Chiral N-fluorodibenzenesulfonimide analogues for enantioselective electrophilic fluorination and oxidative fluorination

Article abstract of DOI:10.1002/ejoc.201300956

This work describes the design, synthesis, and application of de novo chiral fluorinating agents as analogues of popular N-fluorodibenzenesulfonimide (NFSI). The fluorination step by means of elemental fluorine is presented. Enantioselective fluorination

Full text of DOI:10.1002/ejoc.201300956

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201300956
Chiral N-Fluorodibenzenesulfonimide Analogues for Enantioselective
Electrophilic Fluorination and Oxidative Fluorination
Chuan-Le Zhu,[a,b] Mayaka Maeno,[c] Fa-Guang Zhang,[b] Taiki Shigehiro,[d]
Takumi Kagawa,[d] Kosuke Kawada,[d] Norio Shibata,*[c] Jun-An Ma,*[b] and
Dominique Cahard*[a]
Keywords: Chirality / Enantioselectivity / Fluorine / Oxidation
This work describes the design, synthesis, and application of
de novo chiral fluorinating agents as analogues of popular N-
fluorodibenzenesulfonimide (NFSI). The fluorination step by
means of elemental fluorine is presented. Enantioselective
fluorination is demonstrated in cyclic β-keto esters and in the
synthesis of BMS-204352 (up to 86%ee). Oxidative amino-
fluorination is also examined.
fluorinating agents that include chiral, nonracemic
agents.[1,3] In this way, a (pro)chiral substrate is transformed
into a chiral fluorinated product with concomitant creation
of a fluorinated stereogenic center. The most successful
electrophilic fluorinating agents are N-fluorobenzene-
sulfonimide (NFSI)[4] and 1-chloromethyl-4-fluoro-1,4-di-
azoniabicyclo[2.2.2]octane bis(tetrafluoroborate) (Select-
fluor®),[5] both of which have been exploited in enantiocon-
trolled fluorination in organocatalysis and in transition-
metal catalysis. In particular, NFSI is now quite successful
not only as an electrophilic fluorinating agent in enantiose-
lective catalysis[6] but also as an oxidant for organometallic
intermediates to promote reductive elimination through
high-oxidation-state transition metals, as an amination rea-
gent, and even as a phenylsulfonyl group transfer reagent.[7]
Alongside these facts, we were interested in chiral analogues
of NFSI. The chiral analogues of Selectfluor® were inde-
pendently reported by Shibata[8] and Cahard[9] in 2000 as
N-fluoroammonium salts of cinchona alkaloids. The N-
fluoroammonium salts of cinchona alkaloids that feature a
quinuclidine moiety are closely structurally related to Se-
lectfluor® and, as such, could be presented as chiral ana-
logues. Selectfluor® analogues having a chiral C8-BINOL-
derived phosphate as a counteranion was also recently de-
scribed by Toste and co-workers through in situ generation
(BINOL = 1,1Ј-bi-2-naphthol).[10] It is surprising that an
NFSI analogue bearing an element of chirality, that is, chi-
ral N-fluorodiarylsulfonimide, has not yet been reported,
although chiral N-fluorosulfonamides[11,12] and a sterically
very demanding achiral NFSI analogue[13] have been de-
scribed. In this context, we herein disclose the design and
synthesis of de novo fluorinating agents, chiral NFSIs 1,
that combine the sulfonimide moiety of popular NFSI and
the axial chirality of the well-established 1,1Ј-binaphthyl
unit (Figure 1). Enantioselective fluorination of β-keto es-
Introduction
The importance of chirality in pharmaceutical molecules
associated with the astonishing properties of fluorine-con-
taining compounds led to huge efforts in the development
of effective methodologies for the preparation of chiral non-
racemic fluorinated molecules.[1] There are two strategies
for the construction of fluorinated stereogenic centers.[2]
The first strategy involves the use of fluorinated building
blocks that are subjected to asymmetric transformations
early in a multistep process. The second strategy involves
the introduction of the fluorine atom in a late stage of a
synthetic plan with concomitant control of the stereogenic
centers. Basically, in the second strategy, the construction
can be realized by nucleophilic substitution with a fluoride
anion, by addition of an electropositive fluorine, or by radi-
cal fluorination. Asymmetric electrophilic fluorination, in
either a diastereoselective or an enantioselective manner, is
so far the most successful approach.[1a,1c] The success of
this approach relies to a great extent upon the design of
efficient neutral N–F or charged [N–F]+ electrophilic
[a] UMR 6014 CNRS de l’IRCOF, Université de Rouen et INSA
de Rouen,
Rue Tesnière, 76821 Mont-Saint-Aignan Cedex, France
E-mail: dominique.cahard@univ-rouen.fr
http://www.univ-rouen.fr/
[b] Department of Chemistry, Tianjin University,
Tianjin 300072, China
E-mail: majun_an68@tju.edu.cn
http://www.tjuchemistry.org/usr/maja.htm
[c] Department of Frontier Materials, Department of
Nanopharmaceutical Science, Nagoya Institute of Technology,
Gokiso, Showa-ku, Nagoya 466-8555, Japan
E-mail: nozshiba@nitech.ac.jp
http://www.ach.nitech.ac.jp/~organic/shibata/shibata.html
[d] Research Laboratory, TOSOH F-TECH, Inc.,
4988 Kaisei-cho, Shunan, Yamaguchi 746-0006, Japan
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201300956.
Eur. J. Org. Chem. 2013, 6501–6505
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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N. Shibata, J.-A. Ma, D. Cahard et al.
SHORT COMMUNICATION
ters and oxindole was demonstrated for the evaluation of NFSI analogues 1. The ability of fluorinating agents 1 to
reagents 1 to provide the fluorinated products with up to promote enantioselective fluorination was directly com-
86%ee. Aminofluorination of indene was also attempted to pared with organocatalytic approaches. From Equation (1),
explore the potential of 1 for oxidative reactions.
the fluorination only provided moderate yields of expected
α-fluoro-β-keto ester 4a with rather high enantioselectivity
of 86% if more sterically hindered chiral N–F reagent 1b
was used. This level of enantioselection is comparable to
that observed with other enantioselective approaches. No-
tably, 4a was previously obtained by using chiral phase-
transfer catalysts derived from cinchona alkaloids with
69%ee,[16] bifunctional phase-transfer ammonium salts
having hydromethyl appendages with 68%ee,[17] and a bi-
functional chiral thiourea with 99%ee.[18] Substituted NF
reagent 1b is clearly more enantioselective than unsubsti-
tuted reagent 1a [86 vs. 17%ee; Scheme 2, Eq. (1)]. The
fluorination of indanone carboxylate 3b and tetralone carb-
oxylate 3c by 1b gave fluorination products 4b and 4c with
moderate enantioselectivities of 76 and 54%ee, respectively.
The enantioselective synthesis of the potent Maxi-K potas-
sium channel opener MaxiPost[19] was realized under dif-
ferent conditions starting from 5 by using cesium hydroxide
as the base in a mixture of acetonitrile and dichlorometh-
ane to give target product 6 in 51% yield with 57%ee
[Scheme 2, Eq. (4)]. We next examined an oxidative amino-
fluorination,[7c] which is one of the recent alternative uses
of NFSI for nonelectrophilic fluorination reactions. The
Figure 1. Structures of the fluorinating reagents NFSI, Se-
lectfluor®, and chiral NFSIs 1.
Results and Discussion
The NH precursors of 1, 1,1Ј-binaphthyl-2,2Ј-bis(sulfon-
amide) scaffolds 2, were designed by List[14] and Gier-
noth[15] and demonstrated a wide scope in organocatalysis
for this type of chiral Brønsted acid.[14b] The fluorination
step of NH precursors 2 to afford 1 was conducted by
means of elemental fluorine in the presence of sodium
fluoride in acetonitrile. The fluorination and its reaction
vessel, having a supply channel for F2 and N2 to mix, are
shown in Scheme 1. The best yield for the fluorination of
the unsubstituted NH precursor to afford 1a was 67 %,
whereas that for a substituted NH precursor featuring two
sterically demanding 3,5-bis(trifluoromethyl)phenyl groups
at the 3,3Ј-positions was 27%. In both cases, side products
were obtained, although they were not characterized.
Scheme 1. Preparation of enantiopure electrophilic fluorinating
agents, chiral NFSIs 1.
With chiral reagents 1 in hand, we first evaluated the
enantioselective electrophilic fluorination of β-keto ester
derivatives 3a–c [Scheme 2, Eqs. (1–3)]. β-Keto esters 3a–c
were deprotonated by sodium hydride in THF to form the
corresponding sodium enolates, which reacted with chiral 1.
Scheme 2. Enantioselective fluorination by means of chiral NFSIs
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Chiral N-Fluorodibenzenesulfonimides for Fluorination
60N spherical neutral size 63-210 μm or Wako-gel C-300™. 1H
NMR (300 and 400 MHz) and 19F NMR (282 MHz) spectra for
solutions in CDCl3 and CD3CN were recorded with a Bruker Av-
ance 400 and a Varian Mercury 300. Chemical shifts (δ) are ex-
pressed in ppm downfield from internal tetramethylsilane, CDCl3,
or CD3CN. Optical rotations were measured with a Horiba SEPA-
300 operating at 589 nm. HPLC analyses were performed with a
JASCO U-2080 Plus by using a 4.6ϫ250 mm Chiralcel OD-H or
Chiralpak AD-3 column. Mass spectra were recorded with a Shim-
adzu LCMS-2010EV. Infrared spectra were recorded with a Jasco
FTIR-200 spectrometer.
aminofluorination of indene (7) was attempted, for which
1a and 1b acted as a fluorination agent and as an amination
reagent consecutively to provide 1-sulfonimido-2-fluoro-
indane derivatives 8a and 8b in 76–77% yield as a mixture
of four diastereoisomers, although no asymmetric induction
was observed (Scheme 3).
Synthesis of Chiral NFSI: A mixture of 2b (600.8 mg, 0.733 mmol)
and NaF (7.44 g, 177 mmol) in acetonitrile (300 mL) in a Teflon™
vessel was cooled to –40 °C with stirring. F2 gas (0.068 mLmin–1)
diluted with N2 gas (29.8 mLmin–1) was then bubbled through the
mixture for 4 h. Upon completion of the reaction, as monitored by
TLC analysis, N2 (29.8 mLmin–1) was bubbled through the mixture
for 1 h at –40 °C, and then the mixture was warmed to room tem-
perature. The solid was removed from the reaction mixture by fil-
tration, and the filtrate was concentrated under reduced pressure
to provide crude 1b (0.78 g) as a brown-yellow solid. Crude 1b was
purified by SiO2 column chromatography (Wako-gel C-300™), and
then
a yellow solid (357 mg), which contained 1b (248 mg,
0.296 mmol), was obtained (40%).
(S)-N-Fluoro-{3,3Ј-bis[3,5-bis(trifluoromethyl)phenyl]-1,1Ј-binaphth-
yl}-2,2Ј-disulfonimide (1b): [α]2D5 = –4.32 (c = 0.74, THF). 1H NMR
(400 MHz, CD3CN): δ = 7.25 (d, J = 0.8 Hz, 1 H), 7.27 (d, J =
0.8 Hz, 1 H), 7.52 (t, J = 1.6 Hz, 1 H), 7.54 (t, J = 1.2 Hz, 1 H),
7.81–7.85 (m, 2 H), 8.00 (s, 2 H), 8.03 (s, 2 H), 8.06 (s, 2 H), 8.12
(s, 1 H), 8.14 (s, 1 H), 8.23 (s, 2 H) ppm. 19F NMR (376 MHz,
Scheme 3. Oxidative aminofluorination by means of chiral NFSIs
1a and 1b.
CDCl ): δ = –61.94 (s), –61.90 (s), –44.97 (s) ppm. IR (KBr): ν =
˜
3
2963, 1621, 1378, 1280, 1178, 1136, 901, 803, 683, 541 cm–1.
HRMS: calcd. for C36H15NO4F13S2 [M – H]– 836.0235; found
836.0247.
Conclusions
(R)-N-Fluoro-(1,1Ј-binaphthyl)-2,2Ј-disulfonimide (1a): [α]2D5 = –124
Two chiral analogues of NFSI, 1a and 1b, were designed
and synthesized for the first time based on the C2-symmet-
ric chiral binaphthyl bis(sulfonimide) topology as a privi-
leged motif for asymmetric synthesis. The use of chiral
NFSI analogue 1b, which features two bulky 3,5-bis(tri-
fluoromethyl)phenyl groups at the 3,3Ј-positions of the bi-
naphthol backbone, was found to be advantageous from an
enantioselectivity point of view. This level of enantioselec-
tion is comparable to that observed with other enantioselec-
tive approaches for the selected example. Oxidative amino-
fluorination was also possible by using 1 to deliver products
in high chemical yields. Although the present results are
just preliminary examples of the use of chiral NFSIs 1, a
wide variety of applications should be possible on the basis
of recent successful applications of NFSI.[7]
1
(c = 0.33, THF). H NMR (300 MHz, CDCl3): δ = 8.34–8.25 (m,
4 H), 8.11 (d, J = 8.1 Hz, 2 H), 7.76 (t, J = 6.9 Hz, 2 H), 7.47 (t,
J = 8.1 Hz, 2 H), 7.31–7.26 (m, 2 H) ppm. 19F NMR (282 MHz,
CDCl ): δ = –39.00 (s) ppm. IR (KBr): ν = 3079, 2923, 1581, 1389,
˜
3
1376, 1189, 1106, 822, 750, 703, 664, 536 cm–1. HRMS: calcd. for
C20H11NO4FS2 [M – H]– 412.0114; found 412.0112.
Methyl 2-Fluoro-1-oxoindan-2-carboxylate (4a): A solution of 3a
(7.5 mg, 0.0394 mmol) in THF (0.4 mL) was added dropwise to a
suspension of NaH (3.2 mg, 0.0788 mmol) in THF (0.4 mL) at
–80 °C, and the mixture was stirred for 1 h. A solution of 1b
(33 mg, 0.0394 mmol) in THF (0.1 mL) was then added dropwise
to the mixture. The resulting mixture was stirred overnight at
–80 °C. The reaction was quenched by the addition of water, and
the reaction mixture was extracted with ethyl acetate. The com-
bined organic layer was washed with brine, dried with Na2SO4, and
concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (n-hexane/ethyl acetate = 9:1)
to give (–)-4a (3.9 mg, 0.0189 mmol, 48%, 86%ee).
Experimental Section
Compound (–)-4a was obtained from 1b under the same condi-
tions, yield 3.9 mg, 0.0189 mmol, 48%, 86%ee. [α]2D5 = –16.4 (c =
0.13, CHCl3) [(–)-4a, 86%ee]. 1H NMR (300 MHz, CDCl3): δ =
7.85 (d, J = 7.8 Hz, 1 H), 7.72 (t, J = 7.5 Hz, 1 H), 7.52–7.45 (m,
2 H), 3.81 (dd, J = 11.7, 18.0 Hz, 1 H), 3.80 (s, 3 H), 3.45 (dd, J =
18.0, 23.1 Hz, 1 H) ppm. 19F NMR (282 MHz, CDCl3): δ =
–165.04 (dd, J = 11.7, 23.1 Hz) ppm. MS (APCI): m/z = 226 [M
+ H]+. HPLC (Chiralcel OD-H, n-hexane/iPrOH = 99:1, flow =
0.5 mLmin–1, λ = 254 nm): tR = 30.3 (minor), 33.2 (major) min.
General Information: All reactions were performed in oven-dried
glassware under a positive pressure of nitrogen or argon. Solvents
were transferred by syringe and were introduced into the reaction
vessels though a rubber septum. The reactions were monitored by
thin-layer chromatography (TLC) performed with 0.25 mm Merck
silica-gel (60-F254). The TLC plates were visualized with UV light
and KMnO4 in water or p-anisaldehyde in ethanol/heat. Column
chromatography was performed on a column packed with silica-gel
Eur. J. Org. Chem. 2013, 6501–6505
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N. Shibata, J.-A. Ma, D. Cahard et al.
SHORT COMMUNICATION
Compound (+)-4a was obtained from 1a under the same condi-
tions, yield 2.3 mg, 0.011 mmol, 28%, 17%ee. [α]2D5 = +3.44 (c =
0.077, CHCl3) [(+)-4a, 17%ee]. HPLC (Chiralcel OD-H, n-hexane/
δ = –63.33 (s), –154.08 (s) ppm. MS (APCI): m/z = 479 [M +
NH4]+. HPLC (Chiralcel OD-Hx2, n-hexane/iPrOH = 98:2,
0.5 mL/min, 254 nm) tR (major-isomer) = 23.6 min, tR (minor-iso-
iPrOH = 99:1, flow = 0.5 mLmin–1, λ = 254 nm): tR = 36.8 (major), mer) = 30.0 min. The absolute configuration of 6 was corresponded
38.8 (minor) min.
the reference 6b. Lit.[6b] HPLC: (Chiralcel OD-Hx2, n-hexane/
iPrOH = 98:2, flow = 0.5 mLmin–1, λ = 254 nm): tR = 21.8 [(S)-
(+)-isomer], 28.3 [(R)-(–)-isomer] min.
(R)-tert-Butyl 2-Fluoro-1-oxoindan-2-carboxylate (4b): A solution
of 3b (9.2 mg, 0.0394 mmol) in THF (0.4 mL) was added dropwise
to a suspension of NaH (3.2 mg, 0.0788 mmol) in THF (0.4 mL)
at –80 °C, and the mixture was stirred for 1 h. A solution of 1b
(33 mg, 0.0394 mmol) in THF (0.1 mL) was then added dropwise
to the mixture. The resulting mixture was stirred overnight at
–80 °C. The reaction was quenched by the addition of water, and
the reaction mixture was extracted with ethyl acetate. The com-
bined organic layer was washed with brine, dried with Na2SO4, and
concentrated under reduced pressure. The residue was purified by
column chromatography on silica gel (n-hexane/ethyl acetate = 9:1)
to give 4b (6.2 mg, 0.0248 mmol, 63%, 76%ee). [α]2D5 = +1.17 (c =
0.21, CHCl3) [(R)-4b, 76%ee]. 1H NMR (300 MHz, CDCl3): δ =
7.84 (d, J = 8.1 Hz, 1 H), 7.69 (t, J = 7.5 Hz, 1 H), 7.51–7.43 (m,
2 H), 3.73 (dd, J = 10.9, 17.7 Hz, 1 H), 3.40 (dd, J = 17.7, 22.8 Hz,
1 H), 1.44 (s, 9 H) ppm. 19F NMR (282 MHz, CDCl3): δ = –164.51
(dd, J = 10.9, 22.8 Hz) ppm. MS (APCI): m/z = 268 [M + NH4]+.
N-(2-Fluoro-2,3-dihydro-1H-inden-1-yl)-N-(S)-3,3Ј-bis[3,5-bis(tri-
fluoromethyl)phenyl]-1,1Ј-binaphthyl-2,2Ј-disulfonimide (8b): In a
dried Schlenk tube, palladium acetate (1.2 mg, 0.00515 mmol), ba-
thocuproine (2.8 mg, 0.00772 mmol), and 1b (35.9 mg,
0.0429 mmol) were dissolved in 1,4-dioxane (0.1 mL, degassed with
argon) under an argon atmosphere, and then indene (2.0 μL,
0.0172 mmol) was added. The reaction mixture was stirred at 50 °C
for 10 h. The reaction mixture was concentrated under reduced
pressure and purified by silica gel column chromatography (n-hex-
ane/ethyl acetate = 9:1–1:1) to give 8b (12.4 mg, 0.0131 mmol,
trans-8b and cis-8b could not be separated, and the spectrum of
the mixture of isomers is listed below). [α]2D5 = +2.55 (c = 0.41,
THF). 1H NMR (400 MHz, CDCl3): δ = 8.08–6.72 (m, 20 H),
5.90–5.73 (m, 0.8 H), 5.68–5.51 (m, 0.35 H), 5.31–5.14 (m, 0.6 H),
5.02–4.82 (m, 0.15 H), 4.60–4.46 (m, 0.15 H), 4.21 (dq, J = 1.6,
7.2 Hz, 0.6 H), 3.76 (s, 0.1 H), 3.68–3.54 (m, 0.3 H), 3.47 (t, J =
7.6 Hz, 0.2 H), (dt, J = 7.6, 19.0 Hz, 0.45 H), 3.19–3.14 (m, 0.2 H),
3.01–2.77 (m, 1 H), 2.56 (d, J = 6.0 Hz, 0.1 H), 2.47 (t, J = 7.6 Hz,
0.15 H), 2.38–2.28 (m, 0.3 H), 2.19–2.08 (m, 0.15 H) ppm. 13C
NMR (125 MHz, CDCl3): δ = 141.77, 140.47, 136.56, 134.27,
132.19, 130.85, 129.45, 129.40, 129.18, 128.81, 128.63, 127.39,
127.10, 125.22, 125.18, 124.31, 123.68, 122.49, 122.44, 121.99,
121.94, 98.21, 97.62, 69.75, 68.33, 49.63 ppm. 19F NMR (282 MHz,
CDCl3): δ = –63.14 (m), –170.47 (m), –175.88 (m), –185.63 (m)
HPLC (Chiralpak AD-3, n-hexane/iPrOH
= 99:1, flow =
0.5 mLmin–1, λ = 254 nm): tR = 27.4 (minor), 31.8 (major) min.
The absolute configuration of 4b corresponded to that given in
ref.[6b] {ref.[6b] [α]2D4 = –3.93 (c = 0.41, CHCl3) [(S)-2a, 99%ee]}.
Methyl 2-Fluoro-1-oxo-1,2,3,4-tetrahydronaphthalen-2-carboxylate
(4c): A solution of 3c (8.0 mg, 0.0394 mmol) in THF (0.4 mL) was
added dropwise to a suspension of NaH (3.2 mg, 0.0788 mmol) in
THF (0.4 mL) at –80 °C, and the mixture was stirred for 1 h. A
solution of 1b (33 mg, 0.0394 mmol) in THF (0.1 mL) was added
dropwise to the mixture. The resulting mixture was stirred over-
night at –80 °C. The reaction was quenched by the addition of
water, and the reaction mixture was extracted with ethyl acetate.
The combined organic layer was washed with brine, dried with
Na2SO4, and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel (n-hexane/ethyl
acetate = 9:1) to give (–)-4c (2.7 mg, 0.0122 mmol, 31%, 54%ee).
[α]2D5 = –2.56 (c = 0.090, CHCl3) [(–)-4c, 54%ee]. 1H NMR
(300 MHz, CDCl3): δ = 8.09 (d, J = 7.8 Hz, 1 H), 7.56 (t, J =
7.2 Hz, 1 H), 7.40–7.28 (m, 2 H), 3.84 (s, 3 H), 3.23–3.05 (m, 2 H),
2.78–2.66 (m, 1 H), 2.62–2.54 (m, 1 H) ppm. 19F NMR (282 MHz,
CDCl3): δ = –164.68 (dd, J = 11.8, 22.3 Hz) ppm. MS (APCI): m/z
= 223 [M + H]+. HPLC (Chiralcel OD-H, n-hexane/iPrOH = 90:10,
flow = 1.0 mLmin–1, λ = 254 nm): tR = 14.2 (major), 15.2
(minor) min.
ppm. IR (KBr): ν = 1372, 1280, 1177, 1137, 846, 755, 707, 683,
˜
656, 574 cm–1. HRMS: calcd. for C45H24NO4F13NaS2 [M + Na]+
976.0837 found 976.0834.
N-(2-Fluoro-2,3-dihydro-1H-inden-1-yl)-N-(R)-(1,1Ј-binaphthyl)-
2,2Ј-disulfonimide (8a): Same conditions with 1a (15.2 mg,
0.0368 mmol) to give 8a (6.0 mg, 0.0113 mmol, 77%, trans-8a and
cis-8a could not be separated, and the spectrum of the mixture of
1
isomers is listed below). H NMR (600 MHz, CDCl3): δ = 8.27 (s,
1.40 H), 8.17–8.16 (m, 0.80 H), 8.08–8.06 (m, 1.75 H), 7.71–7.68
(m, 1.50 H), 7.48–7.41 (m, 2.55 H), 7.39–7.28 (m, 2.20 H), 7.27–
7.19 (m, 1.35 H), 7.13–7.10 (m, 0.4 H), 7.00–6.99 (m, 0.50 H), 6.30–
6.14 (m, 0.85 H), 5.88–5.75 (m, 0.70 H), 5.60–5.41 (m, 0.17 H),
5.37–5.27 (m, 0.18 H), 3.81–3.68 (m, 0.85 H), 3.56–3.48 (m, 0.20
H), 3.43–3.30 (m, 0.25 H), 3.24–3.06 (m, 1.00 H) ppm. 19F NMR
(282 MHz, CDCl3): δ = –171.02 (m), –171.94 (m), –183.05 (m),
–184.12 (m) ppm. HRMS: calcd. for C29H20NO4FNaS2 [M +
Na]+ 552.0715 found 552.0714.
(S)-N-tert-Butoxycarbonyl-3-(5-chloro-2-methoxyphenyl)-3-fluoro-
6-trifluoromethyl-2-oxindole (6): A mixture of 1b (16.8 mg,
0.02 mmol) and CsOH monohydrate (18.0 mg, 0.12 mmol) in
CH3CN/CH2Cl2 (3:4, 0.3 mL) was stirred under a nitrogen atmo-
sphere at –80 °C for 30 min. A solution of 5 (8.8 mg, 0.02 mmol)
in CH3CN/CH2Cl2 (3:4, 0.1 mL) was added to the mixture. The
reaction mixture was stirred for 2 d with monitoring by TLC, and
the reaction was stopped by the addition of water. The reaction
mixture was then diluted with ethyl acetate; washed with 2 n HCl,
saturated aqueous sodium hydrogen carbonate solution, and brine;
and dried with Na2SO4, and the solvent was evaporated under re-
duced pressure. The residue was purified by column chromatog-
raphy on silica gel (n-hexane/ethyl acetate = 8:2) to give 6 (4.7 mg,
0.0102 mmol, 51%, 57%ee). 1H NMR (300 MHz, CDCl3): δ = 8.25
(s, 1 H), 7.79 (s, 1 H), 7.43–7.28 (m, 3 H), 6.76 (d, J = 9.0 Hz, 1
H), 3.54 (s, 3 H), 1.67 (s, 9 H) ppm. 19F NMR (282 MHz, CDCl3):
Supporting Information (see footnote on the first page of this arti-
1
cle): Copies of the H, 19F, 13C NMR spectra and HPLC analysis.
Acknowledgments
N. S. was financially supported in part by grants-in-Aid for Scien-
tific Research from the Ministry of Education, Culture, Sports, Sci-
ence and Technology (MEXT) (24105513, project number 2304:
Advanced Molecular Transformation by Organocatalysts) and by
the Japan Science and Technology (JST) (ACT-C: Creation of Ad-
vanced Catalytic Transformation for the Sustainable Manufactur-
ing at Low Energy, Low Environmental Load). C-L. Z. is grateful
to the French Ministry of Foreign Affairs for an Eiffel Excellence
Doctorate Scholarship (9/2011 to 6/2012). J.-A. M. was financially
6504
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Eur. J. Org. Chem. 2013, 6501–6505

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Received: June 28, 2013
Published Online: September 3, 2013
Eur. J. Org. Chem. 2013, 6501–6505
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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6505