yield of 5a (%)b
Scheme 2 Two-step synthetic route to α-oxysulfonyl β-ketosulfones 5
1
2
Cu(OAc)2 (1.2)
Cu(NO3)2 (1.2)
CuSO4 (1.2)
Cu(OTf)2 (1.2)
CuF2 (1.2)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
MeNO2 (1)
MeNO2 (10)
AcOH (5)
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
50
20
20
20
20
71
c
–
α-Diazo β-ketosulfones 4 were easily prepared in good
yields (74–88%) by DBU-mediated diazotization of β-keto-
sulfones 3 (Ar = Ph, Tol, 4-FC6H4, 4-MeOC6H4, 4-F3CC6H4, 4-
O2NC6H4, 3-O2NC6H4, 4-PhC6H4, 2-naphthyl, 3,4-Cl2C6H3;
R = Tol, Ph, Me, 3-MeC6H4, 4-FC6H4, 4-MeOC6H4, 4-EtC6H4, 4-
i-PrC6H4, 4-n-BuC6H4, 4-t-BuC6H4, n-Bu) with PhSO2N3 in
THF at room temperature. The structure of 4n was deter-
mined by single-crystal X-ray crystallography.8 With com-
pounds 4 in hand, the next step was to examine the conver-
sion from α-diazo β-ketosulfones 4 (2 equiv) into α-oxysul-
c
3
–
4
60
10
5
d
6
CuCl2 (1.2)
–
d
7
CuBr2 (1.2)
–
d
8
CuI (1.2)
–
c
9
CuO (1.2)
–
c
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
CuCN (1.2)
–
Cu(OAc)2 (2.5)
Cu(OAc)2 (5.0)
Cu(OAc)2 (0.5)
Cu(OAc)2 (1.2)
Cu(OAc)2 (1.2)
Cu(OAc)2 (1.2)
Cu(OAc)2 (1.2)
Cu(OAc)2 (1.2)
Cu(OAc)2 (1.2)
Cu(OAc)2 (1.2)
Cu(OAc)2 (1.2)
–
60
40
35
48
66
58
35
fonyl β-ketosulfones
5 (1 equiv). We employed two
equivalents of 4a (Ar = Ph, R = Tol) as the model substrate to
investigate a range of copper salts in promoting the α-oxy-
sulfonylation reaction. Regarding the control conditions
[reflux, MeNO2 (5 mL), 20 h], the use of commercially avail-
able copper salts (1.2 equiv) [Cu(OAc)2, Cu(NO3)2, CuSO4,
Cu(OTf)2, CuF2, CuCl2, CuBr2, CuI, CuO and CuCN] was ini-
tially studied for the formation of 5a (Table 1, entries 1–10).
Among these screened copper salts, both Cu(OAc)2 and
Cu(OTf)2 provided 5a in moderate yields (71% and 60%) un-
der refluxing MeNO2 conditions (Table 1, entries 1 and 4). In
contrast, the use of Cu(NO3)2 and CuSO4 resulted in the for-
mation of complex mixtures (Table 1, entries 2 and 3). On
using copper halides, 10% of 5a (for CuF2) and three α-halo-
β-ketosulfones (6a–c) with yields of 61% (X = Cl, for CuCl2),
51% (X = Br, for CuBr2) and 22% (X = I, for CuI) were obtained
under the above-stated condition (Table 1, entries 5–8).9 Al-
though the isolated yields of 6a–c are low, the novel copper
halide mediated α-halogenation of 4a has been reported.6b
A plausible mechanism for the formation of 6b is illustrated
in Scheme 3. The initial coordination of 4a gives I by the
complexation of CuBr2 and the nitrogen atom of the diazo
group. Through subsequent intramolecular migration, the
tertiary copper complex II is formed. Following the removal
of molecular nitrogen, intermediate III is afforded. After the
involvement of H2O, IV is produced along with in situ gen-
erated HBr. Finally, the hydroxy group in IV, via a six-mem-
bered ring, promotes the removal of CuO and HBr to pro-
duce 6b via intramolecular rearrangement.
DMF (5)
c
CH2Cl2 (5)
EtNO2 (5)
–
56
MeNO2 (5)
MeNO2 (5)
MeNO2 (5)
50
20e
f
–
Cu(OAc)2 (1.2)
Cu(OAc)2 (1.2)
MeNO2 (aq)g (5)
MeNO2 (dry)h (5)
70
f
–
a The reactions were run on a 1.0 mmol scale with 4a at reflux under N2.
b Yield of isolated product.
c Complex mixture.
d Compounds 6a (61%), 6b (51%) and 6c (22%) were obtained.
e Room temperature.
f No reaction.
g MeNO2/H2O = 10:1.
h Anhydrous MeNO2 and 4 Å MS (100 mg) were added.
10). From the results in hand, Cu(OAc)2 proved to be the
most reactive copper complex compared to the other deriv-
atives. After changing the amounts of Cu(OAc)2 (1.2 → 2.5
and 5.0; 1.2 → 0.5 equivalents) (Table 1, entries 11–13),
lower yields (60% and 40%; 35%) of 5a were detected. Next,
we found that Cu(OAc)2 produced different yields of 5a un-
der concentrated (48% for 1.0 mmol/1 mL) and dilute (66%
for 1.0 mmol/10 mL) conditions (Table 1, entries 14 and 15).
The structures of 5a, 6a and 6b were determined by
single-crystal X-ray crystallography.8 No reactions were ob-
served when using CuO and CuCN (Table 1, entries 9 and
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

C
C.-K. Chan et al.
Paper
Synthesis
4-trifluoromethylphenyl and 3- or 4-nitrophenyl groups.
For the synthesis of 5y (R = n-Bu), only a 12% yield was ob-
tained. A mixture of five- and six-membered cyclic sulfones
was formed by the Cu(OAc)2-mediated intramolecular C–H
insertion process with 4y. The phenomenon is similar to
Maguire’s report.11 The structures of 5d and 5t were deter-
mined by single-crystal X-ray crystallography.8 Although
our synthetic route is not an atom-economic method, we
have developed a novel Cu(OAc)2-mediated route for pre-
paring the structural framework of α-oxysulfonyl β-keto-
sulfones.
O
O
CuBr2
O
O
O
O
O
O
O
S
S
S
N
Ph
Tol
Ph
Tol
Ph
2
Tol
2
2
Br Cu
N
N
N
N
N
Br
Br
Cu
Br
I
II
4a
N2
CuO + HBr
O
O
O
O
O
O
O
O
O
S
H
S
S
Ph
Tol
Ph
Tol
Ph
Br
Tol
2
2
2
Cu
Br
Br
H
Cu
O
Br 2 OH2
6b
Br
H
IV
III
Scheme 3 Proposed mechanism for the formation of 6b
Table 2 Synthesis of α-Oxysulfonyl β-Ketosulfones 5a
Furthermore, three other factors: solvent, time and tem-
perature, were studied. After changing the solvent (from
MeNO2 to AcOH, DMF, CH2Cl2 or EtNO2), the results showed
no observed formation of 5a in CH2Cl2, whilst AcOH and
EtNO2 provided better yields of 5a (58% and 56%) than DMF
(35%) (Table 1, entries 16–19). For an extended reaction
time (10 h → 50 h), the isolated yield of 5a was 50% (Table 1,
entry 20), while a 20% yield was isolated when the tem-
perature was decreased (101 °C → 25 °C) (Table 1, entry 21).
In the absence of Cu(OAc)2, no reaction was observed (Table
1, entry 22). Using a mixed solvent comprising MeNO2 and
H2O (10:1, 5 mL), 5a was isolated in a 70% yield (Table 1, en-
try 23). However, the use of anhydrous MeNO2 in the pres-
ence of molecular sieves did not result in the formation of
5a (Table 1, entry 24). The results showed that water is a
key factor affecting the formation of 5a. According to the
experimental results, the optimum conditions for the syn-
thesis of 5a are: Cu(OAc)2 (2 equiv), wet MeNO2 (5 mL), re-
flux, 20 hours. Aside from the present α-oxysulfonylation
reaction, Cu(OAc)2 has also been reported as a promoter for
different functional group transformations.10
Using the optimized conditions (Table 1, entry 1), we
further explored the substrate scope of the reaction; the re-
sults of the α-oxysulfonylations are shown in Table 2. For
the formation of α-oxysulfonyl β-ketosulfones 5a–y, differ-
ent Ar and R substituents on the β-ketosulfones 4a–y (2
equiv), including an electron-donating aryl group (for
Ar = 4-MeOC6H4), an electron-neutral aryl group (for
Ar = Ph, Tol, biphenyl, 2-naphthyl; R = Ph, Tol, 3-MeC6H4, 4-
EtC6H4, 4-i-PrC6H4, 4-n-BuC6H4, 4-t-BuC6H4), an electron-
withdrawing aryl group (for Ar = 4-O2NC6H4, 3-O2NC6H4, 4-
F3CC6H4) and an alkyl group (for R = Me, n-Bu) performed
differently providing a range of distributed yields of the de-
sired products. However, the conditions were slightly inap-
propriate for compounds 4c, 4o and 4t with a strong elec-
tron-donating 4-methoxyphenyl group (Ar or R), which
gave 5c and 5o in 60% and 45% yields, respectively. Howev-
er, 5t was isolated in only 8% yield. For stronger electron-
withdrawing groups, the conditions were also inappropri-
ate. Lower yields of 5e (47%), 5f (49%) and 5g (54%) were
observed for the α-oxysulfonylation of 4e, 4f and 4g having
O
O
S
O
O
S
Ar
R
Cu(OAc)2
O
Ar
R
2
O
S
R
O
wet MeNO2
N2
O
O
4
5
Entry β-Ketosulfone Ar
R
Product,
yield (%)b
1
2
4a
4b
4c
4d
4e
4f
Ph
4-FC6H4
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Tol
Ph
5a, 71
5b, 73
5c, 60
5d, 82
5e, 47
5f, 49
5g, 54
5h, 65
5i, 66
5j, 67
5k, 72
5l, 74
5m, 63
5n, 56
5o, 45
5p, 72
5q, 67
5r, 70
5s, 72
5t, 8
3
4-MeOC6H4
Tol
4
5
4-F3CC6H4
4-O2NC6H4
3-O2NC6H4
4-PhC6H4
2-naphthyl
3,4-Cl2C6H3
Ph
6
7
4g
4h
4i
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
4j
4k
4l
4-FC6H4
4-PhC6H4
Ph
Ph
4m
4n
4o
4p
4q
4r
Ph
Me
Me
Me
Me
4-MeOC6H4
4-MeC6H4
4-PhC6H4
Ph
3-MeC6H4
4-FC6H4
4s
4t
Ph
Ph
4-MeOC6H4
4-EtC6H4
4-i-PrC6H4
4-n-BuC6H4
4-t-BuC6H4
n-Bu
4u
4v
4w
4x
4y
Ph
5u, 73
5v, 72
5w, 74
5x, 76
5y, 12c
Ph
Ph
Ph
Ph
a The reactions were run on a 1.0 mmol scale with 4, Cu(OAc)2 (220 mg, 1.2
mmol), and wet MeNO2 (95%, 5 mL) under N2 at reflux for 20 h.
b Yield of isolated product.
c A mixture of cyclic sulfones was isolated.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

D
C.-K. Chan et al.
Paper
Synthesis
A plausible mechanism for the formation of 5a is illus-
trated in Scheme 4 via the Cu(OAc)2-mediated one-pot self-
dimerizative debenzoylation of two equivalents of 4a. On
the basis of the preliminary experience for copper triflate
mediated reactions of diazo β-ketosulfones,6b we think that
the initial coordination of 4a could provide two equivalents
of A by the complexation of Cu(OAc)2 and the nitrogen atom
of the diazo group. Through subsequent intramolecular mi-
gration, two equivalents of B, containing a tertiary copper
complex, are formed. Following the involvement of water
(from MeNO2)12 and acetate/water exchange, two equiva-
lents of C are afforded along with AcOH. The hydroxy group
then promotes the removal of molecular nitrogen from C
leading to D. Next, intramolecular rearrangement via a
seven-membered ring produces E. As reported by Luo and
Deng,13a adduct E (an α,β-diketosulfone) was found quite
unstable to isolation.13b,c Subsequently, intermolecular self-
coupling of two equivalents of E occurs to afford one equiv-
alent of F. After a cascade two-step route for the protona-
tion of the carbonyl group and sulfonyl migration, interme-
diate G is formed. Finally, 5a is produced by an in situ ace-
tate ion mediated debenzoylative route along with the
removal of CO. Hydrolysis of the anhydride leads to the iso-
lation of PhCO2H and AcOH. Looking at the proposed mech-
anism, we can understand that the obtained yield should be
halved because one molecule of the product 5a is formed
from two molecules of diazo compound 4a.
gated (Scheme 5). However, the formation of compounds
8a,b was not observed, and ester 9 was generated in only a
35% yield (from 7a). A possible explanation for the reaction
of 7a with Cu(OAc)2 would involve the initial formation of
8a. Subsequent debenzoylation mediated by in situ formed
AcOH (see Scheme 4) leads to the generation of 9 via car-
bon–carbon bond cleavage.14 The structure of 9 was deter-
mined by single-crystal X-ray crystallography.8
AcOH-induced carbon–carbon
bond cleavage
O
O
R
O
O
O
Cu(OAc)2
Ph
R
O
AcOH
O
Ph
2
Ph
R
Ph
O
wet MeNO2
N2
O
7a, R = Ph
7b, R = OEt
8a (not detected)
8b (not detected)
9 (35%, for 7a)
Scheme 5 Reaction of compounds 7 with Cu(OAc)2
To extend this one-pot domino protocol, the Cu(OAc)2-
mediated α-oxysulfonylation of a mixture of 4o and 4q
(1:1) was examined (Scheme 6). Unexpectedly, we ob-
served that the isolated yields of 5o (45% → 15%) and 5q
(67% → 30%) were decreased compared with the individual
Cu(OAc)2-mediated α-oxysulfonylations of 4o or 4q. Ac-
cording to the plausible mechanism (Scheme 4), we believe
that the competition of intermediates E-4o and E-4q is the
key factor affecting the product yields and distribution via
intermolecular cross-coupling (4-methoxyphenyl versus bi-
phenyl) and self-coupling (4-methoxyphenyl versus 4-me-
thoxyphenyl or biphenyl versus biphenyl). From the results,
we understand that the control experiment demonstrated
that a stronger electron-donating 4-methoxyphenyl group
(for E-4o) could trigger electrophilic instability easily such
that the formation of an α-oxysulfonylated product is inhib-
ited.
In summary, we have developed a synthetic method for
the preparation of α-oxysulfonyl β-ketosulfones 5a–y in
good yields via Cu(OAc)2-mediated α-oxysulfonylation of
two equivalents of substituted α-diazo β-ketosulfones 4a–y
in MeNO2 at reflux. The use of different copper salts was in-
vestigated for a facile conversion. A plausible mechanism
has been proposed. The structures of the key products were
confirmed by X-ray crystallography. Further investigations
regarding the synthetic applications of β-ketosulfones are
ongoing in our laboratory.
Cu(OAc)2
O
O
S
O
O
S
O
O
O
S
N
Ph
Tol
2
Ph
Tol
2
Ph
AcO Cu
OAc
Tol
2
O
O
N
N
N
N
N
AcO
Cu
A
B
4a
OAc
AcOH
H2O
AcOH
O
O
O
O
O
O
O
O
O
S
S
S
N
Ph
Tol
Ph
Tol
Ph
2
Tol
2
O
Cu
O
HO Cu
O
E
H
N
N2
Cu
Tol
OAc
O
O
O
S
D
C
Me
Ph
O
PhCO2H + AcOH
H2O
O
E
AcO
H
O
Ph
O
O
S
OH
O
S
O
O
S
AcO
Ph
Tol
Tol
Ph
Ph
Tol
Ph
Tol
O
O
S
O
O
O
O
O
O
S
Ph
O
S
O
Tol
AcO
CO
O
O
O
All reagents and solvents were obtained from commercial sources
and were used without further purification. Reactions were routinely
carried out under an atmosphere of dry nitrogen with magnetic stir-
ring. Products in organic solvents were dried with anhydrous MgSO4
before concentration in vacuo. Melting points were determined with
an SMP3 melting point apparatus. 1H and 13C NMR spectra were re-
corded on a Varian INOVA-400 spectrometer operating at 400 and at
100 MHz, respectively. High-resolution mass spectrometry (HRMS)
O
Tol
O
O
F
G
5a
Scheme 4 A plausible mechanism for the synthesis of 5a
Changing the 1,3-dicarbonyl synthons from α-diazo β-
ketosulfones 4a to β-diketone 7a and β-ketoester 7b, the
Cu(OAc)2-mediated reactions of 7a,b (2 equiv) were investi-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

E
C.-K. Chan et al.
Paper
Synthesis
self-coupling and cross-coupling
O
O
S
O
O
S
O
O
S
Me
Me
2
Me
2
O
O
O
N2
O
O
MeO
MeO
MeO
O
S
O
5o (15%)
4o
Cu(OAc)2
E-4o
Me
+
+
+
wet MeNO2
O
O
S
O
O
O
O
S
S
Me
Me
2
Me
2
O
O
O
O
N2
O
Ph
Ph
Ph
O
S
O
4q
5q (30%)
Me
E-4q
Scheme 6 Cu(OAc)2-mediated reaction of a 1:1 mixture of 4o and 4q
was performed using a Finnigan/Thermo Quest MAT 95XL mass spec-
trometer. X-ray crystal structures were obtained with an Enraf-
Nonius FR-590 diffractometer (CAD4, Kappa CCD). Scanned copies of
NMR (CDCl3) spectroscopic data for all compounds and X-ray crystal
structure analysis data of compounds 4n, 5a, 5d, 5t, 6a, 6b and 9 are
available.
2-Diazo-1-(4-methoxyphenyl)-2-(toluene-4-sulfonyl)ethanone
(4c)7g
Yield: 271 mg (82%); colorless solid; mp 140–142 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 8.8 Hz, 2 H), 7.55 (d, J = 8.8
Hz, 2 H), 7.22 (d, J = 8.8 Hz, 2 H), 6.89 (d, J = 8.8 Hz, 2 H), 3.82 (s, 3 H),
2.41 (s, 3 H).
α-Diazo β-Ketosulfones 4a–y; General Procedure
13C NMR (100 MHz, CDCl3): δ = 181.2, 163.4, 145.2, 138.6, 131.6,
DBU (182 mg, 1.2 mmol) was added to a solution of compound 3 (1.0
mmol) in THF (10 mL) at r.t. The reaction mixture was stirred at r.t. for
10 min. Benzenesulfonyl azide (200 mg, 1.1 mmol) was added to the
reaction mixture at r.t. The resulting mixture was stirred at r.t. for 20
h. The solvent was concentrated, the residue diluted with H2O (10 mL)
and the mixture extracted with CH2Cl2 (3 × 20 mL). The combined or-
ganic layers were washed with brine, dried, filtered and evaporated
under reduced pressure to afford the crude product. Purification on
silica gel (hexanes/EtOAc = 8:1–4:1) afforded compounds 4a–y.
129.7 (×2), 129.6 (×2), 128.1 (×2), 114.0 (×2), 62.4, 55.4, 21.6.
HRMS (ESI): m/z [M + H]+ calcd for C16H15N2O4S: 331.0753; found:
331.0748.
2-Diazo-2-(toluene-4-sulfonyl)-1-p-tolylethanone (4d)7g
Yield: 264 mg (84%); colorless solid; mp 118–120 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.94 (d, J = 8.4 Hz, 2 H), 7.46 (d, J = 8.4
Hz, 2 H), 7.34 (d, J = 8.4 Hz, 2 H), 7.22 (d, J = 8.4 Hz, 2 H), 2.43 (s, 3 H),
2.38 (s, 3 H).
2-Diazo-1-phenyl-2-(toluene-4-sulfonyl)ethanone (4a)7b
Yield: 264 mg (88%); colorless solid; mp 76–78 °C (recrystallized from
hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.93 (d, J = 8.0 Hz, 2 H), 7.56–7.51 (m, 3
H), 7.44–7.40 (m, 2 H), 7.33 (d, J = 8.8 Hz, 2 H), 2.43 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 182.3, 145.2, 143.9 (×2), 138.6, 133.2,
129.6 (×2), 129.4 (×2), 128.1 (×2), 127.5 (×2), 21.62, 21.55.
HRMS (ESI): m/z [M + H]+ calcd for C16H15N2O3S: 315.0803; found:
315.0809.
13C NMR (100 MHz, CDCl3): δ = 182.6, 145.3 (×2), 138.5, 135.7, 132.9,
129.7 (×2), 128.8 (×2), 128.1 (×2), 127.3 (×2), 21.6.
HRMS (ESI): m/z [M + H]+ calcd for C15H13N2O3S: 301.0647; found:
2-Diazo-2-(toluene-4-sulfonyl)-1-(4-trifluoromethylphenyl)eth-
anone (4e)
301.0657.
Yield: 294 mg (80%); colorless solid; mp 121–122 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.86 (d, J = 8.4 Hz, 2 H), 7.69 (d, J = 8.4
Hz, 2 H), 7.64 (d, J = 8.8 Hz, 2 H), 7.33 (d, J = 8.0 Hz, 2 H), 2.44 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 181.8, 145.7, 138.9, 138.4, 134.2 (q,
J = 32.6 Hz), 129.8 (×2), 128.1 (×2), 127.9 (×2), 125.8 (q, J = 3.0 Hz),
124.6, 123.3 (q, J = 271.4 Hz), 121.9, 21.6.
2-Diazo-1-(4-fluorophenyl)-2-(toluene-4-sulfonyl)ethanone (4b)
Yield: 254 mg (80%); colorless solid; mp 95–97 °C (recrystallized from
hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.90 (d, J = 8.4 Hz, 2 H), 7.62–7.57 (m, 2
H), 7.34 (d, J = 7.6 Hz, 2 H), 7.15–7.09 (m, 2 H), 2.44 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 181.4, 165.4 (d, J = 253.9 Hz), 145.5
(×2), 138.5, 132.0 (d, J = 3.0 Hz), 130.2 (d, J = 9.1 Hz, ×2), 129.8 (×2),
128.1 (×2), 116.1 (d, J = 22.0 Hz, ×2), 21.7.
HRMS (ESI): m/z [M + H]+ calcd for C16H12F3N2O3S: 369.0521; found:
369.0530.
2-Diazo-1-(4-nitrophenyl)-2-(toluene-4-sulfonyl)ethanone (4f)7h
HRMS (ESI): m/z [M + H]+ calcd for C15H12FN2O3S: 319.0553; found:
319.0558.
Yield: 279 mg (81%); colorless solid; mp 136–138 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 8.27 (d, J = 8.8 Hz, 2 H), 7.83 (d, J = 8.4
Hz, 2 H), 7.70 (d, J = 8.8 Hz, 2 H), 7.35 (d, J = 8.4 Hz, 2 H), 2.45 (s, 3 H).
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13C NMR (100 MHz, CDCl3): δ = 181.4, 150.0, 145.9, 140.9, 138.3,
1H NMR (400 MHz, CDCl3): δ = 8.07–8.04 (m, 2 H), 7.68–7.63 (m, 1 H),
132.7, 129.9 (×2), 128.7 (×2), 128.0 (×2), 123.9 (×2), 21.7.
7.58–7.54 (m, 5 H), 7.45–7.41 (m, 2 H).
HRMS (ESI): m/z [M + H]+ calcd for C15H12N3O5S: 346.0498; found:
13C NMR (100 MHz, CDCl3): δ = 182.6, 141.4, 135.8, 134.1, 133.0,
346.0502.
129.1 (×2), 128.9, 128.8 (×2), 128.1 (×2), 127.4 (×2).
HRMS (ESI): m/z [M + H]+ calcd for C14H11N2O3S: 287.0490; found:
287.0498.
2-Diazo-1-(3-nitrophenyl)-2-(toluene-4-sulfonyl)ethanone (4g)
Yield: 283 mg (82%); colorless solid; mp 114–116 °C (recrystallized
from hexanes and EtOAc).
2-Benzenesulfonyl-2-diazo-1-(4-fluorophenyl)ethanone (4l)
1H NMR (400 MHz, CDCl3): δ = 8.33–8.26 (m, 2 H), 7.88–7.85 (m, 1 H),
7.79 (d, J = 8.4 Hz, 2 H), 7.65–7.61 (m, 1 H), 7.30 (d, J = 8.0 Hz, 2 H),
2.39 (s, 3 H).
Yield: 255 mg (84%); colorless solid; mp 78–79 °C (recrystallized from
hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 8.03–8.01 (m, 2 H), 7.68–7.53 (m, 5 H),
13C NMR (100 MHz, CDCl3): δ = 180.5, 147.9, 145.7 (×2), 138.1, 137.0,
7.14–7.09 (m, 2 H).
132.9, 130.0, 129.7 (×2), 127.8 (×2), 126.8, 122.3, 21.5.
HRMS (ESI): m/z [M + H]+ calcd for C15H12N3O5S: 346.0498; found:
346.0508.
13C NMR (100 MHz, CDCl3): δ = 181.3, 165.4 (d, J = 253.2 Hz), 141.4,
134.2, 132.0 (d, J = 3.8 Hz), 130.2 (d, J = 9.1 Hz, ×2), 129.2 (×2), 128.0
(×3), 116.1 (d, J = 22.7 Hz, ×2).
HRMS (ESI): m/z [M + H]+ calcd for C14H10FN2O3S: 305.0396; found:
305.0405.
1-Biphenyl-4-yl-2-diazo-2-(toluene-4-sulfonyl)ethanone (4h)
Yield: 278 mg (74%); colorless solid; mp 133–135 °C (recrystallized
from hexanes and EtOAc).
2-Benzenesulfonyl-1-biphenyl-4-yl-2-diazoethanone (4m)
1H NMR (400 MHz, CDCl3): δ = 7.97 (d, J = 8.8 Hz, 2 H), 7.65 (br s, 4 H),
7.59 (d, J = 8.8 Hz, 2 H), 7.49–7.40 (m, 3 H), 7.36 (d, J = 8.0 Hz, 2 H),
2.45 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 182.2, 145.9, 145.4, 139.4, 138.6,
134.5, 130.0, 129.7 (×2), 129.0 (×2), 128.4, 128.2 (×2), 128.1 (×2),
127.4 (×2), 127.2 (×2), 21.7.
Yield: 290 mg (80%); colorless solid; mp 134–136 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 8.10–8.07 (m, 2 H), 7.65 (br s, 4 H),
7.60–7.55 (m, 4 H), 7.49–7.45 (m, 3 H), 7.43–7.39 (m, 1 H).
13C NMR (100 MHz, CDCl3): δ = 182.1, 145.9, 141.5, 139.4, 134.4,
134.1, 131.1, 129.1 (×2), 129.0 (×2), 128.4, 128.14 (×2), 128.08 (×2),
127.4 (×2), 127.2 (×2).
HRMS (ESI): m/z [M + H]+ calcd for C21H17N2O3S: 377.0960; found:
377.0967.
HRMS (ESI): m/z [M + H]+ calcd for C20H15N2O3S: 363.0803; found:
363.0810.
2-Diazo-1-naphthalen-2-yl-2-(toluene-4-sulfonyl)ethanone (4i)
2-Diazo-2-methanesulfonyl-1-phenylethanone (4n)7h
Yield: 263 mg (75%); colorless solid; mp 104–106 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 8.08 (s, 1 H), 7.82 (d, J = 8.4 Hz, 2 H),
7.89–7.85 (m, 3 H), 7.63–7.54 (m, 3 H), 7.35 (d, J = 8.8 Hz, 2 H), 2.44 (s,
3 H).
13C NMR (100 MHz, CDCl3): δ = 182.6, 145.4, 138.6, 135.2, 133.0,
132.0, 129.7 (×2), 129.1, 128.9, 128.7, 128.6, 128.2 (×2), 127.9, 127.4,
127.2, 123.3, 21.7.
Yield: 184 mg (82%); colorless solid; mp 120–122 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.67–7.65 (m, 2 H), 7.62–7.58 (m, 1 H),
7.51–7.47 (m, 2 H), 3.41 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 183.3, 135.5, 133.3 (×2), 129.1 (×2),
127.3 (×2), 44.9.
HRMS (ESI): m/z [M + H]+ calcd for C9H9N2O3S: 225.0334; found:
225.0330.
HRMS (ESI): m/z [M + H]+ calcd for C19H15N2O3S: 351.0803; found:
351.0812.
Single-crystal X-ray analysis: Slow diffusion of EtOAc into a solution
of compound 4n in CH2Cl2 yielded colorless prisms. The compound
crystallizes in the triclinic crystal system, space group P-1,
a = 5.0953(5) Å, b = 9.0098(8) Å, c = 11.5067(11) Å, V = 492.80(8) Å3,
Z = 2, dcalcd = 1.518 mg/cm3, F(000) = 234, 2θ range 1.876–26.414°; R
indices (all data): R1 = 0.0348, wR2 = 0.0822.
2-Diazo-1-(3,4-dichlorophenyl)-2-(toluene-4-sulfonyl)ethanone
(4j)
Yield: 286 mg (78%); colorless solid; mp 118–120 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.85 (d, J = 8.4 Hz, 2 H), 7.57 (d, J = 2.0
Hz, 1 H), 7.50 (d, J = 8.4 Hz, 1 H), 7.39 (dd, J = 2.0, 8.4 Hz, 1 H), 7.33 (d,
J = 8.0 Hz, 2 H), 2.44 (s, 3 H).
2-Diazo-2-methanesulfonyl-1-(4-methoxyphenyl)ethanone (4o)
Yield: 198 mg (78%); colorless solid; mp 93–95 °C (recrystallized from
hexanes and EtOAc).
13C NMR (100 MHz, CDCl3): δ = 180.4, 145.6 (×2), 138.3, 137.4, 135.3,
133.4, 130.8, 129.8 (×2), 129.5, 128.0 (×2), 126.4, 21.6.
HRMS (ESI): m/z [M + H]+ calcd for C15H11Cl2N2O3S: 368.9868; found:
1H NMR (400 MHz, CDCl3): δ = 7.66 (d, J = 8.8 Hz, 2 H), 6.96 (d, J = 8.8
Hz, 2 H), 3.87 (s, 3 H), 3.41 (s, 3 H).
368.9871.
13C NMR (100 MHz, CDCl3): δ = 181.9, 163.7, 129.8 (×2), 128.1 (×2),
114.3 (×2), 55.6, 45.1.
HRMS (ESI): m/z [M + H]+ calcd for C10H11N2O4S: 255.0440; found:
255.0443.
2-Benzenesulfonyl-2-diazo-1-phenylethanone (4k)7c
Yield: 246 mg (86%); colorless solid; mp 125–127 °C (recrystallized
from hexanes and EtOAc).
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2-Diazo-2-methanesulfonyl-1-p-tolylethanone (4p)
1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.0 Hz, 2 H), 7.57–7.53 (m, 3
H), 7.45–7.41 (m, 2 H), 7.37 (d, J = 8.4 Hz, 2 H), 2.74 (q, J = 7.6 Hz, 2 H),
1.27 (t, J = 8.0 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 182.7, 151.4, 138.8, 135.9, 133.0,
129.7, 128.8 (×2), 128.6 (×2), 128.3 (×2), 127.5 (×2), 29.0, 15.0.
Yield: 188 mg (79%); colorless solid; mp 118–120 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.56 (d, J = 8.4 Hz, 2 H), 7.29 (d, J = 8.4
Hz, 2 H), 3.40 (s, 3 H), 2.41 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 183.0, 144.4 (×2), 132.9, 129.7 (×2),
HRMS (ESI): m/z [M + H]+ calcd for C16H15N2O3S: 315.0803; found:
315.0805.
127.5 (×2), 45.0, 21.6.
HRMS (ESI): m/z [M + H]+ calcd for C10H11N2O3S: 239.0490; found:
239.0498.
2-Diazo-2-(4-isopropylbenzenesulfonyl)-1-phenylethanone (4v)
Yield: 272 mg (83%); colorless solid; mp 74–76 °C (recrystallized from
hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.4 Hz, 2 H), 7.57–7.53 (m, 3
H), 7.45–7.41 (m, 2 H), 7.39 (d, J = 8.4 Hz, 2 H), 3.03–2.96 (m, 1 H),
1.27 (d, J = 6.8 Hz, 6 H).
13C NMR (100 MHz, CDCl3): δ = 182.7, 155.9 (×2), 138.8, 135.9, 132.9,
128.8 (×2), 128.3 (×2), 127.4 (×2), 127.2 (×2), 34.3, 23.6 (×2).
1-Biphenyl-4-yl-2-diazo-2-methanesulfonylethanone (4q)
Yield: 240 mg (80%); colorless solid; mp 139–141 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.75 (d, J = 8.4 Hz, 2 H), 7.71 (d, J = 8.4
Hz, 2 H), 7.62–7.60 (m, 2 H), 7.50–7.46 (m, 2 H), 7.44–7.39 (m, 1 H),
3.44 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 182.7, 146.2, 139.2, 134.1 (×2), 129.0
(×2), 128.5, 128.0 (×2), 127.6 (×2), 127.2 (×2), 45.0.
HRMS (ESI): m/z [M + H]+ calcd for C17H17N2O3S: 329.0960; found:
329.0966.
HRMS (ESI): m/z [M + H]+ calcd for C15H13N2O3S: 301.0647; found:
301.0653.
2-(4-n-Butylbenzenesulfonyl)-2-diazo-1-phenylethanone (4w)
Yield: 280 mg (82%); colorless gum.
2-Diazo-1-phenyl-2-(toluene-3-sulfonyl)ethanone (4r)
1H NMR (400 MHz, CDCl3): δ = 7.95–7.93 (m, 2 H), 7.56–7.52 (m, 3 H),
7.44–7.40 (m, 2 H), 7.35–7.33 (m, 2 H), 2.69 (t, J = 7.6 Hz, 2 H), 1.65–
1.58 (m, 2 H), 1.40–1.31 (m, 2 H), 0.93 (t, J = 7.6 Hz, 3 H).
Yield: 243 mg (81%); colorless solid; mp 104–106 °C (recrystallized
from hexanes and EtOAc).
13C NMR (100 MHz, CDCl3): δ = 182.7, 150.2, 138.7, 135.9, 132.9,
129.6, 129.1 (×2), 128.8 (×2), 128.2 (×2), 127.4 (×2), 35.6, 33.0, 22.2,
13.8.
HRMS (ESI): m/z [M + H]+ calcd for C18H19N2O3S: 343.1116; found:
343.1118.
1H NMR (400 MHz, CDCl3): δ = 7.85–7.82 (m, 1 H), 7.81 (s, 1 H), 7.56–
7.53 (m, 3 H), 7.46–7.40 (m, 4 H), 2.43 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 182.7, 141.3, 139.4 (×2), 135.8, 134.9,
132.9, 128.9, 128.8 (×2), 128.3, 127.4 (×2), 125.2, 21.3.
HRMS (ESI): m/z [M + H]+ calcd for C15H13N2O3S: 301.0647; found:
301.0643.
2-(4-tert-Butylbenzenesulfonyl)-2-diazo-1-phenylethanone (4x)
Yield: 294 mg (86%); colorless solid; mp 92–94 °C (recrystallized from
hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.99–7.95 (m, 2 H), 7.58–7.53 (m, 5 H),
7.46–7.41 (m, 2 H), 1.35 (s, 9 H).
13C NMR (100 MHz, CDCl3): δ = 182.7, 158.2, 138.5, 135.9, 133.0,
130.0, 128.8 (×2), 128.0 (×2), 127.5 (×2), 126.1 (×2), 35.3, 31.0 (×3).
HRMS (ESI): m/z [M + H]+ calcd for C18H19N2O3S: 343.1116; found:
343.1118.
2-Diazo-2-(4-fluorobenzenesulfonyl)-1-phenylethanone (4s)
Yield: 243 mg (80%); colorless solid; mp 101–103 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 8.12–8.08 (m, 2 H), 7.58–7.54 (m, 3 H),
7.46–7.42 (m, 2 H), 7.25–7.19 (m, 2 H).
13C NMR (100 MHz, CDCl3): δ = 182.5, 166.0 (d, J = 255.4 Hz), 137.3 (d,
J = 3.0 Hz), 135.6 (×2), 133.1, 131.3 (d, J = 9.9 Hz, ×2), 128.9 (×2), 127.4
(×2), 116.4 (d, J = 22.7 Hz, ×2).
HRMS (ESI): m/z [M + H]+ calcd for C14H10FN2O3S: 305.0396; found:
305.0408.
2-(n-Butane-1-sulfonyl)-2-diazo-1-phenylethanone (4y)
Yield: 223 mg (84%); colorless solid; mp 94–96 °C (recrystallized from
hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.68–7.65 (m, 2 H), 7.62–7.58 (m, 1 H),
7.51–7.48 (m, 2 H), 3.55–3.51 (m, 2 H), 1.86–1.79 (m, 2 H), 1.53–1.44
(m, 2 H), 0.95 (t, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 183.3, 135.6, 133.3, 129.0 (×3), 127.4
(×2), 56.5, 24.6, 21.3, 13.5.
2-Diazo-2-(4-methoxybenzenesulfonyl)-1-phenylethanone (4t)
Yield: 256 mg (81%); colorless solid; mp 104–106 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.98 (d, J = 8.8 Hz, 2 H), 7.55 (d, J = 8.4
Hz, 2 H), 7.54–7.52 (m, 1 H), 7.44–7.40 (m, 2 H), 6.99 (d, J = 9.2 Hz, 2
H), 3.87 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 182.7, 164.1 (×2), 135.9, 133.0, 132.9
(×2), 130.5 (×2), 128.8 (×2), 127.4 (×2), 114.2, 55.7.
HRMS (ESI): m/z [M + H]+ calcd for C12H15N2O3S: 267.0803; found:
267.0807.
HRMS (ESI): m/z [M + H]+ calcd for C15H13N2O4S: 317.0596; found:
317.0602.
α-Oxysulfonyl β-Ketosulfones 5a–y; General Procedure
Cu(OAc)2 (220 mg, 1.2 mmol) was added to a solution of 4 (1.0 mmol)
in MeNO2 (5 mL) at r.t. The reaction mixture was stirred at r.t. for 10
min and then at reflux for 20 h. The mixture was cooled to r.t. and the
solvent was concentrated. The residue was diluted with H2O (10 mL)
2-Diazo-2-(4-ethylbenzenesulfonyl)-1-phenylethanone (4u)
Yield: 264 mg (84%); colorless gum.
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and the mixture was extracted with CH2Cl2 (3 × 20 mL). The com-
bined organic layers were washed with brine, dried, filtered and
evaporated under reduced pressure to afford the crude product. Puri-
fication on silica gel (hexanes/EtOAc = 8:1–4:1) afforded compounds
5a–y.
1H NMR (400 MHz, CDCl3): δ = 7.85 (d, J = 8.4 Hz, 2 H), 7.66 (d, J = 8.4
Hz, 2 H), 7.62 (d, J = 8.4 Hz, 2 H), 7.32 (d, J = 8.8 Hz, 2 H), 7.27 (d,
J = 8.4 Hz, 2 H), 7.20 (d, J = 8.4 Hz, 2 H), 6.36 (s, 1 H), 2.45 (s, 3 H), 2.43
(s, 3 H), 2.39 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 185.8, 146.5, 146.0, 145.9, 131.9 (×2),
131.7, 130.0 (×2), 129.9 (×2), 129.84 (×2), 129.82 (×2), 129.4 (×2),
128.2 (×2), 89.3, 21.8 (×2), 21.7.
Toluene-4-sulfonic Acid 2-Oxo-2-phenyl-1-(toluene-4-sulfo-
nyl)ethyl Ester (5a)5e
HRMS (ESI): m/z [M + H]+ calcd for C23H23O6S2: 459.0936; found:
459.0938.
Yield: 158 mg (71%); colorless solid; mp 180–182 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.95–7.93 (m, 2 H), 7.68 (d, J = 8.4 Hz, 2
H), 7.65–7.60 (m, 1 H), 7.59 (d, J = 8.4 Hz, 2 H), 7.49–7.45 (m, 2 H),
7.33 (d, J = 8.4 Hz, 2 H), 7.20 (d, J = 8.0 Hz, 2 H), 6.36 (s, 1 H), 2.47 (s, 3
H), 2.39 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 186.5, 146.6, 146.0, 134.6, 134.3,
131.8, 131.7, 130.1 (×2), 129.9 (×4), 129.8 (×2), 128.6 (×2), 128.2 (×2),
89.5, 21.8, 21.7.
Slow diffusion of EtOAc into a solution of compound 5d in CH2Cl2
yielded colorless prisms. The compound crystallizes in the monoclinic
crystal system, space group Cc, a = 16.0826(13) Å, b = 12.8002(11) Å,
c = 11.0923(9) Å, V = 2146.9(3) Å3, Z = 4, dcalcd = 1.419 mg/cm3,
F(000) = 960, 2θ range 2.085–26.440°;
R1 = 0.0849, wR2 = 0.2038.
R
indices (all data):
Toluene-4-sulfonic Acid 2-Oxo-1-(toluene-4-sulfonyl)-2-(4-tri-
fluoromethylphenyl)ethyl Ester (5e)
HRMS (ESI): m/z [M + H]+ calcd for C22H21O6S2: 445.0780; found:
445.0788.
Yield: 120 mg (47%); colorless solid; mp 155–158 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 8.06 (d, J = 8.0 Hz, 2 H), 7.72 (d, J = 8.4
Hz, 2 H), 7.70 (d, J = 8.4 Hz, 2 H), 7.57 (d, J = 8.4 Hz, 2 H), 7.35 (d,
J = 8.0 Hz, 2 H), 7.20 (d, J = 8.0 Hz, 2 H), 6.23 (s, 1 H), 2.48 (s, 3 H), 2.40
(s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 186.4, 146.9, 146.3, 136.7, 135.5 (q,
J = 32.6 Hz), 131.6, 130.2 (×2), 130.04 (×2), 129.98 (×6), 128.2 (×2),
125.6 (q, J = 3.8 Hz), 123.3 (q, J = 271.4 Hz), 90.2, 21.9, 21.7.
Single-crystal X-ray analysis: Slow diffusion of EtOAc into a solution
of compound 5a in CH2Cl2 yielded colorless prisms. The compound
crystallizes in the monoclinic crystal system, space group P21/c,
a = 5.8538(6) Å, b = 17.3655(19) Å, c = 20.225(2) Å, V = 2041.4(4) Å3,
Z = 4, dcalcd = 1.446 mg/cm3, F(000) = 928, 2θ range 1.550–26.624°; R
indices (all data): R1 = 0.0623, wR2 = 0.1046.
Toluene-4-sulfonic Acid 2-(4-Fluorophenyl)-2-oxo-1-(toluene-4-
sulfonyl)ethyl Ester (5b)
HRMS (ESI): m/z [M + H]+ calcd for C23H20F3O6S2: 513.0653; found:
513.0657.
Yield: 169 mg (73%); colorless solid; mp 144–146 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 8.03–7.99 (m, 2 H), 7.68 (d, J = 8.4 Hz, 2
H), 7.59 (d, J = 8.4 Hz, 2 H), 7.33 (d, J = 8.0 Hz, 2 H), 7.21 (d, J = 8.4 Hz,
2 H), 7.17–7.12 (m, 2 H), 6.24 (s, 1 H), 2.47 (s, 3 H), 2.40 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 185.1, 166.6 (d, J = 256.9 Hz), 146.7,
146.1, 132.8 (d, J = 9.8 Hz, ×2), 132.3, 132.2, 131.7, 129.98 (×2), 129.95
(×2), 129.91 (×2), 128.2 (×2), 116.0 (d, J = 22.7 Hz, ×2), 89.9, 21.9, 21.7.
Toluene-4-sulfonic Acid 2-(4-Nitrophenyl)-2-oxo-1-(toluene-4-
sulfonyl)ethyl Ester (5f)
Yield: 120 mg (49%); colorless solid; mp 198–200 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 8.31 (d, J = 9.2 Hz, 2 H), 8.15 (d, J = 8.8
Hz, 2 H), 7.69 (d, J = 8.4 Hz, 2 H), 7.57 (d, J = 8.8 Hz, 2 H), 7.35 (d,
J = 8.4 Hz, 2 H), 7.22 (d, J = 8.4 Hz, 2 H), 6.18 (s, 1 H), 2.49 (s, 3 H), 2.42
(s, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C22H20FO6S2: 463.0685; found:
463.0684.
13C NMR (100 MHz, CDCl3): δ = 186.2, 150.8, 147.0, 146.4, 138.4,
131.6, 131.4, 131.0 (×2), 130.1 (×2), 130.0 (×2), 129.9 (×2), 128.2 (×2),
123.7 (×2), 90.4, 21.9, 21.7.
Toluene-4-sulfonic Acid 2-(4-Methoxyphenyl)-2-oxo-1-(toluene-
4-sulfonyl)ethyl Ester (5c)
HRMS (ESI): m/z [M + H]+ calcd for C22H20NO8S2: 490.0630; found:
490.0633.
Yield: 142 mg (60%); colorless solid; mp 131–133 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.95 (d, J = 8.8 Hz, 2 H), 7.67 (d, J = 8.4
Hz, 2 H), 7.63 (d, J = 8.4 Hz, 2 H), 7.32 (d, J = 8.0 Hz, 2 H), 7.21 (d,
J = 8.4 Hz, 2 H), 6.94 (d, J = 8.8 Hz, 2 H), 6.32 (s, 1 H), 3.90 (s, 3 H), 2.46
(s, 3 H), 2.40 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 184.3, 164.8, 146.4, 145.9, 132.4 (×2),
132.0, 131.9, 130.1 (×2), 129.8 (×4), 128.2 (×2), 127.4, 114.0 (×2), 89.6,
55.6, 21.9, 21.7.
Toluene-4-sulfonic Acid 2-(3-Nitrophenyl)-2-oxo-1-(toluene-4-
sulfonyl)ethyl Ester (5g)
Yield: 132 mg (54%); colorless solid; mp 180–182 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 8.65 (s, 1 H), 8.45 (dd, J = 1.6, 7.6 Hz, 1
H), 8.37 (d, J = 7.6 Hz, 1 H), 7.73–7.71 (m, 1 H), 7.70 (d, J = 8.0 Hz, 2 H),
7.56 (d, J = 8.0 Hz, 2 H), 7.35 (d, J = 8.0 Hz, 2 H), 7.20 (d, J = 8.0 Hz, 2
H), 6.20 (s, 1 H), 2.47 (s, 3 H), 2.39 (s, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C23H23O7S2: 475.0885; found:
475.0887.
13C NMR (100 MHz, CDCl3): δ = 185.6, 148.2, 147.0, 146.5, 135.4,
135.2, 135.0, 131.5, 131.3, 130.1 (×2), 130.0 (×2), 129.9 (×2), 128.3,
128.1 (×2), 124.5, 90.4, 21.8, 21.6.
Toluene-4-sulfonic Acid 2-Oxo-1-(toluene-4-sulfonyl)-2-p-tolyl-
ethyl Ester (5d)5e
HRMS (ESI): m/z [M + H]+ calcd for C22H20NO8S2: 490.0630; found:
490.0631.
Yield: 188 mg (82%); colorless solid; mp 176–178 °C (recrystallized
from hexanes and EtOAc).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

I
C.-K. Chan et al.
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Synthesis
Toluene-4-sulfonic Acid 2-Biphenyl-4-yl-2-oxo-1-(toluene-4-sul-
fonyl)ethyl Ester (5h)
1H NMR (400 MHz, CDCl3): δ = 8.03–8.00 (m, 2 H), 7.83–7.80 (m, 2 H),
7.75–7.71 (m, 3 H), 7.64–7.54 (m, 3 H), 7.46–7.42 (m, 2 H), 7.18–7.13
(m, 2 H), 6.30 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 184.7, 166.6 (d, J = 257.0 Hz), 135.3,
134.8, 134.7, 132.9, 132.8 (d, J = 9.8 Hz, ×2), 130.6 (d, J = 3.0 Hz), 129.9
(×2), 129.4 (×2), 129.3 (×2), 128.1 (×2), 116.1 (d, J = 22.0 Hz, ×2), 89.9.
Yield: 169 mg (65%); colorless solid; mp 93–95 °C (recrystallized from
hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 8.03 (d, J = 8.4 Hz, 2 H), 7.71–7.68 (m, 4
H), 7.65–7.62 (m, 4 H), 7.51–7.42 (m, 3 H), 7.34 (d, J = 8.0 Hz, 2 H),
7.21 (d, J = 8.0 Hz, 2 H), 6.38 (s, 1 H), 2.47 (s, 3 H), 2.39 (s, 3 H).
HRMS (ESI): m/z [M + H]+ calcd for C20H16FO6S2: 435.0372; found:
13C NMR (100 MHz, CDCl3): δ = 185.9, 147.3, 146.6, 146.0, 139.4,
132.8, 131.9, 131.8, 130.4 (×2), 130.0 (×2), 129.9 (×4), 129.1 (×2),
128.7, 128.2 (×2), 127.3 (×2), 127.2 (×2), 89.6, 21.9, 21.7.
435.0378.
Benzenesulfonic Acid 1-Benzenesulfonyl-2-biphenyl-4-yl-2-oxo-
ethyl Ester (5m)
HRMS (ESI): m/z [M + H]+ calcd for C28H25O6S2: 521.1093; found:
Yield: 155 mg (63%); colorless solid; mp 176–178 °C (recrystallized
from hexanes and EtOAc).
521.1096.
Toluene-4-Sulfonic Acid 2-Naphthalen-2-yl-2-oxo-1-(toluene-4-
sulfonyl)ethyl Ester (5i)
1H NMR (400 MHz, CDCl3): δ = 8.05–8.02 (m, 2 H), 7.85–7.82 (m, 2 H),
7.78–7.42 (m, 15 H), 6.45 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 185.6, 147.4, 139.4, 135.2, 135.1,
135.0, 134.7, 132.9, 130.4 (×2), 130.1 (×2), 129.34 (×2), 129.28 (×2),
129.1 (×2), 128.7, 128.2 (×2), 127.3 (×4), 89.6.
HRMS (ESI): m/z [M + H]+ calcd for C26H21O6S2: 493.0780; found:
493.0787.
Yield: 163 mg (66%); colorless solid; mp 162–164 °C (recrystallized
from hexanes and EtOAc).
1H NMR (40 MHz, CDCl3): δ = 8.49 (s, 1 H), 7.99 (d, J = 7.6 Hz, 1 H),
7.91–7.87 (m, 3 H), 7.72–7.58 (m, 6 H), 7.34 (d, J = 8.0 Hz, 2 H), 7.13
(d, J = 8.4 Hz, 2 H), 6.49 (s, 1 H), 2.46 (s, 3 H), 2.33 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 186.3, 146.6, 146.0, 136.1, 132.7,
131.9, 131.8, 131.7, 130.2, 130.1 (×2), 129.90 (×2), 129.85 (×2), 129.8,
129.6, 128.5, 128.2 (×2), 127.8, 127.1, 124.2, 89.8, 21.8, 21.6.
Methanesulfonic Acid 1-Methanesulfonyl-2-oxo-2-phenylethyl
Ester (5n)
HRMS (ESI): m/z [M + H]+ calcd for C26H23O6S2: 495.0936; found:
495.0932.
Yield: 82 mg (56%); colorless solid; mp 184–186 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 8.08–8.05 (m, 2 H), 7.72–7.67 (m, 1 H),
Toluene-4-sulfonic Acid 2-(3,4-Dichlorophenyl)-2-oxo-1-(toluene-
4-sulfonyl)ethyl Ester (5j)
7.58–7.53 (m, 2 H), 6.56 (s, 1 H), 3.31 (s, 3 H), 3.08 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 187.3, 135.4, 129.8 (×2), 129.6, 129.1
Yield: 172 mg (67%); colorless solid; mp 174–176 °C (recrystallized
from hexanes and EtOAc).
1H NMR (40 MHz, CDCl3): δ = 7.90 (d, J = 2.0 Hz, 1 H), 7.85 (dd, J = 2.0,
8.4 Hz, 1 H), 7.70 (d, J = 8.0 Hz, 2 H), 7.58 (d, J = 8.4 Hz, 2 H), 7.56 (d,
J = 8.4 Hz, 1 H), 7.35 (d, J = 8.0 Hz, 2 H), 7.22 (d, J = 8.4 Hz, 2 H), 6.13 (s,
1 H), 2.48 (s, 3 H), 2.42 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 185.2, 146.9, 146.4, 139.4, 133.5,
131.59, 131.56, 131.4, 130.7, 130.1 (×2), 130.0 (×4), 129.9, 129.0,
128.2 (×2), 90.3, 21.9, 21.7.
(×2), 87.0, 40.0, 37.7.
HRMS (ESI): m/z [M + H]+ calcd for C10H13O6S2: 293.0154; found:
293.0155.
Methanesulfonic Acid 1-Methanesulfonyl-2-(4-methoxyphenyl)-
2-oxoethyl Ester (5o)
Yield: 72 mg (45%); colorless solid; mp 196–198 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 8.05 (d, J = 9.2 Hz, 2 H), 7.01 (d, J = 8.8
Hz, 2 H), 6.52 (s, 1 H), 3.91 (s, 3 H), 3.30 (s, 3 H), 3.07 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 185.0, 165.6, 132.5 (×2), 126.5, 114.5
HRMS (ESI): m/z [M + H]+ calcd for C22H19Cl2O6S2: 513.0000; found:
513.0002.
(×2), 114.3, 87.0, 55.7, 40.0, 37.7.
HRMS (ESI): m/z [M + H]+ calcd for C11H15O7S2: 323.0259; found:
323.0261.
Benzenesulfonic Acid 1-Benzenesulfonyl-2-oxo-2-phenylethyl Es-
ter (5k)5e
Yield: 150 mg (72%); colorless solid; mp 166–168 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.96–7.93 (m, 2 H), 7.83–7.80 (m, 2 H),
Methanesulfonic Acid 1-Methanesulfonyl-2-oxo-2-p-tolylethyl Es-
ter (5p)
7.76–7.70 (m, 3 H), 7.66–7.41 (m, 8 H), 6.42 (s, 1 H).
Yield: 110 mg (72%); colorless solid; mp 167–169 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.96 (d, J = 8.0 Hz, 2 H), 7.34 (d, J = 8.0
Hz, 2 H), 6.55 (s, 1 H), 3.30 (s, 3 H), 3.06 (s, 3 H), 2.45 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 186.6, 147.0, 131.7, 129.9 (×2), 129.8
13C NMR (100 MHz, CDCl3): δ = 186.2, 135.2, 134.89, 134.87, 134.7
(×2), 134.2, 130.0 (×2), 129.8 (×2), 129.33 (×2), 129.25 (×2), 128.7 (×2),
128.1 (×2), 89.4.
HRMS (ESI): m/z [M + H]+ calcd for C20H17O6S2: 417.0467; found:
417.0463.
(×2), 87.0, 40.0, 37.7, 21.9.
HRMS (ESI): m/z [M + H]+ calcd for C11H15O6S2: 307.0310; found:
307.0315.
Benzenesulfonic Acid 1-Benzenesulfonyl-2-(4-fluorophenyl)-2-
oxoethyl Ester (5l)
Yield: 161 mg (74%); colorless solid; mp 145–147 °C (recrystallized
from hexanes and EtOAc).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

J
C.-K. Chan et al.
Paper
Synthesis
Methanesulfonic Acid 2-Biphenyl-4-yl-1-methanesulfonyl-2-oxo-
ethyl Ester (5q)
4-Ethylbenzenesulfonic Acid 1-(4-Ethylbenzenesulfonyl)-2-oxo-2-
phenylethyl Ester (5u)
Yield: 123 mg (67%); colorless solid; mp 176–178 °C (recrystallized
from hexanes and EtOAc).
Yield: 172 mg (73%); colorless solid; mp 138–140 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 8.14 (d, J = 8.4 Hz, 2 H), 7.77 (d, J = 8.4
Hz, 2 H), 7.65–7.63 (m, 2 H), 7.51–7.42 (m, 3 H), 6.60 (s, 1 H), 3.33 (s, 3
H), 3.10 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 186.7, 148.2, 139.2, 132.7, 130.4 (×2),
129.1, 128.8 (×2), 127.7 (×2), 127.4 (×2), 87.1, 40.0, 37.7.
1H NMR (400 MHz, CDCl3): δ = 7.94–7.91 (m, 2 H), 7.71 (d, J = 8.4 Hz, 2
H), 7.65–7.60 (m, 3 H), 7.48–7.44 (m, 2 H), 7.36 (d, J = 8.4 Hz, 2 H),
7.22 (d, J = 8.4 Hz, 2 H), 6.35 (s, 1 H), 2.76 (q, J = 7.6 Hz, 2 H), 2.68 (q,
J = 7.6 Hz, 2 H), 1.29 (t, J = 7.6 Hz, 3 H), 1.22 (d, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 186.6, 152.6, 152.1, 134.5, 134.3,
131.9, 130.2 (×2), 129.8 (×2), 128.8 (×2), 128.74 (×3), 128.65 (×2),
128.4 (×2), 89.5, 29.0, 28.9, 14.92, 14.86.
HRMS (ESI): m/z [M + H]+ calcd for C16H17O6S2: 369.0467; found:
369.0462.
HRMS (ESI): m/z [M + H]+ calcd for C24H25O6S2: 473.1093; found:
473.1096.
Toluene-3-sulfonic Acid 2-Oxo-2-phenyl-1-(toluene-3-sulfo-
nyl)ethyl Ester (5r)
4-Isopropylbenzenesulfonic Acid 1-(4-Isopropylbenzenesulfonyl)-
2-oxo-2-phenylethyl Ester (5v)
Yield: 155 mg (70%); colorless solid; mp 112–114 °C (recrystallized
from hexanes and EtOAc).
Yield: 180 mg (72%); colorless solid; mp 114–116 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.96–7.94 (m, 2 H), 7.65–7.61 (m, 3 H),
7.53–7.37 (m, 7 H), 7.30 (d, J = 7.6 Hz, 1 H), 6.35 (s, 1 H), 2.41 (s, 3 H),
2.29 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 186.3, 139.8, 139.6, 136.0, 135.5,
134.7, 134.63, 134.57, 134.3, 130.2, 129.8 (×2), 129.13, 129.06, 128.7
(×2), 128.4, 127.2, 125.2, 89.7, 21.3, 21.1.
1H NMR (400 MHz, CDCl3): δ = 7.91–7.89 (m, 2 H), 7.73 (d, J = 8.4 Hz, 2
H), 7.64 (d, J = 8.4 Hz, 2 H), 7.63–7.59 (m, 1 H), 7.47–7.43 (m, 2 H),
7.39 (d, J = 8.4 Hz, 2 H), 7.24 (d, J = 8.4 Hz, 2 H), 6.35 (s, 1 H), 3.05–2.96
(m, 1 H), 2.96–2.89 (m, 1 H), 1.29 (d, J = 7.2 Hz, 6 H), 1.22 (d, J = 7.2 Hz,
6 H).
13C NMR (100 MHz, CDCl3): δ = 186.6, 157.1, 156.9, 134.51, 134.47,
132.0, 130.3 (×2), 129.7 (×2), 128.7 (×2), 128.5, 128.4 (×2), 127.4 (×4),
89.6, 34.4, 34.3, 23.53 (×2), 23.48 (×2).
HRMS (ESI): m/z [M + H]+ calcd for C22H21O6S2: 445.0780; found:
445.0783.
4-Fluorobenzenesulfonic Acid 1-(4-Fluorobenzenesulfonyl)-2-
oxo-2-phenylethyl Ester (5s)
HRMS (ESI): m/z [M + H]+ calcd for C26H29O6S2: 501.1406; found:
501.1412.
Yield: 163 mg (72%); colorless solid; mp 218–220 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.96–7.93 (m, 2 H), 7.83–7.78 (m, 3 H),
7.69–7.65 (m, 2 H), 7.53–7.49 (m, 2 H), 7.25–7.21 (m, 2 H), 7.15–7.11
(m, 2 H), 6.47 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 186.1, 135.5, 135.1 (d, J = 3.6 Hz),
134.2 (d, J = 3.0 Hz), 133.2 (d, J = 10.6 Hz, ×2), 131.2 (d, J = 9.9 Hz, ×2),
130.3 (d, J = 3.0 Hz), 129.7 (×2), 129.1, 129.0, 128.9 (×2), 116.8 (d,
J = 22.7 Hz, ×2), 116.8 (d, J = 22.7 Hz, ×2), 89.1.
4-n-Butylbenzenesulfonic Acid 1-(4-n-Butylbenzenesulfonyl)-2-
oxo-2-phenylethyl Ester (5w)
Yield: 195 mg (74%); colorless solid; mp 95–96 °C (recrystallized from
hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.93–7.91 (m, 2 H), 7.71 (d, J = 8.4 Hz, 2
H), 7.62 (d, J = 8.0 Hz, 2 H), 7.62–7.60 (m, 1 H), 7.48–7.44 (m, 2 H),
7.34 (d, J = 8.0 Hz, 2 H), 7.20 (d, J = 8.4 Hz, 2 H), 6.35 (s, 1 H), 2.71 (t,
J = 7.6 Hz, 2 H), 2.63 (t, J = 7.6 Hz, 2 H), 1.67–1.52 (m, 4 H), 1.42–1.27
(m, 4 H), 0.95 (t, J = 7.6 Hz, 3 H), 0.93 (t, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 186.5, 151.4, 150.9, 134.5, 134.3,
131.94, 131.91, 130.1 (×2), 129.8 (×2), 129.3 (×4), 128.6 (×2), 128.3
(×2), 89.5, 35.8, 35.6, 33.0 (×2), 22.3, 22.2, 13.84, 13.81.
HRMS (ESI): m/z [M + H]+ calcd for C20H15F2O6S2: 453.0278; found:
453.0277.
4-Methoxybenzenesulfonic Acid 1-(4-Methoxybenzenesulfonyl)-
2-oxo-2-phenylethyl Ester (5t)
HRMS (ESI): m/z [M + H]+ calcd for C28H33O6S2: 529.1719; found:
529.1723.
Yield: 19 mg (8%); colorless solid; mp 166–168 °C (recrystallized from
hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.94–7.92 (m, 2 H), 7.74–7.72 (m, 2 H),
7.68–7.61 (m, 3 H), 7.52–7.46 (m, 3 H), 7.39–7.35 (m, 1 H), 6.98–6.94
(m, 2 H), 6.13 (s, 1 H), 3.90 (s, 6 H).
13C NMR (100 MHz, CDCl3): δ = 186.9, 164.8, 163.9, 135.1, 134.5,
133.3, 132.3 (×2), 129.8 (×2), 129.1 (×2), 128.8 (×2), 127.0 (×2), 126.0,
114.4 (×2), 74.5, 55.7 (×2).
4-tert-Butylbenzenesulfonic Acid 1-(4-tert-Butylbenzenesulfo-
nyl)-2-oxo-2-phenylethyl Ester (5x)
Yield: 200 mg (76%); colorless solid; mp 154–156 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 7.90–7.88 (m, 2 H), 7.74 (d, J = 8.8 Hz, 2
H), 7.64 (d, J = 8.0 Hz, 2 H), 7.62–7.58 (m, 1 H), 7.56 (d, J = 8.4 Hz, 2 H),
7.45–7.41 (m, 2 H), 7.39 (d, J = 8.8 Hz, 2 H), 6.36 (s, 1 H), 1.36 (s, 9 H),
1.28 (s, 9 H).
HRMS (ESI): m/z [M + H]+ calcd for C22H21O8S2: 477.0678; found:
477.0684.
Single-crystal X-ray analysis: Slow diffusion of EtOAc into a solution
of compound 5t in CH2Cl2 yielded colorless prisms. The compound
crystallizes in the monoclinic crystal system, space group P21/c,
a = 5.7476(7) Å, b = 18.106(2) Å, c = 20.945(3) Å, V = 2167.4(5) Å3,
Z = 4, dcalcd = 1.460 mg/cm3, F(000) = 992, 2θ range 1.490–26.616°; R
indices (all data): R1 = 0.1974, wR2 = 0.3067.
13C NMR (100 MHz, CDCl3): δ = 186.6, 159.4, 158.9, 134.5, 134.3,
131.8, 131.6, 130.0 (×2), 129.7 (×2), 128.6 (×2), 128.1 (×2), 126.29
(×2), 126.27 (×2), 89.6, 35.4, 35.3, 31.0 (×3), 30.9 (×3).
HRMS (ESI): m/z [M + H]+ calcd for C28H33O6S2: 529.1719; found:
529.1724.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

K
C.-K. Chan et al.
Paper
Synthesis
n-Butane-1-sulfonic Acid 1-(Butane-1-sulfonyl)-2-oxo-2-phenyl-
2-Iodo-1-phenyl-2-(toluene-4-sulfonyl)ethanone (6c)15
ethyl Ester (5y)
Yield: 44 mg (22%); colorless solid; mp 150–152 °C (recrystallized
from hexanes and EtOAc).
Yield: 23 mg (12%); colorless gum.
1H NMR (400 MHz, CDCl3): δ = 8.07–8.05 (m, 2 H), 7.69–7.66 (m, 2 H),
7.56–7.53 (m, 1 H), 6.54 (s, 1 H), 3.54 (t, J = 8.0 Hz, 2 H), 3.36 (t, J = 7.6
Hz, 2 H), 1.95–1.91 (m, 2 H), 1.91–1.85 (m, 2 H), 1.54–1.40 (m, 4 H),
0.99 (t, J = 7.6 Hz, 3 H), 0.96 (t, J = 7.6 Hz, 3 H).
13C NMR (100 MHz, CDCl3): δ = 187.5, 134.5, 133.4, 129.8 (×2), 127.4
(×2), 87.0, 56.6, 52.6, 25.2, 24.7, 21.3, 21.3, 13.4, 13.3.
1H NMR (400 MHz, CDCl3): δ = 7.92–7.87 (m, 4 H), 7.64–7.60 (m, 1 H),
7.49–7.45 (m, 2 H), 7.34 (d, J = 8.0 Hz, 2 H), 6.52 (s, 1 H), 2.44 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 188.2, 146.1, 134.5, 133.6, 132.2,
130.9 (×2), 129.5 (×2), 129.2 (×2), 129.0 (×2), 37.8, 21.8.
HRMS (ESI): m/z [M + H]+ calcd for C15H14IO3S: 400.9708; found:
400.9715.
HRMS (ESI): m/z [M + H]+ calcd for C16H25O6S2: 377.1093; found:
Benzoic Acid 2-Oxo-2-phenylethyl Ester (9)16
377.1098.
Cu(OAc)2 (220 mg, 1.2 mmol) was added to a solution of 7a (250 mg,
1.0 mmol) in MeNO2 (5 mL) at r.t. The reaction mixture was stirred at
r.t. for 10 min and then at reflux for 20 h. The reaction mixture was
cooled to r.t. and the solvent was concentrated. The residue was dilut-
ed 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 evaporated under reduced pressure to afford the
crude product. Purification on silica gel (hexanes/EtOAc = 8:1 to 4:1)
afforded 9.
α-Halo-β-Ketosulfones 6a–c; General Procedure
CuCl2 (80 mg, 0.6 mmol), CuBr2 (134 mg, 0.6 mmol) or CuI (114 mg,
0.6 mmol) was added to a solution of 4a (150 mg, 0.5 mmol) in Me-
NO2 (5 mL) at r.t. The reaction mixture was stirred at r.t. for 10 min
and then at reflux for 20 h. The reaction mixture was cooled to r.t. and
the solvent was concentrated. The residue was diluted with H2O (10
mL) and the mixture was extracted with CH2Cl2 (3 × 20 mL). The com-
bined organic layers were washed with brine, dried, filtered and
evaporated under reduced pressure to afford the crude product. Puri-
fication on silica gel (hexanes/EtOAc = 8:1 to 4:1) afforded com-
pounds 6a–c.
Yield: 42 mg (35%); colorless solid; mp 118–120 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 8.17–8.14 (m, 2 H), 7.99–7.96 (m, 2 H),
7.65–7.58 (m, 2 H), 7.53–7.45 (m, 4 H), 5.58 (s, 2 H).
13C NMR (100 MHz, CDCl3): δ = 192.1, 166.0, 134.3, 133.9, 133.3,
130.0 (×2), 129.4, 128.9 (×2), 128.4 (×2), 127.8 (×2), 66.4.
HRMS (ESI): m/z [M + H]+ calcd for C15H13O3: 241.0865; found:
2-Chloro-1-phenyl-2-(toluene-4-sulfonyl)ethanone (6a)15
Yield: 94 mg (61%); colorless solid; mp 136–138 °C (recrystallized
from hexanes and EtOAc).
1H NMR (400 MHz, CDCl3): δ = 8.04 (d, J = 8.0 Hz, 2 H), 7.78 (d, J = 8.4
Hz, 2 H), 7.70–7.66 (m, 1 H), 7.56–7.52 (m, 2 H), 7.38 (d, J = 8.0 Hz, 2
H), 6.19 (s, 1 H), 2.48 (s, 3 H).
13C NMR (100 MHz, CDCl3): δ = 186.4, 146.6, 134.8, 134.6, 131.2,
130.8 (×2), 129.68 (×2), 129.65 (×2), 129.0 (×2), 72.0, 21.8.
241.0866.
Single-crystal X-ray analysis: Slow diffusion of EtOAc into a solution
of compound 9 in CH2Cl2 yielded colorless prisms. The compound
crystallizes in the monoclinic crystal system, space group P21/c,
a = 9.0669(3) Å, b = 14.1271(5) Å, c = 9.6077(3) Å, V = 1230.53(7) Å3,
Z = 4, dcalcd = 1.297 mg/cm3, F(000) = 504, 2θ range 2.246–26.418°; R
indices (all data): R1 = 0.0683, wR2 = 0.1854.
HRMS (ESI): m/z [M + H]+ calcd for C15H14ClO3S: 309.0352; found:
309.0356.
Single-crystal X-ray analysis: Slow diffusion of EtOAc into a solution
of compound 6a in CH2Cl2 yielded colorless prisms. The compound
crystallizes in the monoclinic crystal system, space group P21/c,
a = 14.5323(19) Å, b = 9.7603(13) Å, c = 10.0176(15) Å, V = 1379.6(3)
Å3, Z = 4, dcalcd = 1.487 mg/cm3, F(000) = 640, 2θ range 1.443–25.274°;
R indices (all data): R1 = 0.0523, wR2 = 0.1110.
Acknowledgment
The authors would like to thank the Ministry of Science and Technol-
ogy of the Republic of China for financial support (MOST 105-2113-
M-037-001).
2-Bromo-1-phenyl-2-(toluene-4-sulfonyl)ethanone (6b)15
Yield: 90 mg (51%); colorless solid; mp 163–165 °C (recrystallized
from hexanes and EtOAc).
Supporting Information
1H NMR (400 MHz, CDCl3): δ = 7.99 (d, J = 8.4 Hz, 2 H), 7.84 (d, J = 8.0
Hz, 2 H), 7.67–7.63 (m, 1 H), 7.53–7.49 (m, 2 H), 7.37 (d, J = 8.4 Hz, 2
H), 6.23 (s, 1 H), 2.46 (s, 3 H).
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0036-1588162.
S
u
p
p
ortiInfogrmoaitn
S
u
p
p
o
nrtogI
f
rmoaitn
13C NMR (100 MHz, CDCl3): δ = 186.7, 146.4, 134.7, 134.3, 131.8,
130.9 (×2), 129.52 (×2), 129.48 (×2), 129.0 (×2), 60.1, 21.8.
References
HRMS (ESI): m/z [M + H]+ calcd for C15H14BrO3S: 352.9847; found:
352.9852.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L

L
C.-K. Chan et al.
Paper
Synthesis
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plementary crystallographic 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.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2017, 49, A–L