Studies on the radical addition reaction of perfluoroalkyl iodides with 2,3-allenols and the Pd-catalyzed kinetic resolution via Sonogashira coupling reaction

Article abstract of DOI:10.1016/j.tet.2011.08.044

A radical addition reaction promoted by Na₂S₂O ₄ of perfluoroalkyl iodides with 2,3-allenols affording E/Z mixtures of 3-iodo-4-perfluoroalkyl-substituted allylic alcohols has been studied. Kinetic resolution with Sonogash

Full text of DOI:10.1016/j.tet.2011.08.044

Tetrahedron 67 (2011) 8808e8818
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Studies on the radical addition reaction of perfluoroalkyl iodides with 2,3-allenols
and the Pd-catalyzed kinetic resolution via Sonogashira coupling reaction
*
Zhichao Ma, Rong Zeng, Chunling Fu, Shengming Ma
Laboratory of Molecular Recognition and Synthesis, Department of Chemistry, Zhejiang University, Hangzhou 310027, Zhejiang, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 April 2011
Received in revised form 18 July 2011
Accepted 9 August 2011
Available online 22 August 2011
A radical addition reaction promoted by Na2S2O4 of perfluoroalkyl iodides with 2,3-allenols affording E/Z
mixtures of 3-iodo-4-perfluoroalkyl-substituted allylic alcohols has been studied. Kinetic resolution with
Sonogashira coupling reaction was applied to afford the Z isomer of 3-iodo-4-perfluoroalkyl-substituted
allylic alcohol (Z-3) and the E isomer of conjugated enynic diols (E-5) in 39e52% and 22e40% yields,
respectively.
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Allenol
Kinetic resolution
Radical addition
1. Introduction
2. Results and discussion
In the last couple of years, allenes have become a very important
class of compounds in organic chemistry. More and more selective
synthetic methodologies have been developed based on the high
reactivity of the allene derivatives.1,2 Compared with the transition
metal-catalyzed1,2bed,f,g,iꢀl or electrophilic reactions,3,4 the radical
addition reactions of allenes have not been well-established.5,6 Re-
cently, we reported the Na2S2O4-promoted radical addition reaction
of simple allenes with perfluoroalkyl iodides affording perfluoroalkyl
group substituted vinyl iodides. In addition, we also developed
a simple kinetic resolution by applying the palladium-catalyzed
Sonogashira coupling to afford 2-iodo-1-perfluoroalkyl-2(Z)-alkenes
and 4-perfluoroalkylmethyl-4(E)-en-2-ynols, stereoselectively.7a,b
However, this reaction could not be extended to allenes with func-
tional groups. In this paper we wish to report the radical addition
reaction of 2,3-allenols4u,8,9 with perfluoroalkyl iodides in aqueous
MeOH and the related kinetic resolution (Scheme 1).
Based on the previous results of the radical addition reaction of
perfluoroalkyl iodide to the simple allenes,7a,b we studied the
addition reaction of 2,3-allenol 1a and n-C4F9I 2a using Na2S2O4/
NaHCO3 as the initiator in 1,4-dioxane/H2O, affording the expected
product10 3a in 34% yield only (entry 1, Table 1). We then started
to optimize the reaction conditions by studying the base effect.
Organic base, such as (i-Pr)2NH or Et3N, afforded 3a in 17% or 28%
yield only with 12% of 1a being recovered (entries 2 and 3, Table
1), respectively, and Cy2NH led to a complicated reaction (entry
11, Table 1). Then some of the inorganic bases were screened:
With Na2CO3, K2CO3, or NaOH, the reaction afforded the product
3a in higher yields (entries 5, 6, and 9, Table 1). The reaction in
benzene, toluene, hexane or ethyl acetate failed to afford the
radical addition product 3a (entries 1e4, Table 2). When DMSO
was used, a mixture of 3a, 1a, and some unknown products were
obtained after flash chromatography on silica gel (entry 5, Table 2).
DMF and DMA gave low yields of 3a (entries 6 and 7, Table 2). The
reaction in CH3CN, pyridine, or acetone is encouraging giving 3a in
30e36% yields (entries 8e10, Table 2). Further study led to the
observation that EtOH can be used as the solvent (entry 11, Table
2), then some of alcohols were screened (entries 11e14, Table 2):
MeOH gave the best result with 1.4% of 1a being recovered (entry
14, Table 2). After raising the concentration of the reaction mixture
to 0.4 M, all of the starting material was converted completely and
3a was afforded in 44% yield (entry 15, Table 2). Further adjusting
on the ratio of organic solvents and water could not improve the
yield (entries 17 and 18, Table 2). After raising the reaction tem-
perature to 40e45 ꢁC, the yield of 3a was improved to 48% (entry
OH
RfI
+
R3
Rf
R3
R2
R1
R3
R2
R1
Na2S2O4
Na2CO3
Pd(PPh3)2Cl2
CuI
R2
+
Z-3
R1
I
Rf
Et2NH, CH3CN
CH3OH/H2O
oC
HO
1
0
HO
E/Z-3
HO
E-5
40-45 o
C
Scheme 1.
* Corresponding author. Tel./fax: þ86 21 62609305; e-mail address: masm@
sioc.ac.cn (S. Ma).
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.08.044

Z. Ma et al. / Tetrahedron 67 (2011) 8808e8818
8809
Table 1
The base effect of the radical addition reaction of 1a with 2a promoted by Na2S2O4
Table 3
The radical addition reaction of perfluoroalkyl iodide with 2-substituted 2,3-allenols
1aec and 1m
I
C4H9-n
1.5 equiv Na2S2O4
1.5 equiv Base
C4H9-n
R2
2.0 equiv Na2S2O4
+
n-C4F9I
1.5 equiv
n-C4F9
R2
n-C4F9
OH
1,4-dioxane/H2O = 3/1
rt, 1-1.5 h
OH
2.0 equiv Na2CO3
R1
n- C4F9I
+
I
R1
CH3OH/H2O = 3/1
40-45 oC, 1 h
1a
2a
HO
1
3a
HO
E/Z-3
2a
(2.0 equiv)
Entry
Base
Isolated yield of 3a (%)
E/Z ratio of 3a
1a
2b
3b
4
5
6
7
8
9
10
11
NaHCO3
(i-Pr)2NH
Et3N
Li2CO3
Na2CO3
K2CO3
Cs2CO3
Na3PO4
NaOH
34
17
28c
29
39
39
32
35
39
28
dc,d
80/20
81/19
75/25
80/20
80/20
77/23
80/20
80/20
79/21
76/24
d
Entry
1
Isolated yield of 3 (%) Ratio of E/Z isomer
R1
R2
1
2
3
4
CH3
n-C4H9 (1a)
48 (3a)
40 (3b)
43 (3c)
75/25
68/32
75/25
76/24
n-C6H13 n-C4H9 (1b)
Ph
H
n-C4H9 (1c)
n-C4H9 (1m) 34 (3p)
KOH
Cy2NH
The significance of the bold values is that Na2CO3 gives the best effect.
ratio ranging from 68/32 to 76/24. The reaction of allenol 1m with
R1 being H afforded the product in 34% yield with the E/Z ratio
being 76/24. The E and Z isomers could not be separated from each
other by flash chromatography on silica gel.
The yields are not ideal, thus, we reasoned that the substituent
group (R2) may affect the radical addition. Thus, the reaction of 1-
phenyl-2,3-butadienol 1d was studied (Table 4). Under the stan-
dard reaction conditions, we were happy to observe that E-3d and
Z-3d were afforded in 31% and 35% yields, respectively. It should be
noted that the E and Z isomers of 3d may be separated by careful
flash chromatography on silica gel. The configuration of the two
isomers was determined by NOESY analysis (Fig. 1).
a
Compound 1a (0.3 mmol), 2a (0.2 mmol), Na2S2O4 (0.2 mmol), and NaHCO3
(0.2 mmol) were used.
b
Compound 1a (12%) was recovered.
The NMR yield was given.
The yield was not able to determine.
c
d
Table 2
The solvent effect of the radical addition reaction of 1a with 2a promoted by Na2S2O4
Na2S2O4/Na2CO3
(1.5 equiv)
I
C4H9-n
C4H9-n
+
n-C4F9I
1.5 equiv
solvent/H2O = 3/1
0.2 M, rt
OH
n-C4F9
OH
We then studied the scope of the radical addition reaction of
perfluoroalkyl iodides with 2-unsubstituted 2,3-allenols (Table 5).
The reaction is very general: When R2 group is H (entries 1e12,
Table 5), R1 group may be phenyl (entry 1, Table 5), substituted
phenyl (entries 2 and 3, Table 5), alkyl (entries 4e6, 8e12, Table 5),
and benzyl group (entry 7, Table 5); Rf group can be n-C4F9 (entries
1e9, Table 5) or n-C6F13 group (entries 10e12, Table 5). The yields of
the reaction are between 60e83%, and the ratio of E/Z isomers
ranged from 36/64 to 46/54. When R1 is an alkyl group, the ster-
eoselectivity is slightly higher than that of the substituent with an
aryl group. When tertiary 2,3-allenol 1k or 1l was used, the prod-
ucts can also be afforded in 62% and 65% yields, respectively. It is
interesting to observe that the stereoselectivity increases with the
ratio of E/Z being 91/9 and 90/10 (entries 13 and 15, Table 5). In
these cases, the two stereoisomers can be easily separated by flash
chromatography because of the remarkable difference of their
polarity. The configurations of E-3o and Z-3o were also established
by the NOESY analysis (Fig. 1). When the allenol 1p was used, the
corresponding product E-3s can be afforded in 49% isolated yield,
but Z-3s could not be isolated in pure form (entry 14, Table 5). The
higher selectivity observed in the reaction of tertiary 2,3-allenol
could be explained by the steric hindrance effect.
2a
1a
3a
Entry
Solvent
Isolated yield of 3a (%)
The E/Z ratio of 3a
1
2
3
4
5
6
7
8
Benzene
Toluene
Hexane
NR
NR
NR
NR
da
20
16
30
36
34
d
d
d
Ethyl acetate
DMSO
DMF
d
d
82/18
84/16
79/21
80/20
82/18
79/21
d
DMA
CH3CN
Py
Acetone
EtOH
Glycol
i-Butanol
MeOH
MeOH
MeOH
MeOHe
MeOHf
MeOHh
i-PrOHh
9
10
11
12
13
14b
15c
16d
17
18
19
20
32
Trace
NR
46
d
80/20
78/22
79/21
81/19
78/22
75/25
d
44
27
35b
42g
48
5i,j
a
A mixture of 3a, 1a, and some unknown products was obtained after flash
chromatography.
b
Compound 1a (1.4%) was recovered.
The concentration of the substrate was 0.4 M.
The concentration of the substrate was 0.1 M, and 3% of 1a was recovered.
The ratio of MeOH/H2O was 2/1.
c
2.0 equiv Na2S2O4
2.0 equiv Na2CO3
n-C3H7
d
+
n-C4F9I
(1)
complicated
e
CH3OH/H2O = 3/1
40-45 oC, 1.5 h
OH
2.0 equiv
f
The ratio of MeOH/H2O was 4/1.
g
1q
2a
Compound 1a (2.5%) was recovered.
h
The reaction temperature was 40e45 ꢁC, 2.0 equiv of 2a were used.
i
Compound 1a (45%) was recovered.
j
NMR yield.
19, Table 2). Thus, this condition was defined as the standard for
further study.
Some of the allenols with substituents on the
a and b positions
1a, 1b, 1c, and 1m were then examined (Table 3). The reaction
afforded the corresponding products in 34e48% yields with the E/Z
Regretfully, the tri- or tetra-substituted allenols 1q or 1r failed
to afford the corresponding products (Eqs. 1 and 2).

8810
Z. Ma et al. / Tetrahedron 67 (2011) 8808e8818
Table 4
The condition optimization of radical addition reaction of 1d with n-C4F9I
I
n-C4F9
Ph
x equiv Na2S2O4
x equiv Na2CO3
+ n-C4F9I
Ph
n-C4F9
+
I
Ph
CH3OH/H2O = 3/1
T, 1.5 h
HO
HO
E-3d
HO
1d
2a
Z-3d
Entry
x
n-C4F9I (equiv)
T (ꢁC)
Conc
Isolated yield (%)
E-3d
E-3d
1a
2b
3
1.5
2.0
2.0
2.5
1.5
2.0
2.0
2.5
rt
rt
40e45
40e45
0.2 M
0.4 M
0.4 M
0.4 M
23
33
31
29
27
31
35
31
4
a
Compound 1d (11%) was recovered.
Compound 1d (1.4%) was recovered.
b
of Pd(PPh3)2Cl2 and CuI with Et2NH as the base, E-3h can un-
dergo Sonogashira coupling reaction with propargyl alcohol 4
smoothly while Z-3h was mostly unreacted11. So we adjusted the
reaction temperature, the amounts of 4 and the catalyst to con-
trol the end of the resolution: finally, it was observed that the
reaction with 0.7 equiv of 4 under the catalysis of 5 mol % of
Pd(PPh3)2Cl2 and CuI at 0 ꢁC is the best conditions for this kinetic
resolution, affording Z-3h and E-5h in 46% and 25% isolated
yields, respectively. NMR yields of both E-3h and Z-5h were less
than 3% (entry 4, Table 6).
H
H
I
H
n-C4F9
H
H
Ph
n-C4F9
I
Ph
OH
H
H H
HO
Z-3d
E-3d
H
n-C4F9
H
I
H
I
n-C4F9
We then demonstrated the scope of this protocol with some
of the typical results being summarized in Table 7. Many differ-
ent radical addition products, 3-perfluoroalkylmethyl-3-iodo
allylic alcohol E/Z-3, were submitted to the optimized condi-
HO
Z-3o
HO
E-3o
Fig. 1. The NOESY spectrum analysis of E/Z-3d and E/Z-3o.
Table 5
The radical addition reaction of perfluoroalkyl iodide with the 2-unsubstituted 2,3-allenols
2.0 equiv Na2S2O4
2.0 equiv Na2CO3
Rf
R2
R1
+
RfI
2.0 equiv
R2
R1
CH3OH/H2O = 3/1
40-45 oC, 1 h
I
HO
HO
1
2
3
E/Z-
Entry
1
2
Isolated yield of E/Z-3 (%)
Ratio of E/Z isomer
R1
R2
Rf
1a
2
3
4
5
6
7
8
9
10
11
12
13
14
15
Ph
H (1d)
H (1e)
H (1f)
H (1g)
H (1h)
H (1i)
n-C4F9 (2a)
n-C4F9 (2a)
n-C4F9 (2a)
n-C4F9 (2a)
n-C4F9 (2a)
n-C4F9 (2a)
n-C4F9 (2a)
n-C4F9 (2a)
n-C4F9 (2a)
n-C6F13 (2b)
n-C6F13 (2b)
n-C6F13 (2b)
n-C4F9 (2a)
n-C4F9 (2a)
n-C4F9 (2a)
69 (3d)
61 (3e)
69 (3f)
77 (3g)
68 (3h)
60 (3i)
60 (3j)
67 (3q)
83 (3r)
73 (3k)
61 (3l)
83 (3m)
56 (E); 6 (Z) (3n)
49 (E) (3s)b
59 (E); 6 (Z) (3o)
46/54
41/59
44/56
38/62
39/61
37/63
43/57
40/60
37/63
38/62
37/63
36/64
91/9
4-CH3C6H4
4-FC6H4
n-C4H9
n-C5H11
n-C6H13
Bn
H (1j)
i-C3H7
H (1n)
H (1o)
H (1g)
H (1h)
H (1i)
t-C4H9
n-C4H9
n-C5H11
n-C6H13
Ph
CH3 (1k)
n-C4H9 (1p)
n-C4H9
e(CH2)5e (1l)
87/13c
90/10
a
The time was 50 min.
b
c
The Z-3s could not be isolated in pure form.
The E/Z ratio was determined by 1H NMR of the crude product.
Due to the difficulty of separating most of E-3 and Z-3, the
tions. It should be noted that the R group may be aryl (entries 1
and 2, Table 7), alkyl (entries 3 and 5e7, Table 7), or Bn group
(entry 4, Table 7), and the Rf group may be n-C4F9 (entries
1e4, Table 7) or n-C6F13 group (entries 5e7, Table 7) to have
a clean and efficient kinetic resolution to afford Z-3 in 39e52%
kinetic resolution developed previously in our group was applied
for these addition products.7 The 10,10,11,11,12,12,13,13,13-
nonafluoro-8-iodo-7-tridecen-6-ol 3h was used as the model
substrate to optimize the conditions (Table 6). Under the catalysis

Z. Ma et al. / Tetrahedron 67 (2011) 8808e8818
8811
Table 6
The condition optimization for kinetic resolution of the 10,10,11,11,12,12,13,13,13-nonafluoro-8-iodo-7-tridecen-6-ol 3h with propargyl alcohol 4 via palladium-catalyzed
Sonogashira coupling reaction
n-C4F9
I
n-C4F9
I
C5H11-n
+
n-C4F9
n-C4F9
C5H11-n
HO
3h
HO
I
C5H11-n
E-3h
HO
Z-
Pd(PPh3)2Cl2/CuI
3h, E/ Z = 39/61
Et2NH, CH3CN
T, time
HO
+
C5H11-n
+
+
OH
HO
n-C4F9
C5H11-n
HO
4
HO
E-5h
5h
Z-
Entry
Catalyst (mol %)
T (ꢁC)
4 or Et2NH (equiv)
Time (min)
NMR yield (%)a
Z-3h
E-3h
E-5h
Z-5h
1
2
3
4
2
2
3
5
31
32
0
0.6
0.7
0.7
0.7
960
60
140
70
45
40
(55)
6
20
29
(22)
5
d
(10)
1
13
d
3
0
49 (46)
28 (25)
a
The numbers in the parenthesis are isolated yields.
Table 7
The kinetic resolution of E/Z-3 via the palladium-catalyzed Sonogashira coupling reaction
HO
Rf
5 mol% Pd(PPh3)2Cl2
5 mol% CuI
Rf
+
R
I
+
OH
0.7 equiv
Et2NH (0.7 equiv)
CH3CN, 0 oC, time
HO
I
R
Rf
R
HO
HO
E-5
Z-3
E/ Z-3
4
Entry
R
Rf
Time (min)
Isolated yield of Z-3
Isolated yield of E-5
1a
2a
3
4
5
Ph
n-C4F9 (3d)
n-C4F9 (3e)
n-C4F9 (3g)
n-C4F9 (3j)
n-C6F13 (3k)
n-C6F13 (3l)
n-C6F13 (3m)
55
45
50
70
75
55
45
48 (Z-3d)
45 (Z-3e)
45 (Z-3g)
39 (Z-3j)
49 (Z-3k)
49 (Z-3l)
52 (Z-3m)
40 (E-5d)
30 (E-5e)
29 (E-5g)
39 (E-5j)
27 (E-5k)
23 (E-5l)
22 (E-5m)
p-MeC6H4
n-C4H9
Bn
n-C4H9
n-C5H11
n-C6H13
6
7
a
Compound 4 (0.9 equiv) and Et2NH were used.
recoveries and E-5 in 22e40% yields. The yields of E-3 and Z-5
are less than 3%.
nitrogen atmosphere in dried glassware. 1H NMR spectra were
recorded on a Bruker-300 or 400 MHz spectrometer, 13C NMR
spectra were recorded at 75 or 100 MHz. Chemical shifts (d) are
given in parts per million (ppm) downfield relative to CDCl3. Cou-
pling constants are given in hertz (Hz). Unless otherwise, stated
deuterochloroform was used as solvent. In assignment of the 1H
NMR spectra, multiplicities and abbreviations used are as follows:
d¼doublet, dd¼doublet of doublets, m¼multiplet, q¼quartet,
s¼singlet, t¼triplet.
3. Conclusions
In summary, we have developed a mild radical addition reaction
of perfluoroalkyl iodide with 2,3-allenols and the subsequent ki-
netic resolution to afford Z isomer of perfluoroalkyl-substituted
allylic alcohols and E isomer of perfluoroalkylmethyl-substituted
conjugated enynic diols stereoselectively. Further studies in this
area are being conducted in our laboratory.
4.2. The Na2S2O4-promoted radical addition reaction of RfI
with 2,3-allenols and the corresponding kinetic resolution
4. Experimental
4.1. General
4.2.1. Synthesis of 3-(n-butyl)-6,6,7,7,8,8,9,9,9-nonafluoro-4-iodo-3-
nonen-2-ol (3a).
2.0 equiv Na2S2O4
C4H9-n
n-C4F9
C4H9-n
2.0 equiv Na2CO3
Chemicals and solvents were all purchased from commercial
suppliers and used without further purification. All the radical
addition reactions were carried out under an air atmosphere while
all the kinetical resolution reactions were carried out under the
+
n-C4F9I
2.0 equiv
CH3OH/H2O = 3/1
40-45 oC, 1 h
CH3
I
CH3
HO
1a
HO
3a
2a

8812
Z. Ma et al. / Tetrahedron 67 (2011) 8808e8818
Following typical procedure 1, the reaction of 1m (62.0 mg,
4.2.1.1. Typical procedure 1. To a mixture of Na2S2O4 (0.2801 g,
0.49 mmol), n-C4F9I 2a (0.17 mL, d¼2.01, 341.7 mg, 0.99 mmol),
Na2S2O4 (175.0 mg, 1.0 mmol), and Na2CO3 (105.9 mg, 1.0 mmol)
in 1.5 mL of CH3OH and 0.5 mL of H2O at 40e45 ꢁC for 1.5 h
afforded 3p (79.5 mg, 34%, E/Z¼76/24) (eluent: petroleum ether/
1.61 mmol), Na2CO3 (0.1708 g,1.61 mmol), and 1.0 mL of CH3OH were
added 3-(n-butyl)-3,4-butadien-2-ol 1a (0.1115 g, 0.80 mmol), 0.5 mL
of CH3OH, n-C4F9I 2a (0.5551 g, 1.60 mmol), and 0.5 mL of H2O with
stirring sequentially. The mixture was stirred at 40e45 ꢁC for 1 h as
monitored by TLC, quenched with 10 mL of brine, extracted with
diethyl ether (25 mLꢂ3), and dried over anhydrous Na2SO4. Filtration,
evaporation, and column chromatography on silica gel (eluent: pe-
troleum ether/ethyl acetate¼20/1) afforded a E/Z mixture of 3a
ethyl acetate¼40/1 to 10/1): 1H NMR (300 MHz, CDCl3):
d [4.32
(Z-isomer, s, 0.48H), 4.19 (E-isomer, s, 1.52H)], 3.80e3.52 (m, 2H),
2.52e2.26 (m, 2H), 1.68 (br s, 1H), 1.54e1.30 (m, 4H), 1.00e0.84
(m, 3H); IR (neat, cmꢀ1): 3347, 2961, 2933, 2875, 1714, 1622, 1468,
1429, 1344, 1235, 1135, 1020; GCeMS (EI, 70 eV) m/z (%): [E-iso-
mer, 472 (Mþ, 0.45), 289 (100)], [Z-isomer, 472 (Mþ, 10.5), 289
(100)]; HRMS calcd for C12H14OF9I (Mþ): 471.9946. found:
471.9943.
(0.1876 g, 48%, E/Z¼75/25): 1H NMR (300 MHz, CDCl3):
d 4.88e4.72
(m, 1H), 3.90e3.38 (m, 2H), 2.45e2.10 (m, 2H), 1.94 (br s, 1H),
1.70e1.34 (m, 4H), 1.34e1.20 (m, 3H), 1.02e0.85 (m, 3H); IR (neat,
cmꢀ1):3377, 2961, 2936, 2875,1615,1461,1344,1236,1135,1089,1061,
1019; MS (EI, 70 eV) m/z (%): 486 (Mþ, 1.61), 303 (MþꢀIꢀC4H8, 100);
Anal. calcd for C13H16F9IO: C 32.12, H 3.32; found: C 32.23, H 3.40.
4.2.5. Synthesis of 5,5,6,6,7,7,8,8,8-nonafluoro-3-iodo-1-phenyl-2-
octen-1-ol (E-3d) and 5,5,6,6,7,7,8,8,8-nonafluoro-3-iodo-1-phenyl-
2-octen-1-ol (Z-3d).
4.2.2. Synthesis of 8-(n-butyl)-11,11,12,12,13,13,14,14,14-nonafluoro-9-
iodo-8-tetra-decen-7-ol (3b).
I
2.0 equiv Na2S2O4
2.0 equiv Na2CO3
CH3OH/H2O = 3/1
40-45 oC, 1.5 h
n-C4F9
+
n-C4F9I
2.0 equiv
C4H9-n
+
2.0 equiv Na2S2O4
2.0 equiv Na2CO3
Ph
n-C4F9
Ph
I
Ph
n-C4F9
C4H9-n
HO
HO
E-3d
n-C4F9I
HO
Z-3d
+
C6H13-n
CH3OH/H2O = 3/1
40-45 oC, 1 h
2a
1d
I
C6H13-n
2.0 equiv
HO
HO
1b
2a
3b
Following typical procedure 1, the reaction of 1d (57.1 mg,
0.39 mmol), n-C4F9I 2a (276.0 mg, 0.80 mmol), Na2S2O4 (140.5 mg,
0.81 mmol), and Na2CO3 (85.2 mg, 0.80 mmol) in 0.75 mL of CH3OH
and 0.25 mL of H2O at 40e45 ꢁC for 1.5 h afforded E-3d (59.7 mg,
31%) and Z-3d (68.0 mg, 35%) (eluent: petroleum ether/ethyl
acetate¼12/1).
Following typical procedure 1, the reaction of 1b (79.7 mg,
0.38 mmol), n-C4F9I 2a (280.3 mg, 0.81 mmol), Na2S2O4 (140.1 mg,
0.81 mmol), and Na2CO3 (85.2 mg, 0.80 mmol) in 0.75 mL of CH3OH
and 0.25 mL of H2O at 40e45 ꢁC for 1 h afforded 3b (84.5 mg, 40%, E/
Z¼68/32) (eluent: petroleum ether/ethyl acetate¼60/1): 1H NMR
(400 MHz, CDCl3):
d [4.67e4.61 (Z-isomer, m, 0.32H), 4.56e4.49 (E-
isomer, m, 0.67H)], 3.80e3.38 (m, 2H), 2.39e2.10 (m, 2H), 1.74e1.51
(m, 3H), 1.51e1.38 (m, 4H), 1.38e1.18 (m, 8H), 0.99e0.84 (m, 6H); IR
(neat, cmꢀ1): 3426, 2960, 2932, 2861, 1612, 1467, 1380, 1343, 1235,
1198, 1134, 1109, 1019; GCeMS (EI, 70 eV) m/z (%): [E-isomer, 499
(MþꢀC4H9, 17.10), 471 (MþꢀC6H13, 23.18), 429 (MþꢀI, 100)], [Z-iso-
mer, 499 (MþꢀC4H9,15.55), 471 (MþꢀC6H13, 21.55), 429 (MþꢀI,100)];
Anal. calcd for C18H26F9IO: C 38.86, H 4.71; found: C 39.07, H 4.93.
4.2.5.1. 5,5,6,6,7,7,8,8,8-nonafluoro-3-iodo-1-phenyl-2(E)-
octen-1-ol (E-3d). Oil, 1H NMR (400 MHz, CDCl3)
d
7.43e7.30 (m,
5H), 6.88 (d, J¼8.8 Hz, 1H), 5.27 (d, J¼8.4 Hz, 1H), 3.81e3.38 (m,
2H), 2.21 (br s, 1H); 13C NMR (100 MHz, CDCl3):
150.6, 140.8,
d
128.9, 128.4, 126.1, 82.8, 72.2, 39.8 (t, JCeF¼21.8 Hz); IR (neat,
cmꢀ1): 3346, 3066, 3034, 2925, 1629, 1494, 1455, 1430, 1345,
1233, 1133, 1030; MS (EI, 70 eV) m/z (%): 492 (Mþ, 0.20), 105
(100); Anal. calcd for C14H10F9IO: C 34.17, H 2.05; found: C 34.52,
H 2.06.
4.2.3. Synthesis of 2-(n-butyl)-5,5,6,6,7,7,8,8,8-nonafluoro-3-iodo-1-
phenyl-2-octen-1-ol (3c).
2.0 equiv Na2S2O4
2.0 equiv Na2CO3
C4H9-n
4.2.5.2. 5,5,6,6,7,7,8,8,8-Nonafluoro-3-iodo-1-phenyl-2(Z)-octen-
n-C4F9
C4H9-n
1-ol (Z-3d). Oil; 1H NMR (400 MHz, CDCl3):
d 7.50e7.44 (m, 2H),
+
n-C4F9I
2.0 equiv
Ph
CH3OH/H2O = 3/1
40-45 oC, 1 h
I
Ph
7.43e7.29 (m, 3H), 6.15 (d, J¼8.0 Hz, 1H), 5.43 (d, J¼7.6 Hz, 1H), 3.44
HO
1c
HO
(t, J¼17.6 Hz, 2H), 2.36 (br s, 1H); 13C NMR (100 MHz, CDCl3)
d 146.2,
2a
3c
141.0, 128.8, 128.2, 126.1, 87.1, 78.3, 45.3 (t, JCeF¼21.0 Hz); IR (neat,
cmꢀ1): 3356, 3065, 3032, 2927, 1636, 1603, 1494, 1453, 1425, 1346,
1235, 1134, 1089, 1019; MS (EI, 70 eV) m/z (%): 492 (Mþ, 0.96), 365
(100); Anal. calcd for C14H10F9IO: C 34.17, H 2.05; found: 34.39,
H 1.98.
Following typical procedure 1, the reaction of 1c (83.0 mg,
0.41 mmol), n-C4F9I 2a (280.1 mg, 0.81 mmol), Na2S2O4 (139.3 mg,
0.80 mmol), and Na2CO3 (84.4 mg, 0.80 mmol) in 0.75 mL of CH3OH
and 0.25 mL of H2O at 40e45 ꢁC for 1 h afforded 3c (95.9 mg, 43%, E/
Z¼75/25) (eluent: petroleum ether/ethyl acetate¼40/1): 1H NMR
4.2.6. Synthesis of 5,5,6,6,7,7,8,8,8-nonafluoro-3-iodo-1-phenyl-2-
octen-1-ol (3d), 5,5,6,6,7,7,8,8,8-nonafluoro-3-iodo-1-phenyl-2(Z)-
octen-1-ol (Z-3d), and 3-(20,20,30,30,40,40,50,50,50-nonafluoropentyl)-1-
phenylhex-5-yn-2(E)-en-1,6-diol (E-5d).
(400 MHz, CDCl3): d 7.57e7.27 (m, 5H), [6.00 (Z-isomer, s, 0.25H), 5.75
(E-isomer, s, 0.75H)], 4.00e3.47 (m, 2H), 2.28e2.00 (m, 2H), 1.58 (br s,
1H),1.50e1.31 (m, 1H), 1.31e1.10 (m, 2H), 1.07e0.91 (m,1H), 0.83e0.75
(m, 3H); IR (neat, cmꢀ1): 3424, 3065, 3031, 2960, 2935, 2874, 1605,
1495, 1452, 1344, 1236, 1134, 1018; GCeMS (EI, 70 eV) m/z (%): [E-
isomer, 548 (Mþ, 0.45), 491 (MþꢀC4H9, 14.06), 421 (MþꢀI, 100)], [Z-
isomer, 548 (Mþ, 0.93), 491 (MþꢀC4H9, 14.11), 421 (MþꢀI, 100)]; Anal.
calcd for C18H18F9IO: C 39.44, H 3.31; found: C 39.56, H 3.54.
4.2.6.1. Radical addition reaction of 1d with 2a.
2.0 equiv Na2S2O4
n-C4F9
2.0 equiv Na2CO3
+
n-C4F9I
2.0 equiv
Ph
CH3OH/H2O = 3/1
40-45 oC, 50 min
I
Ph
HO
HO
3d
4.2.4. Synthesis of 2-(n-butyl)-5,5,6,6,7,7,8,8,8-nonafluoro-3-iodo-2-
octen-1-ol (3p).
1d
2a
2.0 equiv Na2S2O4
Following typical procedure 1, the reaction of 1d (0.3514 g,
2.41 mmol), n-C4F9I 2a (1.6698 g, 4.83 mmol), Na2S2O4 (0.8356 g,
4.80 mmol), and Na2CO3 (0.5087 g, 4.80 mmol) in 4.5 mL of
CH3OH and 1.5 mL of H2O at 40e45 ꢁC for 50 min afforded 3d
(0.8135 g, 69%, E/Z¼46/54) (eluent: petroleum ether/ethyl
C4H9-n
n-C4F9
C4H9-n
2.0 equiv Na2CO3
+
n-C4F9I
2.0 equiv
CH3OH/H2O = 3/1
40-45 oC, 1.5 h
I
HO
1m
HO
3p
2a

Z. Ma et al. / Tetrahedron 67 (2011) 8808e8818
8813
acetate¼10/1): 1H NMR (300 MHz, CDCl3):
d
7.49e7.29 (m, 5H),
Following typical procedure 1, the reaction of 1e (0.3841 g,
2.40 mmol), n-C4F9I 2a (1.6924 g, 4.89 mmol), Na2S2O4 (0.8352 g,
4.80 mmol), and Na2CO3 (0.5090 g, 4.80 mmol) in 4.5 mL of CH3OH
and 1.5 mL of H2O at 40e45 ꢁC for 1 h afforded 3e (0.7459 g, 61%, E/
Z¼41/59) (eluent: petroleum ether/ethyl acetate¼10/1): oil; 1H NMR
[6.89 (E-isomer, d, J¼8.4 Hz, 0.46H), 6.17 (Z-isomer, d, J¼8.1 Hz,
0.54H)], [5.44 (Z-isomer, d, J¼7.8 Hz, 0.52H), 5.29 (E-isomer, d,
J¼8.7 Hz, 0.48H)], 3.80e3.36 (m, 2H), [2.20 (Z-isomer, br s,
0.54H), 2.07 (E-isomer, br s, 0.46H)]. The E/Z mixture was sub-
mitted to the kinetic resolution step without further
characterization.
(300 MHz, CDCl3):
d
7.26 (d, J¼7.8 Hz,1H), 7.19e7.05 (m, 3H), [6.80 (E-
isomer, J¼8.4 Hz, 0.41H), 6.08 (Z-isomer, J¼7.5 Hz, 0.58H)], [5.31 (Z-
isomer, J¼7.8 Hz, 0.55H), 5.17 (E-isomer, J¼8.7 Hz, 0.42H)], 3.70e3.26
(m, 2H), 2.27 (s, 3H),1.96 (br s,1H). The E/Z mixture was submitted to
the kinetic resolution step without further characterization.
4.2.6.2. Kinetical resolution with Sonogashira coupling reaction.
n-C4F9
n-C4F9
4.2.7.2. Kinetical resolution with Sonogashira coupling reaction.
I
Ph
I
Ph
HO
Z-3d
HO
3d
Pd(PPh3)2Cl2 (5.0 mol%)
CuI (5.6 mol%)
+
Et2NH (0.9 equiv)
+
HO
CH3CN, 0 oC, 55 min
OH
0.9 equiv
n-C4F9
Ph
4
HO
E-5d
4.2.6.3. Typical procedure 2. To a Schlenk tube containing a mixture
of Pd(PPh3)2Cl2 (8.8 mg, 1.3ꢂ10ꢀ2 mmol, 5.0 mol %) and CuI
(2.4 mg, 1.4ꢂ10ꢀ2 mol, 5.6 mol %) at 0 ꢁC was added 3d (123.5 mg,
0.251 mmol, E/Z¼46/54) under a nitrogen atmosphere. Then a so-
lution of Et2NH (16.5 mg, 0.226 mmol) and propargyl alcohol 4
(12.7 mg, 0.227 mmol) in 0.5 mL of CH3CN was added. The resulting
mixture was stirred at 0 ꢁC for 55 min monitored by GC, quenched
with 10 mL of brine, extracted with diethyl ether (25 mLꢂ3), and
dried over anhydrous Na2SO4. Filtration, evaporation, and column
chromatography on silica gel afforded Z-3d (59.1 mg, 48%) (eluent:
petroleum ether/ethyl acetate¼10/1) and E-5d (42.0 mg, 40%) (el-
uent: petroleum ether/ethyl acetate¼3/1).
Following typical procedure 2, the reaction of the E/Z mix-
ture of 3e (101.2 mg, 0.200 mmol), propargyl alcohol 4 (10.3 mg,
0.184 mmol), Pd(PPh3)2Cl2 (7.0 mg, 1.0ꢂ10ꢀ2 mmol, 5.0 mol %),
CuI (2.0 mg, 1.1ꢂ10ꢀ2 mol, 5.3 mol %), and Et2NH (13.1 mg,
0.179 mmol) in 0.4 mL of CH3CN at 0 ꢁC for 45 min afforded Z-
3e (45.4 mg, 45%) (eluent: petroleum ether/ethyl acetate¼10/1)
and E-5e (26.4 mg, 30%) (eluent: dichloromethane/ethyl
acetate¼10/1).
4.2.7.3. 5,5,6,6,7,7,8,8,8-Nonafluoro-3-iodo-1-(40-methylphenyl)-
2(Z)-octen-1-ol (Z-3e). Oil; 1H NMR (300 MHz, CDCl3):
d 7.33 (d,
J¼8.1 Hz, 2H), 7.18 (d, J¼7.8 Hz, 2H), 6.15 (d, J¼7.8 Hz, 1H), 5.38 (d,
4.2.6.4. 5,5,6,6,7,7,8,8,8-Nonafluoro-3-iodo-1-phenyl-2(Z)-octen-
1-ol (Z-3d). For the analytical data, see the experiment (4) in this
Supplementary data.
J¼7.8 Hz, 1H), 3.42 (t, J¼17.4 Hz, 2H), 2.35 (s, 3H), 2.32 (br s, 1H); 13C
NMR (75 MHz, CDCl3):
d 146.3, 138.04, 137.99, 129.4, 126.1, 86.7,
78.2, 45.2 (t, JCeF¼21.2 Hz), 21.1; IR (neat, cmꢀ1): 3345, 2955, 2926,
2856, 1512, 1459, 1424, 1346, 1235, 1135, 1082, 1019; MS (EI, 70 eV)
m/z (%): 506 (Mþ, 0.84), 119 (100); Anal. calcd for C15H12F9IO: C
35.59, H 2.39; found: C 35.91, H 2.51.
4.2.6.5. 3-(20,20,30,30,40,40,50,50,50-Nonafluoropentyl)-1-phenylhex-
5-yn-2(E)-en-1,6-diol (E-5d). Oil; 1H NMR (300 MHz, CDCl3):
d
7.41e7.27 (m, 5H), 6.40 (d, J¼8.7 Hz, 1H), 5.34 (d, J¼8.7 Hz, 1H),
4.32 (s, 2H), 3.26e2.94 (m, 2H), 2.63 (br s, 1H), 2.28 (br s, 1H);
4.2.7.4. 3-(20,20,30,30,40,40,50,50,50-Nonafluoropentyl)-1-(40-methyl-
phenyl)hex-5-yn-2(E)-en-1,6-diol (E-5e). Oil; 1H NMR (300 MHz,
13C NMR (75 MHz, CDCl3):
d 145.4, 141.3, 128.8, 128.3, 126.1, 112.1,
87.4, 85.6, 70.4, 51.1, 32.4 (t, JCeF¼21.7 Hz); IR (neat, cmꢀ1): 3334,
2926, 2868, 2224, 1632, 1495, 1455, 1436, 1348, 1220, 1134, 1099,
1023; MS (EI, 70 eV) m/z (%): 402 (MþꢀH2O, 11.87), 105 (100);
Anal. calcd for C17H13F9O2: C 48.58, H 3.12; found: C 48.65, H
3.48.
CDCl3):
d
7.22 (d, J¼8.4 Hz, 2H), 7.16 (d, J¼8.1 Hz, 2H), 6.40 (d,
J¼9.0 Hz, 1H), 5.31 (d, J¼10.5 Hz, 1H), 4.33 (d, J¼5.1 Hz, 2H),
3.25e2.95 (m, 2H), 2.34 (s, 3H), 2.40e2.28 (m, 1H), 2.08e1.96 (m,
1H); 13C NMR (75 MHz, CDCl3):
d 145.6, 138.4, 138.2, 129.5, 126.1,
111.8, 87.2, 85.7, 70.4, 51.2, 32.4, (t, JCeF¼22.0 Hz), 21.1; IR (neat,
cmꢀ1): 3320, 2927, 2869, 2224, 1635, 1616, 1514, 1437, 1349, 1220,
1134, 1099, 1025; MS (EI, 70 eV) m/z (%): 416 (MþꢀH2O, 1.30), 119
(100); Anal. calcd for C18H15F9O2: C 49.78, H 3.48; found: C 49.33, H
3.57.
4.2.7. Synthesis of 5,5,6,6,7,7,8,8,8-nonafluoro-3-iodo-1-(40-methyl-
phenyl)-2-octen-1-ol (3e), 5,5,6,6,7,7,8,8,8-nonafluoro-3-iodo-1-(40-
methylphenyl)-2(Z)-octen-1-ol (Z-3e), and 3-(20,20,30,30,40,40,50,50,50-
nonafluoropentyl)-1-(40-methyl-phenyl)hex-5-yn-2(E)-en-1,6-diol
(E-5e).
4.2.8. Synthesis of 5,5,6,6,7,7,8,8,8-nonafluoro-3-iodo-1-(40-fluo-
rophenyl)-2-octen-1-ol (3f).
4.2.7.1. Radical addition reaction of 1e with 2a.

8814
Z. Ma et al. / Tetrahedron 67 (2011) 8808e8818
Following typical procedure 1, the reaction of 1f (0.3924 g,
4.2.9.4. 4-(20,20,30,30,40,40,50,50,50-Nonafluoropentyl)-dec-2-yn-
4(E)-1,6-diol (E-5g). Oil, 1H NMR (300 MHz, CDCl3):
6.19 (d,
2.39 mmol), n-C4F9I 2a (1.6588 g, 4.79 mmol), Na2S2O4 (0.8388 g,
4.82 mmol), and Na2CO3 (0.5103 g, 4.81 mmol) in 4.5 mL of CH3OH
and 1.5 mL of H2O at 40e45 ꢁC for 1 h afforded 3f (0.8468 g, 69%, E/
Z¼44/56) (eluent: petroleum ether/ethyl acetate¼10/1): oil; 1H
d
J¼9.0 Hz, 1H), 4.37 (s, 2H), 4.33e4.22 (m, 1H), 3.20e2.87 (m, 2H),
2.66 (br s, 1H), 2.31 (br s, 1H), 1.70e1.56 (m, 1H), 1.56e1.42 (m, 1H),
1.42e1.20 (m, 4H), 0.90 (t, J¼6.8 Hz, 3H); 13C NMR (100 MHz,
NMR (300 MHz, CDCl3):
d
7.45e7.36 (m, 1H), 7.36e7.26 (m, 1H),
CDCl3): d 146.6, 111.9, 86.9, 85.7, 68.2, 51.2, 36.5, 32.4 (t,
7.12e6.98 (m, 2H), [6.83 (E-isomer, J¼8.4 Hz, 0.44H), 6.12 (Z-isomer,
J¼7.8 Hz, 0.55H)], [5.40 (d, J¼7.8 Hz, 0.53H), 5.25 (d, J¼8.7 Hz,
0.46H)], 3.79e3.34 (m, 2H), [2.54 (Z-isomer, br s, 0.55H), 2.39 (E-
isomer, br s, 0.45H)]. GCeMS (EI, 70 eV) m/z (%): [E-isomer, 383
(MþꢀI, 99.23), 123 (100)], [Z-isomer, 383 (MþꢀI, 32.45), 123 (100)],
Anal. calcd for C14H9F10OI: C 32.96, H 1.78; found: C 33.24, H 1.76.
JCeF¼22.2 Hz), 27.1, 22.5, 13.8; IR (neat, cmꢀ1): 3346, 2957, 2926,
2856, 2225, 1460, 1377, 1348, 1235, 1221, 1135, 1098, 1024; MS (EI,
70 eV) m/z (%): 382 (MþꢀH2O, 5.27), 85 (100); Anal. calcd for
C15H17F9O2: C 45.01, H 4.28; found: C 45.20, H 4.23.
4.2.10. Synthesis of 10,10,11,11,12,12,13,13,13-nonafluoro-8-iodo-7-
tridecen-6-ol (3h), 10,10,11,11,12,12,13,13,13-nonafluoro-8-iodo-7(Z)-
tridecen-6-ol (Z-3h), and 4-(20,20,30,30,40,40,50,50,50-nonafluoropentyl)-
undec-2-yn-4(E)-1,6-diol (E-5h).
4.2.9. Synthesis of 9,9,10,10,11,11,12,12,12-nonafluoro-7-iodo-6-
dodecen-5-ol (3g), 9,9,10,10,11,11,12,12,12-nonafluoro-7-iodo-6(Z)-
dodecen-5-ol (Z-3g), and 4-(20,20,30,30,40,40,50,50,50-nonafluoropentyl)-
dec-2-yn-4(E)-1,6-diol (E-5g).
4.2.10.1. Radical addition reaction of 1h with 2a.
2.0 equiv Na2S2O4
2.0 equiv Na2CO3
n-C4F9
4.2.9.1. Radical addition reaction of 1g with 2a.
n-C4F9I
2.0 equiv
+
C5H11-n
CH3OH/H2O = 3/1
40-45 oC, 40 min
I
C5H11-n
2.0 equiv Na2S2O4
HO
n-C4F9
HO
3h
2.0 equiv Na2CO3
n-C4F9I
2.0 equiv
+
C4H9-n
1h
2a
CH3OH/H2O = 3/1
40-45 oC, 1 h
I
C4H9-n
HO
HO
3g
Following typical procedure 1, the reaction of 1h (0.2764 g,
1.97 mmol), n-C4F9I 2a (1.3984 g, 4.04 mmol), Na2S2O4 (0.6991 g,
4.02 mmol), and Na2CO3 (0.4270 g, 4.03 mmol) in 6 mL of CH3OH and
2 mL of H2O at 40e45 ꢁC for 40 min afforded 3h (0.6508 mg, 68%, E/
Z¼39/61) (eluent: petroleum ether/ethyl acetate¼10/1): oil; 1H NMR
1g
2a
Following typical procedure 1, the reaction of 1g (0.3045 g,
2.42 mmol), n-C4F9I 2a (1.6716 g, 4.83 mmol), Na2S2O4 (0.8376 g,
4.81 mmol), and Na2CO3 (0.5054 g, 4.77 mmol) in 4.5 mL of CH3OH
and 1.5 mL of H2O at 40e45 ꢁC for 1 h afforded 3g (0.8800 g, 77%, E/
Z¼38/62) (eluent: petroleum ether/ethyl acetate¼10/1): oil; 1H
(400 MHz, CDCl3):
d
[6.67 (E-isomer, d, J¼8.4 Hz, 0.38H), 5.92 (Z-iso-
mer, d, J¼7.2 Hz, 0.60H)], [4.36e4.27 (Z-isomer, m, 0.63H), 4.25e4.16
(E-isomer, m, 0.42H)], 3.66e3.30(m, 2H),1.70e1.47 (m, 3H), 1.47e1.27
(m, 6H), 0.92e0.87 (m, 3H). The E/Z mixture was submitted to the
kinetic resolution step without further characterization.
NMR (300 MHz, CDCl3):
d
[6.67 (E-isomer, d, J¼9.0 Hz, 0.38H), 5.91
(Z-isomer, d, J¼7.8 Hz, 0.62H)], [4.36e4.25 (Z-isomer, m, 0.64H),
4.24e4.14 (E-isomer, m, 0.39H)], 3.70e3.26 (m, 2H), 2.09 (br s, 1H),
1.70e1.45 (m, 2H), 1.45e1.20 (m, 4H), 0.98e0.82 (m, 3H). The E/Z
mixture was submitted to the kinetic resolution step without fur-
ther characterization.
4.2.10.2. Kinetical resolution with Sonogashira coupling reaction.
n-C4F9
n-C4F9
I
C5H11-n
I
C5H11-n
HO
3h
HO
3h
4.2.9.2. Kinetical resolution with Sonogashira coupling reaction.
Pd(PPh3)2Cl2 (4.9 mol%)
CuI (5 mol%)
Z-
n-C4F9
n-C4F9
+
+
Et2NH (0.7 equiv)
HO
CH3CN, 0 oC, 70 min
I
C4H9-n
I
C4H9-n
OH
HO
3g
HO
3g
Pd(PPh3)2Cl2 (5.0 mol%)
CuI (4.8 mol %)
0.7 equiv
Z-
n-C4F9
C5H11-n
4
+
HO
+
HO
Et2NH (0.7 equiv)
CH3CN, 0 oC, 50 min
E-5h
OH
0.7 equiv
Following typical procedure 2, the reaction of the E/Z mixture of 3h
(121.9 mg, 0.251 mmol), propargyl alcohol 4 (9.8 mg, 0.175 mmol),
Pd(PPh3)2Cl2 (8.7 mg, 1.2ꢂ10ꢀ2 mmol, 4.9 mol %), CuI (2.4 mg,
1.3ꢂ10ꢀ2 mol, 5.0 mol %), and Et2NH (12.9 mg, 0.177 mmol) in
0.5 mL of CH3CN at 0 ꢁC for 70 min afforded Z-3h (56.3 mg, 46%)
(eluent: petroleum ether/ethyl acetate¼10/1) and E-5h (25.6 mg,
25%) (eluent: petroleum ether/ethyl acetate¼3/1).
n-C4F9
C4H9-n
4
HO
E-5g
Following typical procedure 2, the reaction of the E/Z mixture of
(9.8 mg,
3g (118.0 mg, 0.250 mmol), propargyl alcohol
4
0.175 mmol), Pd(PPh3)2Cl2 (8.8 mg, 1.3ꢂ10ꢀ2 mmol, 5.0 mol %), CuI
(2.3 mg,1.2ꢂ10ꢀ2 mol, 4.8 mol %), and Et2NH (13.0 mg, 0.179 mmol)
in 0.5 mL of CH3CN at 0 ꢁC for 50 min afforded Z-3g (53.6 mg, 45%)
(eluent: petroleum ether/ethyl acetate¼10/1) and E-5g (29.3 mg,
29%) (eluent: petroleum ether/ethyl acetate¼3/1).
4.2.10.3. 10,10,11,11,12,12,13,13,13-Nonafluoro-8-iodo-7(Z)-tride-
cen-6-ol (Z-3h). Oil, 1H NMR (400 MHz, CDCl3):
d
5.91 (d, J¼8.0 Hz,
1H), 4.35e4.27 (m, 1H), 3.52e3.30 (m, 2H), 1.88 (br s, 1H),1.68e1.50
(m, 2H), 1.50e1.23 (m, 6H), 0.89 (t, J¼7.0 Hz, 3H); 13C NMR
4.2.9.3. 9,9,10,10,11,11,12,12,12-Nonafluoro-7-iodo-6(Z)-dodecen-
(100 MHz, CDCl3):
d
147.3, 86.1, 76.5, 45.3 (t, JCeF¼21.3 Hz), 35.8,
5-ol (Z-3g). Oil; 1H NMR (400 MHz, CDCl3):
d
5.92 (d, J¼7.2 Hz, 1H),
31.7, 24.6, 22.5, 13.9; IR (neat, cmꢀ1): 3346, 2961, 2935, 2863, 1639,
1468, 1426, 1344, 1235, 1135, 1101, 1020; MS (EI, 70 eV) m/z (%): 486
(Mþ, 0.03), 415 [(MꢀC5H11)þ, 100]; Anal. calcd for C13H16F9IO: C
32.12, H 3.32; found: C 32.45, H 3.38.
4.36e4.28 (m, 1H), 3.53e3.30 (m, 2H), 1.76 (br s, 1H), 1.70e1.51 (m,
2H), 1.47e1.28 (m, 4H), 0.92 (t, J¼6.8 Hz, 3H); 13C NMR (100 MHz,
CDCl3):
d
147.3, 86.1, 76.5, 45.3 (t, JCeF¼21.2 Hz), 35.5, 27.0, 22.6,
13.9; IR (neat, cmꢀ1): 3356, 2960, 2930, 2862, 1639, 1580, 1460,
1426, 1378, 1344, 1235, 1135, 1101, 1020; MS (EI, 70 eV) m/z (%): 472
(Mþ, 0.05), 415 (MþꢀC4H9, 100); Anal. calcd for C12H14F9IO: C 30.53,
H 2.99; found: C 30.72, H 3.03.
4.2.10.4. 4-(20,20,30,30,40,40,50,50,50-Nonafluoropentyl)-undec-2-yn-
4(E)-1,6-diol (E-5h). Oil; 1H NMR (400 MHz, CDCl3):
d
6.17 (d,
J¼8.8 Hz, 1H), 4.37 (s, 2H), 4.32e4.23 (m, 1H), 3.16e2.91 (m, 2H),

Z. Ma et al. / Tetrahedron 67 (2011) 8808e8818
8815
1.87 (br s, 2H), 1.66e1.53 (m, 1H), 1.53e1.43 (m, 1H), 1.43e1.20 (m,
5.1 mol %), CuI (2.5 mg, 1.3ꢂ10ꢀ2 mol, 5.3 mol %), and Et2NH
(12.8 mg, 0.175 mmol) in 0.5 mL of CH3CN at 0 ꢁC for 70 min
afforded Z-3j (49.9 mg, 39%) (eluent: petroleum ether/ethyl
acetate¼10/1) and E-5j (42.3 mg, 39%) (eluent: petroleum ether/
ethyl acetate¼2/1).
6H), 0.88 (t, J¼6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 146.6,112.0
(t, JCeF¼3.0 Hz), 86.9, 85.8, 68.2, 51.3, 36.8, 32.5 (t, JCeF¼21.3 Hz),
31.6, 24.7, 22.5, 13.9; IR (neat, cmꢀ1): 3334, 2960, 2934, 2863, 2225,
1438, 1348, 1235, 1134, 1099, 1024; MS (EI, 70 eV) m/z (%): 414 (Mþ,
0.01), 396 (MþꢀH2O, 4.27), 99 (100); Anal. calcd for C16H19F9O2: C
46.38, H 4.62; found: C 46.35, H 4.72.
4.2.12.3. 6,6,7,7,8,8,9,9,9-Nonafluoro-4-iodo-1-phenyl-3(Z)-
nonen-2-ol (Z-3j). Solid; mp: 56e57 ꢁC (n-hexane); 1H NMR
4.2.11. Synthesis of 11,11,12,12,13,13,14,14,14-nonafluoro-9-iodo-8-
tetradecen-7-ol (3i).
(400 MHz, CDCl3): d 7.36e7.29 (m, 2H), 7.29e7.22 (m, 3H), 5.98 (d,
J¼7.2 Hz, 1H), 4.55e4.45 (m, 1H), 3.53e3.28 (m, 2H), 2.94 (dd,
J1¼14.0 Hz and J2¼4.4 Hz, 1H), 2.78 (dd, J1¼13.6 Hz and J2¼8.0 Hz,
1H), 1.94 (d, J¼3.6 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 146.3,
136.6, 129.6, 128.6, 126.9, 86.3, 77.5, 45.2 (t, JCeF¼20.9 Hz), 41.9; IR
(neat, cmꢀ1): 3406, 1638, 1494, 1455, 1421, 1347, 1232, 1212, 1132,
1089, 1056; MS (EI, 70 eV) m/z (%): 506 (Mþ, 0.01), 415
[(MꢀC6H5CH2)þ, 61.11], 92 (100); Anal. calcd for C15H12F9IO: C
35.59, H 2.39; found: C 35.64, H 2.48.
Following typical procedure 1, the reaction of 1i (0.3687 g,
2.39 mmol), n-C4F9I 2a (1.6645 g, 4.81 mmol), Na2S2O4 (0.8334 g,
4.79 mmol), and Na2CO3 (0.5082 g, 4.79 mmol) in 4.5 mL of CH3OH
and 1.5 mL of H2O at 40e45 ꢁC for 1 h afforded 3i (0.7124 g, 60%, E/
Z¼37/63) (eluent: petroleum ether/ethyl acetate¼10/1): oil; 1H
4.2.12.4. 4-(20,20,30,30,40,40,50,50,50-Nonafluoropentyl)-7-phenyl-
hept-2-yn-4(E)-1,6-diol (E-5j). Solid; mp 62e63 ꢁC (n-hexane/ethyl
NMR (300 MHz, CDCl3):
d
[6.67 (E-isomer, d, J¼8.7 Hz, 0.37H), 5.92
acetate); 1H NMR (400 MHz, CDCl3):
d 7.38e7.23 (m, 3H), 7.20 (d,
(Z-isomer, d, J¼7.5 Hz, 0.63H)], [4.37e4.28 (Z-isomer, m, 0.66H),
4.26e4.15 (E-isomer, m, 0.39H)], 3.68e3.20 (m, 2H), 1.84e1.47 (m,
3H), 1.47e1.20 (m, 8H), 0.92e0.80 (m, 3H); GCeMS (EI, 70 eV) m/z
(%): [E-isomer, 415 (MþꢀC6H13, 98.40), 113 (100)], [Z-isomer, 415
(MþꢀC6H13, 15.06), 113 (100)], Anal. calcd for C14H18F9OI: C 33.62, H
3.63; found: C 33.83, H 3.70.
J¼6.9 Hz, 2H), 6.23 (d, J¼8.7 Hz, 1H), 4.49 (q, J¼6.3 Hz, 1H), 4.38 (d,
J¼5.1 Hz, 2H), 3.01e2.73 (m, 4H), 1.85e1.80 (m, 1H), 1.76 (t,
J¼5.4 Hz, 1H); 13C NMR (100 MHz, CDCl3):
d 145.2, 136.5, 129.5,
128.8, 127.0, 112.4, 87.0, 85.7, 69.5, 51.4, 43.2, 32.4 (t, JCeF¼22.0 Hz);
IR (neat, cmꢀ1): 3299, 3036, 2932, 2863, 2223, 1636, 1604, 1496,
1455, 1347, 1216, 1136, 1099, 1046, 1009; MS (EI, 70 eV) m/z (%): 416
(MþꢀH2O, 2.06), 325 (100); Anal. calcd for C18H15F9O2: C 49.78, H
3.48; found: C 49.67, H 3.65.
4.2.12. Synthesis of 6,6,7,7,8,8,9,9,9-nonafluoro-4-iodo-1-phenyl-3-
nonen-2-ol (3j), 6,6,7,7,8,8,9,9,9-nonafluoro-4-iodo-1-phenyl-3(Z)-
nonen-2-ol (Z-3j), and 4-(20,20,30,30,40,40,50,50,50-nonafluoropentyl)-7-
phenylhept-2-yn-4(E)-1,6-diol (E-5j).
4.2.13. Synthesis of 7,7,8,8,9,9,10,10,10-nonafluoro-5-iodo-2-methyl-
4-decen-3-ol 3q.
4.2.12.1. Radical addition reaction of 1j with 2a.
2.0 equiv Na2S2O4
n-C4F9
2.0 equiv Na2S2O4
n-C4F9
2.0 equiv Na2CO3
2.0 equiv Na2CO3
+
n-C4F9I
2.0 equiv
n-C4F9I
2.0 equiv
+
Bn
CH3OH/H2O = 3/1
40-45 oC, 1 h
I
HO
CH3OH/H2O = 3/1
40-45 oC, 1 h
I
Bn
HO
HO
3q
HO
3j
1n
2a
1j
2a
Following typical procedure 1, the reaction of 1n (67.1 mg,
0.60 mmol), n-C4F9I 2a (0.21 mL, d¼2.01, 0.4221 g, 1.22 mmol),
Na2S2O4 (0.2098 g, 1.21 mmol), and Na2CO3 (0.1277 g, 1.20 mmol) in
1.5 mL of CH3OH and 0.5 mL of H2O at 40e45 ꢁC for 1 h afforded 3q
(185.2 mg, 67%, E/Z¼40/60) (eluent: petroleum ether/diethyl
Following typical procedure 1, the reaction of 1j (0.3215 g,
2.01 mmol), n-C4F9I 2a (1.3986 g, 4.04 mmol), Na2S2O4 (0.6971 g,
4.01 mmol), and Na2CO3 (0.4257 g, 4.02 mmol) in 3.75 mL of
CH3OH and 1.25 mL of H2O at 40e45 ꢁC for 1 h afforded 3j
(0.6101 g, 60%, E/Z¼43/57) (eluent: petroleum ether/ethyl
ether¼20/1 to 10/1): oil; 1H NMR (300 MHz, CDCl3):
d [6.69 (E-isomer,
acetate¼10/1): oil; 1H NMR (400 MHz, CDCl3):
d 7.37e7.30 (m, 2H),
d, J¼9.0 Hz), 5.91 (Z-isomer, d, J¼7.8 Hz), 1H], [4.11e4.04 (Z-isomer,
m), 3.96e3.87 (E-isomer, m), 1H], 3.71e3.29 (m, 2H), 1.98e1.58 (m,
7.30e7.23 (m, 2H), 7.21e7.16 (m, 1H), [6.70 (E-isomer, d, J¼8.4 Hz,
0.43H), 6.00 (Z-isomer, d, J¼7.2 Hz, 0.57H)], [4.55e4.47 (Z-isomer,
m, 0.57H), 4.45e4.34 (E-isomer, m, 0.51H)], 3.54e3.16 (m, 2H),
3.00e2.72 (m, 2H), 1.73 (br s, 1H). The E/Z mixture was submitted to
the kinetic resolution step without further characterization.
2H),1.03e0.89 (m, 6H); 13C NMR (75 MHz, CDCl3):
d 150.7, 145.9, 87.3,
83.2, 81.1, 75.1, 45.6 (t, JCeF¼21.3 Hz), 39.7 (t, JCeF¼20.9 Hz), 33.8, 33.6,
18.04, 18.01, 17.74, 17.72, 17.7, 17.6; IR (neat, cmꢀ1): 3363, 2966, 1633,
1470, 1427, 1345, 1236, 1135, 1019; GCeMS (EI, 70 eV) m/z (%): [E-
isomer, 415 (MþꢀC3H7, 100)]; [Z-isomer: 415 (MþꢀC3H7, 100)]; Anal.
calcd for C11H12F9OI: C 28.84, H 2.64; found: C 29.27, H 2.70.
4.2.12.2. Kinetical resolution with Sonogashira coupling reaction.
n-C4F9
n-C4F9
4.2.14. Synthesis of 7,7,8,8,9,9,10,10,10-nonafluoro-5-iodo-2,2-
dimethyl-4-decen-3-ol 3q.
I
Bn
I
Bn
HO
3j
HO
3j
Pd(PPh3)2Cl2 (5.1 mol%)
CuI (5.3 mol%)
Z-
+
+
Et2NH (0.7 equiv)
HO
CH3CN, 0 oC, 70 min
OH
Following typical procedure 1, the reaction of 1o (76.6 mg,
0.61 mmol), n-C4F9I 2a (0.21 mL, d¼2.01, 0.4221 g, 1.22 mmol),
Na2S2O4 (208.9 mg, 1.20 mmol), and Na2CO3 (128.8 mg, 1.22 mmol)
in 1.5 mL of CH3OH and 0.5 mL of H2O at 40e45 ꢁC for 1 h afforded
3r (237.8 mg, 83%, E/Z¼37/63) (eluent: 30e60 ꢁC petroleum ether/
0.7 equiv
n-C4F9
Bn
4
HO
E-5j
Following typical procedure 2, The reaction of the E/Z mixture of
3j (126.5 mg, 0.250 mmol) prepared above, propargyl alcohol 4
(9.7 mg, 0.173 mmol), Pd(PPh3)2Cl2 (8.9 mg, 1.3ꢂ10ꢀ2 mmol,
diethyl ether¼20/1): oil; 1H NMR (300 MHz, CDCl3):
d [6.76 (E-
isomer, d, J¼9.0 Hz, 0.37H), 5.89 (Z-isomer, d, J¼8.4 Hz, 0.63H)],

8816
Z. Ma et al. / Tetrahedron 67 (2011) 8808e8818
[4.00 (Z-isomer, d, J¼8.7 Hz), 3.84 (E-isomer, d, J¼9.0 Hz), 1H],
3.63e3.30 (m, 2H), 1.72 (br s, 1H), [0.97 (s), 0.93 (s), 6H]; 13C NMR
(d, J¼9.0 Hz, 1H), 4.38 (d, J¼3.3 Hz, 2H), 4.28 (q, J¼7.3 Hz, 1H),
3.20e2.88 (m, 2H), 2.44 (br s, 1H), 2.14 (br s, 1H), 1.70e1.56 (m, 1H),
1.56e1.42 (m, 1H), 1.42e1.20 (m, 4H), 0.90 (t, J¼6.8 Hz, 3H); 13C
(75 MHz, CDCl3):
d 149.2, 144.5, 88.5, 83.9, 83.5, 77.4, 45.8 (t,
JCeF¼21.0 Hz), 39.6 (t, JCeF¼21.0 Hz), 35.7, 35.0, 25.6, 25.2; IR (neat,
cmꢀ1): 3424, 2963, 2874, 1719, 1629, 1479, 1467, 1366, 1344, 1236,
1135, 1089, 1035; GCeMS (EI, 70 eV) m/z (%): [E-isomer, 415
(MþꢀC4H9, 7.6), 57 (100)]; [Z-isomer, 415 (MþꢀC4H9, 0.5), 57
(100)]; Anal. calcd for C12H14F9OI: C 30.53, H 2.99; found: C 31.29, H
3.15. HRMS calcd for C12H14F9OI (Mþ): 471.9946. found: 471.9962.
NMR (75 MHz, CDCl3): d 146.6, 111.9, 86.8, 85.7, 68.2, 51.2, 36.4, 32.4
(t, JCeF¼21.9 Hz), 27.1, 22.5, 13.8; IR (neat, cmꢀ1): 3320, 2967, 2936,
2865, 2222, 1635, 1437, 1357, 1238, 1206, 1145, 1122, 1099, 1067,
1023; MS (EI, 70 eV) m/z (%): 482 (MþꢀH2O, 11.03), 425
(MþꢀH2OꢀC4H9, 79.46), 85 (100); Anal. calcd for C17H17F13O2: C
40.81, H 3.42; found: C 41.02, H 3.59.
4.2.15. Synthesis of 9,9,10,10,11,11,12,12,13,13,14,14,14-tridecafluoro-
7-iodo-6-tetradecen-5-ol (3k), 9,9,10,10,11,11,12,12,13,13,14,14,14-
tridecafluoro-7-iodo-6(Z)-tetradecen-5-ol (Z-3k), and 4-(20,20,30,30,
40,40,50,50,60,60,70,70,70-tridecafluoro-heptyl)-dec-2-yn-4(E)-1,6-diol
(E-5k).
4.2.16. Synthesis 10,10,11,11,12,12,13,13,14,14,15,15,15-tridecafluoro-8-
iodo-7-pentadecen-6-ol (3l), 10,10,11,11,12,12,13,13,14,14,15,15,15-
tridecafluoro-8-iodo-7(Z)-pentadecen-6-ol (Z-3l), and 4-(20,20,30,30,
40,40,50,50,60,60,70,70,70-tridecafluoro-heptyl)-undec-2-yn-4(E)-1,6-diol
(E-5l).
4.2.15.1. Radical addition reaction of 1g with 2b.
4.2.16.1. Radical addition reaction of 1h with 2b.
2.0 equiv Na2S2O4
n-C6F13
2.0 equiv Na2S2O4
n-C6F13
2.0 equiv Na2CO3
2.0 equiv Na2CO3
+ n-C6F13
2.0 equiv
I
+ n-C6F13
2.0 equiv
I
C5H11-n
C4H9-n
CH3OH/H2O = 3/1
40-45 oC, 1 h
CH3OH/H2O = 3/1
40-45 oC, 1 h
I
C4H9-n
I
C5H11-n
HO
HO
HO
3k
HO
3l
1h
1g
2b
2b
Following typical procedure 1, the reaction of 1h (0.3369 g,
2.41 mmol), n-C6F13I 2b (2.1682 g, 4.86 mmol), Na2S2O4 (0.8363 g,
4.81 mmol), and Na2CO3 (0.5075 g, 4.79 mmol) in 4.5 mL of CH3OH
and 1.5 mL of H2O at 40e45 ꢁC for 1 h afforded 3l (0.8759 g, 61%, E/
Z¼37/63) (eluent: petroleum ether/ethyl acetate¼10/1): oil; 1H NMR
Following typical procedure 1, the reaction of 1g (0.2517 g,
2.00 mmol), n-C6F13I 2b (1.7856 g, 4.00 mmol), Na2S2O4 (0.6954 g,
4.00 mmol), and Na2CO3 (0.4240 g, 4.00 mmol) in 3.75 mL of
CH3OH and 1.25 mL of H2O at 40e45 ꢁC for 1 h afforded 3k
(0.8304 g, 73%, E/Z¼38/62) (eluent: petroleum ether/ethyl
acetate¼10/1): oil; 1H NMR (400 MHz, CDCl3):
d
[6.67 (E-isomer, d,
(300 MHz, CDCl3):
d
[6.67 (E-isomer, d, J¼9.0 Hz, 0.37H), 5.92 (Z-iso-
mer, d, J¼7.5 Hz, 0.63H)], [4.37e4.27 (Z-isomer, m, 0.65H), 4.26e4.16
(E-isomer, m, 0.39H)], 3.68e3.28 (m, 2H), 1.80e1.47 (m, 3H),
1.47e1.20 (m, 6H), 0.95e0.84 (m, 3H). The E/Z mixture was submitted
to the kinetic resolution step without further characterization.
J¼8.8 Hz, 0.38H), 5.92 (Z-isomer, d, J¼7.6 Hz, 0.61H)], [4.36e4.27
(Z-isomer, m, 0.64H), 4.25e4.17 (E-isomer, m, 0.39H)], 3.70e3.30
(m, 2H), 1.67 (br s, 1H), 1.64e1.47 (m, 2H), 1.47e1.24 (m, 4H),
0.96e0.87 (m, 3H). The E/Z mixture was submitted to the kinetic
resolution step without further characterization.
4.2.16.2. Kinetical resolution with Sonogashira coupling reaction.
4.2.15.2. Kinetical resolution with Sonogashira coupling reaction.
n-C6F13
n-C6F13
n-C6F13
n-C6F13
I
C5H11-n
I
C5H11-n
HO
3l
I
C4H9-n
HO
Z-3l
I
C4H9-n
Pd(PPh3)2Cl2 (4.9 mol%)
CuI (4.3 mol%)
HO
3k
HO
3k
Pd(PPh3)2Cl2 (5.3 mol%)
CuI (4.9 mol%)
Z-
+
HO
+
Et2NH (0.7 equiv)
CH3CN, 0 oC, 55 min
+
+
Et2NH (0.7 equiv)
HO
OH
CH3CN, 0 oC, 75 min
0.7 equiv
OH
0.7 equiv
n-C6F13
C5H11-n
4
HO
5l
n-C6F13
C4H9-n
4
E-
HO
Following typical procedure 2, the reaction of the E/Z mixture of 3l
(235.2 mg, 0.401 mmol) prepared above, propargyl alcohol
5k
E-
4
(15.6 mg, 0.279 mmol), Pd(PPh3)2Cl2 (13.9 mg, 2.0ꢂ10ꢀ2 mmol,
4.9 mol %), CuI (3.3 mg, 1.7ꢂ10ꢀ2 mol, 4.3 mol %), and Et2NH
(20.5 mg, 0.281 mmol) in 0.8 mL of CH3CNat 0 ꢁC for 55 min afforded
Z-3l (115.9 mg, 49%) (eluent: petroleum ether/ethyl acetate¼10/1)
and E-5l (46.6 mg, 23%) (eluent: petroleum ether/ethyl acetate¼3/1).
Following typical procedure 2, the reaction of the E/Z mixture of
3k (129.6 mg, 0.227 mmol) prepared above, propargyl alcohol 4
(8.8 mg, 0.157 mmol), Pd(PPh3)2Cl2 (8.4 mg, 1.2ꢂ10ꢀ2 mmol, 5.3 mol
%), CuI (2.0 mg, 1.1ꢂ10ꢀ2 mol, 4.9 mol %), and Et2NH (12.0 mg,
0.164 mmol) in 0.46 mL of CH3CN at 0 ꢁC for 75 min afforded Z-3k
(64.1 mg, 49%) (eluent: petroleum ether/ethyl acetate¼10/1) and E-
5k (30.8 mg, 27%) (eluent: petroleum ether/ethyl acetate¼3/1).
4.2.16.3. 10,10,11,11,12,12,13,13,14,14,15,15,15-Tridecafluoro-8-
iodo-7(Z)-pentadecen-6-ol (Z-3l). Oil; 1H NMR (300 MHz, CDCl3):
4.2.15.3. 9,9,10,10,11,11,12,12,13,13,14,14,14-Tridecafluoro-7-iodo-
d
5.92 (d, J¼7.8 Hz, 1H), 4.37e4.27 (m, 1H), 3.56e3.27 (m, 2H), 1.88
6(Z)-tetradecen-5-ol (Z-3k). Oil; 1H NMR (400 MHz, CDCl3):
d 5.92
(br s, 1H), 1.72e1.49 (m, 2H), 1.49e1.27 (m, 6H), 0.90 (t, J¼6.9 Hz,
3H); 13C NMR (75 MHz, CDCl3):
d 147.3, 86.0, 76.5, 45.3 (t,
(d, J¼8.0 Hz, 1H), 4.36e4.28 (m, 1H), 3.54e3.30 (m, 2H), 1.84 (br s,
1H), 1.71e1.51 (m, 2H), 1.47e1.28 (m, 4H), 0.92 (t, J¼7.0 Hz, 3H); 13C
JCeF¼21.5 Hz), 35.7, 31.7, 24.6, 22.5, 13.9; IR (neat, cmꢀ1): 3334,
2958, 2934, 2861, 1639, 1468, 1426, 1350, 1240, 1204, 1146, 1122,
1066, 1027; MS (EI, 70 eV) m/z (%): 586 (Mþ, 0.30), 515 (100); Anal.
calcd for C15H16F13IO: C 30.74, H 2.75; found: C 31.08, H 3.07.
NMR (100 MHz, CDCl3):
d
147.3, 86.1, 76.5, 45.4 (t, JCeF¼21.4 Hz),
35.5, 27.0, 22.6, 13.9; IR (neat, cmꢀ1): 3357, 3962, 2935, 2863, 1467,
1426, 1349, 1239, 1206, 1145, 1122, 1102, 1030; MS (EI, 70 eV) m/z
(%): 572 (Mþ, 0.07), 515 [(MꢀC4H9)þ, 100]; Anal. calcd for
C14H14F13IO: C 29.39, H 2.47; found: C 29.70, H 2.37.
4.2.16.4. 4-(20,20,30,30,40,40,50,50,60,60,70,70,70-Tridecafluoro-heptyl)-
undec-2-yn-4(E)-1,6-diol (E-5l). Oil; 1H NMR (300 MHz, CDCl3):
4.2.15.4. 4-(20,20,30,30,40,40,50,50,60,60,70,70,70-Tridecafluoro-heptyl)-
d
6.19 (d, J¼9.3 Hz, 1H), 4.39 (d, J¼5.1 Hz, 2H), 4.35e4.23 (m, 1H),
dec-2-yn-4(E)-1,6-diol (E-5k). Oil; 1H NMR (300 MHz, CDCl3):
d 6.19
3.20e2.90 (m, 2H), 1.94e1.88 (m, 1H), 1.86e1.67 (m, 1H), 1.67e1.52

Z. Ma et al. / Tetrahedron 67 (2011) 8808e8818
8817
(m, 1H), 1.52e1.44 (m, 1H), 1.44e1.20 (m, 6H), 0.89 (t, J¼6.6 Hz, 3H);
(m, 2H), 2.09 (br s, 1H), 1.87 (br s, 1H), 1.70e1.55 (m, 1H), 1.55e1.42
(m, 1H), 1.42e1.18 (m, 8H), 0.88 (t, J¼6.8 Hz, 3H); 13C NMR (75 MHz,
13C NMR (75 MHz, CDCl3):
d 146.6, 112.0, 86.8, 85.8, 68.2, 51.3, 36.7,
32.5 (t, JCeF¼21.8 Hz), 31.6, 24.7, 22.5, 13.9; IR (neat, cmꢀ1): 3333,
2960, 2935, 2863, 2222, 1632, 1462, 1437, 1357, 1238, 1206, 1145,
1122, 1099, 1066, 1024; MS (EI, 70 eV) m/z (%): 514 (Mþ, 0.11), 496
(MþꢀH2O, 6.63), 425 (MþꢀH2O-C5H11, 28.84), 99 (100); Anal. calcd
for C18H19F13O2: C 42.03, H 3.72; found: C 42.45, H 4.08.
CDCl3): d 146.6, 111.9, 86.8, 85.7, 68.2, 51.3, 36.7, 32.5 (t,
JCeF¼21.3 Hz), 31.7, 29.1, 25.0, 22.5, 14.0; IR (neat, cmꢀ1): 3318, 2961,
2933, 2861, 2226,1635,1459,1437,1357,1238,1207,1145,1122,1100,
1066, 1024; MS (EI, 70 eV) m/z (%): 510 (MþꢀH2O, 16.14), 425 (100);
Anal. calcd for C19H21F13O2: C 43.19, H 4.01; found: C 43.45, H 4.20.
4.2.17. Synthesis of 11,11,12,12,13,13,14,14,15,15,16,16,16-tridecafluoro-
9-iodo-8-hexadecen-7-ol (3m), 11,11,12,12,13,13,14,14,15,15,16,16,16-
tridecafluoro-9-iodo-8(Z)-hexadecen-7-ol (Z-3m), and 4-(20,20,30,30,
40,40,50,50,60,60,70,70,70-tridecafluoro-heptyl)-dodec-2-yn-4(E)-1,6-diol
(E-5m).
4.2.18. Synthesis of 6,6,7,7,8,8,9,9,9-nonafluoro-4-iodo-2-phenyl-
3(E)-nonen-2-ol (E-3n) and 6,6,7,7,8,8,9,9,9-nonafluoro-4-iodo-2-
phenyl-3(Z)-nonen-2-ol (Z-3n).
4.2.17.1. Radical addition reaction of 1i with 2b.
2.0 equiv Na2S2O4
2.0 equiv Na2CO3
n-C6F13
+ n-C6F13
2.0 equiv
I
C6H13-n
I
C6H13-n
CH3OH/H2O = 3/1
40-45 oC, 1 h
HO
HO
3m
1i
2b
Following typical procedure 1, the reaction of 1k (0.1314 g,
0.82 mmol), n-C4F9I 2a (0.5661 g, 1.64 mmol), Na2S2O4 (0.2802 g,
1.61 mmol), and Na2CO3 (0.1694 g, 1.60 mmol) in 1.5 mL of CH3OH
and 0.5 mL of H2O at 40e45 ꢁC for 1 h afforded E-3n (0.2337 g, 56%)
(eluent: petroleum ether/diethyl ether¼60/1) and Z-3n (0.0246 g,
6%) (eluent: petroleum ether/diethyl ether¼20/1).
Following typical procedure 1, the reaction of 1i (0.3073 g,
2.00 mmol), n-C6F13I 2b (1.7996 g, 4.03 mmol), Na2S2O4 (0.6964 g,
4.00 mmol), and Na2CO3 (0.4228 g, 3.99 mmol) in 3.75 mL of
CH3OH and 1.25 mL of H2O at 40e45 ꢁC for 1 h afforded 3m
(0.9901 g, 83%, E/Z¼36/64) (eluent: petroleum ether/ethyl
acetate¼10/1): oil; 1H NMR (400 MHz, CDCl3):
d [6.66 (E-isomer, d,
J¼8.4 Hz, 0.36H), 5.91 (Z-isomer, d, J¼8.0 Hz, 0.64H)], [4.36e4.27
(Z-isomer, m, 0.68H), 4.25e4.17 (E-isomer, m, 0.39H)], 3.70e3.30
(m, 2H), 1.65 (br s, 1H), 1.64e1.48 (m, 2H), 1.48e1.21 (m, 8H),
0.92e0.84 (m, 3H). The E/Z mixture was submitted to the kinetic
resolution step without further characterization.
4.2.18.1. 6,6,7,7,8,8,9,9,9-Nonafluoro-4-iodo-2-phenyl-3(E)-
nonen-2-ol (E-3n). Oil; 1H NMR (300 MHz, CDCl3):
d 7.47e7.39 (m,
2H), 7.39e7.31 (m, 2H), 7.31e7.23 (m, 1H), 6.91 (s, 1H), 4.18e3.94 (m,
1H), 3.78e3.56 (m, 1H), 2.09 (br s, 1H), 1.67 (s, 3H); 13C NMR
(100 MHz, CDCl3): d 153.9,145.5,128.7,127.6,124.8, 82.7, 78.2, 39.5 (t,
JCeF¼20.3 Hz), 31.2; IR (neat, cmꢀ1): 3567, 3463, 3062, 3029, 2981,
1677, 1616, 1494, 1448, 1421, 1348, 1236, 1198, 1134, 1093, 1062, 1035,
1002; MS (EI, 70 eV) m/z (%): 491 (MþꢀCH3, 1.89), 379 (MþꢀI, 100);
Anal. calcd for C15H12F9IO: C 35.59, H 2.39; found: C 35.62; H 2.60.
4.2.17.2. Kinetical resolution with Sonogashira coupling reaction.
n-C6F13
n-C6F13
I
C6H13-n
I
C6H13-n
HO
3m
Pd(PPh3)2Cl2(5.0 mol%)
CuI (5.3 mol%)
HO
3m
Z-
4.2.18.2. 6,6,7,7,8,8,9,9,9-Nonafluoro-4-iodo-2-phenyl-3(Z)-
nonen-2-ol (Z-3n). Oil; 1H NMR (300 MHz, CDCl3):
d
7.48e7.41 (m,
+
OH
Et2NH (0.7 equiv)
+
CH3CN, 0 oC, 45 min
2H), 7.40e7.24 (m, 3H), 6.83 (s,1H), 3.63e3.35 (m, 2H), 2.99 (br s,1H),
1.70 (s, 3H); 13C NMR (75 MHz, CDCl3):
d 150.5, 145.6, 128.4, 127.3,
OH
125.8, 84.8, 75.2, 46.7 (t, J¼21.3 Hz), 31.7; IR (neat, cmꢀ1): 3432, 2925,
2853, 1628, 1493, 1448, 1427, 1344, 1235, 1134, 1074, 1029, 1018; MS
(EI, 70 eV) m/z (%): 491 (MþꢀCH3, 5.91), 379 (MþꢀI, 100); HRMS
calcd for C14H9F9IO (MþꢀCH3): 490.9554. found: 490.9556.
0.7 equiv
n-C6F13
C6H13-n
4
HO
E-5m
Following typical procedure 2, the reaction of the E/Z mixture of 3m
(149.4 mg, 0.249 mmol) prepared above, propargyl alcohol
4.2.19. Synthesis of 9,9,10,10,11,11,12,12,12-nonafluoro-7-iodo-5-
butyl-6(E)-dodecen-5-ol E-3s.
4
(9.8 mg, 0.175 mmol), Pd(PPh3)2Cl2 (8.7 mg, 1.2ꢂ10ꢀ2 mmol,
5.0 mol %), CuI (2.5 mg, 1.3ꢂ10ꢀ2 mol, 5.3 mol %), and Et2NH
(12.6 mg, 0.173 mmol) in 0.5 mL of CH3CN at 0 ꢁC for 45 min
afforded Z-3m (77.9 mg, 52%) (eluent: petroleum ether/ethyl
acetate¼10/1) and E-5m (29.1 mg, 22%) (eluent: petroleum ether/
ethyl acetate¼3/1).
4.2.17.3. 11,11,12,12,13,13,14,14,15,15,16,16,16-Tridecafluoro-9-
iodo-8(Z)-hexadecen-7-ol (Z-3m). Oil, 1H NMR (400 MHz, CDCl3):
Following typical procedure 1, the reaction of 1p (54.6 mg,
0.30 mmol), n-C4F9I 2a (0.10 mL, d¼2.01, 0.201 g, 0.58 mmol),
Na2S2O4 (105.3 mg, 0.61 mmol), and Na2CO3 (63.8 mg, 0.60 mmol)
in 1.5 mL of CH3OH and 0.5 mL of H2O at 40e45 ꢁC for 1 h afforded
E-3s (77.2 mg, 49%) and Z-3s (not pure) (eluent: petroleum ether/
d
5.91 (d, J¼8.0 Hz, 1H), 4.32 (q, J¼6.8 Hz, 1H), 3.54e3.29 (m, 2H),
2.04 (br s, 1H), 1.69e1.50 (m, 2H), 1.48e1.21 (m, 8H), 0.88 (t,
J¼6.6 Hz, 3H); 13C NMR (100 MHz, CDCl3):
d 147.3, 86.1, 76.5, 45.4 (t,
JCeF¼20.7 Hz), 35.8, 31.7, 29.2, 24.8, 22.5, 14.0; IR (neat, cmꢀ1):
3346, 2932, 2860, 1637, 1460, 1426, 1349, 1239, 1207, 1145, 1122,
1065; MS (EI, 70 eV) m/z (%): 600 (Mþ, 0.04), 515 (MþꢀC6H13, 100);
Anal. calcd for C16H18F13IO: C 32.02, H 3.02; found: C 32.36, H 3.31.
diethyl ether¼80/1 to 20/1): oil; 1H NMR (300 MHz, CDCl3):
d 6.46
(s, 1H), 3.98 (t, J¼18.0 Hz, 2H), 1.56e1.42 (m, 5H), 1.42e1.20 (m, 8H),
0.97e0.87 (m, 6H); 13C NMR (75 MHz, CDCl3):
d 153.4, 81.4, 80.5,
41.7, 39.5 (t, JCeF¼20.1 Hz), 25.6, 23.0, 14.0; IR (neat, cmꢀ1): 3479,
2960, 2936, 2864, 1631, 1468, 1349, 1236, 1134, 1113, 1038; GCeMS
(EI, 70 eV) m/z (%): [528 (Mþ, 0.02), 471 (MþꢀC4H9, 100)]; HRMS
calcd for C16H21F9OI ([M-1]þ): 527.0493. found: 527.0483.
4.2.17.4. 4-(20,20,30,30,40,40,50,50,60,60,70,70,70-Tridecafluoro-heptyl)-
dodec-2-yn-4(E)-1,6-diol (E-5m). Oil; 1H NMR (300 MHz, CDCl3):
d
6.19 (d, J¼9.0 Hz, 1H), 4.38 (s, 2H), 4.33e4.23 (m, 1H), 3.20e2.88

8818
Z. Ma et al. / Tetrahedron 67 (2011) 8808e8818
4.2.20. Synthesis of 1-(40,40,50,50,60,60,70,70,70-nonafluoro-20-iodo-
10(E)-heptyl)-cyclohexanol (E-3o) and 1-(40,40,50,50,60,60,70,70,70-non-
afluoro-20-iodo-10(Z)-heptyl)-cyclohexanol (Z-3o).
References and notes
1. (a) Patai, S. The Chemistry of Ketenes, Allenes, and Related Compounds; John
Wiley: New York, NY, 1980, Part 1; (b) Schuster, H. F.; Coppola, G. M. Allenes in
Organic Synthesis; John Wiley: New York, NY, 1984; (c) Landor, S. R. The
Chemistry of Allenes; Academic Press: New York, NY, 1982; Vols. 1e3; (d) Ma, S.
Carbopalladation of allenes In Handbook of Organopalladium Chemistry for Or-
ganic Synthesis; Negishi, E., Ed.; John Wiley: New York, NY, 2002; p 1491; (e)
Krause, N.; Hashmi, A. S. K. Modern Allene Chemistry; Wiley-VCH: Weinheim,
Germany, 2004; Vols. 1e2; (f) Ma, S. Pd-Catalyzed two- or three component
cyclization of functionalized allenes In Topics in Organometallic Chemistry; Tsuji,
J., Ed.; Springer: Heidelberg, 2005; p 183.
2. For reviews on the chemistry of allenes, see: (a) Wang, K. K. Chem. Rev. 1996, 96,
207; (b) Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A. Chem. Rev. 2000,
100, 3067; (c) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2000, 39, 3590; (d) Lu, X.;
Zhang, C.; Xu, Z. Acc. Chem. Res. 2001, 34, 535; (e) Bates, R. W.; Satcharoen, V.
Chem. Soc. Rev. 2002, 31, 12; (f) Tius, M. A. Acc. Chem. Res. 2003, 36, 284; (g) Ma,
S. Acc. Chem. Res. 2003, 36, 701; (h) Wei, L.-L.; Xiong, H.; Hsung, R. P. Acc. Chem.
Res. 2003, 36, 773; (i) Ma, S. Chem. Rev. 2005, 105, 2829; (j) Ma, S. Aldrichimica
Acta 2007, 40, 91.
Following typical procedure 1, the reaction of 1l (0.1117 g,
0.81 mmol), n-C4F9I 2a (0.5379 g, 1.55 mmol), Na2S2O4 (0.2800 g,
1.61 mmol), and Na2CO3 (0.1687 g, 1.59 mmol) in 1.5 mL of CH3OH
and 0.5 mL of H2O at 40e45 ꢁC for 1 h afforded E-3o (0.2307 g, 59%)
(eluent: petroleum ether/diethyl ether¼40/1) and Z-3o (0.0216 g,
6%) (eluent: petroleum ether/diethyl ether¼20/1).
3. For the reviews, see Ref. 2j, and Ma, S. Ionic addition to allenes In Modern Allene
Chemistry; Krause, N., Hashmi, A. S. K., Eds.; Wiley-VCH: Weinheim, 2004.
4. (a) Ma, S.; Shi, Z.; Yu, Z. Tetrahedron Lett. 1999, 40, 2393; (b) Ma, S.; Shi, Z.; Yu, Z.
Tetrahedron 1999, 55, 12137; (c) Ma, S.; Wei, Q.; Wang, H. Org. Lett. 2000, 2,
3893; (d) Ma, S.; Ren, H.; Wei, Q. J. Am. Chem. Soc. 2003, 125, 4817; (e) Ma, S.;
Hao, X.; Huang, X. Org. Lett. 2003, 5, 1217; (f) Ma, S.; Hao, X.; Huang, X. Chem.
Commun. 2003, 1082; (g) Ma, S.; Hao, X.; Meng, X.; Huang, X. J. Org. Chem. 2004,
69, 5720; (h) Fu, C.; Huang, X.; Ma, S. Tetrahedron Lett. 2004, 45, 6063; (i) Ma, S.;
Pan, F.; Hao, X.; Huang, X. Synlett 2004, 85; (j) Fu, C.; Li, J.; Ma, S. Chem. Com-
mun. 2005, 4119; (k) Fu, C.; Chen, G.; Liu, X.; Ma, S. Tetrahedron 2005, 61, 7768;
(l) Fu, C.; Ma, S. Eur. J. Org. Chem. 2005, 3942; (m) Chen, G.; Fu, C.; Ma, S. Tet-
rahedron 2006, 62, 4444; (n) Chen, G.; Fu, C.; Ma, S. J. Org. Chem. 2006, 71, 9877;
(o) Gu, Z.; Deng, Y.; Shu, W.; Ma, S. Adv. Synth. Catal. 2007, 349, 1653; (p) Zhou,
C.; Fu, C.; Ma, S. Angew. Chem., Int. Ed. 2007, 46, 4379; (q) Zhou, C.; Fu, C.; Ma, S.
Tetrahedron 2007, 63, 7612; (r) He, G.; Zhou, C.; Fu, C.; Ma, S. Tetrahedron 2007,
63, 3800; (s) Zhou, C.; Ma, Z.; Gu, Z.; Fu, C.; Ma, S. J. Org. Chem. 2008, 73, 772; (t)
4.2.20.1. 1-(40,40,50,50,60,60,70,70,70-Nonafluoro-20-iodo-10(E)-hep-
tyl)-cyclohexanol (E-3o). Oil; 1H NMR (300 MHz, CDCl3):
d
6.68 (s,
1H), 4.01 (t, J¼18.0 Hz, 2H), 1.70e1.42 (m, 10H), 1.38e1.17 (m, 1H);
13C NMR (100 MHz, CDCl3):
d 154.8, 81.8, 76.3, 39.5 (t,
JCeF¼20.1 Hz), 38.2, 24.9, 21.4; IR (neat, cmꢀ1): 3609, 3480, 2937,
2861, 1624, 1452, 1423, 1348, 1235, 1134, 1115, 1057, 1035, 1003; MS
(EI, 70 eV) m/z (%): 484 (Mþ, 0.86), 441 (MþꢀC3H7, 10.20), 357
(MþꢀI, 100); Anal. calcd for C13H14F9IO: C 32.25, H 2.91; found: C
32.46, H 2.84.
4.2.20.2. 1-(40,40,50,50,60,60,70,70,70-Nonafluoro-20-iodo-10(Z)-hep-
tyl)-cyclohexanol (Z-3o). Oil; 1H NMR (300 MHz, CDCl3):
d
6.35 (s,
€
Zhou, C.; Li, J.; Lu, B.; Fu, C.; Ma, S. Org. Lett. 2008, 10, 581; (u) Li, J.; Fu, C.; Chai,
G.; Ma, S. Adv. Synth. Catal. 2008, 350, 1376.
5. For the reviews of radical reactions of allenes, see: (a) Pan, F.; Fu, C.; Ma, S.
Chin. J. Org. Chem. 2004, 24, 1168; (b) Hartung, J.; Kopf, T. In Fundamentals
and Application of Free Radical Addition to Allenes; Krause, N., Hashmi, A. S. K.
1H), 3.45 (t, J¼17.4 Hz, 2H), 2.36 (br s, 1H), 1.79e1.61 (m, 6H),
1.56e1.30 (m, 4H); 13C NMR (75 MHz, CDCl3):
d 149.1, 80.2, 72.1,
47.2 (t, JCeF¼20.6 Hz), 37.3, 25.1, 21.7; IR (neat, cmꢀ1): 3442, 2934,
2859,1627,1451,1345,1235,1134, 1110,1018; MS (EI, 70 eV) m/z (%):
484 (Mþ, 1.15), 441 (MþꢀC3H7, 14.16), 357 (MþꢀI, 100); HRMS calcd
for C13H14F9IO: 483.9946; found: 483.9961.
,
Eds.; Modern Allene Chemistry; Wiley-VCH: Weinheim, Germany, 2004;
Vols. 1e2.
6. Recent reports for radical reaction of allenes, see: (a) Shen, L.; Hsung, R. P. Org. Lett.
2005, 7, 775; (b) Dai, W.; Petersen, J. L.; Wang, K. K. J. Org. Chem. 2005, 70, 6647; (c)
Wu, Z.; Huang, X. Synthesis 2007, 45; (d) Alcaide, B.; Almendros, P.; Aragoncillo, C.;
Redondo, M. C. J. Org. Chem. 2007, 72,1604; (e) Hayashi, N.; Hirokawa, Y.; Shibata, I.;
Yasuda, M.; Baba, A. Org. Biomol. Chem. 2008, 6, 1949; (f) Yang, D.; Cwynar, V.;
Donahue, M. G.; Hart, D. J.; Mbogo, G. J. Org. Chem. 2009, 74, 8726; (g) Curry, L.;
Hallside, M. S.; Powell, L. H.; Sprague, S. J.; Burton, J. W. Tetrahedron 2009, 65,10882;
(h) Kawaguchi, S.; Shirai, T.; Ohe, T.; Nomoto, A.; Sonoda, M.; Ogawa, A. J. Org. Chem.
2009, 74, 1751; (i) Bucher, G.; Mahajan, A. A.; Schmittel, M. J. Org. Chem. 2009, 74,
5850; (j) Mei, Y.; Liu, J.; Liu, Z. Synthesis 2007, 739.
Acknowledgements
Financial support from National Natural Science Foundation of
China (No. 21072167) and the National Basic Research Program of
China (2011CB808700) is greatly appreciated. S.M. is a Qiu Shi
Adjunct Professor at Zhejiang University. We thank Mr. Jian He in
this group for reproducing the results presented in entries 2, 4, and
6 in Table 7.
7. (a) Ma, S.; Ma, Z. Synlett 2006, 1263; (b) Ma, Z.; Ma, S. Tetrahedron 2008, 64,
€
6500; (c) Lu, B.; Jiang, X.; Fu, C.; Ma, S. J. Org. Chem. 2009, 74, 438; (d) and the
corrigendum: Jiang, X.; Fu, C.; Ma, S. Chem.dEur. J. 2008, 14, 9656; Chem.dEur. J.
2009, 15, 1295.
8. For a review of the reaction of 2,3-allenols and their derivatives, see: Deng, Y.;
Gu, Z.; Ma, S. Chin. J. Org. Chem. 2006, 26, 1468.
9. (a) Deng, Y.; Yu, Y.; Ma, S. J. Org. Chem. 2008, 73, 585; (b) Deng, Y.; Li, J.; Ma, S.
Chem.dEur. J. 2008, 14, 4263.
Supplementary data
10. (a) Huang, W.; Wang, W.; Huang, B. Acta Chim. Sinica 1985, 43, 663; (b) Huang,
€
W.; Wang, W.; Huang, B. Acta Chim. Sinica 1986, 44, 488; (c) Huang, W.; Lu, L.;
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2011.08.044.
Zhang, Y. Chin. J. Chem. 1990, 8, 350.
11. Ma, S.; Ren, H.; Wei, Q. J. Am. Chem. Soc. 2003, 125, 4817.