Novel synthesis of 1-aryl-1-trifluoromethylallenes

Article abstract of DOI:10.1016/j.tetlet.2005.10.166

3,3-Bis(phenylthio)-1,1,1,2,2-pentafluorobutane 1 was reacted with aryllithium reagents (6 equiv) in ether at low to room temperature for 1-6 h to provide 2-aryl-1,1,1-trifluoro-3-phenylthio-2-butene 2 in 80-96% yields. Bromination of 2 with NBS in aceton

Full text of DOI:10.1016/j.tetlet.2005.10.166

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 209–212
Novel synthesis of 1-aryl-1-trifluoromethylallenes
Hee Young Han, Myong Sang Kim, Jang Bae Son and In Howa Jeong*
Department of Chemistry, Yonsei University, Wonju, Republic of Korea
Received 8 July 2005; revised 30 September 2005; accepted 28 October 2005
Available online 18 November 2005
Abstract—3,3-Bis(phenylthio)-1,1,1,2,2-pentafluorobutane 1 was reacted with aryllithium reagents (6 equiv) in ether at low to room
temperature for 1–6 h to provide 2-aryl-1,1,1-trifluoro-3-phenylthio-2-butene 2 in 80–96% yields. Bromination of 2 with NBS in ace-
tonitrile at reflux for 1–7 h afforded the corresponding allylic bromides 3 in 61–96% yields. Treatment of 3 with MCPBA (1.5 equiv)
in methylene chloride at reflux temperature for 1–12 h resulted in the formation of 1-aryl-1-trifluoromethylallenes 4 in 74–96%
yields.
Ó 2005 Elsevier Ltd. All rights reserved.
Allenes are very useful synthetic intermediates in a vari-
ety of organic synthetic processes including ionic, radi-
cal and concerted reactions because of their unique
structural property and reactivity toward cumulated
carbon–carbon double bond.1,2 In contrast to good
documentation of nonfluorinated allenic compounds in
recent literatures,3–5 there has been limited synthetic
methods for the preparation of fluorinated counterparts.
In particular, synthesis of trifluoromethylated allenic
compounds as trifluoromethylated building blocks relies
on several limited routes. Most of the methods focused
on the synthesis of trifluoromethylated allenic com-
pounds containing proton at a-position. SN20 substitu-
tion of propargylic halides or tosylates with CF3Cu
provided the corresponding CF3-substituted allene com-
pounds.6,7 CF3-substituted propargylic mesylates also
underwent SN20 displacement with organozinc reagents
in the presence of palladium catalyst to give the corre-
sponding CF3-substituted allene compounds.8,9 Direct
conversion of CF3-substituted propargylic alcohol to
CF3-substituted allene compounds containing trifluo-
romethyl or ethoxycarbonylmethyl group was accom-
plished by the treatment with sulfur tetrafluoride10 or
ethyl orthoacetate in acidic condition.11 a-Trifluoro-
methyl allenol ethers were prepared by the Julia-Lythgoe
process involving b-acetoxy sulfone, which undergoes
desulfonylation with SmI2.12 Recently, a-phenyl-a-tri-
fluoromethylated allene compound was first synthesized
by the reaction of four-coordinate rhodium(I) with CO
in benzene at 10 °C.13,14 However, this method exhibited
only one example from a tedious procedure. In this
letter, we wish to describe an efficient and general prepa-
ration of 1-aryl-1-trifluoromethylallenes from 3,3-
bis(phenylthio)-1,1,1,2,2-pentafluorobutane.
It has been reported that perfluoroalkyated dithio-
ketals15 were reacted with a variety of organolithium
reagents to give the corresponding b-fluorovinyl or b-
trifluoromethylvinyl sulfides.16 Therefore, the reactions
of 3,3-bis(phenylthio)-1,1,1,2,2-pentafluorobutane
1
with aryllithium reagents formed from the reaction of
aryl iodides with n-BuLi, such as naphthalenyllithium
and phenyllithium substituted by proton, trifluoro-
methyl, methoxy, methyl, fluoro, chloro, bromo on meta
or para position of the benzene ring, in ether at low to
room temperature for 1–6 h afforded 2-aryl-1,1,1-triflu-
oro-3-phenylthio-2-butene 2a–m in 80–96% yields as
an E and Z isomeric mixture. The reaction temperature
depends on the stability of generated aryllithium in ether
solution. The use of 6 equiv of aryl iodides and 6 equiv
of n-BuLi to form aryllithium reagents provided the best
results for the formation of the corresponding sulfides.
The reaction of 1 with ortho substituted phenyllithium
such as 2-bromo-, 2-fluoro- or 2-methoxyphenyllithium,
heteroaromatic lithium reagents such as thienyllithium
or pyrazinyllithium, and alkynyllithium reagent did
not provide the desired product 2 and the starting mate-
rial was always recovered. When 1 was reacted with
MeLi and n-BuLi as alkyllithium reagents at ꢀ78 °C,
followed by warming to 0 °C, however, the corresponding
Keywords: 2-Aryl-1,1,1-trifluoro-3-phenylthio-2-butene; Bromination;
Oxidation; Trifluoromethylated allenes.
*
Corresponding author. Tel.: +82 33 760 2240; fax: +82 33 763
4323; e-mail: jeongih@dragon.yonsei.ac.kr
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.10.166

210
H. Y. Han et al. / Tetrahedron Letters 47 (2006) 209–212
products 2n and 2o were obtained in 78% and 82% yield
as an E and Z isomeric mixture. The reaction pathway
seems likely that the initial attack of sulfur atom of 1
by aryllithium generates a carbanion bearing penta-
fluoroethyl group, which undergoes b-defluorination to
give b-fluoro-b-trifluoromethylated vinyl sulfides. These
vinyl sulfides quickly undergo addition–elimination
reaction with another equiv of aryllithium to afford 2.
The assignment of stereoisomer of 2 was based on the
H–F homoallylic coupling constant, in which cis H–F
coupling constant is bigger than trans one.17 The results
of these reactions are summarized in Table 1.
Subsequence allylic bromination of 2 with N-bromosuc-
cinimide (1.2 equiv) in the presence of catalytic amount
of AIBN at reflux temperature of acetonitrile for 1–7 h
Table 1. Preparation of 2-aryl-1,1,1-trifluoro-3-phenylthio-2-butene 2
SC6H5
F3C
R
CH3
RLi/ether
T oC, t h
CF3CF2 C CH3
C
C
SC6H5
SC6H5
2
1
Compounds
R
T
t (h)
Yield (%)a
87
E/Zb
2a
0 °C ! rt
3
70/30
2b
2c
rt
1
6
87
96
82/18
76/24
F3C
F3C
0 °C ! rt
ꢀ50 °C ! rt
ꢀ50 °C ! rt
rt
2d
2e
2f
1
5
1
87
90
86
70/30
80/20
70/30
F
H3CO
2g
2h
2i
rt
1
2
1
2
1
1
1
88
88
84
84
80
86
96
70/30
67/33
66/34
74/26
81/19
56/44
70/30
H3CO
H3C
rt
rt
H3C
Br
2j
0 °C ! rt
0 °C ! rt
rt
2k
2l
Br
Cl
2m
0 °C ! rt
H3CS
2n
2o
2p
CH3
n-C4H9
n-C6H13C„CA
ꢀ78 °C ! 0 °C
ꢀ78 °C ! 0 °C
0 °C ! rt
1
1
24
78
82
—
62/38
65/35
c
S
c
2q
0 °C ! rt
24
24
—
N
N
c
2r
0 °C ! rt
—
a Isolated yield.
b E/Z ratio was determined by 1H and 19F NMR spectroscopy.
c Starting material 1 was recovered.

H. Y. Han et al. / Tetrahedron Letters 47 (2006) 209–212
211
resulted in the formation of the corresponding allylic
bromide 3 as an E and Z isomeric mixture in 61–96%
yields. Although 2n and 2o have two allylic positions,
only allylic methyl proton connected to vinyl carbon
having phenylthio group was brominated regioselec-
tively. The use of acetonitrile as a solvent provided
much better result than use of CCl4. E/Z ratio was
assigned in a similar manner as assignment of 2. The
results of these reactions are summarized in Table 2.
to oxidize methylthio group connected to benzene ring
and the reaction was shown to be temperature depen-
dent since the reaction of 3 with MCPBA at room tem-
perature did not provide any desired product 4.
Methylene chloride having low boiling point was
enough solvent system to afford allenes 4. However, 3n
and 3o did not undergo debromosulfinylation with
MCPBA to give the corresponding allenes under several
reaction conditions such as reflux in CH2Cl2 or CCl4 for
the longer reaction time, but the corresponding vinyl
sulfoxides were obtained in 90% and 92% yield, respec-
tively. Although debromosulfinylation of b-sulfinylated
allylic bromide in the presence of excess amount of
AIBN and tris(trimethylsilyl)silane at reflux temperature
of benzene was successfully carried out to give the corre-
Initially, we tried to prepare vinyl sulfones via oxidation
of 3 with MCPBA, but 1-aryl-trifluoromethylallenes
4a–m were obtained in 61–96% yields. The use of
1.5 equiv of MCPBA was enough to yield 4 except for
formation of 4m, in which 2 equiv of MCPBA was used
Table 2. Bromination of 2-aryl-1,1,1-trifluoro-3-phenylthio-2-butene 2
F3C
R
F3C
R
CH3
CH2Br
SC6H5
NBS/AIBN
C
C
C
C
CH3CN, reflux, t h
SC6H5
3
2
Compounds
R
t (h)
Yield (%)a
87
E/Zb
3a
1
58/42
3b
3c
5
3
76
96
56/44
63/37
F3C
3d
3e
3
3
61
74
62/38
57/43
F3C
F
H3CO
3f
3
3
3
79
72
71
56/44
59/41
59/41
3g
3h
H3CO
H3C
3i
3
7
7
7
5
79
76
70
75
96
56/44
56/44
61/39
57/43
73/27
H3C
Br
3j
3k
3l
Br
Cl
3m
H3CS
3n
3o
CH3
n-C4H9
1
1
85
80
65/35
62/38
a Isolated yield.
b E/Z ratio was determined by 1H and 19F NMR spectroscopy.

212
H. Y. Han et al. / Tetrahedron Letters 47 (2006) 209–212
sponding allene derivatives in the nonfluorinated sys-
tem,18 there has been no report on the synthesis of triflu-
oromethylated allenes directly from trifluoromethylated
b-phenylthio substituted allylic bromides. It seems likely
that the reaction mechanism involves the formation of
b-sulfinylated allylic bromides, which quickly provides
the corresponding allylic radical to form 1-aryl-1-tri-
fluoromethylallenes 4 via b-elimination of sulfinyl radi-
cal. The results of these reactions are summarized in
Table 3.
with 4-bromo-1,1,1-trifluoro-2-(40-methoxy)phenyl-3-
phenylthio-2-butene 3g (0.202 g, 0.5 mmol), MCPBA
(0.260 g, 0.75 mmol, 50% technical purity) and methyl-
ene chloride (5 mL) and then heated to reflux for
12 h. After the reaction mixture was quenched with sat-
urated NaHCO3, and 10% NaHSO3, the reaction mix-
ture was extracted with methylene chloride twice. The
methylene chloride solution was dried over anhydrous
K2CO3 and chromatographed on SiO2 column. Elution
with a mixture of hexane and ethyl acetate (4:1) pro-
vided 0.190 g of 4g in 87% yield. 4g:oil:1H NMR
(CDCl3) d 7.90–6.67 (m, 4H), 4.77 (s, 2H), 3.85 (s,
3H); 19F NMR (CDCl3, internal standard CFCl3) d
ꢀ59.98 (s, 3F); MS, m/z (relative intensity) 214 (M+,
100), 199 (7), 171 (13), 151 (28), 145 (71), 130 (10), 102
(18); IR (neat) 3079, 2927, 2871, 1959, 1596, 1579,
A typical reaction procedure for the preparation of 4g is
as follows. A 25 mL two-neck round bottomed flask
equipped with a magnetic stirrer bar, a septum and
nitrogen tee connected to an argon source was charged
1497, 1384, 1261, 1156, 834 cmꢀ1
. Anal. Calcd
for C11H9F3O: C, 61.66; H, 4.24. Found: C, 61.58; H,
4.21.
Table 3. Preparation of 1-aryl-1-trifluoromethylallenes 4
F3C
R
CH2Br
SC6H5
F3C
R
MCPBA (1.5 equiv)
CH2Cl2, reflux, t h
C
C
CH2
C
C
Acknowledgements
3
4
This work was supported by Korea Research Founda-
tion Grant (KRF-2003-041-C00199).
Compounds
R
t (h)
Yield (%)a
4a
2
5
96
References and notes
4b
4c
78
74
1. The Chemistry of Allenes; Landor, S. R., Ed.; Academic
Press: New York, 1982; Vols. 1–3.
2. Schuster, H. F.; Coppola, G. M. Allenes in Organic
Synthesis; Wiley: New York, 1984.
3. Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A.
Chem. Rev. 2000, 100, 3067–3126.
4. Hashmi, A. S. K. Angew. Chem., Int. Ed. 2000, 39, 3590–
3593.
F3C
F3C
6
4d
4e
6
1
88
79
F
5. Lu, X.; Zhang, C.; Xu, Z. Acc. Chem. Res. 2001, 34, 535–
544.
6. Burton, D. J.; Hartgraves, G. A.; Hsu, J. Tetrahedron Lett.
1990, 31, 3699–3702.
7. Bouillon, J. P.; Maliverney, C.; Merenyl, R.; Viehe, H. G.
J. Chem. Soc., Perkin Trans. 1 1991, 2147–2149.
8. Konno, T.; Tanikawa, M.; Ishihara, T.; Yamanaka, H.
Chem. Lett. 2000, 1360–1361.
9. Hoffmann-Roder, A.; Krause, N. Angew. Chem., Int. Ed.
2002, 41, 2933–2935.
10. Dear, R. E. A.; Gilbert, E. E. J. Org. Chem. 1968, 33, 819–
823.
11. Hanzawa, Y.; Kawagoe, K.; Yamada, A.; Kobayashi, Y.
Tetrahedron Lett. 1985, 26, 219–222.
12. Yoshimatsu, M.; Hibino, M. Chem. Pharm. Bull. 2000, 48,
1395–1398.
13. Werner, H.; Laubender, M.; Wiedemann, R.; Windmuller,
B. Angew. Chem., Int. Ed. 1996, 35, 1237–1239.
14. Werner, H.; Wiedemann, R.; Laubender, M.; Windmuller,
B.; Steinet, P.; Gevert, O.; Wolf, J. J. Am. Chem. Soc.
2002, 124, 6966–6980.
15. Jeong, I. H.; Min, Y. K.; Kim, Y. S.; Cho, K. Y.; Kim, K.
J. Bull. Korean Chem. Soc. 1991, 12, 355–356.
16. Jeong, I. H.; Min, Y. K.; Kim, Y. S.; Cho, K. Y.; Kim, K.
J. Bull. Korean Chem. Soc. 1993, 14, 309–311.
17. Jeong, I. H.; Park, Y. S.; Kim, M. S.; Song, Y. S. J.
Fluorine Chem. 2003, 120, 195–209.
H3CO
4f
12
12
6
81
87
87
87
83
86
81
84
4g
4h
4i
H3CO
H3C
6
H3C
Br
4j
6
4k
4l
Br
6
6
Cl
4mb
3
H3CS
c
4n
4o
CH3
n-C4H9
18
18
—
c
—
a Isolated yield.
b 3.5 equiv of MCPBA was used.
c Allene was not obtained, but vinyl sulfoxide was formed in high yield.
18. Delouvrie, B.; Lacote, E.; Fensterbank, L.; Malacria, M.
Tetrahedron Lett. 1999, 40, 3565–3568.