Asymmetric Synthesis of Chiral Sulfoximines via the S-Arylation of Sulfinamides

Article abstract of DOI:10.1021/jacs.9b11298

Optically active sulfoximines are a promising substance in medicinal chemistry. However, a methodology for preparing chiral sulfoximines in a stereoselective manner has been underdeveloped. Here, we report an asymmetric synthesis of chiral sulfoximines having an aryl group by the newly developed sulfur-selective arylation of easily accessible chiral sulfinamides. The utility of the present method is demonstrated by the asymmetric synthesis of a key intermediate of a COX-2 inhibitor.

Full text of DOI:10.1021/jacs.9b11298

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Communication
Asymmetric synthesis of chiral sulfoximines
via the S-arylation of sulfinamides
Yusuke Aota, Taichi Kano, and Keiji Maruoka
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b11298 • Publication Date (Web): 18 Nov 2019
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Journal of the American Chemical Society
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Asymmetric synthesis of chiral sulfoximines via the S-arylation of
sulfinamides
Yusuke Aota,† Taichi Kano*,†, and Keiji Maruoka*,†,‡,§
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†Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo, Kyoto 606-8502, Japan
‡Laboratory of Organocatalyst Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo, Kyoto
606-8501, Japan
§School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China
Supporting Information Placeholder
ABSTRACT: Optically active sulfoximines are a promising
substance in medicinal chemistry. However, a methodology for
preparing chiral sulfoximines in a stereoselective manner has been
underdeveloped. Here, we report an asymmetric synthesis of chiral
sulfoximines having an aryl group by the newly developed sulfur-
selective arylation of easily accessible chiral sulfinamides. The
utility of the present method is demonstrated by the asymmetric
synthesis of a key intermediate of a COX-2 inhibitor.
a. Previous methods
O
S
R1
R2
imidation path A
NR3
oxidation
S
R1
R2 path B
O
S
O
NR3
S-alkylation
S
R1
NHR3
R1
R2
kinetic
resolution
path E
O
S
+ R2-X
sulfoximine
R1
R1
R2
path C
desymmetrization path D
O
S
NH
Sulfoximines contain a hexavalent sulfur atom having one oxygen,
one nitrogen and two carbon substituents.1 Their sulfur atom is
stereogenic center in the case where the two carbon substituents are
not identical. Since chiral sulfoximines have distinctive properties
such as a basic nitrogen atom and high solubility in polar solvents,
they have recently been considered as promising bioisosteres in
medicinal chemistry.2 Some examples of bioactive sulfoximines
are shown in Figure 1.3 In general, the stereochemistry at the sulfur
atom largely affects their biological activity. Accordingly, the
development of a new methodology for a stereoselective synthesis
of chiral sulfoximines could significantly accelerate an exploration
of bioactive compounds containing such motifs.
NR3
R1
R2
O
S
R1
b. N-Arylation of sulfinamides
Ar2–X
base
O
S
O
S
R1
R1
NHR3
NR3
Ar2
N-arylation
c. This work
Cu cat.
Ar12IX
base
O
N-X
NR3
Ar1
HN
O
O
O
S
S
S
CF3
O
S
H3C
NHR3
S
t-Bu
N
t-Bu
-arylation
1
2
N
N
O
O
readily available from
commercial sources
Cu cat.
H
Ar22IX
base
acid
or base
CH3
O
S
NR3
Ar2
H3C
OH
BAY 1000394
(pan-CDK inhibitor)
Ar1
S-arylation
4
X = H, Me or CN
O
O
NH
S
Vioxx analog
NHR3
H3C
H3C
Ar1
S
C
3
(COX-2 inhibitor)
H2
H
O
NR3
R4CH2-X
S
S
S-alkylation Ar1
CH2R4
O
S
N
NH
5
H
Vitamine D analog
(CYP24 inhibitor)
Figure 2. Strategies for the stereoselective synthesis of
sulfoximines.
Asymmetric synthesis of chiral sulfoximines mainly relies on a
stereospecific nitrene-transfer reaction to chiral sulfoxides (path A)
as shown in Figure 2a.4,5 Enantiomerically enriched chiral
sulfoximines were also provided through stereospecific oxidation
of enantioenriched sulfimides (path B), kinetic resolution of
racemic sulfoxides or sulfoximines (path C) or desymmetrization
OH
NSC 287474
(reverse transcriptase inhibitor)
HO
Figure 1. Examples of bioactive sulfoximines.
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Journal of the American Chemical Society
Page 2 of 7
of prochiral sulfoximines (path D).6-8 Additionally, we have
Table 1. Optimization of Reaction Conditionsa
1
2
3
4
5
6
7
8
recently developed an asymmetric synthesis of sulfoximines via a
stereospecific S-alkylation of chiral sulfinamides with alkyl halides
(R2-X) (path E).9 By employing this methodology, various dialkyl
sulfoximines can be readily prepared in optically pure form. Chiral
aryl sulfoximines are also important structural motifs in medicinal
chemistry as shown in Figure1. In this context, we have become
interested in the asymmetric synthesis of chiral aryl sulfoximines
in optically pure form through the sulfur atom selective arylation
of chiral sulfinamides. However, to the best of our knowledge, the
arylation at the sulfur atom of sulfinamides has never been
explored, probably because they react at the more nucleophilic
nitrogen atom preferentially (Figure 2b).10 Herein, we report the
first sulfur-selective arylation of sulfinamides. A wide variety of
optically pure sulfoximines can be prepared by the S-arylation of
readily available (R)- or (S)-tert-butanesulfinamide derivative 1
with diaryliodonium salts under Cu catalysis (Scheme 2c).11
Moreover, de-tert-butylation of the obtained chiral sulfoximines 2
with trifluoroacetic acid (TFA) or KOt-Bu enables the asymmetric
synthesis of various chiral aryl sulfinamides 3.12,13 The resulting
sulfinamides 3 were applied to the S-alkylation or the second S-
arylation, affording various optically pure sulfoximines 4 and 5
with predictable stereochemistry.
CuI (10 mol%)
(Ar)PhIX (1.2 equiv)
Base (1.5 equiv)
O
O
S
N
Pg
Ph
2b
Pg
S
N
H
t-Bu
t-Bu
DMSO, 4 Å MS
40 °C, 12 h
1b
(R)-
Pg = pivaloyl
(S)-
entry
1c
(Ar)PhIX
base
yield (%)b
26
Ph2IOTf
Ph2IOTf
Ph2IOTf
Ph2IOTf
Ph2IOTf
Ph2IOTf
Ph2IOTf
Ph2IOTf
Ph2IOTf
Ph2IOTf
Ph2IBF4
(Mes)PhIOTf
Ph2IOTf
Ph2IOTf
Ph2IOTf
i-Pr2NEt
i-Pr2NEt
i-Pr2NEt
2d
3
4
5
6
7
8
9
10
11
12
13e
14f
15f,g
20
55
16
39
86
87
<5
<5
33
85
83
81
94
<5
9
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DTBP
N-Me-pyrrolidine
Cy2NMe
PMP
K2CO3
NaH
NaH+15-crown-5
Cy2NMe
Cy2NMe
Cy2NMe
Cy2NMe
Cy2NMe
Sulfoximines 2 having a tert-butyl group on the sulfur atom are
known to be unstable under highly basic conditions.12c While the
aReactions were performed on a 0.1 mmol scale in 1.0 mL of
DMSO. 4 Å MS were added at a concentration of 1.0 g/mmol.
bYields were determined by 1H NMR analysis using 1,1,2,2-
tetrachloroethane as an internal standard. cDCE as solvent. dMeCN
as solvent. Cu(OTf)2 was used instead of CuI. Performed with
Ph2IOTf (1.5 equiv) and Cy2NMe (1.8 equiv) at 60 °C. Without
nucleophilicity of sulfinamides
1 would be improved by
deprotonation, a strong base cannot be used in the synthesis of 2.
Therefore, a combination of a highly electrophilic aryl species and
a weak base would be suitable to achieve the sulfur-selective
arylation of a sulfinamide. In this context, we began our
investigation by examining the sulfur-selective arylation with a
diaryliodonium salt in the presence of a copper catalyst, because a
highly reactive Cu(III)-Ar species for less reactive nucleophiles can
be generated under mild conditions.14 The steric and electronic
properties of the nitrogen atom of a commercially available (rac)-
tert-butanesulfinamide were tuned by introducing various
protective groups to prevent the preferential N-arylation. In 1,2-
dichloroethane (DCE) at 40 °C, sulfinamide derivatives (rac)-1
were treated with 10 mol% of CuI, Ph2IOTf and i-Pr2NEt, and the
results were shown in Scheme 1. Most protective groups were
ineffective, and no desired S-arylation product was observed
(Scheme 1a). In contrast, the reaction of (rac)-1a bearing an N-
benzoyl group gave the S-arylation product in 33% yield albeit with
low regioselectivity ((rac)-2a/(rac)-6a = 4.1/1) (Scheme 1b).15 To
our delight, replacement of the benzoyl group with a pivaloyl group
resulted in the formation of the S-arylation product (rac)-2b
exclusively. Based on these results, the pivaloyl group was selected
as the protective group of choice for further studies.
e
f
g
Cu catalyst. Mes = mesityl.
To improve the yield of 2b, we then investigated effects of
solvents and bases employing optically pure (R)-1b as a substrate
(Table 1). Molecular sieves (4 Å) were added to the reaction
mixture to prevent an unproductive hydrolysis of the
diaryliodonium salt. Among solvents tested, DMSO was found to
be optimal in terms of yield (entries 1–3). In these cases, the N-
arylation product was not observed, suggesting that use of the
pivaloyl group was crucial for achieving high regioselectivity. Use
of 2,6-di-tert-butylpyridine (DTBP) instead of i-Pr2NEt resulted in
lower conversion of (R)-1b probably because of its low basicity
(entry 4). With the less hindered amine such as N-Me-pyrrolidine,
a diminished yield was observed (entry 5). In contrast, sterically
hindered amines such as Cy2NMe and 1,2,2,6,6-
pentamethylpiperidine (PMP) promoted the desired reaction to give
(S)-2b in high yield (entries 6 and 7). Use of inorganic bases led to
decreased yields (entries 8–10). Similar reactivity was observed,
with other diaryliodonium salts such as Ph2IBF4 and (Mes)PhIOTf
instead of Ph2IOTf (entries 11 and 12). Cu(OTf)2 was also an
effective catalyst for this S-arylation (entry 13). Finally, increasing
the equivalents of the diaryliodonium salt and the amine allowed
the formation of (S)-2b in 94% yield (entry 14). No reaction was
observed in the absence of the copper catalyst (entry 15).
Stereochemistry of (S)-2b was determined by single crystal X-ray
diffraction, suggesting that the configuration at sulfur was retained
during the sulfur–carbon bond formation.
Scheme 1. Effect of protective groups on the S-arylation
a.
CuI (10 mol%)
Ph2IOTf (1.2 equiv)
i-Pr2NEt (1.5 equiv)
O
S
O
S
N
R
R
N
t-Bu
t-Bu
Ph
H
DCE, 40 °C
1
2
(rac)-
(rac)-
<5% yield
R = H, Boc, Bn, Ph2CH, t-Bu
2,4,6-Me3-C6H2, 4-NO2-C6H4
We next investigated the scope of the present S-arylation with a
series of diaryliodonium salts (Table 2). Diaryliodonium salts
bearing an electron-donating methyl or methoxy group at the para-
position afforded the corresponding sulfoximines in good yields
(2c and 2d). Halides such as F and Br at the para-position were
well tolerated, allowing further functionalization by nucleophilic
aromatic substitution reactions or cross-coupling reactions,
respectively (2e and 2f).16 Use of symmetrical diaryliodonium salts
(Ar = Ar´) bearing an electron-withdrawing groups such as CF3,
b.
CuI (10 mol%)
Ph2IOTf (1.2 equiv)
i-Pr2NEt (1.5 equiv)
O
R
O
O
O
S
O
S
O
S
N
+
t-Bu
Ph
R
R
N
N
t-Bu
t-Bu
DCE, 40 °C, 12 h
H
Ph
6a 8%
1a
(rac)- (R = Ph)
2a 33%
(rac)-
(rac)-
(rac)-
(rac)-
1b
(rac)- (R = t-Bu)
2b
16%
6b
0%
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acetyl or an ester group at the para-position gave the products in
amine bases tested, i-Pr2NEt was found to be optimal for the S-
arylation of (S)-3 (details are provided in the Supporting
Information). A range
1
2
3
4
5
6
7
8
low yields (30–43% yields). On the other hand, employing
unsymmetrical diaryliodonium salts bearing one bulky mesityl
ligand (Ar´= Mes) led to improved yields (2g, 2h and 2i). The
decreased yield with symmetrical diaryliodonium salts might be
attributed to the formation of an undesired electron donor−acceptor
(EDA) complex with the amine base or the sulfinamide.17
Substituents at the meta- or ortho-position were also tolerated,
albeit in moderate yield for ortho-methoxy group (2j–2n). Despite
its large steric hindrance, a mesityl group was smoothly introduced
in 74% yield (2o). Diaryliodonium salts having a 3-thiophenyl or
1-naphthyl substituent were found to be suitable substrates, giving
S-arylation products (2p and 2q) in good yields. α,β-Unsaturated
sulfoximine (2r) was also successfully obtained by using iodonium
salt 7. Chiral HPLC analysis revealed that this S-arylation
proceeded stereospecifically without racemization (2c, 2d and 2g).
The practicability of our method was demonstrated with a 6 mmol
scale of reaction, providing 1.38 g of (S)-2b in 82% yield without
racemization.
Scheme 2. De-tert-butylation of (S)-2
Conditions A
CF3CO2H, CH2Cl2
rt, 40 min
O
S
O
S
N
Pg
Pg
N
t-Bu
H
Conditions B
KOt-Bu, DMF
80 °C, 2.5 h
R
R
2
(S)-
3
(S)-
Pg = pivaloyl
9
3b
3c
3g
3d
(R = H)
72% (Conditions A)
10
11
12
13
14
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(R = Me) 87% (Conditions A)
(R = CF3) 85% (Conditions A)
(R = OMe) 85% (Conditions B)
of diaryliodonium salts were applicable to the present method and
the S-arylation of sulfinamide (S)-3c (Ar1 = 4-methylphenyl)
proceeded smoothly, affording the corresponding sulfoximines
(4a–4i) in optically pure form. Notably, this method enables
asymmetric synthesis of diaryl sulfoximines ((S)-4a) bearing
sterically and electronically similar two aryl groups on the sulfur
atom. The electron-rich para-methoxyphenyl group was readily
introduced ((R)-4b). Use of diaryliodonium salts having the
electron-withdrawing trifluoromethyl or ester group at the para-
position resulted in good yields of (R)-4c and (R)-4d. Our method
is compatible with the synthesis of a diaryl sulfoximine ((R)-4e)
with a haloalkyl group, providing a platform for further
functionalization. Methyl group at the ortho- or meta-position was
also tolerated ((R)-4f and (R)-4g). Other aryl sulfinamides bearing
phenyl, 4-methoxyphenyl or 4-trifluoromethylphenyl group were
also applicable to the present method, and reactions with (Mes)(4-
Me-C6H4)IOTf afforded the corresponding sulfoximines ((R)-4a,
(S)-4b and (S)-4c) in optically pure form, respectively.
Accordingly, a sequence consisting of the first S-arylation, de-tert-
butylation and the second S-arylation was successfully applied to
transform (R)-1b into various chiral diaryl sulfoximines, and either
enantiomer can be formed by employing two diaryliodonium salts
in reverse order.
Table 2. S-Arylation of (R)-1ba
CuI (10 mol%)
(Ar')ArIX (1.5 equiv)
Cy2NMe (1.8 equiv)
O
S
O
S
N
Pg
Ar
Pg
N
H
1b
t-Bu
t-Bu
DMSO, 4 Å MS
60 °C, 24 h
2
(S)-
(R)-
Pg = pivaloyl
2b R = H
90%b
2c R = Me 88%c,f 2g R = CF3
2f R = Br
76%b
85%c,f
2d R = OMe 87%d,f 2h R = COMe 78%c
2e R = F
R
R
85%d
2i R = CO2Et 90%c
Me
2j R = Me 72%d
2k R = OMe 81%d
2l R = CF3 88%c
Me
Me
2o 74%b
R
2m R = Me 90%d
2n R = OMe 53%d
S
Table 3. S-Arylation of (S)-3a
c
2p
61%
Cu(OTf)2 (10 mol%)
OTf
Me
(Ar')Ar2IX (1.5 equiv)
O
I
Ph
O
N
Pg
Ar1
Ph
Pg
i-Pr2NEt (1.8 equiv)
S
Ar1
S
N
Ar2
H
DMSO, 4 Å MS
60 °C, 24 h
7
d
2q
2r
72%
(R)-
76%e
3
4
(S)-
Pg = pivaloyl
aReactions were performed on a 0.1 mmol scale in 1.0 mL of
DMSO. bAr2IOTf as (Ar')ArIX. c(Mes)ArIOTf as (Ar')ArIX.
dAr2IBF4 as (Ar')ArIX. eUse of 7 instead of (Ar')ArIX. Performed
for 48 h. fNo racemization was confirmed by chiral HPLC.
(S)-
(R)-
(R)-
(R)-
(R)-
(R)-
(R)-
R = H
82%b,e
73%c,e
78%d,e
4a
O
N
Pg
4b
4c
4d
4e
4f
R = 4-OMe
S
S
R = 4-CF3
R = 4-CO2Et 90%d
R = 4-(CH2)3Cl 79%d
R
Having demonstrated the S-arylation of (R)-1b on a range of
diaryliodonium salts, we then explored de-tert-butylation of the
arylation products (Scheme 2). De-tert-butylation of sulfoximines
bearing phenyl, 4-methylphenyl or 4-trifluoromethylphenyl groups
was carried out in the presence of TFA, and the corresponding
sulfinamides (3b, 3c and 3g) were produced in high yield
stereospecifically without racemization. On the other hand, the
sulfoximine bearing an electron-rich 4-methoxyphenyl group was
partially decomposed and racemized under above conditions.18 To
circumvent these undesired reactions, de-tert-butylation under
basic conditions was examined, and treatment with KOt-Bu was
found to give the corresponding product (3d) in high yield without
racemization.
Me
Me
R = 2-Me
R = 3-Me
84%c
86%c
4g
Me
O
N
Pg
O
S
N
Pg
Me
Me
Me
b
c
4h
(R)- 87%
4i
(R)- 68%
O
S
N Pg
4a
4b
4c
(R)-
R = H
91%d,e
R = OMe 89%d,e
R = CF3 86%d,e
(S)-
(S)-
With these sulfinamides (S)-3 having an aromatic group on the
sulfur atom, we then investigated the asymmetric synthesis of
chiral diaryl sulfoximines via the S-arylation (Table 3). Among
R
Me
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aReactions were performed on a 0.1 mmol scale in 1.0 mL of
1
2
3
DMSO. bAr2 IOTf as (Ar')Ar2IX. cAr2 IBF4 as (Ar')Ar2IX.
2 2
d(Mes)Ar2IOTf as (Ar')Ar2IX. eNo racemization was confirmed by
chiral HPLC.
4
5
6
7
8
9
Scheme 5. Asymmetric synthesis of VioxxⓇ analog
By using a combination of the present S-arylation and our
previously reported S-alkylation,9 a variety of chiral sulfoximines
bearing both aryl and alkyl groups can be prepared in essentially
complete optical purity (Scheme 3). (S)-p-Toluenesulfinamide (S)-
3c was prepared by the S-arylation of (R)-tert-butanesulfinamide
(R)-1b and the following TFA-mediated de-tert-butylation. The S-
alkylation of the resulting sulfinamide (S)-3c with ethyl iodide gave
(S)-sulfoximine (S)-5.9 Remarkably, the application of the same
chiral source (R)-1b to the S-alkylation and the subsequent S-
arylation allowed the formation of the opposite enantiomer (R)-5.
This result suggests that the present S-arylation is also applicable
to sulfinamides with an alkyl group other than the tert-butyl group.
Cu(OTf)2
(Mes)ArIOTf
O
O
N
Pg
PMP
Pg
S
S
N
H
11
Me
DMSO, 4 Å MS
40 °C, 20 h
Me
Ar
12
(S)-
(R)-
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
74%
Pg = pivaloyl
Ar = 4-Ac-C6H4
DMAP
BrCN
O
NH
O
N-CN
50% KOH aq.
S
S
THF-MeOH Me
rt, 12 h
Ar
CH2Cl2
rt, 14 h
Me
Me
13
14
(R)-
(R)-
75%
73%
O
O
N-CN
Scheme 3. Access to both enantiomers of sulfoximine 5 from the
same chiral source
S
Me
Vioxx analog
CuI
(COX-2 inhibitor)
O
O
(Mes)ArIOTf
Cy2NMe
Et-I, NaH
15-crown-5
ref 3a
O
S
O
S
N Pg
O
S
N Pg
Et
TFA
Pg
Ar
N
15
(R)-
t-Bu
Ar
Ar
DMSO
CH2Cl2
rt, 1 h
ref 9
H
60 °C, 24 h
2c
3c
5
(S)-
(S)-
(S)-
88%
87%
91%
1b
(R)-
In summary, we have developed an unprecedented S-arylation of
the chiral sulfinamide derivatives having an alkyl or an aryl group
by using the combination of the Cu(I) catalyst and diaryliodonium
salts. Various chiral aryl sulfinamides are also obtained by the
present arylation of tert-butanesulfinamide derivative, followed by
de-tert-butylation under acidic or basic conditions. Additionally,
the asymmetric synthesis of diaryl sulfoximines having sterically
and electronically similar two aryl groups are also achieved by the
second S-arylation of the obtained sulfinamides. By employing our
present method, various chiral sulfoximines, including biologically
active one, can be readily synthesized in optically pure form
without an optical resolution.
Cu(OTf)2
(Mes)ArIOTf
Cy2NMe
Et-I, NaH
15-crown-5
O
O
N Pg
O N Pg
TFA
Et ref 9
S
S
N
H
(S)-
Pg
S
Et
ref 9
t-Bu
DMSO Et
40 °C, 24 h
Ar
8
9
5
(R)-
Pg = pivaloyl
(R)-
Ar = 4-Me-C6H4
95%
81%
85%
While the deprotection of the pivaloyl group can be achieved by
hydrolysis under acidic or basic conditions, the competing de-tert-
butylation of sulfoximines readily occurs.12 On the other hand,
treatment of sulfoximine (S)-2c with LiAlH4 was found to give the
N-unprotected sulfoximine (S)-10 in high yield without loss of tert-
butyl group on the sulfur atom (Scheme 4).9
ASSOCIATED CONTENT
Scheme 4. Removal of the pivaloyl group with LiAlH4
Supporting Information
The Supporting Information is available free of charge on the ACS
Publications
Experimental procedures and spectral data (PDF)
O
S
N
Pg
O NH
LiAlH4 (3 equiv)
website.
S
t-Bu
(S)-
Ar
t-Bu
(S)-
81%
Ar
THF, 0 °C, 20 min
2c
10
Pg = pivaloyl
AUTHOR INFORMATION
Ar = 4-Me-C6H4
Corresponding Author
To demonstrate the synthetic utility of the present S-arylation,
the asymmetric synthesis of VioxxⓇ analog (R)-15 was conducted
(Scheme 5). Sulfoximine (rac)-15 has a COX inhibitory activity
with high COX-2 selectivity.3a,3b Generally, the biological activity
of chiral sulfoximines is significantly affected by its absolute
configuration. By employing our present method, enantiomerically
pure (R)-15 can be readily synthesized without an optical
resolution. An N-unprotected sulfoximine (R)-13 was prepared by
the S-arylation of sulfinamide (S)-11 and the subsequent basic
hydrolysis.15 An N-cyanation of the obtained sulfoximine (R)-13
provided the known intermediate (R)-14.19 Since racemic 14 was
an intermediate in previous total synthesis of VioxxⓇ analog 15 by
Bolm and co-workers, this work contributes to its formal
asymmetric synthesis.3a
*kano@kuchem.kyoto-u.ac.jp
*maruoka@kuchem.kyoto-u.ac.jp
Notes
The authors declare no competing financial interests.
ACKNOWLEDGMENT
This work was supported by JSPS KAKENHI Grant Numbers
JP17H06450, JP26220803, and JP18H01975. Y.A. is grateful for
Fellowships for Young Scientists from the Japan Society for the
Promotion of Science (JSPS).
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Cu(I)
(Ar')ArIX
amine base
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O N Pg
>>
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R
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N
S-arylation
Ar
readily available
R = alkyl, aryl
Pg = pivaloyl
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