An effective preparation of sulfonyl-or sulfinyl-substituted fluorinated alkenes and their stereoselective addition-elimination reactions with organocuprates

Article abstract of DOI:10.1002/asia.201000022

Treatment of trifluorovinyl-or pentafluoropropen-1-yl sulfone or sulfoxide, which are easily prepared from commercially available 1,2-dibromofluoroalkanes, with various organocuprates affords substitution or β-reduction products in good to excellent yields through an addition-elimination reaction sequence.

Full text of DOI:10.1002/asia.201000022

FULL PAPERS
DOI: 10.1002/asia.201000022
An Effective Preparation of Sulfonyl- or Sulfinyl-Substituted Fluorinated
Alkenes and their Stereoselective Addition–Elimination Reactions with
Organocuprates
Shigeyuki Yamada, Kanoko Shimoji, Toshio Takahashi, Tsutomu Konno, and
Takashi Ishihara*[a]
Abstract: Treatment of trifluorovinyl- or pentafluoropropen-1-yl sulfone or sulfox-
ide, which are easily prepared from commercially available 1,2-dibromofluoroal-
kanes, with various organocuprates affords substitution or b-reduction products in
good to excellent yields through an addition–elimination reaction sequence.
Keywords: addition–elimination
reaction
reagents
·
·
cuprates
fluorinated alkenes
· dialkylzinc
·
Grignard reagents
Introduction
Fluorine-substituted a,b-unsaturated compounds are suit-
able substrates for the addition-elimination reaction. We re-
cently reported that fluorinated alkenes that contain an
ester group smoothly underwent the addition–elimination
reaction, leading to b-substituted fluorinated alkenes in
good yields.[3c,d,f] For this study, fluorine-substituted a,b-un-
saturated sulfones or -sulfoxides, such as compounds A–D
(Scheme 2) were chosen as substrates. They might be quite
À
À
Selective C F bond-cleavage as well as C F bond-forming
reactions have become important transformations in organic
chemistry.[1] Recently, new C C bond-forming reactions in-
À
À
volving C F bond-cleavage have been reported by several
groups.[2] Among the synthetic methods that involve C F
À
bond-cleavage reactions, the addition–elimination reaction
of fluorinated alkenes is recognized as one of the most con-
venient and powerful procedures for the transformation of a
[3]
C F bond into other C X bonds (X=C, O,[4] S,[5] N,[6] and
so forth; Scheme 1).
À
À
Scheme 2. Fluorine-substituted a,b-unsaturated sulfones and sulfoxides
(A–D).
À
useful and valuable building blocks for the synthesis of a va-
riety of new organofluorine compounds, and applicable in
the synthesis of various functional materials. So far, there
have been few[7] (for compound A) or no published reports
(for compounds B, C, and D) concerning their synthetic
preparation.
Scheme 1. C F bond-cleavage during the addition–elimination reaction
of fluorinated alkenes.
Herein, we describe the convenient and simple prepara-
tion of trifluorovinyl compounds A and B (in three steps,
starting from 1,2-dibromotetrafluoroethane) and pentafluoro-
propen-1-yl compounds C and D (in two steps starting from
1,2-dibromohexafluoropropane). In addition, we demon-
[a] Dr. S. Yamada, K. Shimoji, T. Takahashi, Prof. Dr. T. Konno,
Prof. Dr. T. Ishihara
Department of Chemistry and Materials Technology
Kyoto Institute of Technology
Matsugasaki, Sakyo-ku, Kyoto 606-8585 (Japan)
Fax : (+81)75-724-7580
À
strate the direct transformation of a C F bond into a
E-mail: ishihara@kit.ac.jp
À
C C bond through an addition–elimination process, by the
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/asia201000022.
reaction of trifluorovinyl compounds (A, B) with organo-
1846
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2010, 5, 1846 – 1853

À
cuprates. We also show that the C F bond at the b position
to the sulfur-containing group of pentafluoropropen-1-yl
Subsequently, the reaction of 6 with various metals or or-
ganometallic reagents was examined in order to obtain the
trifluorovinyl sulfide 7. The results are shown in Table 1.
À
compounds (C, D) can be selectively converted into a C H
bond by reaction with a number of organocuprate reagents
(Scheme 3).
À
Table 1. Reductive Br F elimination by treating with metal or organo-
metallic reagent.
Entry
M/RM
Yield of 7 [%][a]
1
Zn
0
2
Mg
67
3
EtMgBr
EtMgBr
MeLi
62
87 (65)
0
0
4[b]
5[c]
6[d]
Scheme 3. Synthesis and addition-elimination reactions of polyfluorovinyl
compounds.
nBuLi
[a] Determined by 19F NMR spectroscopy. The yield of isolated product
is given in parentheses. [b] Carried out at 08C. [c] Product 8 (shown
below) was obtained in 73% yield. [d] Product 9 (shown below) was ob-
tained in 73% yield.
Results and Discussion
Preparation of Trifluorovinyl and Pentafluoropropen-1-yl
Sulfone and Sulfoxide
As shown in Scheme 4, trifluorovinyl sulfone 1 and sulfoxide
2 could be obtained from the oxidation of trifluorovinyl sul-
fide 7, which was prepared by an addition–elimination reac-
tion of tetrafluoroethene with an arenethiolate. Tetrafluoro-
Thus, the treatment of 6 with zinc dust in THF at room tem-
perature for 3 hours did not lead to 7 at all (Table 1,
entry 1). On the contrary, the organomagnesium reagent,
generated either by direct insertion of 6 with Mg or by Br/
Mg exchange with EtMgBr, was found to immediately un-
ACHTUNGTRENNUNGethene could be generated in situ from commercially avail-
able 1,2-dibromotetrafluoroethane 5.[8]
À
dergo Br F elimination, to provide vinyl sulfide 7 in 67%
and 62% yields, respectively (Table 1, entries 2 and 3). The
best result (87% yield) was obtained by treating 6 with
EtMgBr in THF at 08C for 3 hours. The reaction was at-
tempted using MeLi or nBuLi, but the desired product 7
was not obtained in either case. Instead, the products from
Scheme 4. Retrosynthesis of 1 and 2.
À
successive Br F elimination/addition–elimination sequences
(8 and 9) were each formed in 73% yield (Table 1, entries 5
and 6).
Initially, the generation of tetrafluoroethene from 5, and
the subsequent addition–elimination reaction with arene-
thiolate were examined. On treatment of 5 with sodium
para-toluenethiolate in DMF at 08C for 3 hours, the desired
trifluorovinyl sulfide 7 was not observed at all. Instead, the
substitution product 6 was formed in 49% yield.[9] By chang-
ing the reaction temperature from 08C to À208C or À608C,
the yield of 6 was improved to 88% and 90% yield (72%
isolated), respectively (Scheme 5).
Finally, the trifluorovinyl sulfide 7 was subjected to oxida-
tion with 2.2 equivalents of meta-chloroperbenzoic acid
(mCPBA) in CH2Cl2 at reflux for 12 hours, thus affording
trifluorovinyl sulfone 1 in 83% yield. When the oxidation
reaction was carried out with 1.1 equivalents of mCPBA in
CH2Cl2 at room temperature for 12 hours, trifluorovinyl sulf-
oxide 2 was isolated in 90% yield (Scheme 6).
Scheme 6. Oxidation of 7 to trifluorovinyl sulfone (1) and trifluorovinyl
sulfoxide (2).
Scheme 5. Reaction of 5 with para-toluenethiolate.
Chem. Asian J. 2010, 5, 1846 – 1853
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
1847

T. Ishihara et al.
FULL PAPERS
Table 2. Reaction of sulfone 1 or sulfoxide 2 with PhMgBr (a) in the
presence of copper(I) salt.
Pentafluoropropen-1-yl sulfone (12) and sulfoxide (13)
could also be prepared from 1,2-dibromohexafluoropropane
(10) in a similar manner, as shown in Scheme 7. Thus, the
Entry Substrate CuI
[equiv]
PhMgBr Yield of E/Z[a] Recovered
G
[equiv]
3a or 4a
1 or 2 [%][a]
[%][a]
1
2
3
4
5
6
7
8
1
none
1.1
0
0
6
0
58
–
–
75
73
CuBr (1.1) 2.2
CuI(1.1) 2.2
(1.1) 1.1
(1.1) 2.2
(2.2) 4.4
(1.1) 2.2
(2.2) 4.4
G
0:100 50
87
9:91 25
CuCN
CuCN
CuCN
CuCN
CuCN
G
–
R
E
84 (80)
67 (50)
59
2:98
19:81
15:85
0
0
0
2
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
[a] Determined by 19F NMR spectroscopy. The yield of isolated product
is given in parentheses.
Scheme 7. Preparation of pentafluoropropen-1-yl sulfone (12) and sulfox-
ide (13) from 1,2-dibromohexafluoropropane (10).
acted with 2.2 equivalents of organocuprate, prepared from
2.2 equivalents of CuCN and 4.4 equivalents of PhMgBr (a),
in THF at À788C for 1 hour (isolated in 80% yield, E/Z=
2:98; Table 2, entry 6). Trifluorovinyl sulfoxide 2 was also
subjected to the addition–elimination reaction with diphe-
nylcyanocuprate, giving 2-phenyl-1,2-difluorovinyl sulfoxide
4a in good yield with high stereoselectivity (>59% yield,
E/Z=<19:81).
The addition–elimination reactions of 1 with 2.2 equiva-
lents of organocuprates that were derived from various
Grignard reagents, were then performed under the opti-
mized reaction conditions (entry 6 in Table 2). The results
are shown in Table 3.
treatment of 10 with 2.0 equivalents of sodium para-toluene-
thiolate in THF at À208C for 4 hours gave the fluorinated
vinyl sulfide 11 in 54% yield as a mixture of E and Z iso-
À
mers (E/Z=31:69), formed from successive Br F elimina-
tion/addition–elimination reactions. The vinyl sulfide 11 was
oxidized with mCPBA (2.5 equiv) in CH2Cl2 at reflux for
20 hours into fluorinated vinyl sulfone 12 in 58% yield
(E/Z=<10:90) (after isolation by column chromatography
on silica gel). The pentafluoropropen-1-yl sulfoxide 13 was
isolated in 40% yield (E/Z=<10:90) from the oxidation of
11 with 1.0 equivalent of mCPBA in CH2Cl2 at room tem-
perature for 4 hours.
Table 3. Addition–elimination reaction of 1 or 2 with organocuprates de-
rived from various Grignard reagents.
Reaction of Trifluorovinyl Sulfone (1) and Sulfoxide (2)
with Organocuprates
With the fluorinated vinyl sulfone 1 or sulfoxide 2 in hand,
we studied the reaction of 1 or 2 with organocopper re-
agents that were derived from Grignard reagents and cop-
per(I) salts; the results are summarized in Table 2.
Entry
Substrate
R
Yield of
E/Z[c]
2:98
3 or 4 [%][c]
On treatment of 1 with 1.1 equivalents of PhMgBr (a) in
the absence of a copper(I) salt in THF at À788C for 1 hour,
the addition–elimination product 3a was not obtained at all,
and the starting sulfone 1 was recovered in 75% yield
(Table 2, entry 1). Organocuprates prepared from CuBr or
CuI were obviously not efficient for the addition–elimina-
tion reaction (Table 2, entries 2 and 3). Whilst the use of
1.1 equivalents of “lower-ordered” phenyl organocuprate
CuCN/PhMgBr (a; 1:1) did not lead to a significant im-
provement (Table 2, entry 4), the “higher-ordered cyanocup-
rate”[10] CuCN/PhMgBr (1:2) participated well in the addi-
tion–elimination reaction, thus providing 2-phenyl-1,2-di-
fluorovinyl sulfone 3a in 58% yield (Table 2, entry 5). Im-
portantly, high stereoselectivity was observed in the reaction
(E/Z=9:91). Optimization of the reaction conditions was
performed, and the best result was obtained when 1 was re-
1
2
3
4
5
6
7
8
1[a]
Ph (a)
84 (80)
78 (69)
95 (89)
80 (61)
94 (71)
98 (95)
89 (88)
70 (58)
85 (72)
78 (52)
67 (50)
27
4-MeOC6H4 (b)
3-MeOC6H4 (c)
2-MeOC6H4 (d)
4-MeC6H4 (e)
4-CF3C6H4 (f)
nBu (g)
sBu (h)
c-Hex (i)
b-Styryl (j)
Ph (a)
4-MeC6H4 (e)
nBu (g)
3:97
2:98
5:95
3:97
<1:>99
43:57
4:96
9
14:86
78:22
12:88
22:78
30:70
10
11
12
13
2[b]
44
[a] Conditions A (entries 1–10): Organocuprates were prepared from
2.2 equiv of CuCN and 4.4 equiv of Grignard reagent. [b] Conditions B
(entries 11–13): Organocuprates were prepared from 1.1 equiv of CuCN
and 2.2 equiv of Grignard reagent. [c] Determined by 19F NMR spectros-
copy. The yield of isolated product is given in parentheses.
1848
www.chemasianj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2010, 5, 1846 – 1853

Preparation of Sulfonyl- or Sulfinyl-Substituted Fluorinated Alkenes
As shown in Table 3 (entries 2–6), various aryl Grignard
reagents containing either an electron-donating or electron-
withdrawing group participated well in the Z-selective addi-
tion–elimination reaction, thus leading to the products of
type 3 in good yields (isolated in 69–95% yields) and high
stereoselectivity (E/Z=<5:95). When alkyl Grignard re-
agents such as n-butyl- (g), sec-butyl- (h), and cyclohexyl-
magnesium bromide (i) were used, the addition–elimination
reaction proceeded smoothly to provide the corresponding
b-alkylated products 3g, 3h, and 3i in 89%, 70%, and 85%
yields, respectively (Table 3, entries 7–9). However, for the
products 3g and 3i, the obtained stereoselectivity was low
(E/Z=43:57 and 14:86, respectively). The organocuprate
derived from b-styrylmagnesium bromide (j) was also reac-
tive, but afforded the opposite stereoselectivity (78%, E/Z=
78:22). In addition, the reactions of the trifluorovinyl sulfox-
ide 2 with an organocuprate generated from 4-methylphen-
yl- (e) or n-butylmagnesium bromide (g) were carried out
under the conditions of entry 7 in Table 2. Both Grignard re-
agents e and g were efficient nucleophiles for the reaction,
but the yield of the products 4, as well as their stereoselec-
tivity were low (27–44% yield, E/Z=<12:88).
The treatment of sulfone 12 with 1.1 equivalent of
PhMgBr (a) in the absence of a copper(I) salt in THF at
À788C for 1 hour, followed by work-up (sat. NH4Cl aq), did
not lead to the addition–elimination product 16a, and the
reaction resulted in the quantitative recovery of the starting
sulfone 12 (Table 4, entry 1). It was found that the molar
ratio of copper(I) salt and Grignard reagent was crucial for
the reaction outcome (Table 4, entries 2 and 3). The reaction
of 12 with organocuprates derived from 1.1 equivalents of
each of CuCN and PhMgBr (a) was sluggish, whilst in the
presence of an organocuprate derived from 1.1 equivalents
of CuCN and 2.2 equivalents of PhMgBr, the reaction pro-
ceeded efficiently to give the b-reduction product 14-H in
70% yield after hydrolysis. The use of a higher temperature
(À208C) did not improve the yield (Table 4, entry 4). When
the reaction was performed using 2.2 equivalents of diphe-
nylcyanocuprate in THF at À788C for 1 hour, 14-H was ob-
tained in the highest yield (88%). The use of additives
(TMSCl or DMSO, 1.0 equiv) did not dramatically influence
the reaction, and the formation of the addition–elimination
product 16a was observed in low yield (<20%; Table 4, en-
tries 6 and 7).[11] Interestingly, the reaction in the presence
of CuBr or CuI, instead of CuCN, led to the a-reduction
product 18 as the major product in 56% or 31% yield, re-
spectively (Table 4, entries 8 and 9). When sulfoxide 13 was
used as the substrate, the corresponding addition–elimina-
tion product 17a was produced preferentially, though in
moderate yields (41–45%, entries 10 and 11).
Reaction of Pentafluoropropen-1-yl Sulfone (12) or
Sulfoxide (13) with Organocuprates
Next, our attention was directed toward the reaction of pen-
tafluoropropen-1-yl sulfone 12 or sulfoxide 13 with various
organocuprates. The results of the reactions of 12 or 13 with
PhMgBr (a) in the presence of copper(I) salts are summar-
ized in Table 4.
Various sorts of Grignard reagent were applied to the re-
action using the reaction conditions from Table 4, entry 5
(for 12) and entry 11 (for 13). The results are collected in
Table 5.
The organocuprates derived
from 4-methoxyphenyl- (b) or
3-methoxyphenylmagnesium
Table 4. Reaction of the sulfone 12 or sulfoxide 13 with PhMgBr (a) in the presence of copper(I) salt.
bromide (c) also participated
successfully in this reaction, af-
fording the b-reduction product
14-H in 43% and 40% yield,
along with their corresponding
addition–elimination products
16b and 16c in 16% and 10%
yield, respectively (Table 5, en-
tries 2 and 3). 2-Methoxyphen-
yl- (d), 4-methylphenyl- (e),
and 4-(trifluoromethyl)phenyl-
magnesium bromide (f) were
not effective for the formation
of 14-H. However, when
Grignard reagent e or f was em-
ployed, not only 14-H but also
the a-reduction product 18 and/
or desulfonylative arylation
product 19 were observed
(Table 5, entries 4–6). As shown
in entries 7 and 10, n-butyl- (g)
or b-styrylmagnesium bromide
Entry Substrate CuI salt
[equiv]
PhMgBr [equiv] T [8C] Yield of
Yield
Recovered
ACHTUNGTRENNUNG
b-H [%][a] of 16a or 17a [%][a] 12 or 13 [%][a]
1
12
None
1.1
1.1
2.2
2.2
4.4
4.4
4.4
4.4
4.4
2.2
4.4
À78
À78
À78
À20
À78
À78
À78
À78
À78
À78
À78
0
9
70
0
0
0
0
0
quant.
73
2
3
4
5
CuCN
CuCN
CuCN
CuCN
CuCN
CuCN
N
24
9
trace
trace
trace
41
54
19
trace
62
88 (82)
86
31
trace
7
6[b]
7[c]
8[d]
9[d]
10
11
E
trace
20
0
0
41
45
U
CuBr
CuI
N
U
13
CuCN
CuCN
R
12
0
T
[a] Determined by 19F NMR spectroscopy. The yield of isolated product is given in parentheses. [b] TMSCl
was employed as an additive. [c] DMSO was employed as an additive. [d] In entries 8 and 9, a-reduction prod-
uct 18 (shown below) was obtained in 56% and 31% yields, respectively.
Chem. Asian J. 2010, 5, 1846 – 1853
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
1849

T. Ishihara et al.
FULL PAPERS
Table 5. Addition-elimination reaction of 12 or 13 with organocuprates derived from various Grignard re-
agents.
rived from l or m proceeded to
give the corresponding b-reduc-
tion product 14-H in 57% or
35% yield, respectively, togeth-
er with other side-products,
such as the a-reduction product
18 (for the reaction with l) and
addition–elimination
product
16m (for the reaction with m)
(Table 6, entries 5 and 6). How-
ever, under the same condi-
tions, diphenylzinc (n) was not
reactive at all (Table 6, entry 7).
Similarly, the reaction of the
sulfoxide 13 with an organocup-
rate derived from CuCN·2LiCl
and diethylzinc (k) in THF at
À788C for 1 hour was exam-
ined. It was observed that the
amount of organocuprate signif-
icantly affected the yield of the
Entry
Substrate
R
Yield of
Yield of
Recovered
b-H [%][a]
16 or 17 [%][a]
12 or 13 [%][a]
1
12
Ph (a)
88 (82)
0
16
10
trace
7
trace
83
28
30
trace
75
60
trace
0
2[b]
3[b]
4
4-MeOC6H4 (b)
3-MeOC6H4 (c)
2-MeOC6H4 (d)
4-MeC6H4 (e)
4-CF3C6H4 (f)
nBu (g)
sBu (h)
c-Hex (i)
b-Styryl (j)
Ph (a)
43
40
2
5
0
5[c]
6[d]
7
trace
trace
12
0
12
0
45
50
56
0
10
79 (65)
trace
10
8
9
10
11
12
13
14
15
85 (79)
13
0
0
0
0
0
4-MeOC6H4 (b)
3-MeOC6H4 (c)
2-MeOC6H4 (d)
4-MeC6H4 (e)
0
0
0
0
b-reduction
product
15-H
(Table 6, entries 8 and 9). A
good yield (80%) was obtained
when 2.2 equivalents of organo-
cuprate was used (Table 6,
entry 9). Dimethylzinc (l) also
participates in this process to
afford the b-reduction product
15-H in 44% yield after hydrol-
ysis (Table 6, entry 10). Howev-
41
[a] Determined by 19F NMR spectroscopy. The yield of isolated product is given in parentheses. [b] Trace
amounts of 18 and 19 were observed in the reaction mixture. [c] Products 18 and 19 (shown below) were ob-
tained in 5% and 24% yields, respectively. [d] Product 18 was obtained in 48% yield.
(j) are good nucleophiles for this reaction, leading to 14-H
in 79% or 85% yield, respectively. On the other hand, other
aliphatic Grignard reagents h and i were less successful, and
large amounts of the starting sulfone 12 were recovered
(Table 5, entries 8 and 9). The reaction of 13 with organo-
cuprates that were generated from various aryl Grignard re-
agents, such as a–c, e, and f, gave their corresponding addi-
tion–elimination products 17a–c and 17e, in 41–56% yields,
respectively (Table 5, entries 11–13 and 15). 2-Methoxyphe-
nylmagnesium bromide (b) was found to be unreactive
under these conditions.
The results of the reaction between 12 or 13 and various
organozinc reagents are tabulated in Table 6. Thus, the reac-
tion of the sulfone 12 with 1.1 equivalents of diethylzinc (k)
in the absence of a copper(I) salt in THF at À788C for
1 hour did not provide the corresponding b-reduction prod-
uct 14-H at all (Table 6, entry 1). CuCN as the catalyst was
not efficient in this reaction, although the employment of
CuCN·2LiCl[12] (1.1 equiv) was found to give 14-H in 34%
yield (Table 6, entries 2 and 3). The best result was obtained
when the reaction was performed with 2.2 equivalents of the
mixed organocuprate CuCN·2LiCl/k (1:2), so that the b-re-
duction product 14-H was isolated in 85% yield (Table 6,
entry 4). Dimethylzinc (l), diisopropylzinc (m), and diphe-
nylzinc (n) investigated under the same reaction conditions
(Table 6, entries 5–7). The reaction with organocuprate de-
er, in that case, the side product of a-reduction (20) was
also formed in 44% yield. The reaction of 13 with 2.2 equiv-
alents of an organocuprate derived from m proceeds readily
to give the corresponding b-reduction product 15-H in 93%
yield (Table 6, entry 11). Diphenylzinc (n) was again not ef-
ficient for the addition–elimination reaction, affording in
quantitative recovery of the starting sulfoxide 13 (Table 6,
entry 12).
Next, we considered the cross-coupling reaction of orga-
nocopper intermediates, generated in situ using Method A
(for sulfone 12) or Method B (for sulfoxide 13), with various
electrophiles (Table 7).
When the fluorinated vinyl sulfone 12 was reacted with
diphenylcyanocuprate (2.2 equiv), which was prepared from
CuCN (2.2 equiv) and PhMgBr (a, 4.4 equiv), followed by
treatment with I2 (5.0 equiv) at À788C for 1 hour, 1,3,3,3-tet-
rafluoro-2-iodopropen-1-yl sulfone 14 was obtained in 60%
yield (Table 7, entry 1). However, carbon electrophiles, such
as allyl, methallyl, and crotyl bromide[13] did not afford satis-
factory results (Table 7, entries 2–4). In the case of the sulf-
oxide 13, a vinylcopper intermediate was formed in the reac-
tion with organocuprate (prepared by mixing CuCN·2LiCl
(2.2 equiv) and diethylzinc (k, 4.4 equiv). Whilst this organo-
copper species did not react with I2 at all, allylic electro-
À
philes afforded some C C bond formation product (Table 7,
entries 5–8). The a-reduction side-product 20 was observed
1850
www.chemasianj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2010, 5, 1846 – 1853

Preparation of Sulfonyl- or Sulfinyl-Substituted Fluorinated Alkenes
Table 6. Addition–elimination reaction of 12 or 13 with organocuprates derived from various dialkylzinc re-
agents.
per species Int-C. Such species
may be stabilized by the strong
electron-withdrawing effect of a
CF3 group.[14] By treatment with
various electrophiles (including
H2O), the vinylcopper species
Int-C is converted into the cor-
responding 1,3,3,3-tetrafluoro-
propen-1-yl derivatives 14 and
15, along with the formation of
À
Entry Substrate CuI salt
[equiv]
R2Zn
A
Yield of
Yield
Recovered
homo-coupling product (R R).
G
b-H [%][a]
of 16 or 17 [%][a]
12 or 13 [%][a]
On the other hand, the addi-
tion–elimination products 16
and 17 may be formed from re-
1
12
none
Et2Zn (k;1.1)
Et2Zn(k;2.2)
(1.1) Et2Zn(k;2.2)
(2.2) Et2Zn(k;4.4)
(2.2) Me2Zn (l;4.4)
(2.2) iPr2Zn (m;4.4)
(2.2) Ph2Zn (n;4.4)
(1.1) Et2Zn (k;2.2)
(2.2) Et2Zn(k;4.4)
(2.2) Me2Zn (l;4.4)
0
0
34
0
0
quant.
2
CuCN
N
R
90
46
0
0
3
4
CuCN·2LiCl
CuCN·2LiCl
CuCN·2LiCl
CuCN·2LiCl
CuCN·2LiCl
CuCN·2LiCl
CuCN·2LiCl
CuCN·2LiCl
CuCN·2LiCl
CuCN·2LiCl
G
E
trace
À
ductive elimination of R CuX
E
N
quant. (85)
0
through five-membered inter-
mediate Int-D, in which the co-
ordination of a sulfinyl oxygen
to the copper center would fa-
cilitate the reductive elimina-
tion.
5[b]
6
E
57
35
0
40
80
44
trace
30
0
R
0
7
R
quant.
8[c]
9[c]
10[c]
11
12
13
N
0
0
0
0
44
0
5
0
N
G
R
(2.2) iPr2Zn (m;4.4) 93 (75)
(2.2) Ph2Zn (n;4.4)
A
0
0
quant.
[a] Determined by 19F NMR spectroscopy. The yield of isolated product is given in parentheses. [b] The a-re-
duction product 18 (shown below) was obtained in 40% yield. [c] In entries 8–10, the a-reduction product 20
was obtained in 12%, 18%, and 44% yield, respectively.
Conclusions
In conclusion, we have achieved
the effective preparations of
the trifluorovinyl sulfone 1,
sulfoxide 2, and pentafluoro-
propen-1-yl derivatives 12 and
13 from commercially available
in all of the reactions involving sulfoxide 13, in 16–21%
yield.
1,2-dibromo-tetrafluoroethane (5) or -hexafluoropropane
(10). The trifluorovinyl sulfone 1 and sulfoxide 2 can be
easily subjected to the addition–elimination reaction with
organocuprate reagents that are derived from 1:2 mixtures
of CuCN and Grignard reagents, thus leading to the corre-
sponding substitution products 3 and 4 in good to excellent
yields and high Z selectivity. The reactions of 12 and 13 with
organocuprates proceeded smoothly to form relatively
stable 1,3,3,3-tetrafluoropropen-1-ylcopper intermediates,
which could be converted into 1,3,3,3-tetrafluoropropen-1-yl
derivatives 14 and 15 by trapping with various electrophiles.
Furthermore, the addition–elimination products 16 and 17
were obtained from the reaction using 13 as a substrate or
DMSO as an additive.
Possible Reaction Mechanism for the Stereoselective
Addition–Elimination Reaction of Trifluorovinyl or
Pentafluoropropen-1-yl Derivatives with Organocuprates
A possible reaction mechanism for the stereoselective addi-
tion–elimination reaction of trifluorovinyl (1 and 2) or pen-
tafluoropropen-1-yl derivatives (12 and 13) with organocup-
rates is given in Scheme 8.
The trifluorovinyl derivatives 1 and 2 can react with an or-
ganocuprate to generate an intermediate Int-A, which may
exist in two possible conformations: one is where copper
and sulfonyl group occupy a gauche orientation, and the
other is where they are occupied an anti-periplanar orienta-
tion. In an equilibrium between Int-A
(anti), the latter would be favored over Int-A
owing to steric repulsion between the copper and sulfonyl
groups. Then, the elimination of MgBrF from Int-A(anti)
takes place preferentially to form Int-B, followed by rapid
reductive elimination of RCu, thus finally providing the (Z)-
1,2-difluorovinyl derivatives 3 and 4, respectively. The pen-
tafluoropropen-1-yl derivatives 12 and 13 also undergo nu-
cleophilic cis-addition of organocuprate and successive anti-
ACHTUNGTRENNUNG
Experimental Section
G
ACHTUNGTRENNUNG
Typical procedure for the reaction of the trifluorovinyl sulfone 1 with
PhMgBr (a) in the presence of CuCN: To
a suspension of CuCN
AHCTUNGTRENNUNG
(0.059 g, 0.66 mmol) in THF (1.0 mL), in a 50 mL three-necked round-
bottomed flask equipped with a magnetic stirrer bar, a thermometer, a
rubber septum, and an inlet tube for argon, a 0.8m solution of PhMgBr
(a, 1.6 mL, 1.3 mmol) in THF was added dropwise at À788C. To the re-
sulting solution was slowly added 0.071 g (0.30 mmol) of 1,2,2-trifluoro-
vinyl 4-methylphenyl sulfone (1) in THF (2 mL) from a syringe at
À788C. After stirring for 1 h at À788C, the reaction mixture was poured
into ice-cooled water (50 mL), followed by extraction with Et2O
À
elimination of M F, leading to the corresponding vinylcop-
Chem. Asian J. 2010, 5, 1846 – 1853
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
1851

T. Ishihara et al.
FULL PAPERS
Table 7. Directed cross-coupling of the organocopper intermediate with
various electrophiles.
(30 mLꢁ5). The organic layers were dried over anhydrous Na2SO4, fil-
tered, and concentrated in vacuo. Column chromatography of the residue
using hexane/benzene (2:1) yielded 1,2-difluoro-2-phenylethenyl 4-meth-
ylphenyl sulfone (3a, 0.033 g, 80%).
1,2-Difluoro-2-phenylethenyl 4-methylphenyl sulfone (3a): 80% yield;
IR (KBr) 2371, 2345, 1647, 1345, 1158 cmÀ1; (Z)-3a: 1H NMR (CDCl3):
d=2.47 (s, 3H), 7.43 (m, 5H), 7.67 (dd, J=8.4, 1.6 Hz, 2H), 7.95 (d, J=
8.4 Hz, 2H); 19F NMR (CDCl3): d=À154.09 (d, J=134.2 Hz, 1F),
À136.04 (d, J=134.2 Hz, 1F); (E)-3a: 1H NMR (CDCl3): d=2.46 (s,
3H), 7.36 (dd, J=8.4, 1.6 Hz, 2H), 7.54 (m, 5H), 7.73 (d, J=8.4 Hz, 2H);
19F NMR (CDCl3): d=À141.28 (d, J=4.4 Hz, 1F), À99.63 (d, J=4.4 Hz,
1F); HRMS (FAB) calcd for [M+H] C15H13F2O2S: 295.0606, found
295.0595.
Entry Substrate Electrophile Yield of 14 or Yield of 16 or Yield of
15 [%][c]
17 [%][c]
b-H
Typical procedure for the preparation of 1,3,3,3-tetrafluoropropen-1-yl 4-
methylphenyl sulfone (14-H): A 30 mL two-necked round-bottomed flask
equipped with a magnetic stirrer bar, a rubber septum, and an inlet tube
for argon was charged with a suspended solution of CuCN (0.059 g,
0.66 mmol) in THF (1 mL). To this solution was slowly added a solution
of PhMgBr (a, 1.3 mmol) in THF by syringe at À788C. The mixture was
warmed up to À208C and stirred for 15 minutes. Pentafluoropropen-1-yl
4-methylphenyl sulfone (12, 0.086 g, 0.3 mmol) was added to the resulting
solution by syringe at À788C. After being stirred for 1 hour, the reaction
mixture was poured into ice-cooled saturated aqueous NH4Cl (30 mL),
followed by extraction with ether (30 mLꢁ5). The organic layers were
dried over anhydrous Na2SO4, filtered, and concentrated under reduced
pressure. Column chromatography on silica gel of the residue using
hexane/benzene (5:1) yielded pure 1,3,3,3-tetrafluoropropen-1-yl 4-meth-
ylphenyl sulfone (14-H, 0.071 g, 82%).
[%][c]
1
2
12[a]
I2
60
7
14
7
trace
79
3
6
6
73
4
14
0
44
5
0
0
48
68
31
5[d]
6[d]
13[b]
I2
7[d]
8[d]
47
53
0
0
13
8
[a] Method A (entries 1–4): PhMgBr (a, 4.4 equiv), CuCN (2.2 equiv),
THF, À788C, 1 h; [b] Method B (entries 5–8): Et2Zn (k; 4.4 equiv),
CuCN·2LiCl (2.2 equiv), THF, À788C, 1 h. [c] Determined by 19F NMR
spectroscopy. [d] In entries 5–8, the a-reduction product 20 (shown
below) was obtained in 20%, 21%, 18%, and 16% yield, respectively.
(E)-1,3,3,3-Tetrafluoropropen-1-yl 4-methylphenyl sulfone (14-H): 82%
yield; IR (neat) 3105, 1693, 1594, 1354, 1340, 1262, 1194, 1091 cmÀ1
;
1H NMR (CDCl3): d=2.50 (s, 3H), 6.41 (dq, J=28.0, 7.1 Hz, 1H), 7.44
(ABq, J=8.3 Hz, 2H), 7.85 (ABq, J=8.3 Hz, 2H); 13C NMR (CDCl3):
d=21.82, 104.13 (q, J=37.6 Hz), 120.58 (q, J=272.1 Hz), 129.37, 130.55,
131.83, 147.34, 160.69 (dq, J=323.1, 4.8 Hz); 19F NMR (CDCl3): d=
À109.98 (dq, J=28.0, 16.9 Hz, 1F), À59.62 (dd, J=16.9, 7.1 Hz, 3F);
HRMS (FAB) calcd for [M+H] C10H9F4O2S: 269.0260, found 269.0255.
Acknowledgements
The authors thank Dr. Andrei Gavryushin (Ludwig-Maximilians-Univer-
sitꢂt Mꢃnchen) for polishing the English and proofreading the manu-
script.
[1] H. Amii, K. Uneyama, Chem. Rev. 2009, 109, 2119–2183.
À
[2] For selective reports on the C F bond cleavage of aromatic fluo-
rides using nickel catalysis, see: a) J. W. Dankwardt, J. Organomet.
Chem. 2005, 690, 932–938; b) N. Yoshikai, H. Mashima, E. Naka-
mura, J. Am. Chem. Soc. 2005, 127, 17978–17979; c) K. Lamm, M.
Stollenz, M. Meier, H. Gçrls, D. Walther, J. Organomet. Chem.
2003, 681, 24–36; d) F. Mongin, L. Mojovic, B. Guillamet, F. Trꢄ-
court, G. Quꢄguiner, J. Org. Chem. 2002, 67, 8991–8994; e) T.
Braun, R. N. Perutz, M. I. Sladek, Chem. Commun. 2001, 2254–
2255; f) V. P. W. Bçhm, C. W. K. Gstçttmayr, T. Weskamp, W. A.
Herrmann, Angew. Chem. 2001, 113, 3500–3503; Angew. Chem. Int.
À
Ed. 2001, 40, 3387–3389; for selective reports on the C F bond
cleavage of aryl fluorides using palladium catalysis, see: g) Y. M.
Kim, S. Yu, J. Am. Chem. Soc. 2003, 125, 1696–1697; h) R. Wilhelm,
D. A. Widdowson, J. Chem. Soc. Perkin Trans. 1 2000, 3808–3813;
À
for a report on the C F bond cleavage of aryl fluorides using
copper catalysis, see:i) T. J. Korn, M. A. Schade, S. Wirth, P. Kno-
À
chel, Org. Lett. 2006, 8, 725–728; for selective reports on the C F
Scheme 8. A possible reaction mechanism for the stereoselective addi-
tion–elimination reaction of trifluorovinyl (1 and 2) or pentafluoroprop-
en-1-yl derivatives (12 and 13) with organocuprates.
bond cleavage on alkyl fluorides using transition metal catalysts,
see:j) J. Terao, N. Kambe, Bull. Chem. Soc. Jpn. 2006, 79, 663–672;
k) J. Terao, H. Watabe, N. Kambe, J. Am. Chem. Soc. 2005, 127,
1852
www.chemasianj.org
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Asian J. 2010, 5, 1846 – 1853

Preparation of Sulfonyl- or Sulfinyl-Substituted Fluorinated Alkenes
3656–3657; l) J. Terao, S. A. Begum, A. Oda, N. Kambe, Synlett
2005, 1783–1786; m) J. Terao, H. Todo, H. Watanabe, A. Ikumi, N.
Kambe, Angew. Chem. 2004, 116, 6306–6308; Angew. Chem. Int.
Ed. 2004, 43, 6180–6182; Angew. Chem. 2004, 116, 6306–6308; n) J.
Terao, A. Ikumi, H. Kuniyasu, N. Kambe, J. Am. Chem. Soc. 2003,
Ichikawa, K. Sakoda, H. Moriyama, Y. Wada, Synthesis 2006, 1590–
1598; f) V. V. Rudyuk, D. V. Fedyuk, L. M. Yagupoiskii, J. Fluorine
Chem. 2004, 125, 1465–1471; g) N. K. Park, B. T. Kim, S. S. Moon,
S. L. Jeon, I. H. Jeong, Tetrahedron 2004, 60, 7943–7949; h) J. Ichi-
kawa, Y. Wada, H. Miyazaki, T. Mori, H. Kuroki, Org. Lett. 2003, 5,
1455–1458.
À
125, 5646–5647; for C F bond cleavage of alkenyl fluorides using
low-valent zirconocenes, see: o) M. Fujiwara, J. Ichikawa, T. Okau-
chi, T. Minami, Tetrahedron Lett. 1999, 40, 7261–7265.
[7] a) T. Okano, M. Chokai, M. Hiraishi, M. Yoshizawa, T. Kusukawa,
M. Fujita, Tetrahedron 2004, 60, 4031–4035; b) D. Hass, H. Holfter,
U. Schrçder, J. Fluorine Chem. 1994, 69, 89–95.
[3] a) G. Landelle, P. A. Champagne, X. Barbeau, J. F. Paquin, Org.
Lett. 2009, 11, 681–684; b) F. Babudri, A. Cardone, L. De Cola,
G. M. Farinola, G. S. Kottas, C. Martinelli, F. Naso, Synthesis 2008,
1583–1588; c) S. Yamada, M. Noma, K. Hondo, T. Konno, T. Ishi-
hara, J. Org. Chem. 2008, 73, 522–528; d) S. Yamada, T. Takahashi,
T. Konno, T. Ishihara, Chem. Commun. 2007, 3679–3681; e) S.
Yamada, E. Ishii, T. Konno, T. Ishihara, Org. Biomol. Chem. 2007,
5, 1442–1449; f) S. Yamada, M. Noma, T. Konno, T. Ishihara, H. Ya-
manaka, Org. Lett. 2006, 8, 843–845; g) S. Yamada, T. Konno, T.
Ishihara, H. Yamanaka, J. Fluorine Chem. 2005, 126, 125–133; h) J.
Ichikawa, K. Sakoda, Y. Wada, Chem. Lett. 2002, 282–283; i) V. A.
Petrov, C. G. Krespan, J. Fluorine Chem. 2000, 102, 199–204; j) X.-
H. Huang, P.-Y. He, G.-Q. Shi, J. Org. Chem. 2000, 65, 627–629.
[4] a) H. Ueki, T. Chiba, T. Yamazaki, T. Kitazume, Tetrahedron 2005,
61, 11141–11147; b) J. Ichikawa, Y. Wada, M. Fujiwara, K. Sakoda,
Synthesis 2002, 1917–1936; c) K.-W. Chi, H.-A. Kim, G. G. Furin,
E. L. Zhuzhgov, N. Protzuk, J. Fluorine Chem. 2001, 110, 11–20;
d) Y. Wada, J. Ichikawa, T. Katsume, T. Nohiro, T. Okauchi, T.
Minami, Bull. Chem. Soc. Jpn. 2001, 74, 971–977; e) J. Ichikawa, M.
Fujiwara, Y. Wada, T. Okauchi, T. Minami, Chem. Commun. 2000,
1887–1888; f) P. L. Coe, J. Burdon, I. B. Haslock, J. Fluorine Chem.
2000, 102, 43–50.
[5] a) A. V. Shastin, V. G. Nenajdenko, V. M. Muzalevskiy, E. S. Balen-
kova, R. Froehlich, G. Haufe, Tetrahedron 2008, 64, 9725–9732; b) J.
Ichikawa, R. Nadano, T. Mori, Y. Wada, Org. Synth. 2006, 83, 111–
120; c) C. M. Timperley, M. J. Waters, J. A. Greenall, J. Fluorine
Chem. 2006, 127, 249–256; d) C. M. Timperley, J. Fluorine Chem.
2004, 125, 685–693.
[6] a) H. Wojtzowicz-Rajchel, H. Koroniak, A. Katrusiak, Eur. J. Org.
Chem. 2008, 368–376; b) J. Ichikawa, Y. Wada, H. Kuroki, J.
Mihara, R. Nadano, Org. Biomol. Chem. 2007, 5, 3956–3962; c) H.
Wojtowicz-Rajchel, M. Migas, H. Koroniak, J. Org. Chem. 2006, 71,
8842–8846; d) H. Koroniak, J. Walkowiak, K. Grys, An Rajchel, A.
Alty, R. Du Boisson, J. Fluorine Chem. 2006, 127, 1245–1251; e) J.
[8] a) O. Paleta, V. Dedek, H. Reutschek, H. J. Timpe, J. Fluorine
Chem. 1989, 42, 345–353; b) H. Kimoto, K. Takahashi, H. Muramat-
su, Bull. Chem. Soc. Jpn. 1980, 53, 764–769.
[9] For related publications, see: a) X. Li, H. Pan, X. Jiang, Tetrahedron
Lett. 1987, 28, 3699–3702; b) X. Li, H. Pan, X. Jiang, Tetrahedron
Lett. 1984, 25, 4937–4940; c) I. Rico, C. Wakselman, J. Fluorine
Chem. 1982, 20, 759–764.
[10] For selective reviews on higher-ordered cyanocuprates, see: a) B. H.
Lipshutz, Adv. Met.-Org. Chem. 1995, 4, 1–64; b) B. H. Lipshutz,
Synlett 1990, 119–128; c) B. H. Lipshutz, R. Moretti, R. Crow, Org.
Synth. 1990, 69, 80; d) W. A. Nugent, F. W. Hobbs, Jr. , Org. Synth.
1988, 66, 52.
À
[11] It was expected that the reductive elimination of R CuX was pro-
moted by TMSCl or DMSO, which acts as a Lewis base.
[12] For related reports on the preparation of organocopper reagents by
the treatment of organozinc reagents with CuCN·2LiCl, see: a) P.
Knochel, N. Millet, A. L. Rodriguez, Org. React. 2001, 58, 417–731;
b) P. Knochel, J. J. A. Perea, P. Jones, Tetrahedron 1998, 54, 8275–
8319; c) P. Knochel, Synlett 1995, 393–403; d) P. Knochel, R. D.
Singer, Chem. Rev. 1993, 93, 2117–2188; e) M. J. Rozema, S. Achyu-
thaRao, P. Knochel, J. Org. Chem. 1992, 57, 1956–1958; f) S. Achyu-
thaRao, P. Knochel, J. Am. Chem. Soc. 1991, 113, 5735–5741.
[13] The g product, which may be formed from the reaction with crotyl
bromide at the g position, was not observed at all.
[14] a) T. Yamazaki, N. Shinohara, T. Kitazume, S. Sato, J. Fluorine
Chem. 1999, 97, 91–96; b) T. Yamazaki, H. Umetani, T. Kitazume,
Israel J. Chem. 1999, 39, 193–205; c) T. Yamazaki, H. Umetani, T.
Kitazume, Tetrahedron Lett. 1997, 38, 6705–6708.
Received: January 9, 2010
Revised: April 1, 2010
Published online: June 10, 2010
Chem. Asian J. 2010, 5, 1846 – 1853
ꢀ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemasianj.org
1853