Asymmetric synthesis of trifluoromethylated aziridines from CF 3-substituted N-tert-butanesulfinyl ketimines

Article abstract of DOI:10.1016/j.tetlet.2013.05.048

A convenient and practical method for the asymmetric synthesis of trifluoromethylated aziridines was developed. The reactions of sulfur ylide with (S)-N-tert-butanesulfinyl ketimines gave trifluoromethylated aziridines 3 in moderate to excellent yields (45-93%) and good diastereoselectivities (86:14 to >99:1 dr). The synthetic application of these aziridines was examined through the acidic deprotection of the sulfinyl group and ring-opening reaction with dimethylsulfonium methylide to afford trifluoromethylated cyclopropylamine and α-trifluoromethylallylamine in 80% and 67% yields, respectively.

Full text of DOI:10.1016/j.tetlet.2013.05.048

Accepted Manuscript
Asymmetric Synthesis of Trifluoromethylated Aziridines from CF -substituted
3
N-tert-Butanesulfinyl Ketimines
Yanmei Yang, Yangen Huang, Feng-Ling Qing
PII:
S0040-4039(13)00805-8
DOI:
http://dx.doi.org/10.1016/j.tetlet.2013.05.048
TETL 42948
Reference:
To appear in:
Tetrahedron Letters
Received Date:
Revised Date:
Accepted Date:
5 February 2013
28 April 2013
10 May 2013
Please cite this article as: Yang, Y., Huang, Y., Qing, F-L., Asymmetric Synthesis of Trifluoromethylated Aziridines
from CF -substituted N-tert-Butanesulfinyl Ketimines, Tetrahedron Letters (2013), doi: http://dx.doi.org/10.1016/
3
j.tetlet.2013.05.048
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Asymmetric Synthesis of Trifluoromethylated
Aziridines from CF3-substituted
N-tert-Butanesulfinyl Ketimines
Yanmei Yanga, Yangen Huanga,*, Feng-Ling Qinga,b
a Key Laboratory of Eco-Textile, Ministry of Education, Donghua University, 2999 North Renmin Road, Shanghai 201620,
China; b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 345 Lingling Road, Shanghai 200032, China
1

Asymmetric Synthesis of Trifluoromethylated Aziridines from
CF3-substituted N-tert-Butanesulfinyl Ketimines
Yanmei Yanga, Yangen Huanga,*, Feng-Ling Qinga,b
a Key Laboratory of Eco-Textile, Ministry of Education, Donghua University, 2999 North Renmin
Road, Shanghai 201620, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese
Academy of Sciences, 345 Lingling Road, Shanghai 200032, China
Abstract
A convenient and practical method for the asymmetric synthesis of trifluoromethylated aziridines
was developed. The reactions of sulfur ylide with (S)-N-tert-butanesulfinyl ketimines gave
trifluoromethylated aziridines 3 in moderate to excellent yields (45-93%) and good
diastereoselectivities (86:14 to > 99:1 dr). The synthetic application of these aziridines were
examined through the acidic deprotection of sulfinyl group and ring-opening reaction with
dimethylsulfonium
methylide
to
afford
trifluoromethylated
cyclopropylamine
and
α-trifluoromethylallylamine in 80 % and 67 % yield, respectively.
Keywords: Diasteroselective synthesis; CF3-substituted; Aziridine; Sulfinamide
1. Introduction
Fluorine-containing compounds have attracted extensive attention due to the unique properties
of fluorine (high electronegativity, low polarizability, relative small size) which induce
modifications of physical properties for these compounds and make them suitable for use in life and
material sciences.1 Thereinto, as an essential fluorinated group, CF3 group has attracted much
attention and much effort has been paid in the development of new synthetic methods for
*
Corresponding author. Tel.: +86 21 67792612; fax: +86 21 67792608.
E-mail address: hyg@dhu.edu.cn (Y. Huang)
2

incorporation of the CF3 group into diverse organic compounds. 2 However, although the
introduction of CF3 group usually results in an improvement of the biological properties of bioactive
compounds,3 the direct introduction of a CF3 groups into heterocyclic compounds is often difficult.4
Therefore, a building block approach can provide a useful alternative in some cases. One class of
interesting heterocyclic derivatives is aziridines which are excellent building blocks for the
preparation of a large variety of nitrogen-containing compounds due to the ease and predictable
regioselectivity of their ring-opening reactions with nucleophiles.5 In the last decade, numerous
building block approaches for the preparation of trifluoromethylated aziridine derivatives have been
reported. 6 However, few examples towards the asymmetric synthesis of trifluoromethylated
aziridines can be found,7 and at the same time CF3 substituted chiral carbon center is an essential
motif such as in the commercialized drugs Efavirenz (anti-HIV).8 Here, we report an efficient
method for the asymmetric synthesis of trifluoromethylated aziridines by using the inexpensive
N-tert-butanesulfinyl group as a chiral auxiliary.9
2. Results and discussion
Firstly, chiral CF3-substituted (S)-N-tert- butylsulfinyl ketimines 2a-2g were synthesized in
30-92 % yields according to the method established by Lu10 via condensation of (S)-tert-
butylsulfinyl amide and CF3-substituted ketones 1a-1g in the presence of 2.5 eq. of Ti(OiPr)4
(Scheme 1). As stated in the literature10,11, most of these ketimines were displayed low hydrostability
and need to be isolated quickly and prior to use. It is noteworthy that acetylenic ketimines 2f and 2g
have higher hydrostability and can be isolated in yield of 92 % and 58 %, respectively.12
3

Scheme 1. Preparation of the CF3-substituted (S)-N-tert-butanesulfinyl ketimines 2.
With ketimines 2a-2g in hand, the Corey-Chaykovsky aziridination13 were then investigated
(Table 2). Ketimine 2c was chosen as the model substrate for optimization of the Corey-Chaykovsky
aziridination condition. Initially, in situ generated dimethylsulfonium methylide was used as the
sulfur ylide, and the reaction of 2c with dimethylsulfonium methylide in DMSO at room
temperature afforded a mixture of desired product 3c in 55 % yield and 76:24 dr (Table 1, entry 1).
However, we found that the reproducibility of this result was very poor. It was thought that the high
reactivity of dimethylsulfonium methylide and the relatively unstable nature of the CF3-substituted
ketimine led to a multitude of undesired side reactions upon exposure to sodium hydride. Hence less
reactive sulfur ylide derived from trimethyl sulfoxonium iodide (TMSOI) was then examined. To
our delight, the highly strained aziridine 3c was obtained in higher yield (93 %) and slight better
diastereoselectivity (78:22) (Table 1, entry 2) when dimethyloxosulfonium methylide was used. In
comparison to the reaction of 2c with dimethylsulfonium methylide, the yield was significantly
improved, and the reaction time was also shortened from 4 h to 1.5 h. Solvent effect was then
investigated with TMSOI as the sulfur ylide precusor. Only trace products could be detected by 19F
NMR when low polar THF (Table 1, entry 3) or nonpolar toluene (Table 1, entry 4) was used as
solvent. This result may due to the poor solubility of sulfur ylide in THF or toluene which retarded
the progress of reaction. The effect of DMF (Table 1, entry 5) is comparable to that of DMSO, and
3c was isolated in excellent total yield (95 %), however, the diastereoselectivity was still relatively
4

low (77:23). Fortunately, the dr value was increased from 77:23 to 83:17 as lowering the reaction
temperature from room temperature to -45 oC (Table 1, entry 5 and 8). In addition, the variation of
reaction temperature had no sensible difference on the yields and reaction time for the formation of
trifluoromethylated aziridine (Table 1, entry 5, 6, 7 and 8). Considering that the concentration of
sulfur ylide in the reaction system may have influence on the reaction diastereoselectivity, the
charging sequence of the sulfur ylide and ketimine was then tested. Thankfully, the dropwise
addition of sulfur ylide to 2c in DMF at -45 oC led to a slight higher diastereoselectivity (89:11)
(Table 1, entry 9).
Table 1. Optimization of the Corey-Chaykovsky aziridation of 2c with sulfur ylide.
Entry
1c
Reagent
Me3S+I-
TMSOI
TMSOI
TMSOI
TMSOI
TMSOI
TMSOI
TMSOI
TMSOI
Solvent
DMSO
DMSO
THF
t (h)
4
T (oC)
r.t.
dra(3c)
76:24
78:22
Yieldb(%)
55
2c
1.5
>48
>48
1.5
1.5
1.5
1.5
1.5
r.t.
93
3c
r.t.
-
trace
trace
95
d
4c
Toluene
DMF
r.t.
-
d
5c
r.t.
77:23
79:21
82:18
83:17
89:11
6c
DMF
0
92
7c
DMF
-30
-45
-45
93
8c
DMF
93
9e
DMF
93
a Diastereomeric ratios were determined by 19F NMR spectroscopy of the crude reaction mixture. b Total yield of two
diastereoisomers after flash chromatography. c 2c in DMF was slowly added to the sulfur ylide reaction mixture after 0.5
h. d Not determined. e The in situ generated sulfur ylide solution was slowly added to a solution of 2c in DMF.
The scope with respect to chiral CF3-substituted ketimines for the asymmetric aziridination
under the optimized condition (the in situ generated sulfur ylide was added into a solution of
o
ketimines in DMF at -45 C) is presented in Table 2. Aromatic ketimines as well as aliphatic
5

ketimines were underwent the aziridination smoothly to afford the corresponding aziridine products
in moderate to excellent yield.14,15 In general, the electron-withdrawing groups were beneficial to
the construction of trifluoromethylated aziridines with good diastereoselectivities, but in lower
yields (Table 2, 3d and 3e). The ketimine bearing an electron-donating group gave the highest yield
(93 %) and lower diastereoselectivity (Table 2, 3c). Usually, nucleophile was easy to react with
electron-poor ketimines, but the reactivities of electron-poor ketoimines were further increased by
trifluoromethyl group which resulted in a multitude of undesired side reactions. The acetylenic
trifluoromethylated aziridines were also obtained in excellent diastereoselectivies (> 99:1 dr) and
moderate yields (Table 2, 3f and 3g). The relatively lower yields of 3f and 3g may due to the higher
electronegativity of Csp than that of Csp2 making acetylenic ketimines 2f and 2g more reactive and
leading to undesired side reactions. These results were contrast to the report of Stockman in which
only three of nine ketimines exposed to dimthylsulfonium methylide furnished significant amounts
of the desired aziridines.16
Table 2. Asymmetric synthesis of trifluoromethylated aziridinesa,b,c
o
aReaction conditions: ketimine 2 (0.5 mmol), TMSOI (1.5 mmol) and NaH (1.5 mmol) in DMF (5 mL), -45 C, 1.5 h;
b
the in situ generated sulfur ylide was added into a solution of ketimine in DMF over a 0.5 h period. Diastereomeric
ratios were determined by 19F NMR spectroscopy of the crude reaction mixture. cTotal isolated yield of two
diastereoisomers after flash chromatography.
6

The absolute configuration of the chiral trifluoromethylated aziridine 3d was determined by
X-ray crystallographic analysis which indicated that the newly formed stereocenter was in R
configuration (Fig. 1), and the stereocenter of other major products were tentatively assigned as R by
analogy.17 A possible mechanism was proposed based on the high diastereoselectivity observed and
previous literatures.18 The oxygen present in the dimethyloxosulfonium methylide can promote
chelated transition state as shown in Fig. 2, in which both the sulfinyl oxygen and the
dimethyloxosulfonium methylide oxygen chelate to the sodium ion. In this transition state, the CF3
group prefers to occupy an equatorial position rather than an axial position due to the electrostatic
repulsion between the CF3 group and the lone pair of the sulfur atom, and the nucleophile attack the
C=N bond from the least hindered face to form a chelated transition state.
Figure 1. X-ray crystal structure of (Ss, R)-3d
Figure 2. Transition state of the asymmetric aziridination.
To further demonstrate the synthetic utility of these aziridines, the removal of the sulfinyl group
was firstly investigated. The deprotection of 3c using HCl (4 M in dioxane) at room temperature
gave the desired optically active trifluoromethylated aziridine hydrochloride 4 in 80 % yield.
(Scheme 2). Aziridines are reactive substrates in ring-opening reactions with many nucleophiles due
to their ring strain.19 So the ring-opening reaction of 3b with dimethylsulfonium methylide was then
conducted, but no desired allylamine product was detected even in refluxing THF. This result
7

confirmed that the excess sulfur ylide will not complicate the aziridination reaction. In seeking a
feasibility method to access trifluoromethylated allylic amines, we were attracted to a report from
Hodgson and co-workers20 that focused on the regiodefined conversion of N-sulfonylaziridines to
allylic N-sulfonylamines using dimethylsulfonium methylide. According to Hodgson’s method, the
o
sulfinyl group in aziridine 3b was oxidized into sulfonyl group with m-CPBA at -78 C, then the
21
ring-opening reaction of the resulted sulfonyl aziridine 5 was conducted with in situ generated
dimethylsulfonium methylide to afford chiral allylamine 6 in 67 % yield (Scheme 2).22 This chiral
α-trifluoromethylallylamine may act as important building block in organic chemistry.
Scheme 2
Conclusions
In summary, the chiral CF3-substituted (S)-N-tert-butylsulfinyl ketimines displayed higher
suitabilities than those of their non-fluorinated analogues as substrates for sulfur ylide mediated
aziridination. The high stereo-directing nature of the chiral tert-butyl-sulfinyl group and the unique
electronic property of trifluoromethyl group induced the good diastereoselectivity during the
formation of aziridines. The removal of sulfinyl group from trifluoromethylated aziridine 3c was
readily achieved which provided convenient access to chiral CF3-substituted aziridines. The
synthetic utility of these aziridines was tentatively proved by the successful ring-opening reaction
with dimethylsulfonium methylide.
Acknowledgements
The Innovation Program of Shanghai Municipal Education Commission (13ZZ047), the Scientific
8

Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry and the
Fundamental Research Funds for the Central Universities are greatly acknowledged for funding this
work.
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Smart, B. E. J. Fluorine Chem. 2001, 109, 3-11.
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Fioravanti, S.; Colantoni, D.; Pellacani, L.; Tardella, P. A. J. Org. Chem. 2005, 70, 3296-3298; (c)
Colantoni, D.; Fioravanti, S.; Pellacani, L.; Tardella, P. A. Org. Lett.. 2004 , 6, 197-200; (d)
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Fluorine Chem., 2000, 106, 25-34; (f) Yamauchi, Y.; Kawate, T.; Itahashi, H.; Katagiri, T.;
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Shiosaki, M.; Azema, T.; Hanamoto, T. Org. Lett. 2010, 12, 2548-2550; (h) Higashiyama, K.;
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Kenis, S.; D’hooghe, M.; Verniest, G.; Nguyen, V. D.; Dang, T. A.; Nguyenb, T. V.; Kimpe, N. D.
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9

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Gallon, E. Aldrichim. Acta 2005, 38, 93-104; (d) Daniel, M.; Stockman, R. A. Tetrahedron 2006,
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12 Data for 2f: Pale yellow solid, m.p. 82~83 oC; IR (KBr, cm-1) : 3348, 2190, 162, 1575, 119, 1149,
1039; 1H NMR (400 MHz, CDCl3): δ 1.38 (s, 9 H), 2.95 (s, 3 H), 7.14 (s, 1 H), 7.20 (d, J = 9.0
Hz, 1 H), 7.61 (d, J =8.5 Hz, 1 H), 7.75 (dd, J = 14.5, 8.8 Hz, 2 H), 8.16 (s,1 H); 13C NMR (101
MHz, CDCl3) : δ 22.8, 55.4, 60.3, 79.9, 106.0, 109.2, 114.4, 117.8 (q, J (F,C) =280.8 Hz), 120.0,
127.2, 128.1, 128.9, 130.1, 134.5, 136.0, 145.6（q, J(F,C) =40.4 Hz), 159.7; 19F NMR (375
MHz, CDCl3): δ -71.33; Anal. Calcd for C19H18F3NO2S: C 59.83, H 4.76, N 3.67, Found C 59.97,
H 4.68, N 3.65. 2g: Yellow solid, m.p. 71~72 oC; IR cm-1 : 2973, 2199, 1583, 1466, 1207, 1158,
13
1114 ; 1H NMR (400 MHz, CDCl3): δ 1.37 (s, 9 H), 7.50 (s, 2 H), 7.75 (s, 1 H); C NMR (101
MHz, CDCl3): δ 22.9, 60.9, 80.5, 104.3,117.6 (q, J(F,C) = 279.7 Hz), 119.7, 130.8, 131.9, 133.2,
134.3, 136.3, 144.4 (q, J(F,C) = 40.4 Hz); 19F NMR (375 MHz, CDCl3): δ -71.40; HR-ESI-MS
m/z calcd for C14H13Cl2F3NOS [M + H+] : 370.0047, found 370.0043.
13 (a) Corey, E. J.; Chaykovsky, M. J. Am. Chem. Soc. 1965, 87, 1353-1364; (b) Li, A.-H.; Dai,
L.-X.; Aggarwal, V. K. Chem. Rev. 1997, 97, 2341-2372.
14 General procedure for the preparation of aziridines. NaH (1.5 mmol) was added to a stirred
suspension of trimethyl sulfoxonium iodide (TMSOI) ( 1.5 mmol) in anhydrous DMF (3 mL) at
room temperature. After stirring at room temperature for 0.5 h, the sulfur ylide mixture was
added dropwise to a solution of 2 (0.5 mmol) in anhydrous DMF (2 mL) at -45 °C, and the
reaction was stirred at -45 °C over 1.5 h. After quenching with brine, the cloudy mixture was
10

filtered through Celite, and washed with ethyl acetate, afforded a biphasic solution which was
separated, the aqueous layer was extracted with ethyl acetate (10 mL×3) and washed with brine
(5 mL×3). The combined organic layers were dried (Na2SO4), and solvent was evaporated in
vacuo. The residue was purified by column chromatography with petroleum ether/ethyl acetate
as eluent to give trifluoromethylated aziridine 3.
1
15 Selected data: 3a, dr 84:16; IR(KBr, cm-1): 2926, 2858, 1459, 1163, 1082; H NMR (400 MHz,
CDCl3): δ 0.90 (t, J = 6.6 Hz , 3 H), 1.21-1.35 (m, 27 H), 1.93 (t, J = 8.2 Hz, 2 H), 2.22 (s, 1 H),
2.58 (s, 1 H); 13C NMR (101 MHz, CDCl3): δ 14.1, 22.3, 22.7, 26.2, 26.3, 26.7, 29.2, 29.31, 29.5,
29.6 (d, J(F,C) = 2.0 Hz), 29.7, 30.8 (q, J(F,C) = 123.2 Hz), 31.9, 43.0 (q, J(F,C) = 34.3 Hz), 58.1,
19
124.0 (q, J(F,C) = 277.7 Hz); F NMR (375 MHz, CDCl3): δ -73.33; HR-ESI-MS m/z calcd for
C18H35F3NOS [M+H+]: 370.2391, found 370.2377. 3b, Pale yellow solid, m.p. 39~40 oC; dr 93:7;
1
IR (KBr, cm-1): 2969, 1638, 1344, 1164, 1086; H NMR (400 MHz, CDCl3): δ 1.25 (s, 9 H),
2.56 (s, 1 H), 3.15 (s, 1 H), 7.35-7.66 (m, 5 H); 13C NMR (101 MHz, CDCl3): δ 22.5, 25.5, 45.7
(q, J(F,C) = 36.4 Hz), 57.7, 123.4（q, J(F,C) = 277.8 Hz), 127.9, 128.6, 130.1, 130.7; 19F NMR (375
MHz, CDCl3): δ -73.44; HR-ESI-MS m/z calcd for C13H16F3NNaOS [M + Na+]: 314.0803,
1
found 314.0791. 3c, Colorless oil, dr 86:14; IR (KBr, cm-1): 2965, 1607, 1460, 1174, 1088; H
NMR(400 MHz, CDCl3): δ 1.24 (s, 9 H),2 .54 (s, 1 H), 3.12 (s, 1 H), 3.82 (s, 3 H), 6.93 (d, J =
8.2 Hz, 2 H), 7.43 (d, J = 8.0 Hz, 2 H); 13C NMR (101 MHz, CDCl3): δ 22.4, 25.7, 45.2 (q, J(F,C)
= 36.4 Hz), 55.2, 57.6, 114.0, 119.7, 123.5 (q, J(F,C) = 277.8 Hz), 132.0, 160.7; 19F NMR (375
MHz, CDCl3): δ -73.59; HR-ESI-MS m/z calcd for C14H19F3NO2S [M + H+]: 322.1088, found
322.1081. 3d,white solid, m.p.63~64 oC; dr 92:8; IR (KBr, cm-1): 2961, 1585, 1338, 1174, 1089;
1H NMR (400 MHz, CDCl3): δ 1.25 (s, 9 H), 2.56 (s, 1 H), 3.12 (s, 1 H), 7.42 (dd, J = 19.4 Hz,
7.7 Hz, 4H); 13C NMR (101 MHz, CDCl3): δ 22.4, 25.5, 45.1 (q, J(F,C) = 36.4 Hz), 57.8, 123.4（q,
J(F,C) =277.8 Hz), 126.4, 129.0, 132.0, 136.5; 19F NMR (375 MHz, CDCl3): δ -73.48;
HR-ESI-MS m/z calcd for C13H15ClF3NNaOS [M + Na+]: 348.0413, found 348.0421. 3e, white
o
1
solid, m.p.87~88 C; dr 92:8; IR (KBr, cm-1): 2957, 1580, 1331, 1174, 1080 ; H NMR (400
MHz, CDCl3): δ 1.26 (s, 9 H), 2.60 (s, 1 H), 3.16 (s, 1 H), 7.67 (dd, J = 18.4 Hz, 7.9 Hz, 4H);
13C NMR (101 MHz, CDCl3): δ 22.4, 25.4, 45.2 (q, J(F,C) = 37.4 Hz), 57.9, 123.1 (q, J(F,C)
=
11

278.8 Hz), 123.6 (q, J(F,C) = 273.7 Hz), 125.5 (q, J(F,C) = 4.0 Hz), 131.2, 131.9, 132.2 (q, J(F,C)
=
33.3 Hz); 19F NMR(375 MHz, CDCl3): δ -63.01, -73.31; HR-ESI-MS m/z calcd for
o
C14H16F6NOS [M + H+]: 360.0857, found 360.0861. 3f, pale yellow solid, m.p. 82~83 C; IR
1
(KBr, cm-1): 3064, 2959, 2233, 1619, 1174, 1086; H NMR (400 MHz, CDCl3): δ 1.32 (s, 9 H),
2.56 (s, 1 H), 3.10 (s, 1 H), 3.94 (s, 3 H), 7.12 (d, J = 1.8 Hz, 1 H), 7.18 (dd, J = 8.9 Hz, J = 2.3
Hz, 1 H), 7.52 (d, J = 8.4 Hz, 1.2 Hz, 1 H), 7.70 (dd, J = 12.7 Hz, J = 8.8 Hz, 2 H), 8.00 (s, 1 H);
13C NMR (101 MHz, CDCl3): δ 24.0, 38.2 (q, J(F,C) = 41.4 Hz), 38.3, 55.3, 61.6, 75.7, 90.0,
105.8, 115.7, 119.5, 121.5 (q, J(F,C) = 277.7 Hz), 126.9, 128.2, 128.8, 129.5, 132.5, 134.8, 158.7;
19F NMR (375 MHz, CDCl3): δ -74.28; HR-ESI-MS m/z calcd for C20H21F3NO2S [M + H+]:
418.1065, found 418.1045. 3g, yellow solid, m.p. 68~69; IR cm-1 3060, 2959, 2231, 1598, 1174,
1086 ; 1H NMR (400 MHz, CDCl3): δ 1.29 (s, 9 H), 2.53 (s, 1 H), 3.04 (s, 1 H), 7.34 (d, J =8.3
Hz, 1 H), 7.40 (d, J =8.3 Hz, 1 H), 7.60 (s, 1 H); 13C NMR (101 MHz, CDCl3): δ 22.4, 29.0, 35.6
(q, J(F,C) =40.9 Hz), 58.0, 79.5, 87.1, 120.8, 121.9 (q, J(F,C) =276.7 Hz), 130.4, 131.3, 132.7,
133.7, 134.1; 19F NMR (375 MHz, CDCl3): δ -74.21; HR-ESI-MS m/z calcd for
C15H14Cl2F3NNaOS [M+Na+]: 406.0023, found 406.0027.
16 Morton, D.; Pearson, D.; Field, R. A.; Stockman, R. A. Chem.Commun. 2006, 1833-1835.
17 Further details of the crystal data can be obtained from the Cambridge Crystallographic Data
Centre, 12 Union Road, Cambridge, CB2 1EZ, UK (CCDC deposition No. 886795).
18 (a) Fernandez, I.; Valdivia, V.; Gori, B.; Alcudia, F.; Alvarez, E.; Khiar, N. Org. Lett. 2005, 7,
1307-1310; (b) Garcia Ruano, J. L.; Fernandez, I.; del Prado Catalina, M.; Cruz, A. A.
Tetrahedron: Asymm., 1996, 7, 3407-3414.
19 Katagiri, T.; Katayama, Y.; Taeda, M.; Ohshima, T.; Iguchi, N.; Uneyama K. J. Org. Chem.
2011, 76, 9305-9311.
20 Hodgson, D. M.; Fleming, M. J.; Stanway, S. J. Org. Lett. 2005, 7, 3295-3298.
o
21 Aziridine 3b (120 mg, 0.39 mmol) was dissolved in CH2Cl2 (5 mL) and cooled to -78 C,
m-CPBA (120 mg, 0.59 mmol) was then added in one portion. The reaction mixture was allowed
to warm up to 0 oC and stirred for 1 h at 0 oC. Subsequently the reaction mixture was poured into
a saturated aqueous solution of NaHCO3 (5 mL) and extracted with dichloromethane (5 mL×3).
The combined organic phases were washed with 2 N NaOH (5 mL×3) and dried (Na2SO4),
filtered and evaporated in vacuo. The residue was then purified by column chromatography with
12

petroleum ether/ethyl acetate as eluant to give aziridine 5 (102 mg, 84 %). White solid,
o
1
m.p.120~121 C; IR (KBr, cm-1): 2989, 1638, 1345, 1311, 1166, 1122; H NMR (400 MHz,
CDCl3): δ 1.50 (s, 9 H), 2.98 (s, 1 H), 3.28 (s, 1 H), 7.46 (m, 3 H),7.70 (d, J = 7.3 Hz, 2 H); 13C
NMR (101 MHz, CDCl3): δ 24.0, 36.1, 49.6 (q, J(F,C) = 47.5 Hz), 61.7, 122.8 (q, J(F,C) = 278.8
Hz), 126.8, 128.2, 130.4, 131.5; 19F NMR (375 MHz, CDCl3): δ -73.39; HR-ESI-MS m/z calcd
for C13H16F3NNaO2S [M+ Na+]: 330.0752 , found 330.0745.
22 n-BuLi (1.5 M in THF, 0.60 mL, 0.9 mmol) was added dropwise to a stirred suspension of
trimethylsulfonium iodide (184 mg, 0.9 mmol) in THF (5 mL) at -10 °C and keep stirring for 15
min. Aziridine 5 (70 mg, 0.22 mmol) in THF (2 mL) was added dropwise at -20 °C, and the
reaction mixture was stirred for further 3 h. After quenching with brine solution, the layers were
separated. The aqueous layer was extracted with ethyl acetate; the combined organic layers were
dried (Na2SO4), and solvent was evaporated in vacuo. The residue was purified by column
chromatography with petroleum ether/ethyl acetate as eluent to give allylic sulfonamide 6 (48
mg, 67 %). Yellow oil, IR (KBr, cm-1): 2927, 1636, 1456, 1318, 1170, 1129; 1H NMR (400 MHz,
CDCl3): δ 1.46 (s, 9 H), 4.63 (s, 1 H), 5.43 (d, J = 17.6 Hz, 1 H), 5.65 (d, J = 11.2 Hz, 1 H), 6.43
(dd, J = 17.7 Hz, J = 11.2 Hz, 1 H), 7.34-7.50 (m, 3 H), 7.67 (d, J = 7.4 Hz, 2 H); 13C NMR (101
MHz, CDCl3): δ 24.5, 58.4, 61.2, 70.0 (q, J(F,C) = 27.3 Hz), 121.9, 124.8 (q, J(F,C) = 287.9 Hz),
128.3, 129.0, 132.1, 135.4; 19F NMR (375 MHz, CDCl3): δ -73.33; HR-ESI-MS m/z calcd for
C14H18F3NNaO2S [M + Na+]: 344.0908, found 344.0912.
13