1-tert-Butyl-1H-tetrazol-5-yl fluoromethyl sulfone (TBTSO2CH2F): A versatile fluoromethylidene synthon and its use in the synthesis of monofluorinated alkenes via JuliaKocienski olefination

Article abstract of DOI:10.1016/j.tet.2010.04.113

1-tert-Butyl-IH-tetrazol-5-yl fluoromethyl sulfone (TBTSO ₂CI-1₂F) has been developed as a new and efficient fluoromethylidene synthon for the synthesis of both terminal and internal monofluoroalkenes via JuliaKocienski olefination reaction. The base-mediated reaction between TBTSO₂CI-1₂F and carbonyl compounds (aldehydes and ketones) provided terminal monofluoroalkenes in good yields with moderate E!Z selectivity. The dominance of E- or Z-fluoroalkenes could be controlled by selection of proper reaction solvent and temperature. TBTSO ₂CI-1₂F reagent was also found to be readily CL-alkylated, acylated, and phenylsulfonylated to give corresponding CL-functionalized fluorosulfones, which could be used in the synthesis of alkyl-, acyl-, and phenylsulfonyl-substituted internal monofluoroalkenes via JuliaKocienski olefination reactions.

Full text of DOI:10.1016/j.tet.2010.04.113

Tetrahedron 66 (2010) 5089e5100
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
1-tert-Butyl-1H-tetrazol-5-yl fluoromethyl sulfone (TBTSO2CH2F): a versatile
fluoromethylidene synthon and its use in the synthesis of monofluorinated
alkenes via JuliaeKocienski olefination
*
Lingui Zhu, Chuanfa Ni, Yanchuan Zhao, Jinbo Hu
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Ling-Ling Road, Shanghai 200032, China
a r t i c l e i n f o
a b s t r a c t
Article history:
1-tert-Butyl-1H-tetrazol-5-yl fluoromethyl sulfone (TBTSO2CH2F) has been developed as a new and ef-
ficient fluoromethylidene synthon for the synthesis of both terminal and internal monofluoroalkenes via
JuliaeKocienski olefination reaction. The base-mediated reaction between TBTSO2CH2F and carbonyl
compounds (aldehydes and ketones) provided terminal monofluoroalkenes in good yields with mod-
erate E/Z selectivity. The dominance of E- or Z-fluoroalkenes could be controlled by selection of proper
Received 17 March 2010
Received in revised form 25 April 2010
Accepted 27 April 2010
Available online 24 May 2010
reaction solvent and temperature. TBTSO2CH2F reagent was also found to be readily
a-alkylated, acylated,
Keywords:
and phenylsulfonylated to give corresponding -functionalized fluorosulfones, which could be used in
a
Fluoromethyl sulfone
Monofluroalkene
JuliaeKocienski olefination
Fluoroolefination
the synthesis of alkyl-, acyl-, and phenylsulfonyl-substituted internal monofluoroalkenes via
JuliaeKocienski olefination reactions.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
oxidation (a two-step procedure, Route C).11bec Both Routes A and B
suffer from long synthetic procedures for each a-fluoro sulfone 1
Selective incorporation of fluorine atom(s) into organic com-
pounds can often impart many beneficial properties, which has
stimulated the development of highly efficient and practically
useful synthetic methods for the preparation of fluorinated organic
compounds.1 Among fluorinated compounds, monofluorinated al-
kenes are of particular interest, given their broad applications in
polymeric materials, agrochemistry, as well as pharmaceutical
industry.2e4 Many methods for their preparation have been de-
veloped,5 including electrophilic fluorination of vinylllithiums6 or
vinylstannanes,7 Wittig-type reaction with fluorophosphonates,8
thermal sulfoxide eliminations,9 and fluoroolefination between
fluorinated sulfoximines and nitrones.10 Recently, Lequeux et al.11,
(with a different R2 substituent). Route C (a two-step procedure) is
attractive for this purpose; however, its applicability was limited by
the fact that the functionalized bromofluoromethane compounds
(needed for S-fluoroalkylation in the first step) are not easily
available.
12
Zajc and Ghosh and others13 reported that JuliaeKocienski ole-
fination (sometimes called ‘modified Julia olefination’),14 a one-step
reaction between a sulfone and a carbonyl compound, could serve
as a convenient and efficient method to prepare monofluorinated
alkenes.
a-Fluoro sulfones (1) required for JuliaeKocienski olefi-
nation are commonly prepared according to the following three
routes (Scheme 1): (a) S-alkylation, oxidation, followed by elec-
trophilic fluorination (a three-step procedure, Route A),12,13 (b) S-
alkylation, chlorination, fluorination, followed by oxidation (a four-
step procedure, Route B),11a (c) S-fluoroalkylation, followed by
* Corresponding author. Tel.: þ86 21 54925174; fax: þ86 21 64166128; e-mail
Scheme 1.
address: jinbohu@sioc.ac.cn (J. Hu).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.04.113

5090
L. Zhu et al. / Tetrahedron 66 (2010) 5089e5100
Previously, we reported an efficient monofluoromethylation of
additive) played a crucial role in the reaction (Table 1). In the ab-
sence of HMPA, the olefination reaction between sulfone 2a and 2-
naphthaldehyde failed (2a decomposed completely; Table 1, entry
1), and the reactions with 2b and 2c afforded 5a in 39% and 31%
yield, respectively (entries 3 and 5). However, when HMPA was
added, the product yields were significantly improved for all three
sulfone reagents 2aec (entries 2, 4, and 6), with TBT-sulfone 2c
being the most efficient fluoroolefination reagent among 2aec
(with 75% yield).
thiols [such as 1,3-benzothiazol-2-yl thiol (BT-SH), 1-phenyl-1H-
tetrazol-5-yl thiol (PT-SH), and 1-tert-butyl-1H-tetrazol-5-yl thiol
(TBT-SH)] with chlorofluoromethane, to give corresponding fluo-
romethyl sulfides (R1SeCH2F) in high yields.15 We envisaged that
by simple oxidation, these fluoromethyl sulfides should be readily
converted to corresponding fluoromethyl sulfones 2 (R1SO2CH2F,
R1¼BT, PT, TBT; Scheme 1, Route D). The chemistry of these fluo-
romethyl heteroaryl sulfones 2 are generally unkown,16 and they
may serve as new type of fluoromethylidenation reagents through
JuliaeKocienski olefination reaction. Furthermore, based on our
experience in nucleophilic fluoroalkylation with fluorinated sul-
fones,17 we envisioned that fluoromethyl sulfones 2 can also be
used as a key starting material for the one-step preparation (via
Table 1
Comparison of the reactivity of the sufones 2aec in Julia-Kocienski olefination
nucleophilic fluoroalkylation) of a-functionalized fluorosulfones 1
for other JuliaeKocienski olefinations (Scheme 1, Route D). There-
fore, fluoromethyl sulfones 2 could act as a universal reagent to
prepare both terminal and internal monofluorinated alkenes via
JuliaeKocienski olefinations. In this article, we wish to report our
results toward these goals.
Entry
R
Additivea
Yield (%)b
E/Zb
ec
1
2
3
4
5
6
BT (2a)
BT (2a)
PT (2b)
PT (2b)
TBT (2c)
TBT (2c)
None
HMPA
None
HMPA
None
HMPA
0
68
39
66
31
75
50:50
36:64
54:46
22:78
45:55
2. Results and discussion
a
LiHMDS (2.4 equiv) was added to a solution of 2-naphthaldehyde (1.0 equiv), 2
2.1. Synthesis of fluoromethyl heteroaryl sulfones
(1.2 equiv) and additive (2.4 equiv) in THF (c¼0.2 M) at 0 ꢀC.
b
Yield and the E/Z ratio were determined by 19F NMR spectroscopy using PhCF3
First of all, we carried out the preparation of three fluoromethyl
heteroaryl sulfones: 1,3-benzothiazol-2-yl fluoromethyl sulfone 2a
(BTSO2CH2F), 1-phenyl-1H-tetrazol-5-yl fluoromethyl sulfone 2b
(PTSO2CH2F), and 1-tert-butyl-1H-tetrazol-5-yl fluoromethyl sul-
fone 2c (TBTSO2CH2F) (Fig. 1).16 They were conveniently prepared
through a two-step procedure from easily available reagents.18 The
monofluoromethylation of mercaptans 3aec with chlorofluoro-
methane afforded fluoromethyl sulfides 4aec in 64e86% yields,15
and 4aec were transformed into sulfones 2aec in 84e97% yields
by oxidation with sodium periodate in the presence of catalytic
amount of ruthenium(III) chloride (Scheme 2).19
as an internal standard.
c
The sulfone starting material decomposed.
Encouraged by these results, we further optimized the reaction
conditions with TBT-sulfone 2c (Table 2). It was found that when N,
N,N0,N0-tetramethylethylenediamine (TMEDA) was used as an ad-
ditive (instead of HMPA), the yield decreased (Table 2, entry 2).
Furthermore, after scanning the influence of amount of LiHMDS on
the product yield, we found that the addition of 1.5 equiv of
LiHMDS led to the optimal yield (88%; Table 2, entry 5).
Table 2
The effects of additives and amount of reagents
Entry
LiHMDS (equiv)
Additivea
Yield (%)b
E/Zb
Figure 1. Fluoromethyl sulfones 2aec.
1
2
3
4
5
6
2.4
2.4
3.0
1.8
1.5
1.3
HMPA
TMEDA
HMPA
HMPA
HMPA
HMPA
75
46
66
83
88
79
45:55
28:72
33:67
45:55
42:58
47:53
a
LiHMDS was added to a solution of 2-naphthaldehyde (1.0 equiv), 2c (1.2 equiv),
and additive (equivalent to LiHMDS) in THF (c¼0.2 M) at 0 ꢀC.
b
Yield and the E/Z ratio were determined by 19F NMR spectroscopy using PhCF3
as an internal standard.
Scheme 2.
Next, we sought to evaluate the influence of bases, solvents, and
temperature on the product yield (Table 3). It was found that
LiHMDS was the base of choice for the reaction (entries 1e4), and
the reaction with KHMDS gave the lowest yield (entry 4). However,
the E/Z selectivity of the reaction increases with the following order
of three bases used: LiHMDS<NaHMDS<KHMDS (entries 1, 2, and
4). Among the three solvents used (THF, toluene, and DME), THF
was found to be the best one regarding the yield (entries 1, 5, and
6). Furthermore, there was an interesting temperature effect: re-
actions at lower temperature commonly gave better yields and
preferred the formation of E-isomer of product 5a, while the
2.2. Screening of reaction conditions of JuliaeKocienski
olefination
With the sufones 2aec in hand, we examined their reactivity in
JuliaeKocienski olefination reactions, using 2-naphthaldehyde as
a model substrate (Table 1). The reactions were performed by
adding lithium hexamethyldisilazide (LiHMDS, 2.4 equiv) as a base
to the mixture of 2-naphthaldehyde (1.0 equiv) and a sulfone
(2aec, 1.2 equiv) in THF, according to Berthelette’s procedure.20 It
was found that hexamethylphosphoric triamide (HMPA, as an

L. Zhu et al. / Tetrahedron 66 (2010) 5089e5100
5091
Table 3
Table 4
The Effects of bases, solvents, and temperature
Synthesis of terminal monofluoroalkenes 5aei from aldehydes and 2c
Entry RCHO
1
Product
Isolated yield (%) E/Za
Entry
Basea
Solvent
Yield (%)b
E/Zb
1
2
3
4
5
6
7
8
LiHMDS
NaHMDS
LDA
KHMDS
LiHMDS
LiHMDS
LiHMDS
LiHMDS
THF
THF
THF
THF
toluene
DME
THF
88
63
49
47
66
84
57c
87d
42:58
57:43
47:53
74:26
27:73
43:57
32:68
69:31
87
87
42:58
34:66
2
3
THF
a
Base (1.5 equiv) was added to a solution of 2-naphthaldehyde (1.0 equiv), 2c
(1.2 equiv), and HMPA (1.5 equiv) in various solvents (c¼0.2 M) at 0 ꢀC.
90
47:53
b
Yield and the E/Z ratio were determined by 19F NMR spectroscopy using PhCF3
as an internal standard.
c
The reaction was carried out at room temperature.
The reaction was carried out at ꢁ78 ꢀC.
d
4
5
6
7
8
81
78
86
78
35:65
34:66
42:58
50:50
reactions at higher temperature behaved oppositely (Table 3, en-
tries 1, 7, and 8). Finally, the optimized reaction condition was
chosen as follows: LiHMDS (1.5 equiv), 2c (1.2 equiv), and HMPA
(1.5 equiv), THF as solvent, and 0 ꢀC as the reaction temperature
(Table 3, entry 1).
2.3. Synthesis of terminal monofluoroalkenes
By using the optimized reaction condition (Table 3, entry 1), first
of all, we investigated the scope of JuliaeKocienski olefination be-
tween 2c and aldehydes. As shown in Table 4, the reaction was
found to be amenable to both aromatic and aliphatic aldehydes. For
the reactions with aromatic aldehydes, the product yields were
generally high (Table 4, entries 1e8). Although enolizable aliphatic
aldehyde also reacted with 2c to provide 5i, the yield was merely
moderate (51%, Table 4, entry 9). For terminal monofluoroalkenes
5aei, the E- and Z-isomers were determined by differences of their
3JHeF coupling constants in 19F NMR spectroscopy (3JHeF values of E-
isomers are smaller than those of Z-isomers).21
73
51
47:53
48:52
9
We also extended the fluoroolefination reaction to ketones. By
using acetophenone as a model compound, we examined the re-
action conditions. As shown in Table 5, when we used the pre-
viously optimized reaction condition for aldehydes (as that for
Table 4), product 6a was obtained in 75% yield (Table 5, entry 1).
Neither the decrease of reaction temperature nor the increase of
the amount of LiHMDS brought further improvement of the yield
(Table 5, entries 2e3). With synchronous increase of the amounts of
2c and LiHMDS, the yield was elevated and reached the highest
(88%) when 1.7 equiv of 2c and 2.0 equiv of LiHMDS were used
(Table 5, entry 7).
a
The E/Z ratio was determined by 19F NMR spectroscopy.
Table 5
Reaction conditions of Julia-Kocienski olefination of ketones
With this optimized reaction condition (Table 5, entry 7), we
examined the scope of JuliaeKocienski olefination between 2c and
ketones. As illustrated in Table 6, all ketones could afford terminal
monofluoroalkenes 6aei in moderate to excellent yields. For ace-
tophenones, the ones with electron-withdrawing substituents gave
higher yields than those with electron-donating ones (Table 6,
entries 2e5). It is interesting that the E/Z selectivity for the re-
actions with cyclic ketones (Table 6, entries 6e7) were opposite to
those with acyclic ketones.
Entry
2c (equiv)
LiHMDS (equiv)a
Yield (%)b
E/Zb
1
2
3
4
5
6
7
8
1.2
1.2
1.2
1.5
1.5
1.6
1.7
1.8
1.5
1.5
1.8
1.8
2.0
1.9
2.0
2.1
75
70c
69
79
78
82
88
87
35:65
29:71
34:66
42:58
34:66
35:65
30:70
34:66
Although terminal monofluoroalkenes 5aei and 6aei were
obtained in one-pot from aldehydes and ketones with reagent 2c,
they were a mixture of E- and Z-isomers. Therefore, we paid our
attention to the E/Z control of the monofluoroalkene products.
During the previous examination of reaction conditions (Table 3),
a
LiHMDS was added to a solution of ketone (1.0 equiv), 2c, and HMPA (equivalent
to LiHMDS) in THF (c¼0.2 M) at 0 ꢀC.
b
Yield and the E/Z ratio were determined by 19F NMR spectroscopy using PhCF3
as an internal standard.
c
The reaction was performed at ꢁ78 ꢀC.

5092
L. Zhu et al. / Tetrahedron 66 (2010) 5089e5100
Table 6
Table 7
Synthesis of terminal monofluoroalkenes 6aei from ketones and 2c
The E/Z control of the monofluoroalkene products
Entry
1
R1COR2
Product
Isolated yield (%)
75b
E/Za
Entry
Solvent
T(ꢀC)
E/Za,b
1
2
3
4
5
6
7
8
DMFeHMPA(1:1)
DMSOeHMPA(1:1)
DMSOeHMPA(1:1)
HMPA
0
0
20
8
ꢁ60
ꢁ78
ꢁ78
ꢁ78
ꢁ78
0
0
0
10
20
0
66:34
70:30
66:34
61:39
63:37
74:26
75:25
74:26
72:28
37:63
38:62
30:70
38:62
41:59
26:74
25:75
25:75
30:70
DMF
DMF-HMPA (1:1)
DMFeHMPA (2:1)
DMFeHMPA (3:1)
DMFeDMPU (2:1)
DIPE
MTBE
Et2O
Et2O
Et2O
2
3
4
5
69b
60b
86
30:70
33:67
25:75
28:72
9
10
11
12
13
14
15
16
17
Et2Oetoluene (1:1)
Et2Oetoluene (1:2)
Et2Oetoluene (1:5)
0
0
DMPU¼N,N0-dimethylpropylene urea; DIPE¼diisopropyl ether; MTBE¼methyl tert-
butyl ether.
84
a
Isolated yields in all cases were above 80%.
b
The E/Z ratio was determined by 19F NMR spectroscopy.
conditions (Table 1). We envisaged that sulfone 2c could serve as
a new fluoroalkylating agent to prepare a variety of structurally
diverse a-alkylated fluorinated sulfones. With this consideration,
we examined the reaction conditions between 2c and ethyl iodide
in THF (Table 8). By varying the amounts of n-butyl lithium and
6
7
67
66
76:24
59:41
ethyl iodide, we gained optimized reaction condition of a-alkyl-
ation of 2c (Table 8, entry 8).
8
89
52
d
Table 8
Screening of the condition of a-alkylation of 2c
9
49:51
a
The E/Z ratio was determined by 19F NMR spectroscopy.
The product is volatile.
Entry
n-BuLi (equiv)
EteI(equiv)
Yield (%)a
b
1
2
3
4
5
6
7
8
1.05
1.08
1.10
1.20
1.15
1.10
1.10
1.15
1.2
1.2
1.2
1.2
1.2
2.0
3.0
2.0
52
61
65
65
63
66
66
71
we found that both solvents and temperature played important
roles in the E/Z stereocontrol of the products. So we further in-
vestigated the possibility of improving the E/Z selectivity by care-
fully choosing solvents and reaction temperature. As shown in
Table 7, it was found that a good selectivity for either isomer
could be achieved, with polar solvent system DMFeHMPA (2:1) (at
ꢁ78 ꢀC) mainly affording E-isomer (Table 7, entry 7), whereas less
polar solvent system etheretoluene (1:2) primarily giving Z-isomer
(Table 7, entry 16). The observed E/Z selectivity was consistent with
previous reports.14b,22
a
The yield was determined by 19F NMR spectroscopy using PhCF3 as an internal
standard.
The scope of a-alkylation of 2c is shown in Table 9. Both long-
chain and short-chain alkyl bromides or iodides provided the
alkylated sulfones 7aeb in moderate yields (Table 9, entries 1e4).
2.4. Synthesis of alkyl-substituted internal
a-Allylation and benzylation of 2c were also smoothly accom-
monofluoroalkenes
plished with allyl and benzyl bromides (Table 9, entries 6 and 7).
Even secondary alkyl iodide could afford the product 7c in 62% yield
(Table 9, entry 5).
Previously, we found that
a-fluorinated sulfones can act as
a class of good nucleophilic fluoroalkylating agent, and PhSO2CHFꢁ
anion possesses good thermal stability and nucleophilicity.17beg
Furthermore, the incorporation of bulky steric tert-butyl into tet-
razole ring of 2c enhanced the stability of the corresponding sul-
fone anion,14c as found in optimizing the above mentioned
To date, there are few reports about preparation of alkyl-
substituted internal monofluoroalkenes utilizing JuliaeKocienski
olefination.11a,12a,b,f With the
a-alkylated sulfones 7aee in hand, we
set out to prepare alkyl-substituted internal monofluoroalkenes.
Based on the above-mentioned olefination reactions with 2c and

L. Zhu et al. / Tetrahedron 66 (2010) 5089e5100
5093
Table 9
could react with aldehyde to afford the product 8d in 54% yield,
while in other cases the reactions failed (Table 10, entries 7e10).
Synthesis of a-alkylated sulfones 7aee
2.5. Synthesis of acyl- and phenylsulfonyl-substituted
internal monofluoroalkenes
We also attempted to prepare a-acylated sulfone 9 by treating
Entry
R
X
Product (7)
Isolated yield (%)
ethyl chloroformate with 2c; however, the reaction was not suc-
cessful (Eq. 1). Inspired by our previous success in the nucleophilic
fluoroalkylation of diethyl carbonate with PhSO2CH2F (Eq. 2),17h we
carried out a similar fluoroalkylation reaction between 2c and
1
2
3
4
5
6
7
Et
Et
I
Br
I
Br
I
Br
Br
7a
7a
7b
7b
7c
7d
7e
67
64
60
68
62
57
62
nHex
nHex
iBu
All
diethyl carbonate. To our delight,
fulfilled to provide product 9 in 84% yield (Scheme 3). Under similar
reaction conditions, -phenylsulfinylated sulfone 10 could also be
obtained in 96% yield by nuleophilic fluoroalkylation of methyl
benzenesulfinate with 2c, which was further transformed into
a-acylation of 2c was successfully
Bn
a
previous reports,12a,20 we performed the reactions between 7aec
and aldehydes (or ketones). The results are summarized in Table 10.
It was found that alkyl-substituted internal monofluoroalkenes
8aed and 8a0ec0 were produced in moderate yields, and particu-
larly, 8c0 was obtained with only E-configuration due to the steric
repulsion. For allylated and benzylated sulfones 7dee, only 7d
a
-
phenylsulfonylated sulfone 11 by oxidation with sodium periodate
(Scheme 3).
ð1Þ
ð2Þ
Table 10
Synthesis of alkyl-substituted internal monofluoroalkenes 8
Entry
1
R
Aldehyde or ketone
Product (8)
Yield (%)a E/Zb
33:67
64
52
70
66
66
53
54
dc
dc
Et (7a)
2
3
4
5
6
7
8
9
36:64
27:73
49:51
51:49
100:0
46:54
dc
Scheme 3.
nHex (7b)
Having sulfones
9 and 11 in hand, we carried out the
JuliaeKocienski olefination using 2-naphthaldehyde as a substrate
(Scheme 4). As expected, acyl- and phenylsulfonyl-substituted in-
ternal monofluoroalkenes (12 and 13) were smoothly obtained in
80% and 70% yield, respectively (Scheme 4). In the course of our
investigation, the preparation of a acyl- and phenylsulfonyl-
substituted internal monofluoroalkenes were also reported by us-
ing other fluorinated sulfone reagents.11b,c,12cee,23
iBu (7c)
Allyl (7d)
dc
Scheme 4.
Bn (7e)
10
dc
dc
3. Conclusion
In summary, 1-tert-butyl-1H-tetrazol-5-yl fluoromethyl sulfone
(TBTSO2CH2F) has been developed as a new and efficient fluo-
romethylidene synthon for the synthesis of both terminal and
a
Isolated yield.
b
c
The E/Z ratio was determined by 19F NMR spectroscopy.
The sulfone decomposed.

5094
L. Zhu et al. / Tetrahedron 66 (2010) 5089e5100
internal monofluoroalkenes via JuliaeKocienski olefination re-
action. The base-mediated reaction between TBTSO2CH2F and car-
bonyl compounds (aldehydes and ketones) provided terminal
monofluoroalkenes in good yields and with moderate E/Z selec-
tivity. The dominance of E- or Z-fluoroalkenes could be controlled
by selection of proper reaction solvent and temperature. Further-
283.75 mmol) in i-PrOH (68 mL) via dropping funnel within
45 min. After addition, the mixture was refluxed for 20 h, then
cooled to room temperature and in an ice-water bath concd HCl
(42 mL) was added carefully. The mixture was then concentrated
under reduced pressure and stored in refrigerator. Solid was pre-
cipitated, filtered, and washed twice with water, and then dried in
vacuo in the presence of P2O5 to afford 1-tert-butyl-1H-tetrazolyl-
5-thiol (3c, 38.08 g, 85% yield) as pale yellow solid. 1H NMR
more, TBTSO2CH2F reagent was found to be readily
a
-alkylated,
-func-
acylated, and phenylsulfonylated to give corresponding
a
tionalized fluorosulfones, which could be used in the synthesis of
alkyl-, acyl-, and phenylsulfonyl-substituted internal mono-
fluoroalkenes via Julia-Kocienski olefination reactions. Therefore,
TBTSO2CH2F was demonstrated as a versatile key starting material
in the preparation of a variety of structurally diverse mono-
fluoroalkenes, which deserve further elaboration for many poten-
tial applications.
(300 MHz, CDCl3) d 1.86 (s, 9H).
4.3. General procedure for the preparation of fluoromethyl
sulfides (4) and fluoromethyl sulfones (2)
To a suspension of NaH (2.10 g, 60% dispersion in mineral oil,
52.50 mmol) in anhydrous DMF (80 mL) was added dropwise
a
solution
of
1-tert-butyl-1H-tetrazolyl-5-thiol
(7.91 g,
4. Experimental section
4.1. General information
50.00 mmol) in anhydrous DMF (35 mL) at 0 ꢀC within 15 min.
After addition, the mixture was stirred at 0 ꢀC for 30 min. CH2FCl
(ca. 100 mmol) was then introduced via a needle over 45 min. The
mixture was allowed to warm to room temperature and stirred
overnight. The reaction was quenched with a saturated aqueous
solution of NH4Cl carefully and diluted with EtOAc. The aqueous
layer was extracted with EtOAc. The combined organic layers were
washed with water and brine, dried over Na2SO4, and concentrated.
The residue was purified by flash chromatography (EtOAc/petro-
leum ether¼1:12) to afford 1-tert-butyl-1H-tetrazol-5-yl fluo-
romethyl sulfide (4c, 8.18 g, 86% yield) as white solid.
To a flask with a magnetic stirring bar were added sulfide 4c
(7.99 g, 42.02 mmol), CCl4 (50 mL), CH3CN (50 mL), water (100 mL),
and sodium periodate (26.70 g, 126.07 mmol). To the suspension
was added ruthenium(III) chloride hydrate (15 mg, 0.055 mmol).
The resulting mixture was stirred at room temperature and a white
precipitate was formed. After 19F NMR indicated 4c was dis-
appeared, the precipitate was filtered and washed with Et2O. The
filtrate was diluted with Et2O and washed successively with a sat-
urated aqueous solution of NaHCO3 and brine, dried over MgSO4.
After the removal of half of the solvent under reduced pressure,
filtration through a pad of silica gel and concentration afforded the
sulfone 1-tert-butyl-1H-tetrazol-5-yl fluoromethyl sulfone (2c,
9.09 g, 97% yield) as colorless oil.
Silica gel (200e300 or 300e400 mesh) was used for column
chromatography, and in most cases ethyl acetate/petroleum ether
combination was used as the eluent. Unless otherwise mentioned,
solvents and reagents were purchased from commercial sources
and used as received. THF, DME, MTBE, Et2O, DIPE, and toluene
were freshly distilled over sodium. Anhydrous TMEDA, DMF, DMSO,
HMPA, and CH2Cl2 were distilled over CaH2.
All the melting points were uncorrected. 1H, 13C, and 19F NMR
spectra were recorded on 400 MHz or 300 MHz NMR spectrometer.
1H NMR chemical shifts were determined relative to internal
(CH3)4Si (TMS) at
solvent: CDCl3
7.26. 13C NMR chemical shifts were determined
relative to internal TMS at
0.0. 19F NMR chemical shifts were
determined relative to CFCl3 at 0.0. Chemical shifts are reported in
d 0.0 or to the signal of a residual protonated
d
d
d
part per million. Mass spectra were obtained on a mass spec-
trometer. High-resolution mass data were recorded on a high-res-
olution mass spectrometer in the EI, ESI or MALDI mode.
4.2. The preparation of 1-tert-butyl-1H-tetrazolyl-5-thiol (3c)
Compound 3c was prepared with sodium azide and tert-butyl
isothiocyanate,24 which can be easily prepared in 60 g scale as
following procedure.25
4.3.1. 1,3-Benzothiazol-2-yl fluoromethyl sulfide (4a). White solid;
mp 59e60 ꢀC; IR (KBr): 2930, 1467, 1455, 1431, 1411, 1322, 1311,
1005, 972, 766, 754, 718, 674 cmꢁ1 1H NMR (300 MHz, CDCl3):
;
4.2.1. The preparation of tert-butyl isothiocyanate25. Under N2 at-
mosphere, a 2-L round-bottomed flask was charged with tert-butyl
amine (76 mL, 0.72 mol), triethylamine (332 mL, 2.38 mol), and THF
(600 mL, used as received), and cooled with an ice-water bath.
Carbon disulfide (44 mL, 0.73 mmol) was then added to the re-
action mixture via dropping funnel over 1 h. After the addition was
completed, the mixture was stirred at room temperature for 4 h,
and 1H NMR of the mixture indicated that conversion into di-
thiocarbamate salt was completed. The reaction mixture was
cooled with an ice-water bath, tosyl chloride (152 g, 0.80 mol) was
added in portions, and the mixture was allowed to warm to room
temperature and stirred overnight, 2 M HCl (240 mL) and MTBE
(200 mL) were added to the mixture. The aqueous layer was sep-
arated and extracted with MTBE (3ꢂ250 mL). The organic layers
were then combined, dried over Na2SO4, and filtered. The filtrate
was concentrated and distilled under reduced pressure to afford
tert-butyl isothiocyanate (61.59 g, 74% yield) as colorless oil. 1H
d
7.98e7.80 (m, 2H), 7.50e7.33 (m, 2H), 6.16 (d, 2JFeH¼50.7 Hz, 2H);
19F NMR (282 MHz, CDCl3):
d
ꢁ186.7 (t, 2JHeF¼51.1 Hz, 1F); 13C NMR
(75 MHz, CDCl3):
d
162.4 (d, J¼4.5 Hz), 152.9, 135.8, 126.4, 125.0,
122.4, 121.2, 84.8 (d, 1JFeC¼222.2 Hz); MS (EI, m/z, %): 199 (Mþ, 42),
135 (100). Anal. Calcd for C8H6FNS2: C, 48.22; H, 3.03; N, 7.03.
Found: C, 48.36; H, 7.03; N, 7.04.
4.3.2. Fluoromethyl 1-phenyl-1H-tetrazol-5-yl sulfide (4b). White
solid; mp 86e87 ꢀC; IR (KBr): 2969, 1597, 1591, 1502, 1425, 1396,
1244, 1002, 982, 765, 719, 697, 689, 555 cmꢁ1
;
1H NMR (300 MHz,
2
CDCl3):
(282 MHz, CDCl3):
(75 MHz, CDCl3):
d
7.61e7.53 (m, 5H), 6.22 (d, JFeH¼50.1 Hz, 2H). 19F NMR
2
d
ꢁ188.4 (t, JHeF¼49.8 Hz, 1F); 13C NMR
d
151.4, 133.1, 130.7, 130.0, 124.2, 83.9 (d,
1JFeC¼226.8 Hz); MS (EI, m/z, %): 211 ([MþH]þ, 1), 77 (73), 46 (100).
Anal. Calcd for C8H7FN4S: C, 45.70; H, 3.36; N, 26.65. Found: C,
45.81; H, 3.38; N, 26.32.
NMR (300 MHz, CDCl3)
d
1.44 (s, 9H).26
4.3.3. 1-tert-Butyl-1H-tetrazol-5-yl fluoromethyl sulfide (4c). White
solid; mp 54e55 ꢀC; IR (KBr): 2982, 1476, 1399, 1373, 1336, 1289,
4.2.2. The preparation of 1-tert-butyl-1H-tetrazolyl-5-thiol (3c)24
.
1227, 1139, 1104, 985, 720, 591 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
2
To a refluxing solution of NaN3 (18.64 g, 286.76 mmol) in water
(44 mL) was added the solution of tert-butyl isothiocyanate (36 mL,
d
6.25 (d, JFeH¼49.8 Hz, 2H), 1.75 (s, 9H); 19F NMR (282 MHz,
2
CDCl3):
d
ꢁ187.9 (t, JHeF¼50.0 Hz, 1F); 13C NMR (75 MHz, CDCl3):

L. Zhu et al. / Tetrahedron 66 (2010) 5089e5100
5095
d
149.6, 84.4 (d, 1JFeC¼225.4 Hz), 61.7, 29.1; MS (EI, m/z, %): 190 (Mþ,
3JFeH¼20.1 Hz, 3JHeH¼11.7 Hz, 0.42ꢂ1H, E), 5.76 (dd, 3JFeH¼44.9 Hz,
1), 57 (100). Anal. Calcd for C6H11FN4S: C, 37.88; H, 5.83; N, 29.45.
Found: C, 38.06; H, 5.49; N, 29.79.
3JHeH¼5.4 Hz, 0.58ꢂ1H, Z); 19F NMR (282 MHz, CDCl3):
d
ꢁ121.7
2
3
(dd, JHeF¼83.0 Hz, JHeF¼44.9 Hz, 0.58ꢂ1F, Z), ꢁ129.4 (dd,
2JHeF¼82.2 Hz, JHeF¼18.9 Hz, 0.42ꢂ1F, E); 13C NMR (75 MHz,
3
4.3.4. 1,3-Benzothiazol-2-yl fluoromethyl sulfone (2a)11c. White
solid; mp 152e153 ꢀC (lit.11c: 144e147 ꢀC); IR (KBr): 3001, 2930,
1467, 1459, 1353, 1347, 1328, 1319, 1155, 1056, 1028, 939, 766, 729,
CDCl3):
d
150.5 (d, J¼259.6 Hz, Z), 148.5 (d, J¼270.7 Hz, E), 133.5
(Z), 133.4 (E), 132.8 (d, J¼9.7 Hz, E), 132.7 (d, J¼10.0 Hz, Z), 130.2,
128.4, 128.03 (d, J¼1.9 Hz, Z), 127.96 (Z), 127.9 (E), 127.7 (d,
J¼1.6 Hz, E), 127.6, 126.7 (d, J¼6.5 Hz), 126.4, 126.1 (d, J¼5.6 Hz),
125.9, 125.7 (d, J¼4.7 Hz), 123.31 (Z), 123.29 (E), 114.2 (d, J¼16.8 Hz,
E), 111.0 (d, J¼1.4 Hz, Z); MS (EI, m/z, %): 172 (Mþ, 100), 171 (37),
151 (7); HRMS (EI, m/z): calcd for C12H9F (Mþ): 172.0688; found:
172.0692.
695, 602, 593, 518 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 8.29e8.26
(m, 1H), 8.07e8.04 (m, 1H), 7.71e7.62 (m, 2H), 5.59 (d,
2JFeH¼47.4 Hz, 2H); 19F NMR (282 MHz, CDCl3):
d
ꢁ210.8 (t,
2JHeF¼47.0 Hz, 1F); 13C NMR (75 MHz, CDCl3):
d 162.3, 152.7, 137.3,
128.6, 128.0, 125.8, 122.4, 90.7 (d, 1JFeC¼223.3 Hz); MS (EI, m/z, %):
231 (Mþ, 65), 134 (100). Anal. Calcd for C8H6FNO2S2: C, 41.55; H,
2.62; N, 6.06. Found: C, 41.70; H, 2.82; N, 6.13.
4.4.2. 1-(Benzyloxy)-4-(2-fluorovinyl)benzene (5b). White solid;
mp 42e43 ꢀC. A mixture of E- and Z-isomers (E/Z¼34:66), the E/Z
ratio was determined by 19F NMR spectroscopy; IR (KBr): 3034,
1660, 1608, 1511, 1454, 1249, 1178, 1010, 911, 836, 736, 696 cmꢁ1; 1H
4.3.5. Fluoromethyl 1-phenyl-1H-tetrazol-5-yl sulfone (2b). White
needle solid, mp 59e60 ꢀC; IR (KBr): 3002, 1940, 1593, 1496, 1374,
1160, 1079, 945, 780, 769, 696, 688, 568, 528 cmꢁ1
;
1H NMR
NMR (300 MHz, CDCl3):
d
7.46e6.89 (m, 9Hþ0.34ꢂ1H (E)), 6.58
(300 MHz, CDCl3):
d
7.73e7.59 (m, 5H), 5.75 (d, 2JFeH¼46.3 Hz, 2H);
(dd, 2JFeH¼83.2 Hz, 3JHeH¼5.2 Hz, 0.66ꢂ1H, Z), 6.35 (dd,
19F NMR (282 MHz, CDCl3):
d
ꢁ208.9 (t, JHeF¼46.6 Hz, 1F); 13C
3JHeH¼11.4 Hz, JFeH¼19.5 Hz, 0.34ꢂ1H, E), 5.53 (dd, JHeH¼5.7 Hz,
2
3
3
NMR (75 MHz, CDCl3):
d
151.6, 132.7, 131.8, 129.9, 125.1, 91.7 (d,
3JFeH¼45.2 Hz, 0.66ꢂ1H, Z), 5.06 (s, 0.66ꢂ2H, Z), 5.04 (s, 0.34ꢂ2H,
JFeC¼227.9 Hz); MS (EI, m/z, %): 243 ([MþH]þ, 0.28), 77 (43), 65
(100). Anal. Calcd for C8H7FN4O2S: C, 39.67; H, 2.91; N, 23.13.
Found: C, 39.95; H, 2.72; N, 23.23.
E); 19F NMR (282 MHz, CDCl3):
d
ꢁ125.1 (dd, JHeF¼83.0 Hz,
2
3JHeF¼45.2 Hz, 0.66ꢂ1F, Z), ꢁ132.4 (dd, 2JHeF¼83.1 Hz,
3JHeF¼19.9 Hz, 0.34ꢂ1F, E); 13C NMR (75 MHz, CDCl3):
d 158.2 (d,
J¼2.4 Hz, E), 158.0 (d, J¼2.5 Hz, Z), 149.0 (d, J¼256.8 Hz, E), 147.1 (d,
J¼267.8 Hz, Z), 136.8 (d, J¼2.6 Hz), 130.2, 130.1, 128.6, 127.99, 127.97,
127.4, 127.3 (d, J¼3.5 Hz), 125.6 (d, J¼1.4 Hz), 125.3 (d, J¼11.8 Hz),
115.2, 114.8, 113.2 (d, J¼15.9 Hz, E), 110.2 (Z), 70.0, 69.9; MS (EI, m/z,
%): 228 (Mþ, 5), 91 (100), 77 (14); HRMS (EI, m/z): calcd for
C15H13FO (Mþ): 228.0950; found: 228.0950.
4.3.6. 1-tert-Butyl-1H-tetrazol-5-yl fluoromethyl sulfone (2c). Col-
orless oil, while standing it sometimes became solid; IR (film):
2995, 2946, 1481, 1378, 1361, 1328, 1209, 1170, 1127, 1082, 937, 764,
635, 585, 552 cmꢁ1
; d 5.84 (d,
1H NMR (300 MHz, CDCl3):
2JFeH¼46.3 Hz, 2H), 1.88 (s, 9H); 19F NMR (282 MHz, CDCl3):
2
d
ꢁ207.6 (t, JHeF¼45.9 Hz, 1F); 13C NMR (75 MHz, CDCl3):
d 152.2,
92.1 (d, JFeC¼228.6 Hz), 65.8, 29.7; MS (ESI, m/z): 240 ([MþNH4]þ);
HRMS (MALDI/DHB, m/z): calcd for C6H11N4O2FSNaþ ([MþNa]þ):
245.0479; found: 245.0470.
4.4.3. 2-(2-Fluorovinyl)-1,4-dimethoxybenzene (5c). Colorless oil. A
mixture of E- and Z-isomers (E/Z¼47:53), the E/Z ratio was de-
termined by 19F NMR spectroscopy; IR (film): 2946, 2835,
1653,1489, 1645, 1287, 1220, 1181, 1080, 1048, 919, 881, 866, 801,
4.4. General procedure for the preparation of terminal
monofluoroalkenes (5aei and 6aei)
775, 718 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 7.39e7.38 (m,
2
3
0.53ꢂ1H, Z), 7.38 (dd, JFeH¼85.8 Hz, JHeH¼11.4 Hz, 0.53ꢂ1H, Z),
3
6.82e6.52 (m, 2.47H (ArH)þ0.47ꢂ1H (E)), 6.46 (dd, JFeH¼22.1 Hz,
To the solution of 2c (for aldehydes, 1.2 equiv; for ketones,
1.7 equiv), aldehydes or ketones (1.0 equiv), and HMPA (for alde-
hydes, 1.5 equiv; for ketones: 2.0 equiv) in THF (c¼0.2 M) at 0 ꢀC
were added dropwise a solution LiHMDS in THF (for aldehydes,
1.5 equiv; for ketones, 2.0 equiv). The mixture was stirred at 0 ꢀC
until TLC indicated that the reaction was completed (generally in
1.5e2 h), then quenched with a saturated aqueous solution of
NH4Cl, and extracted with EtOAc. The combined organic layers
were washed with brine, dried over Na2SO4, and concentrated. The
residue was purified by silica column chromatography (0e10%
EtOAc/petroleum ether) to afford the terminal monofluoroalkenes
5aei or 6aei (generally as a mixture of E- and Z-isomers). For
monofluoroalkenes 5aei, the configuration of the two isomers was
3JHeH¼11.3 Hz, 0.47ꢂ1H, E), 6.04 (dd, 3JFeH¼46.2 Hz, 3JHeH¼5.4 Hz,
0.53ꢂ1H, Z), 3.81 (s, 0.47ꢂ3H, E), 3.79 (s, 0.53ꢂ3H, Z), 3.78 (s,
0.47ꢂ3H, E), 3.76 (s, 0.53ꢂ3H, Z); 19F NMR (282 MHz, CDCl3):
d
ꢁ123.1 (dd, 2JFeH¼84.0 Hz, 3JFeH¼45.6 Hz, 0.53ꢂ1F, Z), ꢁ124.7 (dd,
JFeH¼85.8 Hz, JFeH¼22.0 Hz, 0.47ꢂ1F, E); 13C NMR (75 MHz,
3
CDCl3):
d
153.4, 151.8 (d, J¼257.7 Hz, E), 150.6 (d, J¼3.7 Hz), 150.5 (d,
J¼1.4 Hz), 148.3 (d, J¼270.6 Hz, Z), 122.4, 122.3, 122.1 (d, J¼1.5 Hz),
115.7 (d, J¼12.5 Hz), 114.1 (d, J¼2.8 Hz), 113.9 (d, J¼2.4 Hz), 112.8 (d,
J¼2.0 Hz), 111.8, 111.7, 110.4 (d, J¼18.5 Hz, E), 104.4 (d, J¼2.7 Hz, Z),
56.3, 55.9, 55.7; MS (EI, m/z, %): 182 (Mþ, 5), 125 (100), 77 (62);
HRMS (EI, m/z): calcd for C10H11O2F (Mþ): 182.0743; found:
182.0746.
determined by differences of their JHeF coupling constants in 19F
4.4.4. 2-(Benzyloxy)-4-(2-fluorovinyl)-1-methoxybenzene
(5d).
3
NMR spectroscopy (3JHeF values of E-isomers are smaller than those
of Z-isomers),21 and for monofluoroalkenes 6aei, the configuration
of the two isomers was determined by comparing them with
known compounds.8e,27,28
White solid; mp 72e73 ꢀC. A mixture of E- and Z-isomers (E/
Z¼35:65), the E/Z ratio was determined by 19F NMR spectroscopy;
IR (KBr): 2932, 2837, 1661, 1603, 1515, 1455, 1418, 1266, 1227, 1141,
1024, 912, 859, 808, 739, 697 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
2
d
7.47e6.78 (m, 8Hþ0.35ꢂ1H (E)), 6.56 (dd, JFeH¼82.9 Hz,
3
3
4.4.1. 2-(2-Fluorovinyl)naphthalene
(5a). White
solid;
mp
3JHeH¼5.5 Hz, 0.65ꢂ1H, Z), 6.28 (dd, JFeH¼19.6 Hz, JHeH¼11.3 Hz,
3
3
49e50 ꢀC; A mixture of E- and Z-isomers (E/Z¼42:58), the E/Z ratio
was determined by 19F NMR spectroscopy; IR (KBr): 3055, 1660,
1593, 1506, 1363, 1242, 1175, 1126, 1100, 1012, 951, 921, 863, 828,
0.35ꢂ1H, E), 5.48 (dd, JFeH¼45.2 Hz, JHeH¼5.6 Hz, 0.65ꢂ1H, Z),
5.14 (s, 0.65ꢂ2H, Z), 5.13 (0.35ꢂ2H, E), 3.88 (s, 0.65ꢂ3H, Z), 3.87 (s,
0.35ꢂ3H, E); 19F NMR (282 MHz, CDCl3):
d
ꢁ120.9 (dd,
812, 742 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
7.92 (s, 0.58ꢂ1H, Z),
2JHeF¼81.8 Hz, 3JHeF¼44.8 Hz, 0.65ꢂ1F, Z), ꢁ128.3 (dd,
3
7.82e7.75 (m, 3H), 7.68 (dd, JHeH¼1.5 Hz, JHeH¼8.7 Hz, 0.58ꢂ1H, Z),
2JHeF¼82.6 Hz, JHeF¼18.9 Hz, 0.35ꢂ1F, E); 13C NMR (75 MHz,
7.63 (s, 0.42ꢂ1H, E), 7.49e7.43 (m, 2H), 7.38 (dd, JHeH¼1.5, 8.7 Hz,
CDCl3):
d
149.2 (d, JFeC¼257.6 Hz, E), 148.4, 148.0, 147.1 (d,
2
3
0.42ꢂ1H, E), 7.27 (dd, JFeH¼83.4 Hz, JHeH¼11.7 Hz, 0.42ꢂ1H, E),
JFeC¼267.9 Hz, Z), 137.1 (d, JFeC¼6.9 Hz), 128.63, 128.56, 128.0, 127.9,
127.5, 127.4, 122.4, 122.3, 114.7, 114.6, 113.6 (d, JFeC¼15.9 Hz, E), 111.6
2
3
6.72 (dd, JFeH¼83.0 Hz, JHeH¼5.4 Hz, 0.58ꢂ1H, Z), 6.54 (dd,

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L. Zhu et al. / Tetrahedron 66 (2010) 5089e5100
2
3
(Z), 71.2, 71.1, 56.1, 56.0; MS (EI, m/z, %): 258 (Mþ, 5), 91 (100); HRMS
(EI, m/z): calcd for C16H15O2F (Mþ): 258.1056; found: 258.1056.
(ddt, JFeH¼85.5 Hz, JHeH¼6.3, 1.5 Hz, 0.52ꢂ1H, E), 5.37 (dm,
3JFeH¼27.0 Hz, 0.48ꢂ1H, E) 4.75 (ddt, JFeH¼42.6 Hz, JHeH¼11.7,
3
3
3
3.8 Hz, 0.52ꢂ1H, Z), 2.69 (dd, JHeH¼6.9, 15.0 Hz, 2H),
4.4.5. 5-(2-Fluorovinyl)benzo[1,3]dioxole (5e)21. Colorless oil.
A
2.48e2.40 (m, 0.52ꢂ2H, E), 2.27e2.18 (m, 0.48ꢂ2H, Z); 19F NMR
2
3
mixture of E- and Z-isomers (E/Z¼34:66), the E/Z ratio was de-
(282 MHz, CDCl3):
d
ꢁ129.8 (dd, JFeH¼85.7 Hz, JHeH¼18.8 Hz,
2 3
termined by 19F NMR spectroscopy; 1H NMR (300 MHz, CDCl3):
0.48ꢂ1F, E), ꢁ130.1 (dd, JFeH¼85.7 Hz, JHeH¼43.5 Hz, 0.52ꢂ1F,
2
3
d
7.12e6.67 (m, 3H), 7.06 (dd, JFeH¼83.2 Hz, JHeH¼11.3 Hz,
2 3
Z).
0.34ꢂ1H, E), 6.57 (dd, JFeH¼83.1 Hz, JHeH¼5.7 Hz, 0.66ꢂ1H, Z),
3
3
6.31 (dd, JFeH¼18.9 Hz, JHeH¼11.4 Hz, 0.34ꢂ1H, E), 5.95 (s,
4.4.10. (1-Fluoroprop-1-en-2-yl)benzene (6a)8e. Colorless oil.
A
3
0.66ꢂ2H, Z), 5.94 (s, 0.34ꢂ2H, E), 5.51 (dd, JFeH¼44.4 Hz,
mixture of E- and Z-isomers (E/Z¼30:70), the E/Z ratio was de-
3JHeH¼5.1 Hz, 0.66ꢂ1H, Z); 19F NMR (282 MHz, CDCl3):
d
ꢁ124.5
termined by 19F NMR spectroscopy; 1H NMR (300 MHz, CDCl3):
2
3
2
4
(dd, JHeF¼83.2 Hz, JHeF¼44.2 Hz, 0.66ꢂ1F, Z), ꢁ132.2 (dd,
2JHeF¼84.1 Hz, 3JHeF¼19.5 Hz, 0.34ꢂ1F, E); MS (EI, m/z, %): 166 (Mþ,
100), 107 (56).
d
7.51e7.24 (m, 5H), 6.90 (dq, JFeH¼85.1 Hz, JHeH¼1.5 Hz,
2 4
0.30ꢂ1H, E), 6.66 (dq, JFeH¼84.3 Hz, JHeH¼1.5 Hz, 0.70ꢂ1H, Z),
4
4
2.04 (dd, JFeH¼3.6 Hz, JHeH¼1.5 Hz, 0.30ꢂ3H, E), 1.91 (dd,
4JFeH¼4.8 Hz, JHeH¼1.5 Hz, 0.70ꢂ3H, Z); 19F NMR (282 MHz,
4
4.4.6. 4-(2-Fluorovinyl)biphenyl (5f)29. White solid. A mixture of E-
and Z-isomers (E/Z¼42:58), the E/Z ratio was determined by 19F
CDCl3):
d
ꢁ129.0 (dq, JHeF¼84.7 Hz, JHeF¼4.8 Hz, 0.70ꢂ1F, Z),
2
4
ꢁ131.2 (dq, 2JHeF¼85.2 Hz, 4JHeF¼3.8 Hz, 0.30ꢂ1F, E).
NMR spectroscopy; 1H NMR (300 MHz, CDCl3):
d 7.61e7.05 (m,
9Hþ0.42ꢂ1H (E)), 6.67 (dd, 3JHeH¼5.4 Hz, 2JFeH¼82.8 Hz, 0.58H, Z),
4.4.11. 1-(1-Fluoroprop-1-en-2-yl)-4-methoxybenzene (6b). Color-
less oil. A mixture of E- and Z-isomers (E/Z¼30:70), the E/Z ratio was
determined by 19F NMR spectroscopy; IR (film): 2956, 2930, 2837,
1663, 1609, 1574, 1514, 1292, 1251, 1183, 1121, 1101, 1034, 834, 807,
3
3
6.75 (dd, JFeH¼19.4 Hz, JHeH¼11.6 Hz, 0.42ꢂ1H, E), 6.65 (dd,
3JFeH¼44.7 Hz, JHeH¼5.4 Hz, 0.58ꢂ1H, Z); 19F NMR (282 MHz,
3
2
3
CDCl3):
d
ꢁ120.6 (dd, JHeF¼82.7 Hz, JHeF¼44.1 Hz, 0.58ꢂ1F, Z),
ꢁ128.3 (dd, 2JHeF¼82.2 Hz, 3JHeF¼18.6 Hz, 0.42ꢂ1F, E); MS (EI, m/z,
602, 588 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 7.48e7.20 (m, 2H),
%): 198 (Mþ, 100), 77 (18).
6.92e6.85 (m, 2H), 6.84 (dq, 2JFeH¼85.5 Hz, 4JHeH¼1.5 Hz, 0.30ꢂ1H,
2
4
E), 6.61 (dq, JFeH¼84.6 Hz, JHeH¼1.5 Hz, 0.70ꢂ1H, Z), 3.81 (s,
4
4.4.7. 2,4-Dichloro-1-(2-fluorovinyl)benzene (5g). Pale yellow oil. A
mixture of E- and Z-isomers (E/Z¼50:50), the E/Z ratio was de-
termined by 19F NMR spectroscopy; IR (film): 2924, 2854, 1661,
1588, 1553, 1472, 1383, 1208, 1094, 1024, 912, 867, 828, 809,
0.70ꢂ3H, Z), 3.80 (s, 0.30ꢂ3H, E), 2.01 (dd, JFeH¼3.9 Hz,
4JHeH¼1.5 Hz, 0.30ꢂ3H, E), 1.87 (dd, JFeH¼4.8 Hz, JHeH¼1.5 Hz,
4
4
0.70ꢂ3H, Z); 19F NMR (282 MHz, CDCl3):
d
ꢁ130.3 (dq,
(dq,
2JHeF¼84.5 Hz,
4JHeF¼4.6 Hz,
0.70ꢂ1F,
Z),
ꢁ132.0
768 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
7.76 (d, JHeH¼8.7 Hz,
2JHeF¼85.5 Hz, JHeF¼3.8 Hz, 0.30ꢂ1F, E); 13C NMR (75 MHz,
4
0.50ꢂ1H, E), 7.40 (s, 0.50ꢂ1H, E), 7.39 (s, 0.50ꢂ1H, Z), 7.76e7.17 (m,
CDCl3):
d
159.1 (d, J¼1.5 Hz, E), 158.8 (d, J¼2.1 Hz, Z), 145.2 (d,
1Hþ0.50ꢂ1H (Z)), 7.10 (dd, 2JFeH¼82.5 Hz, 3JHeH¼11.4 Hz, 0.50ꢂ1H,
J¼256.1 Hz, E), 143.6 (d, J¼261.6 Hz, Z), 129.0 (d, J¼6.2 Hz, Z), 128.3 (d,
J¼1.1 Hz), 127.0 (d, J¼3.5 Hz, E), 119.5 (d, J¼9.9 Hz, E), 116.3 (d, J¼1.6 Hz,
Z),114.0,113.6, 55.31 (E), 55.26 (Z),16.0 (d, J¼7.2 Hz, Z),12.4 (d, J¼5.4 Hz,
E); MS (EI, m/z, %):166(Mþ, 100), 107 (14), 77 (27); HRMS (EI, m/z): calcd
for C10H11OF (Mþ): 166.0794; found: 166.0786.
2
3
E), 6.75 (dd, JFeH¼82.5 Hz, JHeH¼5.4 Hz, 0.50ꢂ1H, Z), 6.65 (dd,
3JFeH¼18.3 Hz, 3JHeH¼11.4 Hz, 0.50ꢂ1H, E), 6.01 (dd, 3JFeH¼43.2 Hz,
3JHeH¼5.4 Hz, 0.50ꢂ1H, Z); 19F NMR (282 MHz, CDCl3):
d
ꢁ120.6
2
3
(dd, JHeF¼82.7 Hz, JHeF¼44.1 Hz, 0.50ꢂ1F, Z), ꢁ128.3 (dd,
JHeF¼82.2 Hz, JHeF¼18.6 Hz, 0.50ꢂ1F, E); 13C NMR (75 MHz,
CDCl3):
d
151.5 (d, J¼263.3 Hz, Z), 149.6 (d, J¼274.0 Hz, E),
4.4.12. 1-(1-Fluoroprop-1-en-2-yl)-4-methylbenzene (6c). Colorless
oil. A mixture of E- and Z-isomers (E/Z¼33:67), the E/Z ratio was
determined by 19F NMR spectroscopy; IR (film): 2953, 2924, 2859,
131.5 (d, J¼12.5 Hz), 129.7, 129.30, 129.28, 127.59, 127.57,
127.3, 127.2, 110.5 (d, J¼19.2 Hz, E), 106.0 (d, JFeC¼2.3 Hz,
Z); MS (EI, m/z, %): 191 (Mþ, 13), 192 (82), 190 (100); HRMS
(EI, m/z): calcd for C8H5FCl2 (Mþ): 189.9752; found:
189.9757.
1664, 1515, 1441, 1115, 1105, 1064, 823, 808, 718, 602 cmꢁ1; 1H NMR
4
(300 MHz, CDCl3):
d
7.41e7.12 (m, 4H), 6.88 (dq, JHeH¼1.5 Hz,
2JFeH¼85.2 Hz, 0.33ꢂ1H, E), 6.62 (dq, JHeH¼1.5 Hz, JFeH¼84.9 Hz,
4
2
0.67ꢂ1H, Z), 2.35 (s, 0.67ꢂ3H, Z), 2.34 (s, 0.33ꢂ3H, E), 2.02 (dd,
4
4
4.4.8. 1-Bromo-4-(2-fluorovinyl)benzene (5h). Pale yellow oil. A
mixture of E- and Z-isomers (E/Z¼47:53), the E/Z ratio was de-
termined by 19F NMR spectroscopy; IR (film): 2924, 2830, 1660,
4JFeH¼3.9 Hz, JHeH¼1.5 Hz, 0.33ꢂ3H, E), 1.87 (dd, JFeH¼4.8 Hz,
4JHeH¼1.5 Hz, 0.67ꢂ3H, Z); 19F NMR (282 MHz, CDCl3):
d
ꢁ129.5
2
4
(dq, JHeF¼84.6 Hz, JHeF¼5.0 Hz, 0.67ꢂ1F, Z), ꢁ132.2 (dq,
1589, 1486, 1400, 1234, 1107, 1087, 1072, 1010, 911, 836, 803 cmꢁ1
;
2JHeF¼85.3 Hz, JHeF¼3.6 Hz, 0.33ꢂ1F, E); 13C NMR (75 MHz,
4
1H NMR (300 MHz, CDCl3):
d
7.47e7.00 (m, 3H), 7.16 (dd,
CDCl3):
d
145.7 (d, J¼256.8 Hz, E), 144.0 (d, J¼262.3 Hz, Z), 137.2 (d,
2JFeH¼82.4 Hz, 3JHeH¼5.4 Hz, 0.53ꢂ1H, Z), 7.11 (d, JHeH¼8.4 Hz, 1H),
J¼1.5 Hz, Z), 134.7 (d, J¼8.3 Hz), 133.0 (d, J¼1.2 Hz, E), 129.3, 129.0,
127.7 (d, J¼6.6 Hz, Z) 125.8 (d, J¼2.9 Hz, E), 119.9 (d, J¼9.7 Hz, E),
116.8 (d, J¼1.4 Hz, Z), 21.2 (Z), 21.1 (E), 16.0 (d, J¼7.3 Hz, Z), 12.3 (d,
J¼6.2 Hz, E); MS (EI, m/z, %): 150 (Mþ, 100), 91 (75); HRMS (EI, m/z):
calcd for C10H11F (Mþ): 150.0845; found: 150.0850.
3
3
6.67 (dd, JFeH¼82.2 Hz, JHeH¼5.4 Hz, 0.47ꢂ1H, E), 6.33 (dd,
3JFeH¼18.8 Hz, 3JHeH¼11.9 Hz, 0.47ꢂ1H, E), 5.53 (dd, 3JFeH¼44.1 Hz,
3JHeH¼5.7 Hz, 0.53ꢂ1H, Z); 19F NMR (282 MHz, CDCl3):
d
ꢁ120.9
2
3
(dd, JHeF¼81.8 Hz, JHeF¼44.8 Hz, 0.53ꢂ1F, Z), ꢁ128.3 (dd,
2JHeF¼82.6 Hz, JHeF¼18.9 Hz, 0.47ꢂ1F, E); 13C NMR (75 MHz,
3
CDCl3):
d
150.5 (d, J¼260.7 Hz, E), 148.7 (d, J¼272.2 Hz, Z),
4.4.13. 1-Chloro-4-(1-fluoroprop-1-en-2-yl)benzene (6d). Colorless
oil. A mixture of E- and Z-isomers (E/Z¼25:75), the E/Z ratio was
determined by 19F NMR spectroscopy; IR (film): 2955, 2926, 2850,
1662, 1596, 1493, 1402, 1122, 1098, 1014, 988, 834, 815, 762,
131.9, 131.7, 130.6 (d, J¼12.0 Hz), 127.7, 127.6, 121.4 (d,
J¼3.5 Hz), 121.3, 121.2, 113.1(d, J¼16.6 Hz, E), 109.9 (d,
J¼1.3 Hz, Z); MS (EI, m/z, %): 201 (Mþ, 7), 101 (100), 202 (69),
200 (65); HRMS (EI, m/z): calcd for C8H6FBr (Mþ): 199.9637;
found: 199.9640.
604 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d
7.44e7.21 (m, 4H), 6.88 (dq,
2JFeH¼84.3 Hz, JHeH¼1.5 Hz, 0.25ꢂ1H, E), 6.66 (dq, JFeH¼84.3 Hz,
4
2
4JHeH¼1.5 Hz, 0.75ꢂ1H, Z), 2.02 (dd, JFeH¼3.9 Hz, JHeH¼1.5 Hz,
4
4
4.4.9. 1-(4-Fluorobut-3-enyl)benzene (5i)8e. Colorless oil. A mixture
of E- and Z-isomers (E/Z¼48:52), the E/Z ratio was determined by
0.25ꢂ3H, E), 1.89 (dd, 4JFeH¼4.8 Hz, 4JHeH¼1.5 Hz, 0.75ꢂ3H, Z); 19
F
NMR (282 MHz, CDCl3):
d
ꢁ127.5 (dq, 2JHeF¼84.0 Hz, 4JHeF¼4.8 Hz,
19F NMR spectroscopy; 1H NMR (300 MHz, CDCl3):
d
7.32e7.15 (m,
0.75ꢂ1F, Z), ꢁ129.8 (dq, JHeF¼84.6 Hz, JHeF¼3.9 Hz, 0.25ꢂ1F,
2
4
5H), 6.49 (ddt, 2JFeH¼85.5 Hz, 3JHeH¼11.2, 1.5 Hz, 0.48ꢂ1H, E), 6.44
E); 13C NMR (75 MHz, CDCl3):
d
146.2 (d, J¼258.4 Hz, E), 144.7

L. Zhu et al. / Tetrahedron 66 (2010) 5089e5100
5097
(d, J¼264.6 Hz, Z), 136.0 (d, J¼9.2 Hz, E), 134.2, 133.2, 133.1 (d,
J¼2.2 Hz), 129.1 (d, J¼6.3 Hz, Z), 128.7 (E), 128.4 (Z), 127.2 (d,
J¼3.3 Hz, E), 119.2 (d, J¼10.3 Hz, E), 116.0, 15.9 (d, J¼6.9 Hz, Z),
12.2 (d, J¼5.9 Hz, E); MS (EI, m/z, %): 170 (Mþ, 9), 43 (100);
HRMS (EI, m/z): calcd for C9H8FCl (Mþ): 170.0299; found:
170.0303.
(100), 128 (49); HRMS (EI, m/z): calcd for C11H11F (Mþ): 162.0845;
found: 162.0846.
4.4.17. 2-Fluoro-1,1-diphenylethene (6h)30a. Colorless oil; 1H NMR
(300 MHz, CDCl3):
d
7.37e7.22 (m, 10H), 6.96(d, 2JFeH¼83.7 Hz, 1H);
19F NMR (282 MHz, CDCl3):
d
ꢁ128.1 (d,2JHeF¼83.3 Hz, 1F).
4.4.14. 1-Bromo-4-(1-fluoroprop-1-en-2-yl)benzene (6e). Colorless
oil. A mixture of E- and Z-isomers (E/Z¼28:72), the E/Z ratio was
determined by 19F NMR spectroscopy; IR (film): 2954, 2925, 2852,
4.4.18. 1-(4-Fluoro-3-methylbut-3-enyl)benzene (6i)30b. Colorless
oil. A mixture of E- and Z-isomers (E/Z¼49:51), the E/Z ratio was
determined by 19F NMR spectroscopy; 1H NMR (300 MHz, CDCl3):
1662, 1489, 1399, 1124, 1100, 1084, 1009, 831, 813, 751, 603 cmꢁ1
;
d
7.31e7.14 (m, 5H), 6.36 (dm, JFeH¼86.3 Hz, 0.51ꢂ1H, Z), 6.35 (dm,
1H NMR (300 MHz, CDCl3) 7.51e7.14 (m, 4H), 6.89 (dq,
2JFeH¼84.3 Hz, 4JHeH¼1.5 Hz, 0.28ꢂ1H, E), 6.66 (dq, 2JFeH¼84.0 Hz,
JFeH¼86.7 Hz, 0.49ꢂ1H, E), 2.74e2.67 (m, 2H), 2.44e2.38 (m,
0.51ꢂ2H, Z), 2.20e2.14(m, 0.49ꢂ2H, E), 1.69 (dd, J¼3.2 Hz, J¼1.5 Hz,
0.49ꢂ3H, E), 1.53 (dd, J¼3.9 Hz, J¼1.8 Hz, 0.51ꢂ3H, Z); 19F NMR
4
4
4JHeH¼1.5 Hz, 0.72ꢂ1H, Z), 2.01 (dd, JFeH¼3.9 Hz, JHeH¼1.5 Hz,
0.28ꢂ3H, E), 1.87 (dd, 4JFeH¼4.8 Hz, 4JHeH¼1.5 Hz, 0.72ꢂ3H, Z); 19
F
(282 MHz, CDCl3):
d
ꢁ135.3 (dm, 2JHeF¼86.0 Hz, 0.51ꢂ1F, Z), ꢁ136.4
NMR (282 MHz, CDCl3):
d
2
ꢁ127.5 (dq, 2JHeF¼84.0 Hz, 4JHeF¼4.8 Hz,
(dm, 2JHeF¼86.1 Hz, 0.49ꢂ1F, E).
4
0.72ꢂ1F, Z), ꢁ129.8 (dq, JHeF¼84.6 Hz, JHeF¼3.9 Hz, 0.28ꢂ1F, E);
13C NMR (75 MHz, CDCl3):
d
146.1 (d, J¼258.3 Hz, E), 144.6 (d,
J¼263.8 Hz, Z), 136.5 (d, J¼8.4 Hz, E), 134.7 (Z), 131.7 (E), 131.4 (Z),
129.4 (d, J¼6.3 Hz, Z), 127.5 (d, J¼3.0 Hz, E), 121.4 (d, J¼2.3 Hz),
119.3 (d, J¼10.2 Hz, E), 116.3 (Z), 15.7 (d, J¼7.0 Hz, Z), 12.1 (d,
J¼6.5 Hz, E); MS (EI, m/z, %): 215 (Mþ, 10), 216 (59), 214 (50), 115
(100); HRMS (EI, m/z): calcd for C9H8BrF (Mþ): 213.9793; found:
213.9798.
4.5. General procedure for the preparation of
sulfones (7)
a-alkylated
Under a nitrogen atmosphere, to the solution of 2c (267 mg,
1.20 mmol) and HMPA (0.32 mL, 1.83 mmol) in THF (6 mL) was
added a solution of n-BuLi in hexane (1.6 M, 0.86 mL, 1.38 mmol) at
ꢁ78 ꢀC, followed by the addition of iodoethane (0.19 mL,
2.38 mmol) after 30 min. The reaction mixture was stirred for
30 min at ꢁ78 ꢀC and then warmed slowly to room temperature.
When TLC indicated that 2c was disappeared, the reaction was
quenched by the addition of a saturated NH4Cl solution (3 mL). The
aqueous layer was separated and extracted with EtOAc. The com-
bined organic layers were washed with brine, dried over Na2SO4,
and concentrated. The residue was purified by flash column chro-
matography (EtOAc/petroleum ether¼1:20) to afford the alkylated
product 7a as a colorless oil (208 mg, 67% yield).
4.4.15. 1-(Fluoromethylene)-indane (6f). Colorless oil. A mixture of
E- and Z-isomers (E/Z¼76:24), the E/Z ratio was determined by 19F
NMR spectroscopy (the configuration of E- and Z-isomers was de-
termined by comparing 1H NMR spectroscopy with known non-
fluoro compound27); IR (film): 2930, 2850, 1677, 1473, 1462,
1449, 1360, 1210, 1109, 1079, 1068, 790, 755 cmꢁ1
;
1H NMR
7.79e7.75 (m, 0.76ꢂ1H, E), 7.31e7.28 (m,
(300 MHz, CDCl3):
d
2
0.24ꢂ1H, Z), 7.27e7.12 (m, 3H), 7.23 (dt, JFeH¼83.2 Hz,
4JHeH¼2.7 Hz, 0.24ꢂ1H, Z), 6.58 (dt, JFeH¼83.4 Hz, JHeH¼1.8 Hz,
0.76ꢂ1H, E), 3.01 (t, JHeH¼6.9 Hz, 2H), 2.90e2.82 (m, 0.24ꢂ2H,
Z), 2.72e2.65 (m, 0.76ꢂ2H, E); 19F NMR (282 MHz, CDCl3):
2
4
4.5.1. 1-tert-Butyl-5-(1-fluoropropylsulfonyl)-1H-tetrazole
Colorless oil; IR (film): 2988, 2945, 2887, 1480, 1466, 1357, 1273,
1241, 1208, 1171, 1108, 1049, 1023, 981, 906, 817, 661, 627, 584 cmꢁ1
1H NMR (300 MHz, CDCl3):
6.14 (ddd, JFeH¼47.6 Hz, JHeH¼9.0 Hz,
(7a).
2
2
d
ꢁ134.1 (d, JHeF¼83.9 Hz, 0.76ꢂ1F, E), ꢁ139.1 (d, JHeF¼84.1 Hz,
0.24ꢂ1F, Z); 13C NMR (75 MHz, CDCl3):
d
145.7, 142.6 (d,
;
J¼252.0 Hz, Z), 142.3 (d, J¼258.0 Hz, E), 137.7 (E), 137.5 (d,
J¼7.6 Hz, Z), 128.0 (d, J¼2.3 Hz, E), 127.8 (d, J¼2.8 Hz, Z), 126.64
(E), 126.55 (Z), 125.5 (d, J¼10.0 Hz, E), 125.2 (Z), 124.8 (E), 124.7
(d, J¼3.5 Hz), 119.7 (Z), 30.5 (E), 30.2 (Z), 25.4 (d, J¼6.5 Hz, E),
25.2 (d, J¼2.0 Hz, Z); MS (EI, m/z, %): 148 (Mþ, 12), 149 (30), 57
(100); HRMS (EI, m/z): calcd for C10H9F (Mþ): 148.0688; found:
148.0683.
d
JHeH¼3.8 Hz, 1H), 2.44e2.15 (m, 2H), 1.87 (s, 9H), 1.27 (t,
JHeH¼7.5 Hz, 2H); 19F NMR (282 MHz, CDCl3):
d
ꢁ177.6 (ddd,
JHeF¼47.7 Hz, JHeF¼32.6 Hz, JHeF¼17.2 Hz, 1F); 13C NMR (75 MHz,
CDCl3):
d
152.4, 104.0 (d, J¼225.9 Hz), 65.7, 29.6, 20.2 (d, J¼19.9 Hz),
8.6 (d, J¼3.4 Hz); MS (EI, m/z, %): 250 (Mþ, 0.03), 57 (100). Anal.
Calcd for C8H15FN4O2S: C, 38.39; H, 6.04; N, 22.38. Found: C, 38.58;
H, 6.17; N, 22.54.
4.4.16. 1-(Fluoromethylene)-1,2,3,4-tetrahydronaphthalene
(6g).
Colorless oil.; A mixture of E- and Z-isomers (E/Z¼59:41), the E/Z
ratio was determined by 19F NMR spectroscopy(the configuration of
E- and Z-isomers was determined by comparing 1H NMR spec-
troscopy with known non-fluoro compound28); IR (film): 2935,
2865, 1655, 1485, 1454, 1433, 1266, 1228, 1113, 1071, 1005, 808, 796,
4.5.2. 1-tert-Butyl-5-(1-fluoroheptylsulfonyl)-1H-tetrazole
Colorless oil; IR (film): 2960, 2933, 2861, 1467, 1377, 1355, 1209,
1168, 1119, 1087, 627, 586, 549 cmꢁ1 1H NMR (300 MHz, CDCl3):
(7b).
;
d
6.18 (ddd, JFeH¼47.7 Hz, JHeH¼8.9, 4.2 Hz, 1H), 2.34 (m, 2H), 1.87
(s, 9H), 1.77e1.26 (m, 8H), 0.91 (t, JHeH¼6.6 Hz, 3H); 19F NMR
755, 726 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
7.93e7.89 (m,
(282 MHz, CDCl3):
NMR (75 MHz, CDCl3):
29.9, 28.9, 26.4 (d, J¼19.2 Hz), 24.4 (d, J¼2.9 Hz), 22.7, 14.2; MS (ESI,
m/z): 307.2 ([MþH]þ); HRMS (ESI): calcd for C12H23FN4O2SNa
([MþNa]þ): 329.1418; found: 329.1417.
d
ꢁ176.1 (ddd, JHeF¼48.0, 33.5, 18.5 Hz, 1F); 13C
0.41ꢂ1H, Z), 7.34e7.32 (m, 0.59ꢂ1H, E), 7.21e7.08 (m, 3H), 7.15 (d,
d
152.6, 103.5 (d, J¼225.5 Hz), 66.0, 31.6,
2
2JFeH¼84.9 Hz, 0.59ꢂ1H, E), 6.65 (d, JFeH¼84.6 Hz, 0.41ꢂ1H, Z),
2.85 (t, JHeH¼6.5 Hz, 0.41ꢂ2H, Z), 2.76 (t, JHeH¼6.2 Hz, 0.59ꢂ2H, E),
2.62e2.56 (m, 0.59ꢂ2H, E), 2.30e2.25 (m, 0.41ꢂ2H, Z), 1.92e1.78
2
(m, 2H); 19F NMR (282 MHz, CDCl3):
d
ꢁ129.6 (d, JHeF¼84.4 Hz,
0.41ꢂ1F, Z), ꢁ136.5 (d, JHeF¼85.0 Hz, 0.59ꢂ1F, E); 13C NMR
4.5.3. 1-tert-Butyl-5-(1-fluoro-3-methylbutylsulfonyl)-1H-tetrazole
(7c). White solid; mp 66e69 ꢀC; IR (KBr): 2962, 2878, 1474, 1380,
2
(75 MHz, CDCl3):
d
144.3 (d, J¼254.5 Hz, E), 143.5 (d, J¼269.0 Hz, Z),
137.5 (d, J¼5.7 Hz, E), 137.1 (d, J¼2.4 Hz, Z), 131.1 (d, J¼8.3 Hz, E),
130.7 (d, J¼2.9 Hz, Z), 129.2 (E), 129.1 (Z), 129.0 (d, J¼13.8 Hz), 127.3
(d, J¼2.0 Hz, Z), 127.1 (d, J¼2.0 Hz, E), 126.1 (d, J¼1.4 Hz, E), 125.8 (Z),
122.6 (d, J¼1.4 Hz, E), 119.9 (d, J¼11.8 Hz, E), 117.0 (d, J¼2.8 Hz, Z),
30.2 (Z), 30.1 (E), 26.9 (d, J¼7.5 Hz, Z), 23.6 (d, J¼2.7 Hz, Z), 22.3 (d,
J¼6.2 Hz, E), 22.1 (d, J¼1.5 Hz, E); MS (EI, m/z, %): 162 (Mþ, 89), 129
1355, 1210, 1171, 1143, 1120, 1088, 618, 584, 547 cmꢁ1 1H NMR
;
(300 MHz, CDCl3):
d
6.23 (ddd, JFeH¼48.0 Hz, JHeH¼10.2, 2.9 Hz,
1H), 2.17e1.95 (m, 3H), 1.10 (d, JHeH¼4.2 Hz, 3H), 1.08 (d,
JHeH¼4.5 Hz, 3H); 19F NMR (282 MHz, CDCl3):
d
ꢁ175.8 (ddd,
JHeF¼47.4 Hz, JHeF¼39.5 Hz, JHeF¼15.4 Hz, 1F); 13C NMR (75 MHz,
CDCl3):
d
152.7, 102.9 (d, J¼225.6 Hz), 65.7, 34.4 (d, J¼18.7 Hz), 29.7,

5098
L. Zhu et al. / Tetrahedron 66 (2010) 5089e5100
24.6, 23.0, 21.4; MS (ESI, m/z): 279 ([MþH]þ); HRMS (ESI): calcd for
C10H19FN4O2Sna ([MþNa]þ): 301.1105; found: 301.1108.
0.64ꢂ3H, Z), 1.07 (t, JHeH¼7.4 Hz, 0.36ꢂ3H, E); 19F NMR (282 MHz,
CDCl3):
d
ꢁ108.7 (t, JHeF¼24.3 Hz, 0.64ꢂ1F, Z), ꢁ109.9 (t,
JHeF¼24.0 Hz, 0.36ꢂ1F, E); MS (EI, m/z, %): 243 (Mþ, 5), 148 (100);
4.5.4. 1-tert-Butyl-5-(1-fluorobut-3-enylsulfonyl)-1H-tetrazole
(7d). Colorless oil; IR (film): 3087, 2989, 2942, 1644, 1480, 1467,
1431, 1408, 1377, 1355, 1241, 1208, 1168, 1121, 1087, 989, 931, 870,
HRMS (EI): calcd for C11H12BrF (Mþ): 242.0106; found: 242.0111.
4.6.3. 1-Bromo-4-(2-fluorooct-1-enyl)benzene (8b). Colorless oil. A
mixture of E- and Z-isomers (E/Z¼27:73), the E/Z ratio was de-
termined by 19F NMR spectroscopy; IR (film): 2956, 2929, 2858,
817, 662, 582 cmꢁ1 1H NMR (300 MHz, CDCl3):
; d 6.24 (ddd,
JFeH¼47.3 Hz, JHeH¼9.2, 3.9 Hz, 1H), 5.97e5.83 (m, 1H), 5.41e5.33
(m, 2H), 3.15e2.88 (m, 1H), 1.87 (s, 9H); 19F NMR (282 MHz, CDCl3):
1689, 1488, 1466, 1401, 1151, 1704, 1010, 851, 830, 807 cmꢁ1 1H
;
d
ꢁ176.0 (ddd, JHeF¼48.0, 32.0, 18.9 Hz, 1F); 13C NMR (75 MHz,
NMR (300 MHz, CDCl3):
d
7.45e7.03 (m, 4H), 6.10 (d, 3JFeH¼21.3 Hz,
CDCl3):
d
152.6, 128.6 (d, J¼2.8 Hz),121.7,102.3 (d, J¼226.3 Hz), 66.1,
0.27ꢂ1H, E), 5.40 (d, 3JFeH¼39.0 Hz, 0.73ꢂ1H, Z), 2.46e2.24 (m, 2H),
31.2 (d, J¼19.3 Hz), 29.9; MS (ESI, m/z): 263 ([MþH]þ). Anal. Calcd
for C9H15FN4O2S: C, 41.21; H, 5.76; N, 21.36. Found: C, 41.76; H, 5.99;
N, 21.32.
1.64e1.53 (m, 2H), 1.41e1.23 (m, 6H), 0.92e0.85 (m, 3H); 19F NMR
3
(282 MHz, CDCl3):
d
ꢁ97.4 (pseudo q, dt, JHeF¼21.9, 21.9 Hz,
0.27ꢂ1F, E), ꢁ99.6 (dt, 3JHeF¼38.1, ¼18.8 Hz, 0.73ꢂ1F, Z); MS (ES, m/
z, %): 285 (Mþ, 7), 134 (100); HRMS (EI): calcd for C14H18BrF (Mþ):
284.0576; found: 284.0573.
4.5.5. 1-tert-Butyl-5-(1-fluoro-2-phenylethylsulfonyl)-1H-tetrazole
(7e). White solid; mp 70e72 ꢀC; IR (KBr): 2984, 2941, 1602, 1494,
1481, 1456, 1432, 1376, 1363, 1353, 1266, 1238, 1208, 1199, 1169,
4.6.4. 1-(3-Fluoronon-2-en-2-yl)benzene (8b0). Colorless oil.
A
1079, 1007, 861, 784, 755, 704, 630, 583, 541 cmꢁ1
;
1H NMR
mixture of E- and Z-isomers (E/Z¼51:49), the E/Z ratio was de-
termined by 19F NMR spectroscopy; IR (film): 3024, 2957, 2929,
2858, 1689, 1601, 1494, 1465, 1444, 1379, 1198, 1174, 1053, 1027, 763,
(300 MHz, CDCl3):
d
7.42e7.31 (m, 5H), 6.33 (ddd, JFeH¼47.3 Hz,
JHeH¼10.3, 2.6 Hz, 1H), 3.69e3.37 (m, 2H), 1.88 (s, 9H); 19F NMR
(282 MHz, CDCl3):
NMR (75 MHz, CDCl3):
d
ꢁ175.8 (ddd, JHeF¼47.7, 37.5, 18.9 Hz, 1F); 13C
669 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d
7.37e7.17 (m, 5H), 2.39 (dt,
3
3
d
152.5, 132.8, 129.9, 129.3, 128.2, 103.5 (d,
3JFeH¼23.7, JHeH¼7.2 Hz, 0.49ꢂ2H, Z), 2.17 (dt, JFeH¼23.4 Hz,
4
J¼228.5 Hz), 66.1, 32.3 (d J¼19.4 Hz), 29.9; MS (ESI, m/z): 313
([MþH]þ); HRMS (ESI): calcd for C13H17FN4O2Snaþ ([MþNa]þ):
335.0948; found: 335.0947.
3JHeH¼7.6 Hz, 0.51ꢂ2H, E), 1.96 (d, JFeH¼3.3 Hz, 0.49ꢂ3H, Z), 1.95
4
(d, JFeH¼3.3 Hz, 0.51ꢂ3H, E), 1.62e1.16 (m, 8H), 0.90 (t,
3
3JHeH¼6.6 Hz, 0.49ꢂ3H, Z), 0.85 (t, JHeH¼6.9 Hz, 0.51ꢂ3H, E); 19F
NMR (282 MHz, CDCl3):
d
ꢁ107.7 (t, JHeF¼24.0 Hz, 0.49ꢂ1F, Z),
4.6. General procedure for the preparation of alkyl-
substituted internal monofluoroalkenes (8)
ꢁ109.7 (t, JHeF¼22.6 Hz, 0.51ꢂ1F, E); MS (EI, m/z, %): 220 (Mþ, 83),
129 (100); HRMS (EI): calcd for C15H21F (Mþ): 220.1627; found:
220.1632.
Under N2 atmosphere, to a solution of aldehydes (or ketones)
and
a
-alkylated sulfones 7aee (condition A: 1.2 equiv, condition B:
4.6.5. 1-Bromo-2-(2-fluoro-4-methylpent-1-enyl) benzene (8c).
Colorless oil. A mixture of E- and Z-isomers (E/Z¼51:49), the E/Z
ratio was determined by 19F NMR spectroscopy; IR (film): 3068,
2959, 2927, 2871, 1687, 1590, 1561, 1467, 1436, 1369, 1155, 1115,
1.7 equiv), and HMPA (condition A: 2.4 equiv, condition B: 3.4 equiv)
in THF (c¼0.2 M) a solution of LiHMDS in THF (condition A:
2.4 equiv, condition B: 3.4 equiv) was added at 0 ꢀC. When the re-
action was completed by TLC, a saturated aqueous NH4Cl was added
to the reaction mixture and the mixture was extracted with EtOAc.
The combined organic layers were washed with brine, dried over
Na2SO4, and the solvent was evaporated under reduced pressure.
The residue was purified by flash column chromatography on silica
gel (0e5% EtOAc/petroleum ether) to afford the corresponding al-
kenes 8aed. and 8a0ec0. For 8aed, the configuration of E- or Z-
1025, 750 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
7.78e7.03 (m, 4H),
3
3
6.25 (d, JFeH¼21.0 Hz, 0.51ꢂ1H, E), 5.82 (d, JFeH¼38.1 Hz,
0.49ꢂ1H, Z), 2.27e2.24 (m, 0.51ꢂ2H, E), 2.20e2.16 (m, 0.49ꢂ2H, Z),
3
2.04e1.95 (m, 1H), 1.01 (d, JHeH¼6.9 Hz, 0.49ꢂ6H, E), 0.91 (d,
3JHeH¼6.6 Hz, 0.51ꢂ6H, E); 19F NMR (282 MHz, CDCl3):
d
ꢁ98.0
(pseudo q, dt, 3JHeF¼22.4, 22.4 Hz, 0.51ꢂ1F, E), ꢁ101.0 (pseudo q, dt,
3JHeF¼38.1, 20.0 Hz, 0.49ꢂ1F, Z); MS (EI, m/z, %): 257 (Mþ, 2), 134
(100); HRMS (EI): calcd for C12H14BrF (Mþ): 256.0263; found:
256.0272.
3
isomers was determined by differences of their JHeF. coupling
constants.21 For 8a0ec0, the configuration of E- or Z-isomers was
determined by comparing with known compounds.31
4.6.6. 1-(3-Fluoro-5-methylhex-2-en-2-yl)-4-methoxy
benzene
4.6.1. 2-(2-Fluorobut-1-enyl)naphthalene (8a)12b. Colorless oil,
while standing it became solid; A mixture of E- and Z-isomers (E/
Z¼33:67), the E/Z ratio was determined by 19F NMR spectroscopy;
IR (film): 3056, 3019, 2977, 2918, 2881, 1687, 1598, 1507, 1462, 1362,
(8c0). Colorless oil. Only E-isomer, the configuration of 8c0 was
determined by its NOE spectroscopy (Fig. 2); IR (film): 3035, 2958,
2870, 2836,1693,1609,1513,1465,1443,1288,1245,1175,1037, 859,
832 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d
7.08 (d, J¼6.3 Hz, 2H), 6.85
3
1328, 1271, 1179, 1149, 1371, 973, 895, 837, 816, 746 cmꢁ1; 1H NMR
(d, J¼6.3 Hz, 2H), 3.81 (s, 3H), 2.06 (dd, JFeH¼22.7 Hz,
3
(300 MHz, CDCl3):
d
7.88e7.21 (m, 7H), 6.30 (d, JFeH¼21.6 Hz,
3JHeH¼7.2 Hz, 2H), 1.94 (d, JFeH¼3.6 Hz, 3H), 1.92e1.83 (m, 1H), 0.84
3
0.33ꢂ1H, E), 5.60 (d, 3JFeH¼39.6 Hz, 0.67ꢂ1H, Z), 2.61e2.33 (m, 2H),
(d, JHeH¼6.3 Hz, 6H); 19F NMR (282 MHz, CDCl3):
d
ꢁ109.1 (t,
3
3
1.22 (t, JHeH¼7.2 Hz, 0.33ꢂ3H, E), 1.20 (t, JHeH¼7.2 Hz, 0.67ꢂ3H,
Z); 19F NMR (282 MHz, CDCl3):
d
ꢁ100.1 (pseudo q, dt, JHeF¼21.6,
3
3
21.6 Hz, 0.33ꢂ1F, E), ꢁ100.4 (dt, JHeF¼39.8, 15.6 Hz, 0.67ꢂ1F, Z);
MS (EI, m/z, %): 200 (Mþ, 100); HRMS (EI): calcd for C14H13F (Mþ):
200.1001; found: 200.1002.
4.6.2. 1-Bromo-4-(3-fluoropent-2-en-2-yl)benzene (8a0). Colorless
oil. A mixture of E- and Z-isomers (E/Z¼36:64), the E/Z ratio was
determined by 19F NMR spectroscopy; IR (film): 2968, 2925, 2854,
1686, 1489, 1464, 1396, 1187, 1077, 1028, 1010, 963, 828, 720 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d 7.46e7.04 (m, 4H), 2.40 (dq,
JFeH¼23.2 Hz, JHeH¼7.6 Hz, 0.64ꢂ2H, Z), 2.18 (dq, JFeH¼23.0 Hz,
JHeH¼7.6 Hz, 0.36ꢂ2H, E), 1.94e1.92 (m, 3H), 1.16 (t, JHeH¼7.5 Hz,
Figure 2. NOE of the product 8c0.

L. Zhu et al. / Tetrahedron 66 (2010) 5089e5100
5099
JHeF¼22.7 Hz, 1F, E); 13C NMR (75 MHz, CDCl3): 158.3, 156.3 (d,
J¼250.6 Hz), 132.9 (d, J¼9.5 Hz), 129.6 (d, J¼2.9 Hz), 114.8 (d,
J¼20.7 Hz), 113.6, 55.1, 38.0 (d, J¼27.6 Hz), 26.1, 22.2, 16.4 (d,
J¼9.4 Hz); MS (EI, m/z, %): 222 (Mþ, 40), 179 (100); HRMS (EI): calcd
for C14H19OF (Mþ): 222.1420; found: 222.1421.
with a saturated aqueous solution of NaHCO3 and brine, dried over
MgSO4. After the removal of half of the solvent under vacuum, fil-
tration through a pad of silica gel and concentration afforded 11
(599 mg, 82% yield) as white solid.
4.8.1. 1-tert-Butyl-5-(fluoro(phenylsulfinyl)methyl sulfinyl)-1H-tet-
razole (10). White solid; mp 135e136 ꢀC. A mixture of two di-
astereomers (downfield/upfield¼8:92); IR (KBr): 2997, 2950, 1476,
4.6.7. 5-(2-Fluoropenta-1,4-dienyl)benzo[d][1,3] dioxole (8d). Pale
yellow oil. A mixture of E- and Z-isomers (E/Z¼46:54), the E/Z ratio
was determined by 19F NMR spectroscopy; IR (film): 3026, 2961,
2925, 1603, 1503, 1489, 1444, 1336, 1249, 1213, 1103, 1040, 939,
1445, 1358, 1169, 1122, 1104, 1086, 691, 613, 582 cmꢁ1 1H NMR
;
(300 MHz, CDCl3):
d 7.88e7.85 (m, 2H), 7.66e7.61 (m, 3H), 6.68 (d,
809 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d
7.10e6.64 (m, 3H), 6.20 (d,
J¼45.3 Hz, 0.92ꢂ1H), (d, J¼46.2 Hz, 0.08ꢂ1H), 1.87 (s, 0.92ꢂ9H),
3JFeH¼21.0 Hz, 0.46ꢂ1H, E), 5.97e5.81 (m, 1H), 5.96 (s, 0.46ꢂ2H, E),
5.94 (s, 0.54ꢂ2H, Z), 5.41 (d, 3JFeH¼39.0 Hz, 0.54ꢂ1H, Z), 5.28e5.16
(m, 2H), 3.16 (ddt, J¼1.7, 5.7, 24.3 Hz, 0.46ꢂ2H, E), 3.06 (dd, J¼6.6,
1.86 (s, 0.08ꢂ9H); 19F NMR (282 MHz, CDCl3):
d
ꢁ166.19 (d,
J¼48.6 Hz, 0.08ꢂ1F), ꢁ182.78 (d, J¼47.1 Hz, 0.92ꢂ1F); 13C NMR
(100 MHz, CDCl3):
d
152.1, 137.69 (d, J¼3.0 Hz), 137.67, 133.4, 133.1,
15.0, 0.54ꢂ2H, Z); 19F NMR (282 MHz, CDCl3):
d
ꢁ99.5 (pseudo q, dt,
129.8, 129.5, 126.0 (d, J¼1.4 Hz), 125.3, 109.8 (d, J¼283.6 Hz), 66.0,
29.4; MS (EI, m/z, %): 346 (Mþ, 0.24), 125 (100); HRMS (EI): calcd for
C12H15FN4O3S2 (Mþ): 346.0570; found: 346.0571.
3JHeF¼22.9, 22.9 Hz, 0.46ꢂ1F, E), ꢁ102.4 (dt, JHeF¼38.6, 15.5 Hz,
0.54ꢂ1F, Z); MS (ES, m/z, %): 206 (Mþ, 5), 186 (100); HRMS (EI):
calcd for C12H11FO2 (Mþ): 206.0743; found: 206.0746.
3
4.8.2. 1-tert-Butyl-5-(fluoro(phenylsulfonyl)methyl sulfonyl)-1H-tet-
razole (11). White solid; mp 141e142 ꢀC; IR (KBr): 3074, 2984,
2952, 1585, 1484, 1450, 1367, 1353, 1192, 1178, 1098, 1077, 803, 760,
4.7. The preparation of ethyl 2-(1-tert-butyl-1H-tetrazol-5-yl-
sulfonyl)-2-fluoroacetate (9)17h
751, 562 cmꢁ1; 1H NMR (300 MHz, CDCl3):
d
8.07 (d, J¼8.1 Hz, 2H),
7.84 (t, J¼7.5 Hz, 1H), 7.67 (t, J¼8.0 Hz, 2H), 7.02 (d, J¼45.0 Hz, 1H),
1.83 (s, 9H); 19F NMR (282 MHz, CDCl3):
ꢁ167.8 (d, J¼44.9 Hz, 1F);
13C NMR (100 MHz, CDCl3):
152.6, 136.3, 134.8, 130.3, 129.7, 105.2
Under N2 atmosphere, a solution of LiHMDS in THF (1.06 M,
13.0 mL, 13.78 mmol) was added to the solution of 2c (1.53 g,
6.88 mmol) and diethyl carbonate (1.67 g, 13.75 mmol) in THF
(25 mL) at ꢁ78 ꢀC. The mixture was stirred at this temperature until
TLC indicated the reaction was completed, and followed by
quenching with a saturated aqueous of NH4Cl. After warming to
room temperature, the mixture was extracted with EtOAc, and then
the organic layers were washed with brine and dried over Na2SO4.
After removal of solvent under vacuum, the residue was purified by
silica gel column chromatography (petroleum ether/ethyl
acetate¼10:1) to afford ethyl 2-(1-tert-butyl-1H-tetrazol-5-yl-sul-
fonyl)-2-fluoroacetat (9, 1.70 g, 84% yield) as colorless oil. IR (film):
d
d
(d, J¼269.5 Hz), 66.2, 29.5; MS (EI, m/z, %): 306 ([Mꢁ(CH3)3CþH]þ,
1), 57 (100). Anal. Calcd for C12H15FN4O4S2: C, 39.77; H, 4.17; N,
15.46. Found: C, 39.59; H, 4.10; N, 15.39.
4.9. The preparation of acyl-substituted internal
monofluoroalkene 1211b
Under N2 atmosphere, to a stirred solution of sulfone 9 (589 mg,
2.00 mmol) and 2-naphthaldehyde (375 mg, 2.40 mmol) in THF
(10 mL), DBU (0.42 mL, 2.85 mmol) was added dropwise at ꢁ78 ꢀC.
After addition the mixture was stirred for 30 min at ꢁ78 ꢀC and
then 2 h at room temperature. The reaction was quenched with
a saturated aqueous solution of NH4Cl (5 mL) and then extracted
with EtOAc (30 mL). The organic layers were combined and washed
with brine, dried over Na2SO4, filtered, and evaporated under re-
duced pressure. The crude product was purified by silica gel column
chromatography (EtOAc/petroleum ether¼1:120) to afford ethyl 2-
fluoro-3-(naphthalen-2-yl)acrylate (12, 391 mg, 80% yield) as col-
orless oil. A mixture of E- and Z-isomers (E/Z¼64:36), the E/Z ratio
was determined by 19F NMR spectroscopy; 1H NMR (300 MHz,
2991, 1771, 1469, 1369, 1244, 1172, 1116, 1020, 857, 638, 585 cmꢁ1
;
1H NMR (300 MHz, CDCl3):
d
6.53 (d, J¼46.8 Hz, 1H), 4.45 (dq, J¼7.1,
1.8 Hz, 2H), 1.87 (s, 9H), 1.38 (t, J¼7.2 Hz, 3H); 19F NMR (282 MHz,
CDCl3):
d
ꢁ179.20 (d, J¼48.0 Hz, 1F); 13C NMR (100 MHz, CDCl3):
d
159.2, 159.0, 151.9, 97.3 (d, J¼238.2 Hz), 97.2 (d, J¼237.9 Hz), 66.0,
64.19, 64.18, 29.5, 29.4, 13.7; MS (EI, m/z, %): 238 ([Mꢁ(CH3)3CþH]þ,
2), 57(100); HRMS (EI): calcd for C9H15FN4O4S2 (Mþ): 294.0798;
found: 294.0785.
4.8. The preparation of 1-tert-butyl-5-(fluoro
(phenylsulfonyl)-methyl-sulfonyl)-1H-tetrazole (11)
CDCl3):
d
8.10 (s, 0.36ꢂ1H, Z), 7.93 (s, 0.64ꢂ1H, E), 7.87e7.76 (m,
Under N2 atmosphere, a solution of LiHMDS in THF (1.06 M,
13.21 mL, 14.00 mmol) was added to the solution of 2c (1.56 g,
7.02 mmol) and methyl benzenesufinate (2.19 g, 14.02 mmol) in
THF (25 mL) at ꢁ78 ꢀC. The mixture was stirred at this temperature
until TLC indicated the reaction was completed, followed by
quenching with a saturated aqueous solution of NH4Cl. After
warmed to room temperature, the mixture was extracted with
EtOAc, and then the organic layers were washed with brine and
dried over Na2SO4. After removal of solvent under vacuum, the
residue was purified by silica gel column chromatography (EtOAc/
petroleum ether¼1:5) to afford 10 (2.32 g, 96% yield) as white solid.
Into a flask equipped with a magnetic stirrer were sequentially
added 10 (696 mg, 2.01 mmol), CCl4 (4 mL), CH3CN (4 mL), water
(8 mL), and sodium periodate (651 mg, 3.04 mmol). Thereafter,
ruthenium trichloride hydrate (5 mg, 0.018 mmol) was added to
the reaction flask. The resulting mixture was stirred at room tem-
perature and a white precipitate was formed. The completion of the
reaction was monitored by 19F NMR (the signal of compound 10
disappeared), and the precipitate was filtered and washed with
Et2O. The filtrate was diluted with Et2O and washed successively
3H), 7.59e7.47 (m, 3H), 7.08 (d, J¼35.1 Hz, 0.36ꢂ1H, Z), 7.06 (d,
J¼22.8 Hz, 0.64ꢂ1H, E), 4.38 (q, J¼7.1 Hz, 0.36ꢂ2H, Z), 4.26 (q,
J¼7.1 Hz, 0.64ꢂ2H, E),1.41 (t, J¼7.2 Hz, 0.36ꢂ3H, Z),1.22 (t, J¼7.5 Hz,
0.64ꢂ3H, Z); 19F NMR (282 MHz, CDCl3):
d
ꢁ115.9 (d, J¼21.5 Hz,
0.64ꢂ1F, E), ꢁ124.4 (d, J¼35.0 Hz, 0.36ꢂ1F, Z).
4.10. The preparation of phenylsulfonyl-substituted internal
monofluoroalkene 1312d
Under N2 atmosphere, to a stirred solution of 2-naphthaldehyde
(100 mg, 0.64 mmol) and sulfone 11 (302 mg, 0.83 mmol) in freshly
distilled CH2Cl2 (4 mL), DBU was added (0.15 mL, 0.97 mmol) at
room temperature. The reaction was continued at room tempera-
ture until the aldehyde was consumed and quenched with a satu-
rated aqueous solution of NH4Cl (4 mL) and then extracted with
EtOAc (20 mL). The organic layers were combined and washed with
brine, dried over Na2SO4, filtered, and evaporated under reduced
pressure. The crude product was purified by silica gel chromatog-
raphy (EtOAc/petroleum ether¼1:50) to afford 2-(2-fluoro-2-
(phenylsulfonyl)vinyl)naphthalene (13, 140 mg, 70% yield) as pale

5100
L. Zhu et al. / Tetrahedron 66 (2010) 5089e5100
Tetrahedron 2009, 65, 3967e3973; (d) Calata, C.; Pfund, E.; Lequeux, T. J. Org.
Chem. 2009, 74, 9399e9405.
yellow oil. A mixture of E- and Z-isomers (E/Z¼27:73), the E/Z ratio was
determined by 19F NMR spectroscopy; 1H NMR (300 MHz, CDCl3):
12. (a) Ghosh, A. K.; Zajc, B. Org. Lett. 2006, 8, 1553e1556; (b) Zajc, B.; Kake, S. Org.
Lett. 2006, 8, 4457e4460; (c) del Solar, M.; Ghosh, A. K.; Zajc, B. J. Org. Chem.
2008, 73, 8206e8211; (d) He, M.; Ghosh, A. K.; Zajc, B. Synlett 2008, 999e1004;
(e) Ghosh, A. K.; Banerjee, S.; Sinha, S.; Kang, S. B.; Zajc, B. J. Org. Chem. 2009, 74,
3689e3697; (f) Ghosh, A. K.; Zajc, B. J. Org. Chem. 2009, 74, 8531e8540.
13. Alonso, D. A.; Fuensanta, M.; Gomez-Bengoa, E.; Najera, C. Adv. Synth. Catal.
2008, 350, 1823e1829.
14. (a) Baudin, J. B.; Hareau, G.; Julia, S. A.; Ruel, O. Tetrahedron Lett. 1991, 32,
1175e1178; (b) Blakemore, P. R.; Cole, W. J.; Kocienski, P. J.; Morley, A. Synlett
1998, 26e28; (c) Kocienski, P. J.; Bell, A.; Blakemore, P. R. Synlett 2000,
365e366; (d) Blakemore, P. R. J. Chem. Soc., Perkin Trans. 1 2002, 2563e2585; (e)
Aissa, C. Eur. J. Org. Chem. 2009, 1831e1844; (f) Takeda, T. Modern Carbonyl
Olefination; Wiley-VCH: Weinheim, 2004.
15. Zhang, W.; Zhu, L.; Hu, J. Tetrahedron 2007, 63, 10569e10575.
16. Both PTSO2CH2F (2b) and TBTSO2CH2F (2c) are previously unknown, and
BTSO2CH2F (2a) was recently reported as an undesired product [see Ref. 11c].
We found that fluoromethyl heteroaryl sulfone compounds were difficult to be
prepared by electrophilic fluorination of corresponding methyl sulfones (see
below).
d
8.06e7.81 (m, 6H), 7.70e7.48(m, 6H), 7.22(d, J¼35.1 Hz, 0.27ꢂ1H, E),
7.06(d, J¼21.9 Hz,0.73ꢂ1H, Z); 19F NMR (282 MHz, CDCl3):
d
ꢁ111.5 (d,
J¼23.7 Hz, 0.73ꢂ1F, Z), ꢁ125.1 (d, J¼33.0 Hz, 0.27ꢂ1F, E).
Acknowledgements
We thank the National Natural Science Foundation of China
(20772144, 20825209, 20832008) and the Chinese Academy of
Sciences (Hundreds-Talent Program and Knowledge Innovation
Program) for financial support.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tet.2010.04.113. These data in-
clude MOL files and InChiKeys of the most important compounds
described in this article.
References and notes
1. (a) Uneyama, K. Organofluorine Chemistry; Blackwell: Oxford, UK, 2006; (b)
Kirsch, P. Modern Fluoroorganic Chemistry: Synthesis, Reactivity, Applications;
Wiley-VCH: Weinheim. (c) Chambers, R. D. Fluorine in Organic Chemistry;
Blackwell: Oxford, 2004; (d) Bégué, J.-P.; Bonnet-Delpon, D. Bioorganic and
Medicinal Chemistry of Fluorine; Wiley: Hoboken, USA, 2008; (e) Organofluorine
Compounds. Chemistry and Applications; Hiyama, T., Ed.; Springer: New York, NY,
2000; (f) Organofluorine Chemistry: Principles and Commercial Applications;
Banks, R. E., Smart, B. E., Tatlow, J. C., Eds.; Plenum: New York, NY, 1994.
2. Ameduri, B.; Boutevin, B. J. Fluorine Chem. 2000, 104, 53e62.
3. McCarthy, J. R.; Matthews, D. P.; Stemerick, D. M.; Huber, E. W.; Bey, P.; Lippert, B. J.;
Synder, R. D.; Sunkara, P. S. J. Am. Chem. Soc. 1991, 113, 7439e7440; (b) Welch, J. T.
Slective Fluorination in Organic and Bioorganic Chemistry; American Chemical Soci-
ety: Washington, D.C,1991; (c) Weintraub, P. M.; Holland, A. K.; Gates, C. A.; Moore,
W. R.; Resvick, R. J.; Beye, P.; Peet, N. P. Bioorg. Med. Chem. 2003, 11, 427e431.
4. Fluorine-Containing Synthons; Soloshonok, V. A., Ed.; American Chemical Soci-
ety: Washington, DC, 2005.
17. (a) Li, Y.; Hu, J. Angew. Chem., Int. Ed. 2005, 44, 5882e5886; (b) Li, Y.; Ni, C.; Liu,
J.; Zhang, L.; Zheng, J.; Zhu, L.; Hu, J. Org. Lett. 2006, 8, 1693e1696; (c) Ni, C.; Li,
Y.; Hu, J. J. Org. Chem. 2006, 71, 6829e6833; (d) Ni, C.; Liu, J.; Zhang, L.; Hu, J.
Angew. Chem., Int. Ed. 2007, 46, 786e789; (e) Prakash, G. K. S.; Hu, J. Acc. Chem.
Res. 2007, 40, 921e930; (f) Liu, J.; Li, Y.; Hu, J. J. Org. Chem. 2007, 72, 3119e3121;
(g) Ni, C.; Zhang, L.; Hu, J. J. Org. Chem. 2008, 73, 5699e5713; (h) Ni, C.; Zhang,
L.; Hu, J. J. Org. Chem. 2009, 74, 3767e3771; (i) Hu, J. J. Fluorine Chem. 2009, 130,
1130e1139.
18. Please see experimental section.
19. Su, W. Tetrahedron Lett. 1994, 35, 4955e4958.
20. Surprenant, S.; Chan, W. Y.; Berthelette, C. Org. Lett. 2003, 5, 4851e4854.
21. Kataoka, K.; Tsuboi, S. Synthesis 1999, 452e456.
22. Liu, P.; Jacobsen, E. N. J. Am. Chem. Soc. 2001, 123, 10772e10773.
23. Prakash, G. S. K.; Chacko, S.; Vaghoo, H.; Shao, N.; Gurung, L.; Mathew, T.; Olah,
G. A. Org. Lett. 2009, 11, 1127e1130.
24. (a) Quast, H.; Bieber, L. Chem. Ber. 1981, 114, 3253e3272; (b) Aïssa, C. J. Org.
Chem. 2006, 71, 360e363.
25. Wang, R.; Dolman, S. J. J. Org. Chem. 2007, 72, 3969e3971.
26. Adam, W.; Bargon, R. M.; Bosio, S. G.; Schenk, W. A.; Stalke, D. J. Org. Chem.
2002, 67, 7037e7041.
27. Pearson, W. H.; Fang, W.-K. J. Org. Chem. 2000, 65, 7158e7174.
28. Oku, A.; Harada, T.; Hattori, K.; Nozaki, Y.; Yamaura, Y. J. Org. Chem. 1988, 53,
3089e3098.
29. Uno, H.; Sakamoto, K.; Semba, F.; Suzuki, H. Bull. Chem. Soc. Jpn. 1992, 65,
210e217.
30. (a) Asakura, N.; Usuki, Y.; Iio, H. J. Fluorine Chem. 2003, 124, 81e88; (b) Mc-
Carthy, J. R.; Huber, E. W.; Le, T.-B.; Laskovics, M. F.; Matthews, D. P. Tetrahedron
1996, 52, 45e58.
5. Steenis, J. H.; Gen, A. J. Chem. Soc., Perkin Trans. 1 2002, 2117e2133.
6. Lee, S. H.; Schwartz, J. J. Am. Chem. Soc. 1986, 108, 2445e2447.
7. (a) Tius, M. A.; Kawakami, J. K. Synlett 1993, 207e208; (b) Tius, M. A.; Kawa-
kami, J. K. Tetrahedron 1995, 51, 3997e4010.
8. (a) Manfre, F.; Kern, J. M.; Biellmann, J.-F. J. Org. Chem. 1992, 57, 2060e2065; (b)
Burton, D. J.; Cox, D. G. J. Am. Chem. Soc. 1983, 105, 650e651; (c) Cox, D. G.;
Gurusamy, N.; Burton, D. J. J. Am. Chem. Soc. 1985, 107, 2811e2812; (d) Wheaton,
G. A.; Burton, D. J. J. Org. Chem. 1983, 48, 917e927; (e) van Steenis, J. H.; van der
Gen, A. Eur. J. Org. Chem. 2001, 897e910.
9. (a) McCarthy, J. R.; Matthews, D. P.; Edwards, M. L.; Stemerick, D. M.; Jarvi, E. T.
Tetrahedron Lett. 1990, 31, 5449e5452; (b) Khrimian, A. P.; DeMilo, A. B.; Wa-
ters, R. M.; Liquido, N. J.; Nicholson, J. M. J. Org. Chem. 1994, 59, 8034e8039.
10. Zhang, W.; Huang, W.; Hu, J. Angew. Chem., Int. Ed. 2009, 48, 9858e9861.
11. (a) Chevrie, D.; Lequeux, T.; Demoute, J. P.; Pazenok, S. Tetrahedron Lett. 2003,
44, 8127e8130; (b) Pfund, E.; Lebargy, C.; Rouden, J.; Lequeux, T. J. Org. Chem.
2007, 72, 7871e7877; (c) Calata, C.; Catel, J.-M.; Pfund, E.; Lequeux, T.
31. Andrei, D.; Wnuk, S. F. J. Org. Chem. 2006, 71, 405e408.