Sodium dithionite initiated reaction of pent-4-en-1-amines with fluoroalkyl iodides for the synthesis of 2-fluoroalkyl pyrrolidine derivatives

Article abstract of DOI:10.1016/j.tet.2010.11.090

Pent-4-en-1-amines are reactive to fluoroalkyl iodides with respect to sodium dithionite initiated free radical addition reactions. We report here the development of a novel and efficient synthesis of 2-fluoroalkyl pyrrolidine derivatives by sodium dithio

Full text of DOI:10.1016/j.tet.2010.11.090

Tetrahedron 67 (2011) 1251e1257
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Tetrahedron
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Sodium dithionite initiated reaction of pent-4-en-1-amines with fluoroalkyl
iodides for the synthesis of 2-fluoroalkyl pyrrolidine derivatives
,
b
,
a
a
a
Yaoping Zhu a, Xueyan Yang a, Xiang Fang a, Xianjin Yang a , LingLing Ye , Wei Cai , Yan Zhang ,
*
,b,
Fanhong Wu a
*
a Key Lab for Advanced Materials and Institute of Fine Chemicals, East China University of Science and Technology, Shanghai 200237, China
b Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 28 May 2010
Received in revised form 23 November 2010
Accepted 26 November 2010
Available online 1 December 2010
Pent-4-en-1-amines are reactive to fluoroalkyl iodides with respect to sodium dithionite initiated free
radical addition reactions. We report here the development of a novel and efficient synthesis of 2-flu-
oroalkyl pyrrolidine derivatives by sodium dithionite initiated one-pot reaction of pent-4-en-1-amines
bearing various protecting groups with fluoroalkyl iodides. Among which, the N-benzyl-pent-4-en-1-
amine exhibited the best tolerance toward the reaction condition in the present study, affording the
desired adducts 3 in moderate to good yields of 65e85%.
Keywords:
Crown Copyright Ó 2010 Published by Elsevier Ltd. All rights reserved.
Free radical addition-intramolecular
nucleophilic substitution
Fluoroalkyl iodide
Pent-4-en-1-amine
2-Fluoroalkyl pyrrolidine
and basicity of the acid-absorbed reagent might impact such re-
action greatly, therefore problems, such as incomplete conversion
of starting materials, termination at the addition stage or un-
satisfactory side reactions may occur during this reaction process.
To address the issues above, we report here a novel one-pot re-
action of pent-4-en-1-amines with fluoroalkyl iodides initiated by
sodium dithionite to afford 2-fluoroalkyl pyrrolidine derivatives.
1. Introduction
Because of the acknowledged effect of fluorine on the physical
and chemical properties of organic compounds,1,2 and in particular
its potential influence on the biological activity of pharmaceutical
and agrochemical compounds,3e5 the synthesis of fluorine-con-
taining compounds has fueled great interest among the academia.
The addition of fluoroalkyl halide with unsaturated functional
groups has provided a convenient method for the introduction of
fluoroalkyl group into organicmolecules. Such synthetic method has
been used for the reaction of various fluoroalkyl halides with dif-
ferent alkenes and alkynes to afford the corresponding versatile
adductsthat simultaneously bearsynthetically useful CeX bond that
could be further converted to other fluorine-containing derivatives.6
Recently, on a continuing program in the chemistry of fluo-
roalkyl iodides, we have demonstrated sodium dithionite was
effective as an initiator toward the additionelactonization of
4-pentenoic acids with fluoroalkyl iodides, easily affording fluo-
roalkyl lactones.7 On the basis of these results, we envisioned that
the reaction of pent-4-en-1-amines with fluoroalkyl iodides
would result in a series of novel 2-fluoroalkyl pyrrolidines via
2. Results and discussion
We began our investigation with the Na2S2O4-mediated one-
pot addition-intramolecular amination reaction of pent-4-en-1-
amines with fluoroalkyl iodide according to the conditions in our
previous reports.7 Upon the addition of 3,3-dimethyl-pent-4-en-1-
amine (1a) and ClC2F4I (2a) into the solution of CH3CN/H2O (3:1) at
25 ꢀC, followed by introduction of the mixture of 1.4 equiv of
Na2S2O4 and 1.4 equiv of base (NaHCO3 or NaOH) portion wise,
a complicated mixture was afforded. To optimize the reaction
condition for the formation of 2-fluoroalkyl pyrrolidines, a com-
bination of N-protecting groups, fluoroalkyl iodides, and bases was
then attempted.
a
tandem radical addition-intramolecular nucleophilic sub-
2.1. Reaction of N-acyl-3,3-dimethyl-pent-4-en-1-amine (1b,
1c, 1d) with fluoroalkyl iodide
stitution process. However, many factors including the nucleo-
philicity of the amino group, spatial hindrance of the substrate
As shown in Table 1, by investigating the addition of N-acyl-
3,3-dimethyl-pent-4-en-1-amine 1 (1b, 1c, 1d) with 2, we found
* Corresponding authors. E-mail addresses: yxj@ecust.edu.cn (X. Yang), wfh@
ecust.edu.cn (F. Wu).
0040-4020/$ e see front matter Crown Copyright Ó 2010 Published by Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.11.090

1252
Y. Zhu et al. / Tetrahedron 67 (2011) 1251e1257
out that the electron-withdrawing N-acyl groups were un-
satisfactory as N-protecting group toward this reaction.
2.2. Reaction of N-phenyl-3,3-dimethyl-pent-4-en-1-amine
(1e) with fluoroalkyl iodide
a
However, there are still some notable points: (1) In the reaction
of N-acetyl-3,3-dimethyl-pent-4-en-1-amine (1b) with 2a,
additionereduction reaction occurred advantageously (entries
1, 2), giving 5 as the major product, whereas the reaction of 1b
with 2c led to predominantly proceed addition reaction (entry
3), which gave 4 as the major product. (2) In the case of N-Cbz-
3,3-dimethyl-pent-4-en-1-amine (1c) with 2, the major adduct
4 was obtained with no desired product 3 and very few addi-
tionereduction product 5 (entries 4e9), whereas addition be-
Wethenattemptedtoprepare2-fluoroalkylpyrrolidinesbyusing
N-phenyl-3,3-dimethyl-pent-4-en-1-amine (1e) as a starting ma-
terial. However, as shown in Table 2, the reaction unsatisfactorily led
to major additionereduction product 5 and aromatic substitution
product 6 without the formation of the desired 2-fluoroalkyl pyr-
rolidines. In addition, GC analysis indicated 1e was not converted
thoroughlyevenbyprolonged reactiontime in the presenceof either
NaOH or NaHCO3. We speculated the nucleophilicity of amino group
was decreased due to the electron-withdrawing effect of phenyl
group, thus preventing the desired intramolecular substitution,
whereas the additionereduction product 5 was generated by free
radical addition of Rf to C]C and direct subsequent H-abstraction
from the solvent. Meanwhile, the aromatic substitution product 6
was presumably produced via free radical aromatic substitution
reaction promoted by electron-donating amino group.
tween N-PhSO2-3,3-dimethyl-pent-4-en-1-amine (1d) and
2
gave adduct 4 as major products with the minor generation of
the desired 2-fluoroalkyl pyrrolidines (entries 10e15). (3) Al-
though the product 4 was similarly given in the presence of
both bases, however, the use of NaHCO3 or NaOH was inclined
to lead to the concomitant generation of product 5 or 3,
respectively.
Table 1
Reaction of N-acyl-3,3-dimethyl-pent-4-en-1-amines with fluoroalkyl iodides
I
H
H
N
H
N
R I(2),
Na S O /Base
F
2
2 4
N
R
F
R
F
R
+
+
R
R
N
R
R
F
CH CN/H O
3
2
4
1
3
5
R=CH CO, 1b;
3
R =ClC F , 2a;
F 2 4
C F , 2b,
6 13
PhCH OCO, 1c;
2
PhSO , 1d;
2
PhSCF , 2c
2
Entry
1
2
Base
Reaction resultsa(%)
3
4
5
1
2
3
4
5
6
7
8
1b
1b
1b
1c
1c
1c
1c
1c
1c
1d
1d
1d
1d
1d
1d
2a
2a
2c
2a
2a
2b
2b
2c
2c
2a
2a
2b
2b
2c
2c
NaHCO3
NaOH
NaOH
NaOH
NaHCO3
NaOH
NaHCO3
NaOH
NaHCO3
NaOH
NaHCO3
NaOH
NaHCO3
NaOH
db
4ba (41)
4ba (23)
4bc (85)
4ca (68)
4ca (85)
4cb (73)
4cb (78)
4cc (83)
4cc (90)
4da (68)
4da (87)
4db (78)
4db (88)
4dc (86)
4dc (85)
5ba (59)
5ba (77)
d
d
d
d
5ca (32)
5ca (15)
5cb (27)
5cb (12)
5cc (17)
5cc (10)
d
d
d
d
d
9
d
10
11
12
13
14
15
3ca (32)
d
d
3cb (22)
d
d
d
d
d
d
NaHCO3
d
a
The yields were determined by GC analysis of the crude reaction mixture.
The symbol ‘–’ means that the corresponding product was not detected by GC analysis of the crude reaction mixture.
b
Table 2
Reaction of N-phenyl-3,3-dimethyl-pent-4-en-1-amine with fluoroalkyl iodides
H
N
H
H
N
N
Na2S2O4/Base
RFI(2),
RF
+
CH3CN/H2O
RF
5ea, 5eb
6ea, 6eb
1e
Entry
2
Conditions
Reaction resultsa(%)
1e
5
6
1
2
3
4
5
2a
2a
2a
2a
2b
NaOH, 5h
NaOH, 7h
NaOH, 10h
NaHCO3, 5h
NaHCO3, 5h
51.2
51.0
49.0
30.8
20.7
16.3
16.6
16.3
31.7
20.4
24.1
24.0
24.1
25.4
55.7
a
The reaction results were determined by GC analysis of the crude reaction mixture.

Y. Zhu et al. / Tetrahedron 67 (2011) 1251e1257
1253
2.3. Reaction of N-benzyl-3,3-dimethyl-pent-4-en-1-amine
(1f) with fluoroalkyl iodide
Since the development of potent synthetic method for the prep-
aration of chiral fluoroalkyl pyrrolidine derivatives remains chal-
lenging and valuable, we envision that the chiral carbon generated
duringthereactionprocessonpyrrolidinescaffoldinthepresentcase
would potentially lead to a pair of diastereoisomers by introducing
another chiral auxiliary into the substrate. Chiral 2-fluoroalkyl pyr-
rolidine would then be obtained by the subsequent removal of the
chiral auxiliary. The reaction of compound 1g, (S)-N-(1-phenylethyl)-
3,3-dimethyl-pent-4-en-1-amine, which is synthesized by Scheme 1,
with PhSCF2I was initiated, affording the 2-fluoroalkyl pyrrolidine
3gc in 86% yield with 1.27:1 dr.
To our delight, when substrate 1f was used as the starting ma-
terial with the electron-donating benzyl substitution on amino
group of 3,3-dimethyl-pent-4-en-1-amine, the desired 2-fluo-
roalkyl pyrrolidine products were favorably obtained. As revealed
in Table 3, the reaction of 1f with 2a in the presence of NaHCO3
afforded 2-fluoroalkyl pyrrolidine 3fa in 57% GC yield together with
adduct 4fa in 24% GC yield (entry 1 in Table 3). We then found out
that replacement of NaHCO3 by NaOH led to considerably higher GC
yield of 3fa (79%, entry 2 in Table 3). This might be ascribable to the
strong neutralization ability of relatively stronger base toward
certain acidic byproducts during the reaction process (i.e., SO2,
H2SO3, etc.), therefore facilitating the intramolecular nucleophilic
substitution to form pyrrolidine derivatives. With the optimized
reaction condition in hand, several other RFI reactants were
employed to explore the scope of the one-pot preparation of
2-fluoroalkyl pyrrolidines. As summarized in Table 3, all the re-
actions went smoothly, affording the corresponding 2-fluoroalkyl
pyrrolidines in moderate to good yields.
3. Conclusions
In conclusion, the reaction of fluoroalkyl iodides with pent-4-
en-1-amines bearing different protecting groups in the presence of
Na2S2O4 and base (NaHCO3 or NaOH) in aqueous acetonitrile at
room temperature was investigated. The protecting group effect
was found crucial toward such reaction as the electron-with-
drawing acyl- or phenyl-groups led to the major formation of
byproducts, whereas the electron-donating benzyl group favorably
furnished the desired 2-fluoroalkyl pyrrolidine products in good
yields. Our one-pot synthesis of 2-fluoroalkyl pyrrolidines from the
reaction of fluoroalkyl iodides with pent-4-en-1-amines using
Na2S2O4 as the initiator may provide new insights toward the fur-
ther development of novel fluoroalkyl pyrrolidine derivatives that
are of wide applications in organic chemistry. Further studies on
the generality and applicability of this method toward the prepa-
ration of fluoroalkyl-containing natural product analogues are in
progress in our laboratory.
Table 3
The reaction of N-benzyl-3,3-dimethyl-pent-4-en-1-amine (1f) with fluoroalkyl
iodides
R I,
Na2S2O4/Base
F
H
N
N
RF
CH3CN/H2O
1f
RF = ClC2F4, 2a; C6F13, 2b; PhSCF2, 2c
3
4. Experimental
4.1. General
Entry
1
2
Base
3
Yileda(%)
1
2
3
4
1f
1f
1f
1f
2a
2a
2b
2c
NaHCO3
NaOH
NaOH
NaOH
3fa
3fa
3fb
3fc
57b
79
65
85
Melting points were uncorrected. IR spectra were taken on
a PerkineElmer Jeol 983 spectrophotometer. 1H NMR spectra were
recorded on a Bruker AM500 (500 MHz) spectrometer with TMS as
internal standard. 19F NMR spectra were recorded on a Bruker
AM500 (470 MHz) spectrometer with CFCl3 as external standard.
13C NMR spectra were recorded on a Bruker AM500 (125 MHz)
spectrometer. Mass spectra were taken on an HP 5989A spec-
trometer. High-resolution mass data were obtained on a Finnigan
MAT 8430 spectrometer. Column chromatography was performed
a
The yields were determined by GC analysis of the crude reaction mixture.
Meanwhile, 4fa was afforded in 24% GC yield.
b
On the basis of these results observed, the rationale of the for-
mation of 2-fluoroalkyl pyrrolidine products upon the change of
N-protecting group from acyl and phenyl to benzyl moiety may be
explained via SN2 mechanism. The N-acyl in 1b,1c,1d and N-phenyl
in 1e withdrew electron from nitrogen atom, whereas the N-benzyl
in 1f donated electron to nitrogen. Therefore, the nitrogen atom in
the latter case held stronger nucleophilicity to facilitate the intra-
molecular SN2 procedure, forming the 2-fluoroalkyl pyrrolidine
derivatives in good yields.
using silica gel H, particle size 10e40 mm.
4.2. General reaction procedure for the preparation of
substrate 1
4.2.1. The preparation of 3,3-dimethyl-pent-4-en-1-amine (1a). To
a NaOH solution (300 mL, 10 M) was added 3,3-dimethyl-pent-4-
LiAlH
NBS, PPh
CH Cl
OH
Br
4
OCH
3
3
THF
2
2
O
B
C
A
F
S
F
NH
(s)
2
Na S O /NaOH
2c,
2
2 4
NH
N
CH CN/H O
NaI/K CO , DMF
3
2
2
3
1g
d.r. (3gc1:3gc2)
1.27:1
=
Scheme 1.

1254
Y. Zhu et al. / Tetrahedron 67 (2011) 1251e1257
enoic acid methyl ester (A) (113.6 g, 0.8 mol). The mixture was
stirred at reflux for 5 h. After the reaction was completed, diluted
HCl solution was added to acidify the solution. The mixture was
abstracted with methyl tert-butyl ether (30 mL). The combined
organic layer was washed with brine, dried over anhydrous MgSO4.
The mixture was filtered through a plug of Celite. After the solvent
was removed, 92.8 g 3,3-dimethyl-pent-4-enoic acid (D) was
obtained, yield 90.6%.
Compound D (51.2 g, 0.4 mol) in anhydrous CH2Cl2 (300 mL) in
an ice bath was added SOCl2 (95.2 g, 0.8 mol) in 30 min. Five drops
of DMF was added into the mixture. The mixture was refluxed for
5 h. After the removal of volatile solvents under vacuum, a yellow
oil 3,3-Dimethyl-pent-4-enoyl chloride (E) was obtained. The oil
was added dropwise into 25% ammonia aqueous solution. The
mixture was stirred at room temperature for 10 h. After the reaction
was completed, two layers were afforded. The water layer was
abstracted with methyl tert-butyl ether (100 mLꢁ3). The combined
organic layer was washed with saturated brine and dried over
anhydrous MgSO4. The mixture was filtered, the filtrate was con-
centrated to afford 32.3 g crude product F, yield 63.6%. The crude
product could be further purified by recrystallization in petroleum
ether, mp: 98 ꢀC.
Under the N2 atmosphere, to the mixture of LiAlH4 (2.3 g,
0.06 mol) and anhydrous Et2O (20 mL) in an ice bath was added
compound F (3.8 g, 0.03 mol) in Et2O (30 mL) solution. The mixture
was stirred at room temperature for 20 h. Water (6 mL) was added to
quench the reaction. Methyl tert-butyl ether (30 mL) was added to
dilute the mixture. The mixture was filtered, and the filtrate was
dried over anhydrous MgSO4. After the removal of volatile solvents
under vacuum, 2.8 g crude product 1a was obtained, yield 82.5%.
Crude product 1a could be further purified by distillation, bp: 106 ꢀC.
1,4-dioxane (50 mL), and water (80 mL) was added CbzCl (3.7 g,
22 mmol). The mixture was stirred at room temperature for 1 h.
After the reaction was completed, the mixture was abstracted with
methyl tert-butyl ether (50 mLꢁ3). The combined organic layer was
washed with brine and dried over anhydrous MgSO4. The mixture
was filtered through a plug of Celite. After the solvent was removed,
5.6 g crude product 1c was obtained, yield 80.6%. The crude product
could be further purified by distillation under vacuum (2.5 mmHg,
168e171 ꢀC).
4.2.3.1. N-Cbz-3,3-dimethyl-pent-4-en-1-amine (1c). Colorless
oil, bp: 168e171 ꢀC, 0.1 mmHg, 1H NMR (CDCl3)
d 7.29e7.23 (5H, m,
C6H5), 5.74e5.68 (1H, m, CH2]CH), 5.02 (2H, s, CH2Ph), 4.89e4.86
(2H, m, CH2]CH), 4.61(1H, s, NH), 3.11e3.07 (2H, m, CH2CH2NH),
1.47e1.44 (2H, m, CH2CH2NH), 0.95 (6H, s, C(CH3)2).
4.2.4. The preparation of N-phenylsulfonyl-3,3-dimethyl-pent-4-en-
1-amine (1d). To the mixture of D (1.1 g, 10 mmol), pyridine (1.2 g,
15 mmol), and NaOH solution (30 mL, pH¼11) was added phenyl-
sulfonyl chloride (1.8 g, 10 mmol). The mixture was stirred at room
temperature for 3 h. After the reaction was completed, the mixture
was abstracted with methyl tert-butyl ether (20 mLꢁ3). The com-
bined organic layer was washed with brine and dried over anhy-
drous MgSO4. The mixture was filtered through a plug of Celite.
After the solvent was removed, 2.4 g crude product 1d was
obtained, yield 95.1%. The crude product could be further purified
by column chromatography with eluent PE/EA¼10:1.
4.2.4.1. N-Phenylsulfonyl-3,3-dimethyl-pent-4-en-1-amine
(1d). Light yellow oil, 1H NMR (CDCl3)
d 7.87e7.53 (5H, m, C6H5),
5.71e5.66 (1H, m, CH2]CH), 4.94e4.86 (2H, m, CH2]CH), 4.42 (1H,
s, NH), 2.89e2.93 (2H, m, CH2NH), 1.49e1.46 (2H, m, CH2CH2NH),
0.94 (6H, s, C(CH3)2).
4.2.1.1. 3,3-Dimethyl-pent-4-enoicacid methyl ester (A). Colorless
oil, bp: 59 ꢀC, 33 mmHg, 1H NMR (CDCl3)
d 5.93e5.87 (1H, m, CH2]
CH), 5.00e4.94 (2H, m, CH2]CH), 3.65 (3H, s, OCH3), 2.31 (2H, s,
CH2CO), 1.14 (6H, s, C(CH3)2).
4.2.5. The preparation of N-phenyl-3,3-dimethyl-pent-4-en-1-amine
(1e). To a mixture of 3,3-dimethyl-pent-4-enoic acid (D) (13.7 g,
0.11 mol) and benzene (50 mL) in an ice bath was added SOCl2
(15.5 mL, 0.21 mol) in 30 min. The mixture was refluxed for 6 h.
After the removal of volatile solvents under vacuum, a yellow crude
product (E) was obtained.
To a mixture of phenylamine (9.9 g, 0.11 mol), Et3N (10.8 g,
0.11 mol), and methyl tert-butyl ether (50 mL) in an ice bath was
added crude sample E in 30 min, and then stirred at room
temperature for 10 h. Diluted HCl aqueous solution was added
dropwise into the solution to adjust pH to 2e3, a brown solution
was obtained. After the reaction was completed, two layers was
obtained, the water layer was abstracted with CH2Cl2
(30 mLꢁ3). The combined organic layer was dried over anhy-
drous MgSO4. The mixture was filtered through a plug of Celite.
The filtrate was concentrated under vacuum to obtain brown
crude product 3,3-dimethyl-pent-4-enoic acid phenylamide (G)
19.0 g, yield 87.6%.
Under the N2 atmosphere, to the mixture of LiAlH4 (1.5 g,
0.04 mol) and anhydrous THF (40 mL) in a bath was added com-
pound G (4.1 g, 0.02 mol) in THF (40 mL) solution. The mixture was
stirred at room temperature for 20 h. Water (10 mL) was added to
quench the reaction, and methyl tert-butyl ether (50 mL) was added
to dilute the mixture. The mixture was filtered, the filtrate was
dried over anhydrous MgSO4, After the removal of volatile solvents
under vacuum, 2.3 g crude product 1e was obtained, yield 61.7%.
Crude product 1e could be further purified by distillation under
vacuum. Bp: 105e106 ꢀC, 0.1 mmHg.
4.2.1.2. 3,3-Dimethyl-pent-4-enoic amide (F). White solid, mp:
97.3e98.1 ꢀC, 1H NMR (CDCl3)
d 5.97e5.91 (1H, m, CH2]CH), 5.86
(1H, s, NH2), 5.59 (1H, s, NH2), 5.08e5.03 (2H, m, CH2]CH), 2.23
(2H, s, CH2CO), 1.14 (6H, s, C(CH3)2).
4.2.1.3. 3,3-Dimethyl-pent-4-enoic amine (1a). Colorless oil, bp:
160 ꢀC, 760 mmHg, 1H NMR (CDCl3)
d 5.82e5.76 (1H, m, CH2]CH),
4.93e4.89 (2H, m, CH2]CH), 2.66e2.62 (2H, m, CH2CH2NH2), 1.60
(2H, s, CH2NH2), 1.48e1.45 (2H, m, CH2CH2NH2), 1.00 (6H, s, C
(CH3)2).
4.2.2. The preparation of N-acetyl-3,3-dimethyl-pent-4-en-1-amine
(1b). To the mixture of 1a (4.5 g, 40 mmol) and diethyl ether
(200 mL) was added Ac2O (11.2 g,110 mmol). Themixturewas stirred
at roomtemperaturefor8 h. After the reactionwas completed, NaOH
solution (1 M, 200 mL) was added and stirred for 10 h. The organic
layer was separated. The water layer was abstracted with EtOAc
(100 mLꢁ3). The combined organic layer was dried over anhydrous
MgSO4. The mixture was filtered through a plug of Celite. After the
solvent was removed, 5.0 g 1b was obtained, yield 80.3%.
4. 2. 2.1. N-ac etyl-3, 3-d im ethyl-pent-4-en-1-amine
(1b). Colorless oil, 1H NMR (CDCl3)
d 5.82e5.76 (1H, m, CH2]CH),
5.58 (1H, s, NH), 4.98e4.94 (2H, m, CH2]CH), 3.24e3.19 (2H, m,
CH2NH), 1.96 (3H, s, COCH3), 1.53e1.50 (2H, m, CH2CH2NH), 1.03
(6H, s, C(CH3)2).
4.2.5.1. N-phenyl-3,3-dimethyl-pent-4-en-1-amine (1e). Yellow
4.2.3. The preparation of N-Cbz-3,3-dimethyl-pent-4-en-1-amine
oil, bp: 105e106 ꢀC, 0.1 mmHg, 1H NMR (CDCl3)
d
7.21e6.60 (5H, m,
(1c). To the mixture of 1a (2.3 g, 20 mmol), K2CO3 (6.1 g, 44 mmol),
C6H5), 5.89e5.83 (1H, m, CH2]CH), 5.02e4.98 (2H, m, CH2]CH),

Y. Zhu et al. / Tetrahedron 67 (2011) 1251e1257
1255
3.11e3.08 (2H, m, CH2CH2NH), 1.66e1.63 (2H, m, CH2CH2NH), 1.09
(6H, s, C(CH3)2).
1.60e1.55 (m, 1H, 1/2CH2), 1.28e1.24 (m, 1H, 1/2CH2), 0.95 (s, 3H,
CH3), 0.51 (s, 3H, CH3). 19F NMR (CDCl3)
ꢂ72.58 (2F, d, J¼35.3 Hz),
111.81 (2F, m). 13C NMR (CDCl3)
137.4, 133.6,129.9, 128.1, 62.9, 47.1,
d
d
4.2.5.2. The preparation of N-benzyl-3,3-dimethyl-pent-4-en-1-
amine (1f). To a mixture of LiAlH4 (8.1 g, 0.21 mol) and THF
(100 mL) in an ice bath was added 3,3-dimethyl-pent-4-enoic acid
methyl ester (A) (20.2 g, 0.14 mol) in THF (100 mL) and then stirred
at room temperature for 20 h. After the reaction was completed,
water (30 mL) was added and the mixture was diluted with methyl
tert-butyl ether (30 mL). The resulting suspension was filtered. The
filtrate was dried over anhydrous MgSO4. After the removal of
volatile solvents under vacuum, 13.9 g crude product 3,3-dimethyl-
pent-4-en-1-OH (B) was obtained, yield 87.0%. Compound B could
be further purified by distillation under reduced pressure
(65e66 ꢀC, 15 mmHg).
To a mixture of NBS (1.0 g, 5.7 mmol), PPh3 (1.6 g, 6.1 mmol), and
CH2Cl2 (5 mL) in an ice bath was added B (0.5 g, 4.3 mmol) and then
stirred at room temperature for 2 h. After the reaction was com-
pleted, the solvent was removed under vacuum. The residue was
washed with n-hexane (15 mLꢁ4). The suspension was filtered, the
filtrate was concentrated under vacuum, then 0.6 g 5-bromo-3,3-
dimethyl-pent-1-ene (C) was obtained, yield 76.2%.
A mixture of compound C (3.5 g, 20 mmol), benzylamine (2.4 g,
20 mmol), K2CO3 (7.7 g, 60 mmol), NaI (9.0 g, 60 mmol), and DMF
(100 mL) was stirred at 100 ꢀC for 20 h. After the reaction was
completed, The mixture was cooled to room temperature and ab-
stracted with methyl tert-butyl ether (60 mLꢁ3). The combined
organic layer was washed with brine, dried over anhydrous MgSO4.
The mixture was filtered through a plug of Celite. After the solvent
was removed, 3.2 g 1f was obtained, yield 79.5%. The crude product
could be further purified by distillation under vacuum (2.5 mmHg,
108e109 ꢀC).
42.5, 38.9, 34.8, 26.9, 23.4. IR (cmꢂ1, KBr) 2960, 1465, 1445, 1348,
1160, 1095, 935. HRMS calcd for C15H18ClF4NO2S: 387.0683, found:
387.0680.
4.3.2. 3,3-Dimethyl-1-phenylsulfonyl-2-(2,2,3,3,4,4,5,5,6,6,7,7,7-tri-
decafluoroheptyl)-pyrrolidine (3db). Light yellow oil, 1H NMR
(CDCl3)
d 7.88e7.55 (m, 5H, C6H5), 3.51e3.46 (m, 2H, CH2),
3.28e3.22 (m, 1H, CH), 2.90e2.78 (m, 1H, 1/2CH2), 2.53e2.40 (m,
1H, 1/2CH2), 1.72e1.57 (m, 1H, 1/2CH2), 1.36e1.31 (m, 1H, 1/2CH2),
1.02 (s, 3H, CH3), 0.58 (s, 3H, CH3). 19F NMR (CDCl3)
d
ꢂ81.67 (3F, t,
J¼9.9 Hz), ꢂ112.11 (2F, m), ꢂ122.60 (2F, s), ꢂ123.74 (2F, s), ꢂ124.47
(2F, s), ꢂ127.03 (2F, s). 13C NMR (CDCl3)
d 137.4, 133.7, 129.8, 128.2,
62.6, 47.2, 42.5, 39.0, 35.1, 26.9, 23.5. IR (cmꢂ1, KBr) 2966, 2929,
1471, 1447, 1352, 1238, 1095. HRMS calcd for C19H18F13NO2S:
571.0851, found: 571.0854.
4.3.3. 1-Benzyl-2-(3-chloro-2,2,3,3-tetrafluoropropyl)-3,3-dimethyl-
pyrrolidine (3fa). Light yellow oil, 1H NMR (CDCl3)
d 7.26e7.15 (m,
5H, C6H5), 4.01 (d, 1H, J¼13.43 Hz, 1/2CH2), 3.23 (d, 1H, J¼13.43 Hz,
1/2CH2), 2.83 (m, 1H, 1/2CH2), 2.55 (m, 1H, 1/2CH2), 2.37e2.28 (m,
2H, CH2), 2.16e2.08 (m, 2H, CH2), 1.51 (t, 2H, J¼7.07 Hz, CH2), 0.97
(s, 3H, CH3), 0.95 (s, 3H, CH3). 19F NMR (CDCl3)
d
ꢂ72.19 (2F, d,
J¼9.4 Hz), ꢂ112.21 (2F, m). 13C NMR (CDCl3)
d 138.6, 127.6, 127.5,
125.8, 65.4, 57.7, 49.9, 39.7, 38.1, 30.1, 26.4, 23.3. IR (cmꢂ1, KBr) 3315,
2961, 2924, 1788, 1689, 1467, 1261. HRMS calcd for C16H20ClF4N:
337.1220, found: 337.1216.
4.3.4. 1-Benzyl-3,3-dimethyl-2-(2,2,3,3,4,4,5,5,6,6,7,7,7-trideca-
fluoroheptyl)pyrrolidine (3fb). Light yellow oil, 1H NMR (CDCl3)
d
7.32e7.24 (m, 5H, C6H5), 4.06 (d, 1H, J¼13.38 Hz, 1/2CH2), 3.28 (d,
4.2.5.3. N-Benzyl-3,3-dimethyl-pent-4-en-1-amine (1f). Yellow
1H, J¼13.38 Hz, 1/2CH2), 2.87 (m, 1H, 1/2CH2), 2.62 (m, 1H, 1/2CH2),
2.40e2.21 (m, 3H, CHþCH2), 2.22 (m, 2H), 1.59 (m, 2H, CH2), 1.04 (s,
oil, bp: 108e109 ꢀC, 2.5 mmHg, 1H NMR (CDCl3)
d 7.33e7.26 (5H, m,
C6H5), 5.82e5.77 (1H, m, CH2]CH), 4.93e4.90 (2H, m, CH2]CH),
3.77 (2H, s, CH2Ph), 2.62e2.59 (2H, m, CH2CH2NH), 1.55e1.52 (2H,
m, CH2CH2NH), 1.00 (6H, s, C(CH3)2).
In the similar way, with (s)-1-phenyl-ethylamine instead of
benzylamine, 1g was obtained in 82.0% yield.
3H, CH3), 1.03 (s, 3H, CH3). 19F NMR (CDCl3)
d
ꢂ81.69 (3F, t,
J¼11.8 Hz), ꢂ112.35 (2F, m), ꢂ122.63 (2F, s), ꢂ123.78 (2F, s), ꢂ124.27
(2F, s), ꢂ127.05 (2F, s). 13C NMR (CDCl3)
d 138.7, 127.4, 127.2, 125.8,
66.0, 57.7, 49.9, 39.7, 38.1, 28.7, 26.4, 23.4. IR (cmꢂ1, KBr) 2960, 2928,
1659, 1463, 1240, 1204, 1144, 807. HRMS calcd for C20H20F13N:
521.1388, found: 521.1390.
4.2.5.4. N-(1-phenyl-ethyl)-3,3-dimethyl-pent-4-en-1-amine
(1g). Light yellow oil, bp: 97e98 ꢀC, 0.1 mmHg, 1H NMR (CDCl3)
4.3.5. 1-Benzyl-2-(2,2-difluoro-2-phenylthioethyl)-3,3-dimethyl-pyr-
d
7.35e7.22 (5H, m, C6H5), 5.78e5.72 (1H, m, CH2]CH), 4.88e4.85
rolidine (3fc). Light yellow oil, 1H NMR (CDCl3)
d 7.61e7.25 (m, 10H,
(2H, m, CH2]CH), 3.76e3.72 (1H, m, CH(CH3)Ph), 2.49e2.38 (2H,
m, CH2CH2NH), 1.55e1.39 (2H, m, CH2CH2NH), 1.34e1.33 (3H, m,
CHCH3(Ph)), 0.95 (6H, s, C(CH3)2).
2C6H5), 4.09 (d, 1H, J¼13.4 Hz, 1/2CH2), 3.23 (d, 1H, J¼13.4 Hz, 1/
2CH2), 2.83 (m, 1H, 1/2CH2), 2.59 (m, 1H, 1/2CH2), 2.49 (m, 1H, 1/
2CH2), 2.31 (m, 1H, 1/2CH2), 2.17 (m, 1H, CH), 1.25 (m, 2H, CH2), 1.01
(s, 3H, CH3), 0.97 (s, 3H, CH3). 19F NMR (CDCl3)
d 71.37 (ABXY,
4.3. General reaction procedure for the preparation for
compound 3, 4, 5, 6
J¼202.1, 22.1, 11.8 Hz), 71.77 (ABXY, J¼202.1, 16.7, 12.2 Hz). 13C NMR
(CDCl3)
d 24.5, 27.7, 39.3, 50.9, 58.9, 67.8, 126.6, 128.1, 128.5, 129.0,
129.7, 136.2. IR (cmꢂ1, KBr) 3061, 2955, 1667, 1453, 1369, 1170, 1045,
905. HRMS calcd for C21H25F2NS: 361.1676, found: 361.1678.
To a mixture of 1 (1.0 mmol), 2 (1.1 mmol), acetonitrile (9 mL),
and water (3 mL), was added a mixture of sodium dithionite
(244 mg, 1.4 mmol) and sodium hydroxide (56 mg, 1.4 mmol) or
sodium dicarbonate (56 mg, 1.4 mmol) in portions under stirring at
room temperature for 5 h. After the reaction was completed, the
mixture was extracted with methyl tert-butyl ether (3ꢁ30 mL). The
combined organic layer was washed with saturated brine and dried
over anhydrous Na2SO4. The solvent was removed under reduced
pressure and the crude product was purified by column chroma-
tography to give the products 3, 4, 5, 6.
4.3.6. 2-(2,2-Difluoro-2-phenylthioethyl)-3,3-dimethyl-1-((S)-1-
phenylethyl)-pyrrolidine (3gc). Compound 3gc1: light yellow oil, 1H
NMR (CDCl3)
d 7.66e7.25 (m, 10H, 2C6H5), 3.98e3.97 (m, 1H, CH),
2.85e2.84 (m, 2H, CH2), 2.56e2.53 (m, 1H, CH), 2.43e2.29 (m, 2H,
CH2), 1.45e1.44 (m, 3H, CH3), 1.32e1.19 (m, 2H, CH2), 0.91 (s, 3H,
CH3), 0.61 (s, 3H, CH3). 19F NMR (CDCl3)
d
71.19 (ABXY, J¼202.1, 23.0,
9.4 Hz), 71.34 (ABXY, J¼202.1, 23.0, 11.8 Hz). 13C NMR (CDCl3)
d
135.4, 129.1, 128.8, 128.1, 127.1, 124.7, 38.1, 36.1, 30.9, 28.7, 28.4,
22.0, 13.1. IR (cmꢂ1, KBr) 3062, 2959, 2926, 1661, 1446, 1374, 1256.
HRMS calcd for C22H27F2NS: 375.1832, found: 375.1834.
4.3.1. 2-(3-Chloro-2,2,3,3-tetrafluoropropyl)-3,3-dimethyl-1-phenyl-
sulfonyl-pyrrolidine (3da). Light yellow oil, 1H NMR (CDCl3)
Compound 3gc2: light yellow oil, 1H NMR (CDCl3)
d 7.62e7.19
d
7.81e7.48 (m, 5H, C6H5), 3.43e3.38 (m, 2H, CH2), 3.20e3.15 (m,
(m, 10H, 2C6H5), 4.08e4.04 (m, 1H, CH), 2.96e2.94 (m, 1H, 1/2CH2),
2.54e2.43 (m, 4H, CHþ1/2CH2þCH2), 1.52e1.46 (m, 2H, CH2),
1H, CH), 2.84e2.72 (m, 1H, 1/2CH2), 2.46e2.34 (m, 1H, 1/2CH2),

1256
Y. Zhu et al. / Tetrahedron 67 (2011) 1251e1257
1.36e1.34 (d, 3H, CH3), 1.04(s, 3H, CH3), 0.97(s, 3H, CH3). 19F NMR
4.06e4.04 (m, 1H, CH), 3.05e2.99 (m, 2H, CH2), 2.88e2.70 (m, 2H,
CH2), 1.72e1.39 (m, 2H, CH2), 1.04 (s, 3H, CH3), 1.00 (s, 3H, CH3). 19
(CDCl3)
d
ꢂ70.49 (1F, ABXY, J¼201.6 Hz, 23.6, 11.5 Hz), ꢂ71.67 (1F,
F
ABXY, J¼201.6, 22.2, 11.5 Hz). 13C NMR (CDCl3)
d
136.1, 129.7, 129.0,
NMR (CDCl3)
d
ꢂ81.71 (3F, t, J¼9.6 Hz), ꢂ115.98 (2F, m), ꢂ122.72 (2F,
128.0, 127.4, 126.3, 63.5, 54.7, 42.7, 39.6, 29.7, 27.3, 23.7, 11.0. IR
(cmꢂ1, KBr) 3061, 2963, 2929, 1685, 1441, 1375, 1260. HRMS calcd
for C22H27F2NS: 375.1832, found: 375.1833.
s), ꢂ123.80 (2F, s), ꢂ124.53 (2F, s), ꢂ127.07 (2F, s). 13C NMR (CDCl3)
d
139.8, 132.8, 129.3, 127.1, 40.9, 39.2, 37.4, 32.4, 26.5, 24.9. IR (cmꢂ1
,
KBr) 3255, 2980, 1448, 1423, 1322, 1207, 1142, 1064. HRMS calcd for
C19H19F13INO2S: 698.9974, found: 572.0947, lost I (127).
4.3.7. N-(6,6-difluoro-4-iodo-3,3-dimethyl-6-(phenylthio)hexyl)
acetamide (4bc). Light yellow oil, 1H NMR (CDCl3)
d
7.63e7.27 (m,
4.3.13. N-(6,6-difluoro-4-iodo-3,3-dimethyl-6-(phenylthio)-hexyl)-
benzenesulfonamide (4dc). Light yellow solid, 1H NMR (CDCl3)
5H, C6H5), 5.53 (s, 1H, NH), 4.20e4.18 (m,1H, CH), 3.34e3.19 (m, 2H,
CH2), 2.95e2.85 (m, 2H, CH2), 1.99 (s, 3H, CH3), 1.73e1.52 (m, 2H,
d
7.90e7.38 (m, 10H, 2C6H5), 4.33 (t, J¼37.6 Hz, 1H, NH), 4.08e4.06
CH2), 1.09 (s, 3H, CH3), 1.05 (s, 3H, CH3). 19F NMR (CDCl3)
d
ꢂ71.95
(m, 1H, CH), 3.02e2.97 (m, 2H, CH2), 2.85e2.78 (m, 2H, CH2),
(1F, ABX, J¼203.5, 13.4, 13.4 Hz), ꢂ73.65 (1F, ABX, J¼203.5, 14.6,
1.69e1.47 (m, 2H, CH2), 1.00 (s, 3H, CH3), 0.97 (s, 3H, CH3). 19F NMR
14.6 Hz). 13C NMR (CDCl3)
d
170.0, 136.2, 130.0, 129.1, 128.9, 126.3,
(CDCl3)
d
ꢂ72.27 (1F, ABX, J¼204.5, 13.4, 13.4 Hz), ꢂ73.74 (1F, ABX,
45.7, 40.8, 38.1, 37.7, 35.6, 25.2, 24.2, 23.4. IR (cmꢂ1, KBr) 3285, 3080,
2967, 1648, 1554, 1473, 1369, 1287, 1172, 1043. HRMS calcd for
C16H22F2INOS: 441.0435, found: 441.0446.
J¼204.5, 14.8, 14.8 Hz). 13C NMR (CDCl3)
d 140.5, 136.8, 133.4, 130.6,
129.8, 129.7, 127.7, 126.9, 46.2, 41.6, 39.8, 38.1, 37.7, 25.9, 24.8, 23.3.
IR (cmꢂ1, KBr) 3284, 2968, 1584, 1474, 1445, 1327, 1160, 1045. HRMS
calcd for C20H24F2INO2S2: 539.0261, found: 412.1218, lost I (127).
4.3.8. Benzyl-7-chloro-6,6,7,7-tetrafluoro-4-iodo-3,3-dime-
thylheptylcarbamate (4ca). Light yellow oil, 1H NMR (CDCl3)
4.3.14. N-(7-chloro-6,6,7,7-tetrafluoro-3,3-dimethyl-heptyl)-acet-
d
7.36e7.30 (m, 5H, C6H5), 5.10 (s, 2H, CH2), 4.76 (s, 1H, NH), 4.16 (d,
amide (5ba). Light yellow oil, 1H NMR (CDCl3)
d 5.53 (s, 1H, NH),
1H, J¼8.48Hz, CH), 3.25e3.17 (m, 2H, CH2), 2.89e2.73 (m, 2H, CH2),
3.28e3.23 (m, 2H, CH2), 2.06e1.95 (m, 2H, CH2), 1.97 (s, 3H, CH3),
1.54e1.50 (m, 2H, CH2), 1.46e1.43 (m, 2H, CH2), 0.95 (s, 6H, 2CH3).
1.75e1.69 (m, 1H, 1/2CH2), 1.63e1.55 (m, 1H, 1/2CH2), 1.12 (s, 3H,
CH3), 1.08 (s, 3H, CH3). 19F NMR (CDCl3)
d
ꢂ72.59 (2F, d, J¼20.7 Hz),
19F NMR (CDCl3)
d
ꢂ71.81 (2F, s), ꢂ115.46 (2F, t, J¼18.8 Hz). 13C NMR
115.57 (2F, m). 13C NMR (CDCl3)
d
158.0, 138.2, 130.2, 129.8, 68.4,
(CDCl3) d
170.8, 41.5, 36.3, 32.6, 32.3, 27.2, 26.3, 23.9. IR (cmꢂ1, KBr)
42.6, 39.4, 39.2, 39.1, 38.7, 35.6, 28.0, 26.7, 26.0. IR (cmꢂ1, KBr) 3400,
3300, 3059, 2930, 1723, 1531. HRMS calcd for C17H21ClF4INO2:
509.0242, found: 509.0244.
3287, 2963, 1653, 1558, 1474, 1370, 1262, 1151. HRMS calcd for
C11H18ClF4NO: 291.1013, found: 291.1015.
4.3.15. N-(7-chloro-6,6,7,7-tetrafluoro-3,3-dimethyl-heptyl)-benzen-
4.3.9. Benzyl-6,6,7,7,8,8,9,9,10,10,11,11,11-tridecafluoro-4-iodo-3,3-
dimethyl-undecylcarbamate (4cb). Light yellow oil, 1H NMR (CDCl3)
amine (5ea). Light yellow oil, 1H NMR (CDCl3)
d 7.20e6.59 (m, 5H,
C6H5), 3.14e3.11 (m, 2H, CH2), 2.06e2.03 (m, 2H, CH2), 1.58e1.53
d
7.35e7.30 (m, 5H, C6H5), 5.10 (m, 2H, CH2), 4.73 (s, 1H, NH),
(m, 4H, CH2þCH2), 0.99 (s, 6H, 2CH3). 19F NMR (CDCl3)
ꢂ71.75 (2F,
d
4.18e4.16 (m, 1H, CH), 3.28e3.13 (m, 2H, CH2), 2.96e2.74 (m, 2H,
s), ꢂ115.39 (2F, t, J¼16.5 Hz). 13C NMR (CDCl3)
d 148.9, 130.0, 118.1,
CH2), 1.57 (m, 2H, CH2), 1.12 (s, 3H, CH3), 1.08 (s, 3H, CH3). 19F NMR
113.5, 41.8, 40.3, 32.7, 32.5, 27.5, 26.4. IR (cmꢂ1, KBr) 2957, 2926,
1603, 1506,1465,1151, 1088. HRMS calcd for C15H20ClF4N: 325.1220,
found: 325.1221.
(CDCl3)
d
ꢂ81.68 (3F, t, J¼9.4 Hz), ꢂ115.94 (2F, m), ꢂ122.70 (2F, s),
ꢂ123.76 (2F, s), ꢂ124.51 (2F, s), ꢂ127.04 (2F, s). 13C NMR (CDCl3)
d
156.9,137.1,129.2,128.8,128.7, 67.4, 41.6, 38.4, 38.1, 37.7, 33.7, 30.3,
27.5, 27.2, 26.9, 25.6, 25.0, 24.9. IR (cmꢂ1, KBr) 3335, 3067, 3034,
2968, 1699, 1533, 1239, 1143. HRMS calcd for C21H21F13INO2:
693.0409, found: 693.0411.
4.3.16. N-(6,6,7,7,8,8,9,9,10,10,11,11,11-tridecafluoro-3,3-dimethyl-
undecyl)-benzenamine (5eb). Light yellow oil, 1H NMR (CDCl3)
d
7.21e6.63 (m, 5H, C6H5), 3.15e3.12 (m, 2H, CH2), 2.06e2.02 (m,
2H, CH2), 1.58e1.50 (m, 3H, CHþCH2), 0.99 (s, 6H, 2CH3). 19F NMR
4.3.10. Benzyl-6,6-difluoro-4-iodo-3,3-dimethyl-6-(phenylthio)-hex-
(MHz, CDCl3)
d
ꢂ81.70 (3F, t, J¼9.4 Hz), ꢂ115.51 (2F, t, J¼16.5 Hz),
ylcarbamate (4cc). Light yellow oil, 1H NMR (CDCl3)
d
7.62e7.61 (m,
ꢂ122.85 (2F, s), ꢂ123.80 (2F, s), ꢂ124.19 (2F, s), ꢂ127.06 (2F, q,
2H, C6H5), 7.47e7.30 (m, 8H, C6H5), 5.15 (s, 2H, CH2), 4.70 (s, 1H,
NH), 4.18 (d, 1H, J¼7.70 Hz, CH), 3.26e3.17 (m, 2H, CH2), 2.97e2.81
(m, 2H, CH2), 1.73e1.67 (m, 1H, 1/2CH2), 1.57e1.51 (m, 1H, 1/2CH2),
J¼14.1, 9.4 Hz). 13C NMR (CDCl3)
d 153.1, 136.8, 128.3, 127.8, 39.8,
30.7, 30.5, 28.7, 25.7, 25.1. IR (cmꢂ1, KBr) 2960, 2928, 1602, 1505,
1474, 1240, 1143. HRMS calcd for C19H20F13N: 509.1388, found:
509.1389.
1.07 (s, 3H, CH3), 1.04 (s, 3H, CH3). 19F NMR (CDCl3)
d
ꢂ71.97 (1F,
ABX, J¼203.7, 13.2,13.2 Hz), ꢂ73.62 (1F, ABX, J¼203.7, 14.6, 14.6 Hz).
13C NMR (CDCl3)
d 156.9, 137.2, 136.8, 130.6, 129.8, 129.5, 129.2,
Acknowledgements
128.8, 127.0, 67.4, 46.3, 41.7, 38.6, 38.1, 37.7, 26.0, 25.0. IR (cmꢂ1, KBr)
3418, 3336, 3062, 3032, 2966, 1885, 1721, 1441. HRMS calcd for
C22H26F2INO2S: 533.0679, found: 406.1668 (lost I).
The support by the National Natural Science Foundation of China
(Grant No 20972050), Doctoral Fund of Ministry of Education of
China, and Postdoctoral Fund of China is gratefully acknowledged.
4.3.11. N-(7-chloro-6,6,7,7-tetrafluoro-4-iodo-3,3-dimethylheptyl)-
benzenesulfonamide (4da). Yellow oil, 1H NMR (CDCl3)
d 7.90e7.53
Supplementary data
(m, 5H, C6H5), 4.72 (t, J¼5.6 Hz, 1H, NH), 4.06e4.04 (m, 1H, CH),
3.02e2.97 (m, 2H, CH2), 2.87e2.67 (m, 2H, CH2), 1.72e1.50 (m, 2H,
CH2), 1.04 (s, 3H, CH3), 1.00 (s, 3H, CH3). 19F NMR (MHz, CDCl3)
Supplementary data associated with this article can be found in
the online version, at doi:10.1016/j.tet.2010.11.090. These data in-
clude MOL files and InChiKeys of the most important compounds
described in this article.
d
d
ꢂ72.63 (2F, d, J¼20.7 Hz), ꢂ115.62 (2F, m). 13C NMR (CDCl3)
140.5, 133.5, 129.9, 127.7, 39.8, 38.1, 33.9, 30.4, 26.9, 25.6. IR (cmꢂ1
,
KBr): 3282, 2926, 1668, 1448, 1327, 1257, 1158, 1092. HRMS calcd for
C15H19ClF4INO2S: 514.9806, found: 388.0737 (lost I).
References and notes
4.3.12. N-(6,6,7,7,8,8,9,9,10,10,11,11,11-tridecafluoro-4-iodo-3,3-di-
methylundecyl)benzenesulfonamide (4db). Yellow oil, 1H NMR
1. O’Hagan, D. Chem. Soc. Rev. 2008, 37, 308e319.
2. Muller, K.; Faeh, C.; Diederich, F. Science 2007, 317, 1881e1886.
€
(CDCl3)
d
7.90e7.52 (m, 5H, C6H5), 4.67 (t, J¼7.1 Hz, 1H, NH),
3. Gouverneur, V. Science 2008, 325, 1630e1631.

Y. Zhu et al. / Tetrahedron 67 (2011) 1251e1257
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