Intramolecular Aminotrifluoromethanesulfinyloxylation of ω-Aminoalkenes by CF 3 so 2 Na/Pd(OAc) 2 /PhI(OAc) 2 / t BuOCl/PivOH System

Article abstract of DOI:10.1055/s-0036-1591720

The first example of palladium-catalyzed intramolecular aminotrifluoromethanesulfinyloxylation of unactivated ω-aminoalkenes has been achieved. Reaction conditions are rather unique with a complex consisting of CF ₃ SO ₂ Na/Pd(OAc) ₂ /PhI(OAc) ₂ / ^t BuOCl/PivOH to provide 6- endo -cyclized type products with a piperidine skeleton. Yields are moderate, and SO ₂ is not extruded. This method also provides the first synthesis of 3-trifluoromethanesulfinyloxy piperidine derivatives.

Full text of DOI:10.1055/s-0036-1591720

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© Georg Thieme Verlag Stuttgart · New York
2017, 28, A–E
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S. Suzuki et al.
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Intramolecular Aminotrifluoromethanesulfinyloxylation of ω-Ami-
noalkenes by CF3SO2Na/Pd(OAc)2/PhI(OAc)2/tBuOCl/PivOH System
Satoru Suzukia
OAc
PdII
R3
CF3SO2Na
Pd cat.
PhI(OAc)2
tBuOCl
R1
R2
CF3
S
Tomohiro Kamoa
Kazunobu Fukushia
Etsuko Tokunagab
R3
R1
R2
O
O
R3
OAc
PdIV
OAc
R4
N
O
CF3
R1
R2
R3
S
R1 R2
0
0
0
0
0-
0
0
3
0-
6
2
1
3-
7
9
8
PivOH
Ts
+
O
TsHN
O
R4
N
Yuji Sumiia
0
0
0
0
0-
0
0
3
3-
9
0
0
1-
0
8
9
R4
N
O
S
R4
1
CH3CN
Ts
3
F3C
Norio Shibata*a,b
0
0
0
0
0-
0
0
2
3-
7
4
2
4-
0
6
4
Ts
S
R1, R2 = H, Ph, Me, alkyl
R3 = H, Me
O
CF3
O
7 examples
up to 60 % yield
a Department of Life Science and Applied Chemistry, Nagoya
Institute of Technology, Gokiso-cho, Showa-ku, Nagoya
466-8555, Japan
6-endo
aminocyclization
R4 = H, Ph, alkyl
trifluoromethanesulfinyloxylation
nozshiba@nitech.ac.jp
b Department of Nanopharmaceutical Sciences, Nagoya
Institute of Technology, Gokiso-cho, Showa-ku, Nagoya
466-8555, Japan
Published as part of the Cluster Alkene Halofunctionalization
Received: 15.09.2017
Accepted after revision: 16.10.2017
Published online: 13.11.2017
there is the potential for the introducing five kinds of fluo-
rinated functional groups, CF3, SO2CF3, OS(O)CF3, S(O)CF3,
and SCF3 using CF3SO2X reagents (Scheme 1).
DOI: 10.1055/s-0036-1591720; Art ID: st-2017-r0691-c
well known
Abstract The first example of palladium-catalyzed intramolecular ami-
notrifluoromethanesulfinyloxylation of unactivated ω-aminoalkenes has
been achieved. Reaction conditions are rather unique with a complex
consisting of CF3SO2Na/Pd(OAc)2/PhI(OAc)2/tBuOCl/PivOH to provide 6-
endo-cyclized type products with a piperidine skeleton. Yields are mod-
erate, and SO2 is not extruded. This method also provides the first syn-
thesis of 3-trifluoromethanesulfinyloxy piperidine derivatives.
CF3-R
known
CF3S-R
known
O
F3C
S
R
CF3-SO2-X
rare
O
O
known
O
F3C
S O R
Key words amination, alkenes, cyclization, fluorine, halogenation,
F3C
S R
sulfur, palladium
Scheme 1 Potential use of CF3SO2X reagents for fluoro-functionalization
The fluoro functionalization of organic molecules often
creates unique properties of parent molecules due to the
high lipophilicity, strong electron negativity, and small size
of the fluorine atom.1 Hence, the development of effective
methods for the introduction of fluorinated functional
groups into target molecules has gained the attention of
synthetic chemists in the fields of pharmaceuticals, agro-
chemicals, and specialty materials.2,3 Considerable efforts
have been expended to install fluorinated functional units
such as trifluoromethyl (CF3)4 and trifluoromethylthio
(SCF3)5 groups. We are interested in the use of reagents, tri-
fluoromethanesulfinate derivatives, CF3SO2X (X = Na, K, and
Cl), and in particular, CF3SO2Na, also known as the Langlois
reagent.6 These reagents are commercially available and are
going to be a popular source for the installation of the CF3
unit, especially under radical conditions.6c,7 In this context,
we envisaged that the use of CF3SO2X as a source of trifluo-
romethanesulfonyl (SO2CF3) or trifluoromethanesulfinyloxy
(OS(O)CF3) instead of the CF3 reagent for direct introduction
into target compounds without extrusion of SO2 is of great
importance to expand the utility of these reagents. Indeed,
As briefly mentioned above, numerous reports of
trifluoromethylation by CF3SO2X have been disclosed in re-
cent years,7 as well as methods to introduce SO2CF3,8
5e,10
S(O)CF3,9 and SCF3
using CF3SO2X. On the other hand,
the direct introduction of the OS(O)CF3 unit using CF3SO2X
has been studied much less than other types of reac-
tions.11,12 In 2014, we reported the iodoarene-catalyzed in-
tramolecular aminofluorination of ω-aminoalkenes 1 using
an ArI/HF·pyridine/mCPBA system to produce six-mem-
bered cyclic amines 2 with a fluorinated stereogenic center.
The reaction proceeds by in situ generation of a hyperva-
lent iodine compound ArIF2 (Scheme 2).13 The asymmetric
version of this reaction was also achieved by using chiral
ArI. As an extension of this catalytic aminofluorocyclization
reaction and our continuous research program focusing on
the synthesis of trifluoromethanesulfonyl compounds (tri-
flone),10a,14 we were interested in the reaction of 1 with
CF3SO2Na. We disclose herein the first example of the intra-
molecular aminotrifluoromethanesulfinyloxylation of lin-
ear ω-aminoalkenes 1 under palladium (Pd) catalysis.
Namely, the treatment of ω-aminoalkenes 1 with CF3SO2Na
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

B
S. Suzuki et al.
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Synlett
under a rather complex catalysis system consisting of the
Pd(II) catalyst, iodobenzene diacetate (PhI(OAc)2, PIDA),
tert-butyl hypochlorite (tBuOCl), and pivalic acid (PivOH) to
furnish previously unknown piperidine derivatives 3 with a
3-trifluoromethanesulfinyloxy (3-OS(O)CF3) substituent in
good yields, instead of expected 3-trifluoromethanesulfo-
nyl (3-SO2CF3) compounds.
for the reaction of aminoalkenes and CF3SO2X and related
reagents,7p,16,17 there is no report on the aminotrifluoro-
methanesulfinyloxylation reaction.
Table 1 Optimization of Reaction Conditions from 1a to 3aa
CF3SO2Na (5.0 equiv)
Pd(OAc)2 (10 mol%)
oxidant (2.0 equiv)
acid (5.0 equiv)
Me
Me
O
CF3
previous work
S
Me Me
additive (1.0 equiv)
R1
TsHN
O
F
HF, mCPBA
PhI (5–15 mol%)
N
R2
R3
solvent
1a
3a
Ts
R4
N
R3
2
Entry Oxidant
Additive
Acid
Solvent
Yield (%)
PG
R1 R2
CF3SO2Na
Pd cat.
PhI(OAc)2
tBuOCl
PivOH
MeCN
PGHN
1
2
PIDA
none
–
–
–
–
–
–
MeCN
MeCN
MeCN
MeCN
0
R4
R3
PIDA
TBHP
0
R1
R2
1
O
CF3
S
3
PIDA
(NH4)2S2O8
tBuOCl
tBuOCl
tBuOCl
tBuOCl
tBuOCl
tBuOCl
tBuOCl
tBuOCl
tBuOCl
tBuOCl
0
O
R4
N
4
PIDA
34
this work
PG
3
5
PIDA
MeCN/H2O (9:1)
MeCN/H2O (1:1)
MeCN
16
Scheme 2 Fluoro aminocyclization (previous work) and trifluorometh-
anesulfinyloxy aminocyclization (this work) of ω-aminoalkenes 1
6
PIDA
28
7
PIDA
PivOH
53
8b
9
PIDA
–
MeCN
trace
trace
33
First, we attempted the reaction using 10 mol% of Pd(II)
acetate (Pd(OAc)2), 2.0 equiv of PIDA, and 5.0 equiv of
CF3SO2Na in acetonitrile (MeCN, Table 1, entry 1). A compli-
cated mixture containing fluorinated compounds was ob-
served based on 19F NMR analysis, presumably due to the
distributions of several trifluoromethylated compounds, in-
cluding CF3, SO2CF3, and OS(O)CF3. We thus examined addi-
tives aimed at preparing a sole product (Table 1, entries 2–
PhI(OPiv)2
PhI(OPiv)2
PIFA
PivOH
PivOH
PivOH
PivOH
PivOH
MeCN
10c
11
12
13d
MeCN
MeCN
38
DDQ
MeCN
trace
60
PhI(OAc)2
MeCN
a Reaction was conducted with 1 (0.1 mmol), CF3SO2Na (5.0 equiv),
PhI(OAc)2 (2.0 equiv), Pd(OAc)2 (10 mol%), PivOH (5.0 equiv), and tBuOCl
(1.0 equiv) in MeCN (0.5 mL) at rt for 15 h under N2.
b CF3SO2K was used instead of CF3SO2Na.
t
4). Interestingly, when BuOCl was used as the additive, 6-
c Reaction was performed at 30 °C.
endo-cyclized trifluoromethanesulfinate 3a was obtained
in 34% yield (Table 1, entry 4). Since the direct synthesis of
trifluoromethanesulfinate using CF3SO2Na is rare,11 we de-
cided to advance the examination of this condition. The use
of mixed solvent with MeCN and water did not improve
yield (Table 1, entries 5 and 6) due to the formation of by-
products such as 3-hydroxy and 3-acetoxy piperidines.15 In
order to stabilize CF3SO2Na by suppressing the extrusion of
SO2, we next added pivalic acid (PivOH) to form CF3SO2H in
situ. Gratifyingly, 3a was obtained with a moderate yield of
53% (Table 1, entry 7). A potassium salt, CF3SO2K, was use-
less (Table 1, entry 8). Other oxidants such as di-(pivaloy-
loxy)iodobenzene (PhI(OPiv)2), [bis(trifluoroacetoxy)io-
do]benzene (PIFA), and 2,3-dichloro-5,6-dicyano-p-benzo-
quinone (DDQ) were also attempted instead of PIDA, but
yields did not improve (Table 1, entries 9–12). Finally, the
reaction was carried out at 10 °C, and at best, the trifluoro-
methanesulfinyloxy compound 3a was obtained in 60%
yield (Table 1, entry 13). Although there are several reports
d Reaction was performed at 10 °C.
With optimized reaction conditions in hand,18 we ex-
amined the generality of ω-aminoalkenes 1 (Table 2). In the
intramolecular
aminotrifluoromethanesulfinyloxylation,
the protecting group of amine strongly influenced reactivi-
ty. 4-Nitrobenzenesulfonyl- (Ns) and Boc-protected ω-ami-
noalkenes 1b,c provided the corresponding cyclized prod-
uct 3b,c in low yields under the same reaction conditions
(Table 2, entries 2 and 3). 2-Monosubstituted ω-aminoke-
tones 1d,e and spiro-ω-aminoalkene 1f were nicely con-
verted into the corresponding six-membered cyclized prod-
ucts 3d–f in 42–53% yields (Table 2, entries 4–6). On the
other hand, highly methyl-substituted vinyl sulfonyl amide
1g decreased reactivity and product 3g was observed in a
trace amount (Table 2, entry 7). The cis-cyclohexyl amine
substrate 1h afforded the trifluoromethanesulfinyloxylated
octahydro quinoline 3h in moderated yield (48%) having a
cis-configuration selectively. On the other hand, the trans-
cyclohexyl amine substrate 1i afforded the trifluorometh-
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

C
S. Suzuki et al.
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Synlett
Table 2 (continued)
anesulfinyloxylated octahydro quinoline 3i in moderated
yield (48%) as a mixture of two isomers. The N-Ts aniline
derivative 1j did not afford the desired product 3j. In all cas-
es, the sulfinates 3, which have a stereocenter on the sulfur
atom, were obtained as inseparable diastereomixtures. It
should be noted that while the synthesis of 3-trifluoro-
Entry
Product 3
Yield (%)
48c
dr
O
CF3
S
3i 55:45
3i′ 55:45
O
9
N
3i (trans: major)
3i' (cis: minor)
Ts
methanesulfonyloxypiperidines
(3-OSO2CF3-piperidines)
has been reported,19 3-trifluoromethanesulfinyloxy piperi-
dines such as 3 have never appeared in the literature. This is
the first example of their synthesis.
O
CF3
S
10
O
trace
ND
N
3j
Ts
a Reaction was conducted with 1 (0.1 mmol), CF3SO2Na (5.0 equiv),
PhI(OAc)2 (2.0 equiv), Pd(OAc)2 (10 mol%), PivOH (5.0 equiv), tBuOCl (1.0
equiv) in MeCN (0.5 mL) at rt for 15 h under N2.
b cis/trans = 4:1.
Table 2 Substrate Scope of ω-Aminoalkenes 1a
CF3SO2Na (5.0 equiv)
Pd(OAc)2 (10 mol%)
R3
c cis/trans = 1:2.7.
R1
R2
O
CF3
PIDA (2.0 equiv)
tBuOCl (1.0 equiv)
PivOH (5.0 equiv)
R3
R1 R2
S
O
TsHN
R4
Yield (%)
60
N
All of the structures obtained for 3 were assigned by 1H
NMR, 19F NMR, 13C NMR spectroscopy and HRMS. They
were also rigorously characterized by comparison to spec-
tral data of reported hydroxylated product 4a15 after hydro-
lysis of 3a using 0.1 M NaOH in MeOH at room temperature
for 18 h. The hydrolysis of 3 was also carried out for three
more compounds 3e, 3e′, and 3h to show the generality to
furnish 4e, 4e′, and 4h15 in good yields.
R4
3
Ts
1
MeCN
Entry
Product 3
dr
Me
Me
O
O
CF3
S
1
2
3
4
5
54:46
56:44
ND
O
N
3a
Ts
Me
Me
CF3
Table 3 Base Hydrolysis of Sulfinates
S
7
O
R1
R2
R1
R2
N
O
CF3
OH
S
3b
Ns
0.1 M aq NaOH (3.5 equiv)
MeOH (0.1 M), rt
O
R3
N
R3
N
Me
Me
3
4
O
CF3
S
Ts
Ts
trace
42
O
N
Entry
1
Sulfinate
Product
Yield (%)
60
3c
Boc
Me
Me
Me
O
CF3
OH
Ph
O
CF3
S
S
Me
O
O
54:46
N
N
Ts
N
3a
4a
Ts
Ts
3d
Me
Me
OH
Me
Me
O
CF3
Me
O
CF3
S
S
3e 55:45
3e′ 58:42
O
2
43
53b
O
N
N
N
3e (cis: major)
3e' (trans: minor)
Ts
Ts
3e
4e
Ts
OH
O
CF3
S
O
CF3
O
3
4
61
64
S
N
N
6
49
52:48
O
Ts
Ts
3e'
N
4e'
Ts
3f
O
CF3
OH
S
Me
Me
Me
O
CF3
O
S
N
N
7
8
trace
48
ND
3h
4h
O
Ts
Ts
N
a Reaction was conducted with trifluoromethanesulfinate 3 (0.1 mmol), 1 N
NaOH (0.35 mL, 0.35 mmol, 3.5 equiv) in MeOH (1 mL, 0.1 M) at rt.
Ts
3g
O
CF3
S
O
65:35
N
3h
Ts
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

D
S. Suzuki et al.
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A plausible mechanism for this trifluoromethanesulfinyl-
oxy aminocyclization could be explained by a Pd(II)-mediat-
ed oxidative addition/reductive elimination process from 1a
to 3a, as outlined in Scheme 3 (a). Initially, the alkene moi-
ety in 1a is activated by Pd(II) inducing an intramolecular
attack of the nitrogen in a 6-endo fashion via TS-I to provide
TS-II upon deprotonation by acetate. PIDA (PhI(OAc)2) oxi-
dizes Pd(II) in TS-II in the presence of trifluoromethane-
sulfinyl triflate (CF3SO2OS(O)CF3, 7)9d to form intermediate
TS-III, with the release of trifluoromethanesulfonyl acetate
(CF3SO2OAc) and iodobenzene (PhI). The trifluoromethane-
sulfinyl triflate (7) is generated in situ by the reaction of
PdII
Me Me
a)
1a
AcOH
TsHN
Pd(OAc)2
OAc
PdII
TS-I
Me
Me
3a
PhI(OAc)2
CF3
N
TS-II
S
Ts
O
O
OAc
PdIV
OAc
O
Me
O
F3C
S
S
Me
O
CF3
CF3SO2OAc
O
N
7
+
PhI
TS-III
Ts
CF3SO2Na
O
CF3SO2Na
with
trifluoromethanesulfonyl
chloride
tBuO-Cl
PivOH
F3C
(CF3S(O)2Cl, 6)20 resulting from the oxidation of CF3SO2H
CF3SO2Na
CF3SO2H
S
NaCl
Cl
t
O
tBuOH
with BuOCl. The in situ generated species, CF3SO2H, 6, and
6
PivONa
7, were detected by 19F NMR analysis.21 Finally, direct re-
ductive elimination in TS-III would afford an observed ami-
no-cyclized trifluoromethanesulfinyloxy product 3a with
the regeneration of Pd(OAc)2, which enters the catalytic cy-
cle. Stereoselective formation of cis-product 3h from 1h
could be explained by the transition-state model TS-III′
(Scheme 3, b). Another reaction pathway containing 5-exo-
cyclization (TS-I′ to TS-IV), oxidative addition (TS-IV to TS-
V) followed by aziridine formation (TS-V to TS-VI) and ring
opening by the OS(O)CF3 anion (TS-VI to 3a) is also possible
(Scheme 3, c). Details of the reaction mechanism are not
clear and a more mechanistic study is required.
In summary, the first palladium-catalyzed intra-
molecular aminotrifluoromethanesulfinyloxylation of un-
activated ω-aminoalkenes 1 has been achieved. Reaction
conditions are rather unique with a complex consisting of
CF3SO2Na/Pd(OAc)2/PhI(OAc)2/tBuOCl/PivOH to provide 6-
endo-cyclized type products 3 with a piperidine skeleton in
moderate yields. Trifluoromethanesulfinyloxy products 3
were obtained without the extrusion of SO2. This method is
not only the first example of an aminotrifluoromethane-
sulfinyloxylation reaction, but is also the first synthesis of
3-trifluoromethanesulfinyloxy piperidine derivatives. Al-
though plausible reaction pathways have been suggested,
detailed studies to elucidate the reaction mechanism are
currently underway.
CF3
b)
S
O
O
PdIV
1h
3h
H
N
OAc
OAc
Ts
H
TS-III'
AcO
c)
PdII
PdII
Me Me
7
PhI(OAc)2
Pd(OAc)2
1a
N
TsHN
TS-IV
Ts
TS-I'
CF3
CF3
S
OAc
O
N
O
S
PdIV
O
O
3a
OAc
N
Pd(OAc)2
Ts
TS-V
Ts
TS-VI
Scheme 3 Proposed reaction mechanisms of intramolecular aminotri-
fluoromethanesulfinyloxylation reaction: a) 6-endo-mode pathway; b)
stereoselective formation of cis-product; c) 5-exo-mode pathway.
References and Notes
(1) (a) Wang, J.; Sánchez-Roselló, M.; Aceña, J. L.; del Pozo, C.;
Sorochinsky, A. E.; Fustero, S.; Soloshonok, V. A.; Liu, H. Chem.
Rev. 2014, 114, 2432. (b) Zhou, Y.; Wang, J.; Gu, Z.; Wang, S.;
Zhu, W.; Aceña, J. L.; Soloshonok, V. A.; Izawa, K.; Liu, H. Chem.
Rev. 2016, 116, 422.
Funding Information
(2) (a) Uneyama, K. Organofluorine Chemistry; Blackwell: Oxford,
2006. (b) Hong, Z.; Weber, S. G. Teflon AF Materials, In Topics in
JSPS KAKENHI Grant Number JP 16H01142 in Middle Molecular Strat-
Current Chemistry;
3
V08o.
l
Horváth, I. T., Ed.; Springer: Berlin, 2012,
307. (c) Kirsch, P. Modern Fluoroorganic Chemistry; Wiley-VCH:
Weinheim, 2013.
egy.
S
JP
S
K
A
K
E
N
H
I
PJ(
1
6
H
0
1
1
4
2)
Acknowledgment
(3) For selected reviews, see: (a) Purser, S.; Moore, P. R.; Swallow,
S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320. (b) Liang, T.;
Neumann, C. N.; Ritter, T. Angew. Chem. Int. Ed. 2013, 52, 8214.
(c) Kawai, H.; Shibata, N. Chem. Rec. 2014, 14, 1024.
(d) Campbell, M. G.; Ritter, T. Chem. Rev. 2015, 115, 612.
(e) Yang, X.; Wu, T.; Phipps, R. J.; Toste, F. D. Chem. Rev. 2015,
115, 826. (f) Fustero, S.; Simon-Fuentes, A.; Barrio, P.; Haufe, G.
Chem. Rev. 2015, 115, 871. (g) Huang, Y.-Y.; Yang, X.; Chen, Z.;
Verpoort, F.; Shibata, N. Chem. Eur. J. 2015, 21, 8664.
CF3SO2Na was a gift from Central Glass Co., Ltd.
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0036-1591720.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E

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S. Suzuki et al.
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(h) Champagne, A.; Desroches, J.; Hamel, J.-D.; Vandamme, M.;
Paquin, J.-F. Chem. Rev. 2015, 115, 9073. (i) Shibata, N. Bull.
Chem. Soc. Jpn. 2016, 89, 1307.
(10) (a) Xu, X.-H.; Matsuzaki, K.; Shibata, N. Chem. Rev. 2015, 115,
731. (b) Barata-Vallejo, S.; Bonesi, S.; Postigo, A. Org. Biomol.
Chem. 2016, 14, 7150. (c) Gadais, C.; Saraiva-Rosa, N.; Chelain,
E.; Pytkowicz, J.; Brigaud, T. Eur. J. Org. Chem. 2017, 246. (d) Bu,
M.-J.; Lu, G.-P.; Cai, C. Org. Chem. Front. 2017, 4, 266.
(4) For selected reviews, see: (a) Prakash, G. K. S.; Yudin, A. K. Chem.
Rev. 1997, 97, 757. (b) Ma, J.-A.; Cahard, D. Chem. Rev. 2008, 108,
PR1. (c) Shibata, N.; Matsnev, A.; Cahard, D. Beilstein J. Org.
Chem. 2010, 6, No. 65. (d) Nie, J.; Guo, H.-C.; Cahard, D.; Ma, J.-
M. Chem. Rev. 2011, 111, 455. (e) Barata-Vallejo, S.; Lantaño, B.;
Postigo, A. Chem. Eur. J. 2014, 20, 16806. (f) Egami, H.; Sodeoka,
M. Angew. Chem. Int. Ed. 2014, 53, 8294. (g) Liu, X.; Xu, C.; Wang,
M.; Liu, Q. Chem. Rev. 2015, 115, 683. (h) Ni, C.; Hu, M.; Hu, J.
Chem. Rev. 2015, 115, 765.
(5) For selected reviews, see: (a) Tlili, A.; Billard, T. Angew. Chem.
Int. Ed. 2013, 52, 6818. (b) Besset, T.; Poisson, T.; Pannecoucke,
X. Chem. Eur. J. 2014, 20, 16830. (c) Toulgoat, F.; Alazet, S.;
Billard, T. Eur. J. Org. Chem. 2014, 2415. (d) Zhang, M.; Chen, J.;
Chen, Z.; Weng, Z. Tetrahedron 2016, 72, 3525. (e) Chachignon,
H.; Cahard, D. Chin. J. Chem. 2016, 34, 445. (f) Sebastian, B.-V.;
Sergio, B.; Al, P. Org. Biomol. Chem. 2016, 14, 7150. (g) Huang, Z.;
Shibata, N. New Horizons of Process Chemistry; Tomioka, K.;
Shioiri, T.; Sajiki, H., Eds.; Springer Nature: Heidelberg, 2017, 63.
(6) (a) Langlois, B. R.; Laurent, E.; Roidot, N. Tetrahedron Lett. 1991,
32, 7525. (b) Langlois, B. R.; Laurent, E.; Roidot, N. Tetrahedron
Lett. 1992, 33, 1291. (c) Tommasino, J.-B.; Brondex, A.;
Médebielle, M.; Thomalla, M.; Langlois, B. R.; Billard, T. Synlett
2002, 1697.
(7) For selected recent articles, see: (a) Pan, X.; Xia, H.; Wu, J. Org.
Chem. Front. 2016, 3, 1163. (b) Wang, D.; Deng, G.-J.; Chen, S.;
Gong, H. Green Chem. 2016, 18, 5967. (c) Jin, L.-K.; Lu, G.-P.; Cai,
C. Org. Chem. Front. 2016, 3, 1309. (d) Fu, H.; Wang, S.-S.; Li, Y.-
M. Adv. Synth. Catal. 2016, 358, 3616. (e) Shen, C.; Xu, J.; Ying, B.;
Zhang, P. ChemCatChem 2016, 8, 3560. (f) Chang, B.; Shao, H.;
Yan, P.; Qiu, W.; Weng, Z.; Yuan, R. ACS Sustainable Chem. Eng.
2017, 5, 334. (g) Qin, H.-T.; Wu, S.-W.; Liu, J.-L.; Liu, F. Chem.
Commun. 2017, 53, 1696. (h) Liu, Z.-Q.; Liu, D. J. Org. Chem.
2017, 82, 1649. (i) Wu, Z.; Wang, D.; Liu, Y.; Huan, L.; Zhu, C.
J. Am. Chem. Soc. 2017, 139, 1388. (j) Li, C.; Suzuki, K.;
Yamaguchi, K.; Mizuno, N. New J. Chem. 2017, 41, 1417. (k) Yang,
H.-B.; Selander, N. Org. Biomol. Chem. 2017, 15, 1771. (l) Torviso,
M. R.; Mansilla, D.; Garcia, S.; Lantaño, B.; Barata-Vallejo, S.;
Postigo, A. J. Fluorine Chem. 2017, 197, 42. (m) van der Werf, A.;
Hribersek, M.; Selander, N. Org. Lett. 2017, 19, 2374. (n) Kong,
W.; An, H.; Song, Q. Chem. Commun. 2017, 53, 8968. (o) Konik, Y.
A.; Kudrjashova, M.; Konrad, N.; Kaabel, S.; Järving, I.; Lopp, M.;
Kananovich, D. G. Org. Biomol. Chem. 2017, 15, 4635. (p) Zhang,
H.-Y.; Huo, W.; Ge, C.; Zhao, J.; Zhang, Y. Synlett 2017, 28, 962.
(8) For selected recent articles, see: (a) Cullen, S. C.; Shekhar, S.;
Nere, N. K. J. Org. Chem. 2013, 78, 12194. (b) Chu, X.-Q.; Meng,
H.; Xu, X.-P.; Ji, S.-J. Chem. Eur. J. 2015, 21, 11359. (c) Liao, J.;
Guo, W.; Zhang, Z.; Tang, X.; Wu, W.; Jiang, H. J. Org. Chem. 2016,
81, 1304. (d) Smyth, L. A.; Phillips, E. M.; Chan, V. S.; Napolitano,
J. G.; Henry, R.; Shekhar, S. J. Org. Chem. 2016, 81, 1285. (e) Han,
J.-B.; Yang, L.; Chen, X.; Zha, G.-F.; Zhang, C.-P. Adv. Synth. Catal.
2016, 358, 4119.
(11) In our knowledge, there is no report for the introduction of
OS(O)CF3 using CF3SO2Na.
(12) The direct introduction of OS(O)CF3unit is also rare. Two exam-
ples are reported: (a) Binkley, R. W.; Ambrose, M. G. J. Org. Chem.
1983, 48, 1776. (b) Miyamoto, K.; Iwasaki, S.; Doi, R.; Ota, T.;
Kawano, Y.; Yamashita, J.; Sakai, Y.; Tada, N.; Ochiai, M.; Hayashi,
S.; Nakanishi, W.; Uchiyama, M. J. Org. Chem. 2016, 81, 3188.
(13) Suzuki, S.; Kamo, T.; Fukushi, K.; Hiramatsu, T.; Tokunaga, T.;
Dohi, T.; Kita, Y.; Shibata, N. Chem. Sci. 2014, 5, 2754.
(14) Xu, X.-H.; Shibata, N. J. Synth. Org. Chem. Jpn. 2013, 71, 1195.
(15) Helena, M. L.; Forrest, E. M. J. Am. Chem. Soc. 2010, 132, 1249.
(16) Wu, T.; Yin, G.; Liu, G. J. Am. Chem. Soc. 2009, 131, 16354.
(17) Chen, C.; Chen, P.; Liu, G. J. Am. Chem. Soc. 2015, 137, 15648.
(18) General Procedure
To a stirring mixture of ω-aminoalkenes 1 (0.1 mmol), PIDA
(64.2 mg, 0.2 mmol, 2.0 equiv), Pd(OAc)2 (2.2 mg, 0.01 mmol, 10
mol%), CF3SO2Na (78.0 mg, 0.5 mmol, 5.0 equiv), and PivOH
(51.0 mg, 0.5 mmol, 5.0 equiv) in MeCN (0.5 mL, 0.2 M) at 10 °C,
tBuOCl (10.9 mg, 11 μL, 0.1 mmol, 1.0 equiv) was added under
nitrogen atmosphere. The mixture was stirred at room tem-
perature for 15 h. The resulting mixture was cooled to 0 °C,
quenched with sat. NaHCO3 aqueous solution, and extracted
with EtOAc three times. The combined organic layer was
washed with brine, dried with Na2SO4, and concentrated under
reduced pressure. The residue was purified by silica gel column
chromatography (benzene/EtOAc = 98:2) to give product 3.
5,5-Dimethyl-1-tosylpiperidin-3-yl Trifluoromethanesulfi-
nate (3a)
60% yield (dr = 54:46, mixture of diastereoisomer at sulfur
atom); white solid.1H NMR (300 MHz, CDCl3): δ = 7.64 (q, J = 3.2
Hz, 2 H), 7.36–7.33 (m, 2 H), 4.82–4.68 (m, 1 H), 4.00 (q, J = 5.4
Hz, 0.5 H), 3.85 (q, J = 5.4 Hz, 0.5 H), 3.28 (d, J = 11.5 Hz, 0.5 H),
3.20 (d, J = 11.5 Hz, 0.5 H), 2.44 (s, 3 H), 2.37–2.30 (m, 1 H), 2.18
(d, J = 11.5 Hz, 0.5 H), 2.10 (d, J = 11.5 Hz, 0.5 H), 1.87 (td, J =
12.1, 4.6 Hz, 1 H), 1.43–1.26 (m, 1 H), 1.11 (s, 1.5 H), 1.10 (s, 1.5
H), 1.01 (s, 1.5 H), 0.99 (s, 1.5 H). 19F NMR (282 MHz, CDCl3): δ =
–80.0 (major, s), –80.2 (minor, s). 13C NMR (176 MHz, CDCl3): δ =
143.9, 133.2, 129.8, 127.4, 127.3, 122.5 (q, J = 336.9 Hz), 122.4
(q, J = 336.0 Hz), 56.4, 56.3, 50.1, 50.0, 43.8, 43.5, 32.4, 32.3,
28.0, 27.9, 26.9, 24.9, 24.7, 21.4. IR (KBr) 2962, 2928, 1470,
1346, 1196, 1159, 1129, 950, 907, 857, 677 cm–1. ESI-MS: m/z =
422 [M + Na]+. ESI-HRMS: m/z calcd for C15H20NO4F3NaS2:
422.0684; found: 422.0679.
(19) (a) Di, J.; Rajanikanth, B.; Szarek, W. A. J. Chem. Soc., Perkin
Trans. 1 1992, 2151. (b) Tschamber, T.; Siendt, H.; Boiron, A.;
Gessier, F.; Deredas, D.; Frankowski, A.; Picasso, S.; Steiner, H.;
Aubertin, A.-M.; Streith, J. Eur. J. Org. Chem. 2001, 1335.
(c) Golubev, A. S.; Schedel, H.; Radics, G.; Fioroni, M.; Thust, S.;
Burger, K. Tetrahedron Lett. 2004, 45, 1445.
(9) (a) Billard, T.; Greiner, A.; Langlois, B. R. Tetrahedron 1999, 55,
7243. (b) Chen, X.; Tordeux, M.; Desmurs, J.-R.; Wakselman, C.
J. Fluorine Chem. 2003, 123, 51. (c) Hasegawa, A.; Ishikawa, T.;
Ishihara, K.; Yamamoto, H. Bull. Chem. Soc. Jpn. 2005, 78, 1401.
(d) Magnier, E.; Blazejewski, J.-C.; Tordeux, M.; Wakselman, C.
Angew. Chem. Int. Ed. 2006, 45, 1279. (e) Chachignon, H.;
Cahard, D. J. Fluorine Chem. 2017, 198, 82.
(20) The 19F NMR (282 MHz) spectra of the mixture of CF3SO2Na
(1.0 equiv), PivOH (1.0 equiv), and tBuOCl (1.0 equiv) in CD3CN
indicated two singlet signals at δ = –74.01 ppm (CF3SO2Cl) and
–77.14 ppm (7).
(21) The19F NMR (282 MHz) spectra of the mixture of 6 (1.0
equiv) and CF3SO2Na (1.0 equiv) in CD3CN indicated three
singlet signals at δ = –73.98 ppm (CF3SO2Cl), –77.14 ppm (7),
and –83.00 ppm (CF3SO2Na).
© Georg Thieme Verlag Stuttgart · New York — Synlett 2017, 28, A–E