Free radical fluoroalkylation of terminal alkenes and alkynes with iododifluoromethanesulfonamides

Article abstract of DOI:10.1007/s11426-010-4139-0

Free radical fluoroalkylation of terminal alkenes and alkynes with iododifluoromethanesulfonamides has been successfully achieved. It was found that both the catalytic amount of sodium dithionite (Na₂S ₂O₄) and the stoichiometric amount of triethylborane (Et₃B)/air can efficiently initiate the current free-radical atom transfer reaction.

Full text of DOI:10.1007/s11426-010-4139-0

SCIENCE CHINA
Chemistry
January 2011 Vol.54 No.1: 95–102
doi: 10.1007/s11426-010-4139-0
• ARTICLES •
· SPECIAL TOPIC · The Frontiers of Chemical Biology and Synthesis
Free radical fluoroalkylation of terminal alkenes and alkynes with
iododifluoromethanesulfonamides
ZHU JieMing, WANG Fei & HU JinBo*
CAS Key Laboratory of Organofluorine Chemistry; Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences,
Shanghai 200032, China
Received August 1, 2010; accepted September 16, 2010
Free radical fluoroalkylation of terminal alkenes and alkynes with iododifluoromethanesulfonamides has been successfully
achieved. It was found that both the catalytic amount of sodium dithionite (Na2S2O4) and the stoichiometric amount of triethyl-
borane (Et3B)/air can efficiently initiate the current free-radical atom transfer reaction.
radical fluoroalkylation, sulfonamide, fluorine, alkene, alkyne
come an important useful synthetic strategy for the prepara-
1 Introduction
tion of partially fluorinated organic molecules [20]. In 2007,
we found that iododifluoromethyl phenyl sulfone (PhSO2CF2I,
1) could serve as a free radical (phenylsufonyl)difluoro-
methylation reagent toward terminal alkenes [21]. This
method was further extended to the stereoselective prepara-
tion of PhSO2CF2- and CF2H-substituted alkenes from termi-
nal alkynes and 1 [22]. Intrigued by these results and by the
practical importance of the ,-difluorinated sulfonamide
functionality, we envisioned that a similar free radical di-
fluoromethanesulfonamide moiety transfer could be possi-
ble by using iododifluoromethanesulfonamides (2) as the
radical fluoroalkylation reagents.
Selective introduction of the fluorine atom(s) or fluorine-
containing moieties into organic compounds to modulate
their biological properties has become a routine and powerful
strategy in both drug design and agrochemical development
[1–12]. In this context, -alkyl or -alkenyl ,-difluori-
nated sulfonamides have recently drawn much attention,
since the introduction of two fluorine atoms into the carbon
atom  to the sulfonamide functionality results in a decrease
of the basicity of sulfonamide as well as an increase of
lipophilicity [13]. Both of these features have important
impacts on biological activity [13–16]. However, the syn-
thetic methods for the efficient preparation of -alkyl or
-alkenyl ,-difluorinated sulfonamides are scarce, except
for the two major methods being the electrophilic fluorination
[13, 17, 18] and nucleophilic fluoroalkylation [19]. In this
paper, we wish to disclose a mild and efficient method to
selectively introduce the (sulfonamido)difluoromethyl moiety
into terminal alkenes or alkynes via a free radical protocol.
Over the past decades, free radical fluoroalkylation of
alkenes and alkynes with fluoroalkyl iodides (RfI) has be-
2 Experimental
2.1 General information
Unless otherwise mentioned, all chemicals were purchased
from commercial sources. Tetrahydrofuran (THF) was
*Corresponding author (email: jinbohu@sioc.ac.cn)
© Science China Press and Springer-Verlag Berlin Heidelberg 2011
chem.scichina.com
www.springerlink.com

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Zhu JM, et al. Sci China Chem January (2011) Vol.54 No.1
freshly distilled over sodium. Anhydrous dimethyl sulfoxide
(DMSO) was distilled over calcium hydride (CaH2) and
stored over activated molecular sieves under N2. Silica gel
(300–400 mesh) was used for column chromatography. All
the melting points were uncorrected. 1H, 13C and 19F nuclear
magnetic resonance (NMR) spectra were recorded on 400
(petroleum ether/ethyl acetate, 3:1 v/v) to afford product
4-(difluoroiodomethylsulfonyl)morpholine 2a (2.7 g, 64%)
as white solid, mp 110–112 °C. H NMR (CDCl3, 300
MHz):  3.77–3.74 (t, J = 5.1, Hz 4H), 3.54–3.51 (t, J =5.2
Hz, 4H); 19F NMR (CDCl3, 270 MHz):  50.6 (s, 2F); 13C
NMR (CDCl3, 75 MHz):  97.3 (t, J = 262.5 Hz), 66.7, 47.1;
IR (Film): 2970, 1455, 1373, 1266, 1173, 1135, 1096 cm1;
MS (EI, m/z, %) 327 (M+, 3.44), 120 (100.00), 56 (17.46),
136 (12.41), 77 (9.84); HRMS (EI) calcd for C5H8F2O3SNI
(M+) 326.9238; found: 326.9239.
1
1
MHz or 300 MHz NMR spectrometer. H NMR chemical
shifts were determined relative to internal tetramethylsilane
(TMS) at  0.0 or to the signal of a residual protonated sol-
vent deuterated chloroform (CDCl3) at  7.26. 13C NMR
chemical shifts were determined relative to internal TMS at
 0.0. 19F NMR chemical shifts were determined relative to
CFCl3 at  0.0. Chemical shifts are reported in parts per
million (ppm). Mass spectra (MS) were obtained on a mass
spectrometer. High-resolution mass (HRMS) data were re-
corded on a high-resolution mass spectrometer using Elec-
tron Impact Ionization (EI) and Electrospray Ionization (ESI).
1-(Difluoroiodomethylsulfonyl)pyrrolidine (2b)
53% yield. Colorless liquid. 1H NMR (CDCl3, 300 MHz): 
3.78–3.74 (t, J = 5.1 Hz, 4H), 3.54–3.51 (t, J = 5.1 Hz, 4H);
19F NMR (CDCl3, 270 MHz):  50.9 (s, 2F); 13C NMR
(CDCl3, 75 MHz):  98.9 (t, J = 262.5 Hz), 49.6, 26.0; IR
(Film): 2936, 1477, 1368, 1210, 1163, 1109, 1066 cm1; MS
(EI, m/z, %) 311 (M+H +, 15.16), 134 (100.00), 120 (57.20),
177 (31.37), 41 (24.81); Anal. calcd for: C5H8F2INO2S C,
19.30; H, 2.59; N, 4.50; found: C, 19.38; H, 2.71; N, 4.45.
2.2 Typical procedure for the preparation of iododi-
fluoromethanesulfonamides (2)
1-(Difluoroiodomethylsulfonyl)piperidine (2c)
4-(Difluoroiodomethylsulfonyl)morpholine (2a)
83% yield. Colorless liquid. 1H NMR (CDCl3, 300 MHz): 
3.63–3.36 (m, 4H), 1.77–1.61 (m, 6H); 19F NMR (CDCl3,
270 MHz):  50.6 (s, 2F); 13C NMR (CDCl3, 75 MHz): 
98.0 (t, J = 260.5 Hz), 48.1, 25.8, 23.5; IR (Film): 2949,
1467, 1371, 1261, 1215, 1097, 958 cm1; MS (EI, m/z, %)
325 (M+, 19.61), 148 (100.00), 134 (63.34), 84 (41.20), 42
(34.68); Anal. calcd for : C6H10F2INO2S C, 23.66; H, 3.61;
N, 3.98; found: C, 23.85; H, 3.54; N, 3.98.
Into a 250 mL round-bottom flask equipped with a reflux
condenser, were added acetonitrile (CH3CN) (100 mL),
water (100 mL) and sodium sulfate (Na2SO4) (2.8 g, 20
mmol). Thereafter, 2,2-difluoro-2-(fluorosulfonyl)acetic acid
(FSO2CF2COOH) (35.6 g, 200 mmol, prepared from tetra-
fluorosultone) was added into the solution [29–32]. The
reaction mixture was stirred at room temperature until the
FSO2CF2COOH was completely consumed (monitored by
19F NMR). The organic layer was separated and distilled,
and the fraction at 63–65 °C was collected to afford
FSO2CF2H (6.5g) [29–32].
2.3 Typical procedures for the reactions between iododi-
fluoromethanesulfonamides (2) and terminal alkenes (7)
Into a 250 mL round-bottom flask, were added mor-
pholine (16.9 g, 190 mmol) and ether (Et2O) (120 mL).
FSO2CF2H (6.5 g, 49 mmol), dissolved in 30 mL of Et2O,
was added into the solution. Thereafter, the reaction mixture
was stirred at room temperature overnight. Water (60 mL)
was then added into the reaction mixture, followed by ex-
traction with Et2O (30 mL × 3). The combined organic
phase was dried over anhydrous Na2SO4. After filtration and
solvent removal, product 4-(difluoromethylsulfonyl)mor-
pholine (6a, 3.2 g) was obtained.
Under N2 atmosphere, a mixture of 6a (2.6 g, 13 mmol),
iodine (I2) (13.2 g, 52 mmol) and dimethyl formamie (DMF)
(80 mL) were stirred at 30 °C. Potassium tert-butoxide
(t-BuOK) (8.7 g, 76 mmol), dissolved in 50 mL of DMF,
was added slowly into the reaction mixture over 1. The so-
lution was stirred for another 4 h. The reaction was then
quenched with aqueous hydrochloric acid (HCl) (1 M) and
extracted with Et2O (50 mL × 3). The combined organic
phase was washed with brine and water, and then dried over
anhydrous Na2SO4. After filtration and solvent removal, the
crude product was purified by silica gel chromatography
Method A. Na2S2O4 (5 mg, 0.03 mmol) was added into a
mixture of 2a (100 mg, 0.3 mmol), 1-hexene (38 mg, 0.45
mmol), sodium bicarbonate (NaHCO3) (3 mg, 0.04 mmol),
actonitrile (1.0 mL) and water (1.0 mL). The reaction mix-
ture was stirred at room temperature for 20 min, and water
(10 mL) was then added into the reaction mixture, followed
by extraction with Et2O (10 mL × 3). The combined organic
phase was washed with brine and water, and then dried over
anhydrous Na2SO4. After filtration and solvent removal, the
crude product was purified by silica gel chromatography
(petroleum ether/ethyl acetate, 10:1 v/v) to afford pure
product 4-(1,1-difluoro-3-iodoheptylsulfonyl)morpholine (8a)
1
(89 mg, 80%) as a colorless liquid. H NMR (CDCl3, 300
MHz):  4.39–4.30 (m, 1H), 3.77–3.74 (t, J = 5.2 Hz, 4H),
3.53–3.49 (t, J = 5.2 Hz, 4H), 3.16–2.87 (m, 2H), 1.87–1.74
(m, 2H), 1.47–1.25 (m, 5H); 19F NMR (CDCl3, 270 MHz):
 102.8 (ddd, J = 9.9 Hz, J = 26.3 Hz, J = 229.6 Hz, 1F),
104.5 (ddd, J = 9.5 Hz, J = 26.7 Hz, J = 229.6 Hz, 1F); 13C
NMR (CDCl3, 75 MHz):  124.7 (t, J = 217.5 Hz), 66.6,
46.8, 42.3 (t, J = 15.1 Hz), 39.9, 31.5, 21.6, 21.4, 13.8; IR

Zhu JM, et al. Sci China Chem January (2011) Vol.54 No.1
97
(Film): 2863, 1456, 1369, 1263, 1176, 1116, 1084 cm1; MS
(ESI, m/z, %) 434 (M+Na+); Anal. calcd for: C11H20F2INO3S
C, 32,72; H, 5.11; N, 5.11; found: C, 32.72; H, 5.11; N,
3.41.
231.2 Hz, 1F), 103.4 (ddd, J = 10.5 Hz, J = 27.2 Hz, J =
231.2 Hz, 1F); 13C NMR (CDCl3, 75 MHz):  140.3, 128.7,
124.9, 66.7, 47.0, 42.5 (t, J=14.1 Hz), 35.8, 20.9; IR (Film):
3026, 1599, 1370, 1259, 1176, 1116, 1069 cm1; MS (EI,
m/z, %) 459 (M+ 3.16), 91 (100.00), 117 (67.79), 134
(33.59), 88 (20.40); HRMS (EI) calcd for C15H20F2O3SNI
(M +) 459.0177; found: 459.0176.
7,7-Difluoro-5-iodo-7-(morpholinosulfonyl)heptan-2-one (8b)
91% yield. Colorless liquid. 1H NMR (CDCl3, 300 MHz): 
4.43–4.33 (m, 1H), 3.78–3.74 (t, J = 5.1 Hz, 4H), 3.54–3.50
(t, J = 5.2 Hz, 4H), 3.22–2.90 (m, 2H), 2.78–2.60 (m, 2H),
2.20 (s, 3H), 2.13–1.94 (m, 2H); 19F NMR (CDCl3, 270
MHz):  102.0 (ddd, J = 8.8 Hz, J = 27.2 Hz, J = 231 Hz,
1F), 104.4 (ddd, J = 8.8 Hz, J = 27.2 Hz, J = 231 Hz, 1F);
13C NMR (CDCl3, 75 MHz):  206.9, 124.8 (t, J=210.1 Hz),
66.9, 47.0, 43.7, 42.7 (t, J = 14.3 Hz), 34.1, 30.3, 20.7; IR
(Film): 2927, 1716, 1453, 1363, 1264, 1174, 1115 cm1; MS
(EI, m/z, %) 82 (100.00), 83 (54.28), 298 (35.09), 56
(28.47); HRMS (EI) calcd for C11H18NF2O4S (M–I+)
298.0925; found: 298.0927.
4-(1,1-Difluoro-3-iodononylsulfonyl)morpholine (8h)
66% yield. Colorless liquid. 1H NMR (CDCl3, 300 MHz): 
4.38–4.31 (m, 1H), 3.73–3.71 (t, J = 5.2 Hz, 4H), 3.49–3.47
(t, J = 5.2 Hz, 4H), 3.11–2.82 (m, 2H), 1.67–1.54 (m, 2H),
1.29–1.26 (m, 8H), 0.85–0.84 (t, J = 6.8 Hz, 3H); 19F NMR
(CDCl3, 270 MHz):  107.8 (ddd, J=10.5 Hz, J=25.6 Hz,
J = 230.5 Hz, 1F), 109.7 (ddd, J=10.4 Hz, J=25.2 Hz, J=
230.5 Hz, 1F); 13C NMR (CDCl3, 75 MHz):  124.7 (t, J=
210.5 Hz), 66.7, 46.7, 42.4 (t, J = 15.1 Hz), 40.3, 31.7, 31.5,
29.3, 28.1, 22.5, 21.5, 14.0; IR (Film): 2926, 1455, 1370,
1263, 1176, 1116, 1085 cm1; MS (EI, m/z, %) 87 (100.00),
120 (99.03), 86 (76.70), 58 (73.29); HRMS (EI) calcd for
C13H24F2O3SNI (M +) 439.0490; found: 439.0941.
4,4-Difluoro-2-iodo-4-(morpholinosulfonyl)butan-1-ol (8c)
80% yield. Colorless liquid. 1H NMR (CDCl3, 300 MHz): 
4.50–4.41 (m, 1H), 3.82–3.73 (m, 6H), 3.53–3.50 (t, J=5.1
Hz, 4H), 3.27–2.85 (m, 2H), 2.25–2.21 (t, J = 6.8 Hz, 1H);
19F NMR (CDCl3, 270 MHz):  101.4 (ddd, J = 13.8 Hz,
J = 22.2 Hz, J = 232.3 Hz, 1F), 103.1 (ddd, J=13.5 Hz, J=
22.6 Hz, J = 232.3 Hz, 1F); 13C NMR (CDCl3, 75 MHz): 
124.5, 67.8, 66.7, 46.8, 38.4 (t, J = 23.4 Hz), 22.7 (t, J=1.7
Hz); IR (Film): 3367, 2933, 1488, 1372, 1266, 1179, 1070
cm1; MS (EI, m/z, %) 385 (M+, 3.15), 107 (100.00), 88
(75.96), 56 (65.26), 134 (56.86); HRMS (EI) calcd for
C8H14F2O4SNI (M+) 384.9656; found: 384.9661.
1-(1,1-Difluoro-3-iodoheptylsulfonyl)pyrrolidine (8i)
69% yield. Colorless liquid. 1H NMR (CDCl3, 300 MHz): 
4.41–4.31 (m, 1H), 3.59–3.49 (m, 4H), 3.17–2.86 (m, 2H),
2.01–1.25 (m, 12H), 0.95–0.90 (t, J = 6.9 Hz 3H); 19F NMR
(CDCl3, 270 MHz):  101.5 (ddd, J=10.9 Hz, J=25.6 Hz,
J = 242.6 Hz, 1F), 103.2 (ddd, J=10.7 Hz, J=25.4 Hz, J=
242.6 Hz, 1F); 13C NMR (CDCl3, 75 MHz):  130.1 (t, J=
215.5 Hz), 53.7, 47.2 (t, J = 15.0 Hz), 44.7, 36.2, 30.7, 26.7,
26.4, 18.6; IR (Film): 2961, 1362, 1260, 1165, 1092, 1015,
798 cm1; MS (EI, m/z, %) 118 (100.00), 70 (51.06), 136
(28.68), 268 (20.24); HRMS (EI) calcd for C11H20F2O2SNI
(M+) 395.0228; found: 395.0238.
4-(1,1-Difluoro-2-(4-(iodomethyl)-tetrahydrofuran-3-yl)ethyl-
sulfonyl)morpholine (8d)
1
79% yield. White solid, mp 95–97 °C. H NMR (CDCl3,
1-(1,1-Difluoro-3-iodoheptylsulfonyl)piperidine (8j)
300 MHz):  4.05–3.97 (m, 2H), 3.76–3.72 (t, J = 5.2 Hz,
4H), 3.66–3.59 (t, J = 8.9 Hz, 2H), 3.52–3.49 (t, J = 5.2 Hz,
4H), 3.25–3.14 (m, 1H), 3.08–3.02 (t, J = 10.7 Hz, 1H),
2.86–2.18 (m, 4H); 19F NMR (CDCl3, 270 MHz):  102.1
(ddd, J=9.2 Hz, J=29.2 Hz, J=231.9 Hz, 1F), 104.2 (ddd,
J=9.1 Hz, J=28.7 Hz, J=231.9 Hz, 1F); 13C NMR (CDCl3,
75 MHz):  125.3 (t, J = 210.5 Hz), 73.9, 73.8, 71.5, 66.7,
46.8, 45.1, 36.3, 29.3 (t, J = 15.1 Hz), 6.7, 3.1; IR (Film):
2978, 1448, 1365, 1262, 1135, 1017, 954 cm1; MS (EI, m/z,
%) 147 (100.00), 134 (59.04), 87 (56.92), 56 (55.88); Anal.
calcd for: C11H18F2INO4S C, 30.88; H, 4.54; N, 3.21; found:
C, 31.07; H, 4.27; N, 3.29.
63% yield. Colorless liquid. 1H NMR (CDCl3, 300 MHz): 
4.40–4.31 (m, 1H), 3.55–3.38 (m, 4H), 3.22–2.86 (m, 2H),
1.89–1.27 (m, 12H), 0.96–0.91 (t, J = 7.3 Hz 3H); 19F NMR
(CDCl3, 270 MHz):  102.3 (ddd, J=11.2 Hz, J=27.2 Hz,
J = 230.6 Hz, 1F), 104.1 (ddd, J=11.1 Hz, J=27.5 Hz, J=
230.6 Hz, 1F); 13C NMR (CDCl3, 75 MHz):  124.7 (t, J=
210.5 Hz), 66.7, 46.7, 42.5 (t, J = 15.1 Hz), 40.0, 31.5, 21.6,
21.4, 13.9; IR (Film): 2958, 1491, 1363, 1163, 1116, 1015,
910 cm1; MS (EI, m/z, %) 118 (100.00), 70 (48.69), 268
(26.89), 136 (26.22); Anal. calcd for: C12H22F2INO2S C,
33.52; H, 5.42; N, 3.42; found: C, 33.60; H, 5.21; N, 3.39.
Method B. Under nitrogen (N2) atmosphere, into a 10 mL
Schlenk flask were added 2a (163 mg, 0.5 mmol),
trimethyl(vinyl)silane (100 mg, 1.0 mmol) and benzene (2.0
mL), followed by the addition of Et3B (0.5 mL, 1 M in
hexane) at °C. Thereafter, air (ca. 1 equiv) was injected into
the flask via a syringe. The reaction mixture was then
stirred for 20 min. After the solvent was removed under
4-(1,1-Difluoro-3-iodo-5-phenylpentylsulfonyl)morpholine (8g)
1
70% yield. White solid, mp 40–42 °C. H NMR (CDCl3,
300 MHz): 7.33–7.20 (m, 5H), 4.33–4.24 (m, 1H),
3.75–3.72 (t, J = 5.2 Hz, 4H), 3.51–3.48 (t, J = 5.2 Hz, 4H),
3.22–2.67 (m, 4H), 2.16–2.05 (m, 2H); 19F NMR (CDCl3,
270 MHz):  101.8 (ddd, J = 10.9 Hz, J = 27.0 Hz, J =

98
Zhu JM, et al. Sci China Chem January (2011) Vol.54 No.1
vacuum, the crude product was purified by silica gel chro-
matography (petroleum ether/ethyl acetate, 5:1 v/v) to afford
pure product 4-(1,1-difluoro-3-iodo-3-(trimethylsilyl)propy-
lsulfonyl)morpholine 8e (147 mg, 87% yield) as white solid.
mp 77–79 °C. 1H NMR (CDCl3, 300 MHz):  3.78–3.74 (t,
J = 5.0 Hz, 4H), 3.54–3.51 (t, J=5.2 Hz, 4H), 3.27–3.22 (dd,
J=2.9 Hz, J=10.2 Hz 1H), 3.06–2.61 (m, 2H), 0.21 (s, 9H);
19F NMR (CDCl3, 270 MHz):  103.4 (ddd, J=6.8 Hz, J=
26.9 Hz, J = 230.1 Hz, 1F), 105.1 (ddd, J=7.1 Hz, J=25.7
Hz, J = 230.1 Hz, 1F); 13C NMR (CDCl3, 75 MHz):  124.2
(t, J = 210.1 Hz), 66.7, 46.8, 35.8 (t, J = 15.1 Hz), 1.9, 2.5;
IR (Film): 2921, 1455, 1371, 1174, 1133, 1081, 1050 cm1;
MS (EI, m/z, %) 73 (100.00), 134 (45.22), 86 (43.27), 56
(39.97).; HRMS (EI) calcd for C10H20F2O3SNISi (M+)
426.9946; found: 426.9943.
purified by silica gel chromatography (petroleum ether/ethyl
acetate, 20:1 v/v) to afford product 10a (135 mg, 71%) with
E/Z = 7:1 (determined by 19F NMR).
2-(6,6-Difluoro-4-iodo-6-(morpholinosulfonyl)hex-4-enyl)is-
oindoline-1,3-dione (10b)
39% yield, with E/Z = 4:1 (determined by 19F NMR). White
1
solid, mp 133–135 °C. H NMR (CDCl3, 300 MHz): 
7.96–7.88 (m, 2H), 7.77–7.74 (m, 2H), 6.48–6.39 (t, J=14.1
Hz, 1H), 3.71–3.69 (t, J = 5.2 Hz, 4H), 3.60–3.51 (m, 2H),
3.41–3.38 (t, J = 5.2 Hz, 4H), 2.84–2.73 (m, 2H), 2.09–1.96
(m, 2H); 19F NMR (CDCl3, 270 MHz):  94.7 (d, J = 15.7
Hz, 2F; E-isomer), 97.7 (d, J = 15.5 Hz, 2F; Z-isomer); 13
C
NMR (CDCl3, 75 MHz):  168.4 (d, J = 7.7 Hz), 134.3,
132.2, 128.1 (t, J = 17.3 Hz), 123.5, 121.0, 67.0 (d, J=10.1
Hz), 47.1, 38.8, 36.9, 28.5; IR (Film): 3459, 2927, 1712,
1623, 1466, 1361, 1259 cm1; MS (EI, m/z, %) 118 (100.00),
70 (49.83), 136 (26.12), 268 (22.01).; HRMS (EI) calcd For
C18H19F2O5SN2 (M–I +) 413.0983; found: 413.0986.
2.4 Typical procedures for the reactions between iododi-
fluoromethanesulfonamides (2) and terminal alkynes (9)
Method A. Na2S2O4 (17 mg, 0.1 mmol) was added into a
mixture of 2a (327 mg, 1.0 mmol), 1-hexyne (123 mg, 1.5
mmol), NaHCO3 (8 mg, 0.1 mmol), actonitrile (3.0 mL) and
H2O (3.0 mL). The reaction mixture was stirred at room
temperature for 20 min, and then water (20 mL) was
added into the mixture, which was then extracted with Et2O
(10 mL × 3). The combined organic phase was washed with
brine and water, and then dried over anhydrous Na2SO4.
After filtration and solvent removal, the crude product was
purified by silica gel chromatography (petroleum ether/ethyl
acetate, 20:1 v/v) to afford recycled starting material 2a
(151 mg) and pure product 4-(1,1-difluoro-3-iodohept-2-
enylsulfonyl)morpholine (10a) as colorless liquid (115 mg,
4-(1,1-Difluoro-3-iodonon-2-enylsulfonyl)morpholine (10c)
73% yield, with E/Z = 5:1 (determined by 19F NMR). Col-
orless liquid. H NMR (CDCl3, 300 MHz):  6.44–6.34 (t,
1
J = 14.1 Hz, 1H), 3.77–3.73 (t, J=5.1 Hz, 4H), 3.52–3.50 (t,
J = 5.1 Hz, 4H), 2.69–2.64 (t, J=8.4 Hz, 2H), 1.64–1.53 (m,
2H), 1.38–1.26 (m, 6H), 0.92–0.87 (t, J = 7.1 Hz 3H); 19F
NMR (CDCl3, 270 MHz):  94.5 (d, J = 9.4 Hz, 2F; iso-
mer); 13C NMR (CDCl3, 75 MHz):  126.8 (t, J = 15.3 Hz),
123.7, 121.2, 66.8, 46.9, 41.3, 31.5, 30.1, 28.2, 22.5, 14.1;
IR (Film): 2930, 1628, 1371, 1263, 1177, 1117, 955 cm1;
MS (EI, m/z, %) 103 (100.00), 246 (92.97), 226 (86.57), 56
(72.72); HRMS (EI) calcd for C13H22F2O3SN (M–I+)
310.1288; found: 310.1282.
1
52% yield), with E/Z = 6:1 (determined by 19F NMR). H
NMR (CDCl3, 300 MHz):  6.44–6.36 (t, J = 14.4 Hz, 1H),
3.77–3.74 (t, J = 5.0 Hz, 4H), 3.56–3.53 (t, J = 5.2 Hz, 4H),
2.70–2.65 (t, J = 8.4 Hz, 2H), 1.60–1.33 (m, 4H), 0.96–0.91
(t, J = 6.9 Hz, 3H); 19F NMR (CDCl3, 270 MHz):  94.6 (d,
J = 3.9 Hz, 2F; E-isomer), 97.4 (d, J = 4.0 Hz, 2F;
Z-isomer); 13C NMR (CDCl3, 75 MHz):  127.1 (t, J = 9.8
Hz), 121.3 (t, J = 210.5 Hz), 67.0, 47.1, 41.2, 32.4, 21.9,
14.1; IR (Film): 2960, 1627, 1371, 1262, 1201, 1116, 953
cm1; MS (ESI, m/z) 432 (M+Na+); Anal. calcd for:
C11H18F2INO3S C, 32.28; H, 4.43; N, 3.42; found: C, 32.63;
H, 4.79; N, 3.39.
Method B. Under N2 atmosphere, into a 10 mL Schlenk
flask were added 2a (163 mg, 0.5 mmol), 1-hexyne (82 mg,
1.0 mmol) and benzene (1.0 mL), followed by the addition
of Et3B (0.5 mL, 1M in hexane) at 0 °C. Thereafter, air
(ca. 1 equiv) was injected into the flask. The reaction mix-
ture was stirred for additional 30 min. Water (10 mL) was
added into the mixture, which was then extracted with Et2O
(10 mL × 3). The combined organic phase was washed with
brine and water, and then dried over anhydrous MgSO4.
After filtration and solvent removal, the crude product was
4-(1,1-Difluoro-3-iodo-5-phenylpent-2-enylsulfonyl)morph-
oline (10d)
55% yield, with E/Z = 99:1 (determined by 19F NMR).
1
White solid. mp 79–81 °C. H NMR (CDCl3, 300 MHz): 
7.34–7.19 (m, 5H), 6.48–6.39 (t, J = 14.5 Hz, 1H), 3.76–3.73
(t, J = 5.2 Hz, 4H), 3.52–3.48 (t, J = 5.2 Hz, 4H), 3.00–2.82
(m, 4H); 19F NMR (CDCl3, 270 MHz):  95.0 (d, J =14.6
Hz, 2F; E-isomer); 13C NMR (CDCl3, 75 MHz):  139.7,
128.5, 127.5 (t, J = 18.3 Hz), 126.4, 121.1, 66.7, 46.9, 43.3,
36.2; IR (Film): 3852, 2860, 1633, 1453, 1357, 1261, 1173
cm1; MS (EI, m/z, %) 91 (100.00), 180 (28.12), 56 (14.03),
246 (11.01); HRMS (EI) calcd C15H18F2O3SNI (M+)
457.0020; found: 457.0013.
4-(1,1-Difluoro-3-iodoundec-2-enylsulfonyl)morpholine (10e)
50% yield, with E/Z = 6:1 (determined by 19F NMR). Col-
1
orless liquid. H NMR (CDCl3, 300 MHz):  6.46–6.36 (t,
J = 14.2 Hz, 1H), 3.79–3.76 (t, J=5.1 Hz, 4H), 3.55–3.51 (t,
J = 5.1 Hz, 4H), 2.70–2.65 (t, J = 8.4 Hz 2H), 1.64–1.26 (m,
12H), 0.93–0.88 (t, J = 7.2 Hz, 3H); 19F NMR (CDCl3, 270

Zhu JM, et al. Sci China Chem January (2011) Vol.54 No.1
99
First of all, we examined the free radical fluoroalkylation
reaction by using iododifluoromethanesulfonamide 2a and
1-hexene as model compounds (Table 1). We first examined
the reaction of 1a with 1-hexene 2a under different reaction
conditions (Table 1). It was interesting to found that, unlike
our previous radical reactions with iododifluoromethyl
phenyl sulfone (PhSO2CF2I) (1) [21, 22], Na2S2O4 was an
efficient initiating system for the radical polyfluoroalkyla-
tion reactions with 2a. We found that when we used 1.3
equiv of Na2S2O4 initiator (in combination of NaHCO3), 2a
was mostly transformed into corresponding sodium di-
fluoromethanesulfinate via a classical sulfinatodehalogena-
tion process [28], which was determined by 19F NMR (Table
1, entry 1). Product 8a was obtained in 81% yield when the
Na2S2O4 (0.1 equiv) was used (entry 4). After a quick scan-
ning of the reactant ratio, an optimal yield of 8a (80%) was
obtained when the reaction proceeded in CH3CN/H2O at
room temperature for 20 min with a molar ratio 2a:7a =
1:1.5 (entry 5).
MHz):  94.4 (d, J = 9.4 Hz, 2F; E-isomer), 97.3 (d, J =
9.1 Hz 2F; Z-isomer); 13C NMR (CDCl3, 75 MHz):  127.0
(t, J = 15.1 Hz), 123.8, 121.3, 66.9, 48.7, 41.5, 32.0, 30.3,
29.5, 29.3, 28.7, 28.2, 22.8, 14.3; IR (Film): 2930, 1627,
1454, 1371, 1262, 1176, 1116 cm1; MS (EI, m/z, %) 274
(100.00), 254 (82.21), 103 (61.46), 145 (50.59); HRMS (EI)
calcd.C15H26F2O3SNI (M+) 465.0646; found: 465.0653.
3 Results and discussion
N,N-Disubstituted iododifluoromethanesulfonamides 2 were
not previously known. Inspired by the simple preparation of
iododifluoromethyl phenyl sulfone (PhSO2CF2I, 1) [23], we
prepared 2a–c with 53%–83% yields via t-BuOK-mediated
iodination of the corresponding difluoromethanesulfonamides
6a–c (Scheme 1). Difluoromethanesulfonamides 6 was pre-
pared according to the previous reports by Chen, Jiang and
their coworkers [24–27].
Furthermore, we found that the Et3B/air initiating system
could also work in this reaction (Table 2), which is similar
to the radical fluoroalkylation reactions with PhSO2CF2I (1)
[21, 22]. As shown in Table 2, the reactions were carried
out in dichloromethane (DCM), THF, toluene, or benzene to
give the product 3a in moderate yields (Table 2, entries
1–5). The concentration of 1a had little effect on the prod-
uct yield (entries 6–8). The optimal yield (81%) was ob-
tained when the reaction was carried out in benzene at 0 °C,
with a reactant ratio of 1a and 2a being 1:2 (entry 8).
By choosing the above reaction conditions (method A:
Table 1, entry 5; and method B: Table 2, entry 8) as stan-
dard, we next investigated the scope of the reaction between
2a and alkenes 7 (Table 3). In most cases as shown in Table
3, the reactions proceeded smoothly and regioselectively to
give the corresponding products 8a–h in satisfactory to
good yields, with the reaction being compatible with different
Scheme 1 Preparation of iododifluoromethanesulfonamides 2a–c (yields
of 2 were determined based on 6).
Table 1 Survey of reaction conditions between 2a and 7a (method A)
Entry
Initiator a)
Molar ratio (2a:7a)
Solvent b)
Temp.
Yield (%) c)
d)
1
2
3
4
5
6
7
Na2S2O4/NaHCO3 (1.3 equiv)
Na2S2O4/NaHCO3 (0.5 equiv)
Na2S2O4/NaHCO3 (0.2 equiv)
Na2S2O4/NaHCO3 (0.1 equiv)
Na2S2O4/NaHCO3 (0.1 equiv)
Na2S2O4/NaHCO3 (0.1 equiv)
Na2S2O4/NaHCO3 (0.1 equiv)
1:2
1:2
H2O/CH3CN
H2O/CH3CN
H2O/CH3CN
H2O/CH3CN
H2O/CH3CN
H2O/CH3CN
H2O/CH3CN
rt
rt
–
45
81
81
80
52
79
1:2
rt
1:2
rt
1:1.5
1:1
rt
rt
1:1.5
0 °C
a) The molar ratio of Na2S2O4/NaHCO3 = 1:1, and the equivalent amount is relative to 2a; b) v/v = 1:1; c) isolated yield; d) no desired product was observed
by 19F NMR.

100
Zhu JM, et al. Sci China Chem January (2011) Vol.54 No.1
Table 2 Survey of reaction conditions between 1a and 2a (method B)
Entry
Molar ratio 2a:7a
Solvent
DCM
T (°C)
Concentration of 2a (mmol/mL)
Yield (%) a)
1
2
3
4
5
6
7
8
9
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:2
1:1.5
1:1
0
30
0
0.15
0.15
0.15
0.15
0.15
0.15
0.25
0.31
0.31
0.31
55
62
57
52
56
74
79
81
58
26
DCM
THF
toluene
benzene
benzene
benzene
benzene
benzene
benzene
30
rt
0
0
0
0
10
0
a) Isolated yield.
Table 3 The reaction between compound 2a and terminal alkenes 7
Entry
1
Substrate
Method a)
A
Product
Yield (%) b)
80
2
A
91
3
4
5
6
A
A
B
A
80
79
87
21 c)
7
8
A
A
70
66
a) Method A: Na2S2O4/NaHCO3 (0.1 equiv relative to 2a) as the initiator, molar ratio 2a:7 = 1:1.5, room temperature, H2O/CH3CN as the solvent (see Ta-
ble 1, entry 5); Method B: Et3B/air (ca. i.0 equiv) as the initiator, molar ratio 2a:7 = 1:2, benzene as the solvent, 0 °C (see Table 2, entry 8); b) isolated yield;
c) determined by 19F NMR using PhCF3 as an internal standard.

Zhu JM, et al. Sci China Chem January (2011) Vol.54 No.1
101
functionalities such as carbonyl, hydroxyl, ether, trimethyl-
silyl (TMS), and aryl groups. Next, we further examined the
reactions between 2a and various alkynes 9 (Table 4). To
our delight, the reactions with alkynes occurred smoothly to
give products 10 in medium yields and with satisfactory E/Z
ratios. It should be mentioned that when the similar radical
(sulfonamido)difluoromethylation was applied to internal
alkenes or alkynes (instead of terminal ones), very low
yields of products were observed.
Furthermore, the Na2S2O4-initiated fluoroalkylation reac-
tions was also extended to other two iododifluoromethane-
sulfonamides, 1-(difluoroiodomethylsulfonyl)pyrrolidine (2b)
and 1-(difluoroiodomethylsulfonyl)piperidine (2c). It was
found that under similar reaction conditions as Method A
(Table 1, entry 5), the fluoroalkylation of 1-hexene with 2b
and 2c give the corresponding products 8i and 8j in 69%
and 63% yield, respectively (Scheme 2).
4 Conclusions
In summary, free radical fluoroalkylation of terminal alkenes
and alkynes with iododifluoromethanesulfonamides has
been successfully achieved for the first time. It was found
that both the catalytic amount of Na2S2O4 and the stoichiomet-
ric amount of Et3B/air can efficiently initiate the current
free-radical atom transfer reaction. Given the high impor-
tance of fluorinated sulfonamide functionality, this synthetic
method promises to find applications in life sciences.
Scheme 2 Reaction between iododifluoromethanesulfonamides 2b–c and
1-hexene.
Table 4 Reaction between compound 1 and terminal alkynes 5
Entry
1
Substrate
Method a)
A
Product
Yield (%) b)
52 (6:1)
B
B
71 (7:1)
39 (4:1)
2
3
4
5
B
B
B
73 (5:1)
55 (99:1)
50 (6:1)
a) Method A: Na2S2O4/NaHCO3 (0.1 equiv relative to 2a) as the initiator, molar ratio 2a:9 = 1:1.5, room temperature, H2O/CH3CN as the solvent (see Ta-
ble 1, entry 5); Method B: Et3B/air (ca. i.0 equiv) as the initiator, molar ratio 2a:9 = 1:2, benzene as the solvent, 0 °C (see Table 2, entry 8); b) isolated yield;
the data in the parentheses are the E/Z isomeric ratios that were determined by 19F NMR.

102
Zhu JM, et al. Sci China Chem January (2011) Vol.54 No.1
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