From ketones, aldehydes or alkyl halides to terminal 1,1-difluoroolefins using BrF3

Article abstract of DOI:10.1016/j.jfluchem.2005.06.003

Terminal difluoromethylenes were prepared by two different routes: (a) by treating ketones and aldehydes with bis(methylthio)methane, producing 2-alkyl-1,1-bis(methylthio)alkene (2) (b) reacting alkyl halides with tris(methylthio)methane forming 1-alkyl-1

Full text of DOI:10.1016/j.jfluchem.2005.06.003

Journal of Fluorine Chemistry 126 (2005) 1239–1245
www.elsevier.com/locate/fluor
From ketones, aldehydes or alkyl halides to terminal
1,1-difluoroolefins using BrF3
*
Aviv Hagooly, Shlomo Rozen
School of Chemistry, Raymond and Beverly Sackler Faculty of Exact Sciences, Tel-Aviv University, Tel-Aviv 69978, Israel
Received 22 April 2005; received in revised form 28 May 2005; accepted 4 June 2005
Available online 5 July 2005
Abstract
Terminal difluoromethylenes were prepared by two different routes: (a) by treating ketones and aldehydes with bis(methylthio)methane,
producing 2-alkyl-1,1-bis(methylthio)alkene (2) (b) reacting alkyl halides with tris(methylthio)methane forming 1-alkyl-1,1,1-tris(-
methylthio)alkane derivatives (7). The reaction of either 2 or 7 with BrF3, followed by oxidation with HOFÁCH3CN gave the difluorosulfonyl
derivatives 4. Consecutive treatment with Zn led to the target difluoroolefins (5) in overall yields of 60–75%.
# 2005 Elsevier B.V. All rights reserved.
Keywords: Bromine trifluoride; Difluoroolefin; Hypofluorous acid
1. Introduction
The naked fluoride, thus brought next to the reaction center,
can react selectively with the activated site forming the
desired product and minimizing unwanted radical destruc-
tive reactions (Scheme 1).
Terminal difluoroalkenes command high interest in
organic chemistry. They are used as starting materials for
different fluorine containing products or polymers [1].
Beside their synthetic applications, the gem-difluorovinyl
group can contribute to the biological activity of molecules
that act as enzyme inhibitors or as pesticides [2].
Consequently, new methods for the synthesis of 1,1-
difluoroalkenes have become a highly desirable goal.
Several different approaches are known in the literatures
for the preparation of this family of compounds. They utilize
reagents based on boron [3] or metals [4], Wittig type
reactions using the difluoromethylene ylides [5], alkyl or
aryl iodides [6] and more [7].
2. Results and discussion
Recently, we have shown that b,b-difluoroacrylates can
be synthesized using bromine trifluoride [12]. We are
describing here yet another method, using similar starting
materials leading to an efficient synthesis of various
difluorovinyl compounds.
Following a known procedure [13], we reacted the
lithium salt of the commercial bis(methylthio)methane with
5-nonanone (1a) to produce 2-butyl-1,1-bis(methylthio)-
hexene (2a). Reacting this derivative with two mol-
equivalent of BrF3 gave an oily mixture that contained 2-
bromo-2-butyl-1,1-difluoro-1-methylthiohexane (3a, x = 0)
as the main product together with about 10% of the
corresponding sulfoxide and sulfone derivatives combined
(3a, x = 1 and 2 correspondingly) (Scheme 2). We believe
that the S–O bond (3, x = 1, 2) is formed during the work-up
through the hydrolysis of some S–Br and S–F derivatives
initially formed. In any event, the next obvious task was to
remove the sulfur containing moiety together with the
During the last decade we have started to reveal the power
of bromine trifluoride as a fluorinating agent, especially in
constructing and placing the CF2 [8], CHF2 [9], OCF3 [10]
and the CF3 [11] moieties at different sites of various
molecules. The main feature of the mechanism, which
governs most reactions with bromine trifluoride calls for the
soft acidic bromine in BrF3 to complex itself with soft bases,
mainly of sulfur or nitrogen atoms in the target molecule.
* Corresponding author. Tel.: +972 3 6408378; Fax: +972 3 6409293.
E-mail address: rozens@post.tau.ac.il (S. Rozen).
0022-1139/$ – see front matter # 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2005.06.003

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A. Hagooly, S. Rozen / Journal of Fluorine Chemistry 126 (2005) 1239–1245
gave 2b, which when reacted with bromine trifluoride
followed by oxidation with HOFÁCH3CN gave 4b in good
yields. It should be noted that the SoxMe group in 3b and 4b
was also fluorinated forming the SoxCH2F one. This bromo
sulfone was again treated with Zn producing 1-[difluor-
omethylene]-3,3,5,5-tetramethylcyclohexane (5b) [15] in
60% overall yield. Even the more complexed steroidal
skeleton of cholestanone (1c) was not harmed in the reaction
process, and the desired difluoroolefin 5c was eventually
formed in 70% overall yield. Despite their greater sensitivity
toward oxidation, aldehydes can serve also as substrates and
in the case of octanal (1d) the unknown 1,1-difluorononene
(5d) was obtained in 70% overall yield (Scheme 2).
Scheme 1. The reaction of BrF3 with soft bases.
bromine atom a to it. Since sulfone is a better leaving group
than sulfide or sulfoxide we treated the crude mixture 3a
(x = 0, 1, 2) with the HOFÁCH3CN complex, which is known
to be able to oxidize readily even electron depleted sulfides in
excellentyields [14]. In a few minutes all thesulfur containing
compounds were converted to the desired single sulfone
derivative 1-bromo-1-butyl-1-[difluoro-1-(methylsulfonyl)-
methyl]pentane (4a). After a few trials we found that treating
4a with activated Zn led to elimination of both the sulfone
group and the bromine atom and 1,1-difluoro-2-butylhex-1-
ene (5a) was produced in 65% yield (from 2a, Scheme 2).
Cyclic ketones can also serve as good substrates for the
reaction above. The reaction of 3,3,5,5-tetramethylcyclohex-
anone (1b) with the lithium salt of bis(methylthio)methane
Apart from carbonyls, alkyl bromides proved also to be
suitable substrates for the preparation of 1,1-difluoroolefins.
We have already shown that alkyl halides when reacted with
the commercial tris(methylthio)methane produced 1-alkyl-
1,1,1-tris(methylthio)alkane derivatives (7) (Scheme 3) [16].
When such compounds were reacted with two mol-
equivalent of bromine trifluoride, materials of type 3 were
obtained. Reacting 1,1,1-tris(methylthio)undecane (7e) with
BrF3 formed 3e, which after oxidation with HOFÁCH3CN
gave 4e in a very good yield. Elimination of both the sulfone
group and the bromine atom with Zn, produced the desired
1,1-difluoroundecene (5e) in 75% overall yield (Scheme 3).
Different branched alkyl halides such as 3,7-dimethyloctyl
bromide (6f), 3-cyclohexylpropyl bromide (6g) and exo-2-
(norbornyl)ethyl bromide (6h) also reacted well. The 1,1,1-
tris(methylthio) intermediates 7f, 7g and 7h were obtained in
good yields and then reacted with BrF3 forming the desired
new products 5f, 5g and 5h in about 70% overall yield each.
Although bromine trifluoride in certain conditions is known
Scheme 2. The preparation of difluoroolefins form carbonyls.
Scheme 3. The preparation of difluoroolefins form alkyl halides.

A. Hagooly, S. Rozen / Journal of Fluorine Chemistry 126 (2005) 1239–1245
1241
to act as an electrophile and substitute tertiary hydrogens
with fluorine [17], no such exchange took place in any of the
examples above, including cholestanone 1c, where electro-
philic fluorination proceeds quite smoothly [18]. This
stability of the tertiary hydrogens points to the high affinity
of bromine trifluoride to the sulfur atoms.
(ca. 95%) through 0.2 mol of bromine placed in a copper
reactor and held at temperatures between 0 and +10 8C.
Under these conditions the higher oxidation state of
bromine, BrF5, will not be formed in any appreciable
amount [22]. The reagent can be stored in Teflon1
containers indefinitely. BrF3 is a strong oxidizer and tends
to react very exothermically with water and oxygenated
organic solvents such as acetone or THF. Alkanes, like petrol
ether, cannot serve as solvents either since they also react
quickly with BrF3. Solvents such as CHCl3, CH2Cl2, CFCl3
or, if solubility is not a issue, any perfluoroalkane or
perfluoroether can be used. Any work using BrF3 should be
conducted in a well-ventilated area, and caution and
common sense should be exercised. It is recommended
that face shield and comfortable, yet heavy-duty gloves,
should be wear when working with this reagent.
Since bromine trifluoride will brominate even deactivated
aromatic rings [19], this method is not well suited for
compounds possessing such a moiety. However, halides,
which can react with bromine trifluoride as demonstrated in
the synthesis of various anesthetics [20], were not affected
since BrF3 reacts much faster with the soft basic sulfur atoms.
Thus, 7-chloro-1,1,1-tris(methylthio)heptane 7i was reacted
with bromine trifluoride, oxidized with HOFÁCH3CN and
then treated with Zn forming 7-chloro-1,1-difluoroheptene
(5i) in 72% overall yield (Scheme 3).
In conclusion, for decades most organic chemists have
shied away from BrF3 because of mythical fears and
prejudice. Under proper conditions, however, it can react
selectively with organic compounds without destroying
them. This work shows that bromine trifluoride can be an
effective reagent in the synthesis of the important family of
the 1,1-difluoroolefins, starting either from carbonyl
derivatives, or from appropriate alkyl halides.
3.1.2. General procedure for the preparation of 2-alkyl-
1,1-bis(methylthio)alk-1-ene derivatives (2) [13]
Bis(methylthio)methane (8 g, 74 mmol) in 100 mL of dry
THF was cooled to À78 8C under inert atmosphere. Fifty-
three mL of BuLi (1.6 M in hexane) were added and the
mixture allowed to warm slowly (4 h) to 0 8C. The reaction
mixture was cooled again to À78 8C and trimethylsi-
lylchloride (17 g, 160 mmol) was added. The reaction was
allowed to warm to room temperature and stirred for another
15 h at that temperature. Water was added, the organic layer
separated and the aqueous layer extracted with pentane. The
combined organic layers were washed with water, dried over
K2CO3, filtered and evaporated. The product bis(-
methylthio)trimethylsilylmethane can be isolated by dis-
tillation (75 8C/10 mbar) in 90% yield. This product (4 g,
27 mmol) was dissolved in 100 mL dry THF, cooled to
À78 8C under inert atmosphere and BuLi (16.9 mL, 1.6 M in
hexane) was added and the mixture allowed to reach 0 8C in
4 h. The reaction was cooled again to À78 8C and the
corresponding ketone or aldehyde (1) (27 mmol) was added.
The reaction was allowed to reach room temperature and
then stirred for another 12 h. Water was added, the organic
layer separated and the aqueous one extracted with pentane.
The combined organic layers were washed with water, dried
over K2CO3, filtered and evaporated. The 2-alkyl-1,1-
bis(methylthio)alk-1-ene derivatives (2) were isolated by
flash chromatography in about 90% yield.
3. Experimental
3.1. General
1H NMR spectra were recorded using a 200 MHz
spectrometer with CDCl3 as a solvent and Me4Si as an
internal standard. Only relevant and characteristic signals
are reported. The 19F NMR spectra were measured at
188.1 MHz and are reported lower applied frequency from
CFCl3, serving as an internal standard. The proton broad-
band decoupled 13C NMR spectra were recorded at
100.5 MHz. Here too, CDCl3 served as a solvent and Me4Si
as an internal standard. MS spectra were measured under CI
condition. For compounds of type 5, save 5c, the molecular
ion could not be detected by standard CI MS. In these cases
we have used Amirav’s supersonic GC–MS, which revealed
the molecular ion without any difficulties [21]. Due to the
high volatility of compounds 5 (with the exception of 5c) we
were unable to meet acceptable (C, H, 0.4%) microanalysis.
All other criteria, including GC, pointed toward proper
analytic purity of these compounds and were in excellent
agreement with the proposed structures. Silica gel 60H
(Merck) and petrol ether/ethyl acetate were used for flash
chromatography. All starting carbonyl and alkyl halide
derivatives were commercial and used without further
purification.
3.1.3. General procedure for the preparation of 1-alkyl-
1,1,1-tris(methylthio)alkane derivatives (7) [16]
To a cold (À78 8C) solution of tris(methylthio)methane
(4 mL, 30.2 mmol) in dry THF, BuLi (20 mL, 1.6 M in
hexane) was added. The reaction mixture was kept at that
temperature for 2 h under inert atmosphere. The relevant
alkyl halide (6) (30.2 mmol) was added and left at À78 8C
for 3 h and then stirred at room temperature for additional
12 h. Water was added, the organic layer was separated, and
the aqueous one extracted with ether. After drying over
MgSO4, the solvent was evaporated and the crude products 7
3.1.1. Preparing and handling of BrF3
Although commercially available, we usually prepare our
own BrF3 simply by passing 0.6 mol commercial fluorine

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A. Hagooly, S. Rozen / Journal of Fluorine Chemistry 126 (2005) 1239–1245
obtained in about 90% yield were isolated by flash
chromatography.
2.21 (3H, s), 0.90 ppm (3H, t, J = 7 Hz); 13C NMR (only the
relevant signals) 135.5, 131.9, 16.6, 13.9 ppm.
3.1.4. General procedure for the preparation of 1,1-
difluoroalkenes (5)
3.1.9. 1,1,1-Tris(methylthio)undecane (7e) [16]
This product was prepared from 6e as described above in
1
90% yield: oil; H NMR 2.10 (9H, s), 1.91–1.83 (2H, m),
The 1-alkyl-1,1,1-tris(methylthio)methane derivative (7)
or the 2-alkyl-1,1-bis(methylthio)alk-1-ene derivative (2)
(each usually 4 mmol) was dissolved in 15 mL dry CFCl3
and cooled to 0 8C. About 10 mmol of BrF3 was dissolved in
15 mL of the same solvent, cooled to 0 8C, and added
dropwise, during 1–2 min. The reaction was quenched with
saturated aqueous Na2SO3 and washed until colorless. The
aqueous layer was extracted with CH2Cl2 and the organic
layer dried over MgSO4. Evaporation of the solvent left
crude 2-bromo-1,1-difluoro-1-methylthioalkane derivative
3. The oily crude 3 was dissolved in 40 mL of CH2Cl2,
oxidized with three-fold excess of HOFÁCH3CN at 0 8C for
10 min [12], and quenched with NaHCO3. Extraction with
CH2Cl2, drying over MgSO4 and evaporation of the solvent
gave an oily crude containing the 2-bromo-1-[difluoro-1-
(methylsulfonyl)methyl]alkane derivative (4) which could
be isolated if needed by flash chromatography. This crude 4
(1 g) was dissolved in 8 mL of ethanol and activated zinc
powder (1.2 g) was added. The mixture was refluxed for 15–
30 min and because most of products 5 are too volatile, we
used internal standard GC, which showed 85–90% yield for
this step. After filtration of the zinc, the solvent was
evaporated and the desired 1,1-difluoroalkene derivative (5)
were isolated by flash chromatography in 60–75% overall
yield. A comment on microanalysis of compounds 5 appears
at the beginning of the Section 3. The final purity, however,
achieved for all these compounds was greater than 97%
according to GC and all other spectral data.
0.90 ppm (3H, t, J = 7 Hz); 13C NMR 70.8, 37.9, 29.4, 29.2,
24.6, 22.5, 13.9, 12.9 ppm.
3.1.10. 4,8-Dimethyl-1,1,1-tris(methylthio)nonane (7f)
[16]
This product was prepared from 6f as described above in
90% yield: oil; 1H NMR 2.09 ppm (9H, s); 13C NMR 70.8,
38.9, 36.8, 35.1, 32.4, 31.4, 27.6, 24.5, 22.4, 22.3, 19.5,
12.7 ppm.
3.1.11. 4-Cyclohexyl-1,1,1-tris(methylthio)butane (7g)
This product was prepared from 6g as described above in
90% yield: oil; 1H NMR 2.10 ppm (9H, s); 13C NMR 70.8,
38.3, 37.4, 37.1, 33.3, 26.6, 26.3, 22.0, 12.9 ppm.
3.1.12. exo-3-Norbornyl-1,1,1-tris(methylthio)propane
(7h) [16]
This product was prepared from 6h as described above in
80% yield: oil; 1H NMR 2.11 ppm (9H, s); 13C NMR (only
the relevant signals) 70.8, 12.9 ppm.
3.1.13. 7-Chloro-1,1,1-tris(methylthio)heptane (7i)
This product was prepared from 6i as described above in
1
90% yield: oil; H NMR 3.52 (2H, t, J = 7 Hz), 2.10 ppm
(9H, s); 13C NMR 70.8, 44.9, 37.9, 32.4, 28.6, 26.7, 24.6,
13.0 ppm.
3.1.14. 2-Bromo-2-butyl-1,1-difluoro-1-
methylthiohexane (3a x = 0)
3.1.5. 2-Butyl-1,1-bis(methylthio)hex-1-ene (2a)
This product was prepared from 1a as described above in
85% yield: oil; 1H NMR 2.45 (4H, t, J = 7 Hz), 2.23 (6H, s),
1.38–1.30 (8H, m), 0.91 ppm (6H, t, J = 7 Hz); 13C NMR
152.4, 126.6, 35.0, 31.1, 22.7, 17.1, 14.0 ppm.
This product was prepared from 2a as described above:
oil; 1H NMR 2.35 (3H, s), 2.05 (4H, t, J = 7 Hz), 0.95 ppm
(6H, t, J = 7 Hz); 19F NMR À77.0 ppm (s); 13C NMR 131.9
(t, J = 285 Hz), 74.0 (t, J = 21 Hz), 38.2, 27.5, 22.9,
13.8 ppm.
3.1.6. 1-[Bis(methylthio)methylene]-3,3,5,5-
tetramethylcyclohexane (2b)
This product was prepared from 1b as described above in
85% yield: oil; 1H NMR 2.41 (4H, s), 2.24 (6H, s), 1.02 (2H,
s), 0.93 ppm (12H, s); 13C NMR (only the relevant signals)
148.5, 126.1, 16.8 ppm.
3.1.15. 1-[Difluoro-1-(fluoromethylsulfide)methyl]-
3,3,5,5-tetramethylcyclohexane (3b x = 0)
This product was prepared from 2b as described above:
oil; 1H NMR 5.75 (2H, d, J = 48 Hz), 0.95 ppm (12H, s); 19
F
NMR-82.4 (2F, dm, J = 8 Hz), À185.7 ppm (1F, tt,
J1 = 48 Hz, J2 = 8 Hz); 13C NMR (only the relevant signals)
130.9 (t, J = 290 Hz), 81.6 (dt, J1 = 220 Hz, J2 = 7 Hz),
67.5 ppm (t, J = 21 Hz).
3.1.7. 3-[Bis(methylthio)methylene]cholestane (2c)
This product was prepared from 1c as described above in
85% yield: white solid; 1H NMR 2.65 (1H, dm, J = 13 Hz),
2.52 (1H, dm, J = 13 Hz), 2.23 ppm (6H, s); 13C NMR (only
the relevant signals) 151.5, 122.7, 17.3, 17.2 ppm.
3.1.16. 3-[Bromo-1-(fluoromethylsulfide)methyl]-
cholestane (3c x = 0)
This product was prepared from 1c as described above:
1
3.1.8. 1,1-Bis(methylthio)non-1-ene (2d)
This product was prepared from 1d as described above in
85% yield: oil; 1H NMR 5.89 (1H, t, J = 7 Hz), 2.23 (3H, s),
white solid; H NMR 2.36 (3H, s); 19F NMR-84.2 (s); 13C
NMR (only the relevant signals) 131.1 (t, J = 282 Hz), 72.0
(t, J = 23 Hz), 10.5 ppm.

A. Hagooly, S. Rozen / Journal of Fluorine Chemistry 126 (2005) 1239–1245
1243
3.1.17. 2-Bromo-1,1-difluoro-1-methylthiononane
(3d x = 0)
This product was prepared from 2d as described above:
3.1.23. 2-Bromo-7-chloro-1,1-difluoro-1-
methylthioheptane (3i x = 0)
This product was prepared from 7i as described above:
oil; 1H NMR 4.20–4.05 (1H, m), 2.34 (3H, s), 0.90 ppm (3H,
t, J = 7 Hz); 19F NMR À80.4 (1F, dd, J1 = 204 Hz,
J2 = 9 Hz), À83.3 ppm (1F, dd, J1 = 204 Hz, J2 = 11 Hz);
13C NMR (only the relevant signals) 128.5 (t, J = 280 Hz),
54.0 (t, J = 25 Hz), 14.0, 10.1 ppm.
oil; H NMR 4.20–4.00 (1H, m), 3.54 (2H, t, J = 7 Hz),
1
2.34 ppm (3H, s); 19F NMR À78.3 (1F, dd, J1 = 204 Hz,
J2 = 8 Hz), À80.7 ppm (1F, dd, J1 = 204 Hz, J2 = 11 Hz);
13C NMR 128.8 (t, J = 280 Hz), 54.2 (t, J = 26 Hz), 44.7,
32.6, 32.1, 26.5, 25.8, 10.1 ppm.
3.1.18. 2-Bromo-1,1-difluoro-1-methylthioundecane
(3e x = 0) [16]
3.1.24. 2-Bromo-2-butyl-1-[difluoro-1-
(methylsulfonyl)methyl]pentane (4a)
This product was prepared from 7e as described above:
oil; 1H NMR 4.20–4.05 (1H, m), 2.34 (3H, s), 0.90 ppm (3H,
t, J = 7 Hz); 19F NMR À83.4 (1F, dd, J1 = 204 Hz,
J2 = 9 Hz), À85.6 ppm (1F, dd, J1 = 204 Hz, J2 = 11 Hz);
13C NMR 129.3 (t, J = 278 Hz), 54.3 (t, J = 26 Hz), 31.9,
31.6, 29.4, 29.2, 28.5, 22.5, 14.0, 10.1 ppm; MS (CI) m/z 316
and 318, both (MH)+.
This product was prepared from 3a as described above:
1
oil; H NMR 3.08 (3H, m) ppm; 19F NMR À93.3 ppm (s);
13C NMR 121.6 (t, J = 295 Hz), 71.2 (t, J = 18 Hz), 38.0,
37.7, 27.7, 22.7, 13.7 ppm.
3.1.25. 1-[Difluoro-1-(fluoromethylsulfonyl)methyl]-
3,3,5,5-tetramethylcyclohexane (4b)
This product was prepared from 3b as described above:
3.1.19. 2-Bromo-1,1-difluoro-1-methylthioundecane
(3e x = 0) [16]
oil; 1H NMR 5.45 (2 H, d, J = 48 Hz), 0.99 ppm (12H, s); 19
F
NMR À99.6 (2F, dm, J = 8 Hz), À208.4 ppm (1F, tt,
J1 = 48 Hz, J2 = 8 Hz); 13C NMR (only the relevant signals)
120.5 (t, J = 297 Hz), 89.5 (d, J1 = 230 Hz), 64.7 ppm
(t, J = 18 Hz).
This product was prepared from 7e as described above:
oil; 1H NMR 4.20–4.05 (1H, m), 2.34 (3H, s), 0.90 ppm (3H,
t, J = 7 Hz); 19F NMR À83.4 (1F, dd, J1 = 204 Hz,
J2 = 9 Hz), À85.6 ppm (1F, dd, J1 = 204 Hz, J2 = 11 Hz);
13C NMR 129.3 (t, J = 278 Hz), 54.3 (t, J = 26 Hz), 31.9,
31.6, 29.4, 29.2, 28.5, 22.5, 14.0, 10.1 ppm; MS (CI) m/z 316
and 318, both (MH)+.
3.1.26. 3-Bromo-3-[difluoro -1-
(methylsulfonyl)methyl]cholestane (4c)
This product was prepared from 1c as described above:
white solid; 1H NMR 3.12 (3H, s); 19F NMR À99.8 (s); 13
C
3.1.20. 2-Bromo-1,1-difluoro-4,8-dimethyl-1-
methylthiononane (3f x = 0) [16]
NMR (only the relevant signals) 120.7 (t, J = 295 Hz),
70.5 ppm (t, J = 18 Hz); MS (CI) m/z 349 and 351, both
(MH)+.
This product was prepared from 7f as described above, as
a mixture of two diastereoisomers: oil; 1H NMR 4.31–4.11
(1H, m), 2.33 ppm (3H, s); 19F NMR À78.3 (1F, dm,
J = 214 Hz), À80.9 and À81.09 ppm (1F, dd, J1 = 214 Hz,
J2 = 12 Hz); 13C NMR (only the relevant signals) 128.8
(t, J = 279 Hz), 52.5 ppm (m, J = about 26 Hz).
3.1.27. 1-Bromo-1-
[difluoro(methylsulfonyl)methyl]octane (4d)
This product was prepared from 3d as described above:
1
oil; H NMR 4.70–4.35 (1H, m), 3.10 (3H, m), 0.90 ppm
(3H, t, J = 7 Hz); 19F NMR À95.0 (1F, dm, J = 230 Hz),
À109.8 ppm (1F, dd, J1 = 230 Hz, J2 = 20 Hz); 13C NMR
120.2 (t, J = 288 Hz), 47.3 (t, J = 21 Hz), 36.8, 31.5, 31.2,
28.7, 28.2, 26.8, 22.5, 13.9 ppm.
3.1.21. 2-Bromo-4-cyclohexyl-1,1-difluoro-1-
methylthiobutane (3g x = 0)
This product was prepared from 7g as described above:
1
oil; H NMR 4.22–3.98 (1H, m), 2.34 ppm (3H, s); 19F
˙
NMR À78 5 (1F, dd, J1 = 204 Hz, J2 = 8 Hz), À80.5 ppm
3.1.28. 1-Bromo-1-
[difluoro(methylsulfonyl)methyl]decane (4e)
This product was prepared from 3e as described above:
(1F, dd, J1 = 204 Hz, J2 = 11 Hz); 13C NMR (only the
relevant signals) 129.0 (t, J = 280 Hz), 55.0 (t, J = 26 Hz),
10.5 ppm.
1
oil; H NMR 4.70–4.35 (1H, m), 3.12 (3H, m), 0.90 ppm
(3H, t, J = 7 Hz); 19F NMR À94.8 (1F, dm, J = 230 Hz),
À109.8 ppm (1F, dd, J1 = 230 Hz, J2 = 20 Hz); 13C NMR
120.3 (t, J = 285 Hz), 47.3 (t, J = 22 Hz), 36.9, 31.7, 31.2,
29.3, 29.2, 28.3, 26.9, 22.5, 14.0 ppm; MS (CI) m/z 579 and
361, both (MH)+.
3.1.22. 2-Bromo-1,1-difluoro-1-methylthio-3-exo-
norbornylpropane (3h x = 0) [16]
This product was prepared from 7h as described above, as
a mixture of two diastereoisomers: oil; 1H NMR 4.27–4.07
(1H, m), 2.34 ppm (3H, s); 19F NMR À78.4 and À78.5 (1F,
dd, J1 = 204 Hz, J2 = 8 Hz), À80.7 ppm (1F, dd, J1 =
204 Hz, J2 = 11 Hz); 13C NMR (only the relevant signals)
128.9 and 128.8 (t, J = 280 Hz), 53.3 and 52.5 ppm
(t, J = 26 Hz).
3.1.29. 1-Bromo-1-[difluoro(methylsulfonyl)methyl]-
3,7dimethyloctane (4f)
This product was prepared from 3f as described above, as
a mixture of two diastereoisomers: oil; 1H NMR 4.70–4.45

1244
A. Hagooly, S. Rozen / Journal of Fluorine Chemistry 126 (2005) 1239–1245
19
˙
(1H, m), 3.11 ppm (3H, m); F NMR À94 8 (1F, dm,
J = 228 Hz), À109.8 and À110.1 ppm (1F, dd, J1 = 228 Hz,
J2 = 20 Hz); 13C NMR (only the relevant signals) 120.5
(t, J = 290 Hz), 46.0 and 45.7 ppm (t, J = 20 Hz); MS (CI)
m/z 349 and 351, both (MH)+.
C, 79.95; H, 11.02; F, 9.03. Found: C, 79.74; H, 10.92;
F, 8.88.
3.1.36. 1,1-Difluorononene (5d) [23]
This product was prepared from 2d as described above in
1
70% overall yield: oil; H NMR 4.12 (1H, dtd, J1 = 25 Hz,
3.1.30. 1-Bromo-1-cyclohexyl-1-
[difluoro(methylsulfonyl)methyl]propane (4g)
J2 = 8 Hz, J3 = 3 Hz), 2.34–1.90 ppm (4H, m); 19F NMR
À90.5 (1F, dm, J = 50 Hz), À92.9 ppm (1F, dd, J1 = 50 Hz,
J2 = 25 Hz); 13C NMR 156.2 (t, J = 285 Hz), 78.0 (t, J =
21 Hz), 31.8, 29.4, 29.0, 28.9, 22.6, 22.1, 14.0 ppm; MS
(supersonic GC–MS) m/z 162 (M)+.
This product was prepared from 3g as described above:
oil; 1H NMR 4.61–4.30 (1H, m), 3.11 ppm; 19F NMR À94.7
(1F, dm, J = 230 Hz), À109.6 ppm (1F, dd, J1 = 230 Hz,
J2 = 20 Hz); 13C NMR 120.4 (t, J = 290 Hz), 47.7 (t, J =
21 Hz), 36.9, 36.7, 34.6, 33.5, 32.6, 28.9, 26.5, 26.2,
26.1 ppm; MS (CI) m/z 333 and 335, both (MH)+.
3.1.37. 1,1-Difluoroundec-1-ene (5e) [16]
This product was prepared from 7e as described above in
1
75% overall yield: oil; H NMR 4.13 (1H, dtd, J1 = 25 Hz,
3.1.31. 1-Bromo-1-[difluoro(methylsulfonyl)methyl]-2-
norbornylethane (4h)
J2 = 8 Hz, J3 = 3 Hz), 2.34–1.90 ppm (4H, m); 19F NMR
À90.2 (1F, dm, J = 49 Hz), À92.5 ppm (1F, dd, J1 = 49 Hz,
J2 = 25 Hz); 13C NMR 156.1 (t, J = 285 Hz), 78.0 (t, J =
21 Hz), 31.8, 29.6, 29.5, 29.3, 29.2, 28.8, 22.6, 22.1,
14.0 ppm; MS (supersonic GC–MS) m/z 190 (M)+.
This product was prepared from 3h as described above, as
a mixture of two diastereoisomers: oil; 1H NMR 4.70–4.30
(1H, m), 3.10 ppm (3H, m); 19F NMR À94.6 and À95.1 (1F,
dm, J = 229 Hz), À110.1 ppm (1F, dd, J1 = 229 Hz,
J2 = 20 Hz); 13C NMR (only the relevant signals) 120.4
(t, J = 290 Hz), 46.4 and 45.6 ppm (t, J = 19 Hz); MS (CI)
m/z 331 and 333, both (MH)+.
3.1.38. 1,1-Difluoro-4,8-dimethylnon-1-ene (5f)
This product was prepared from 7f as described above in
1
70% overall yield: oil; H NMR 4.16 (1H, dtd, J1 = 25 Hz,
J2 = 8 Hz, J3 = 3 Hz), 2.07–1.70 ppm (3H, m); 19F NMR
À89.6 (1F, dm, J = 50 Hz), À92.5 ppm (1F, dd, J1 = 50 Hz,
J2 = 25 Hz); 13C NMR 156.5 (t, J = 285 Hz), 76.4 (t, J =
21 Hz), 36.4, 33.0, 29.3, 27.9, 24.7, 22.5, 19.1 ppm; MS
(supersonic GC–MS) m/z 190 (M)+.
3.1.32. 1-Bromo-6-chloro-1-
[difluoro(methylsulfonyl)methyl]hexane (4i)
This product was prepared from 3i as described above:
1
oil; H NMR 4.65–4.39 (1H, m), 3.54 (3H, t, J = 7 Hz),
3.09 ppm (3H, m); 19F NMR À94.7 (1F, dm, J = 230 Hz),
À109.7 ppm (1F, dd, J1 = 230 Hz, J2 = 20 Hz); 13C NMR
120.2 (t, J = 290 Hz), 47.0 (t, J = 22 Hz), 44.6, 36.8, 32.0,
26.2, 25.7 ppm; MS (CI) m/z 327 and 329, both (MH)+.
3.1.39. 4-Cyclohexyl-1,1-difluorobut-1-ene (5g)
This product was prepared from 7g as described above in
1
69% overall yield: oil; H NMR 4.09 (1H, dtd, J1 = 25 Hz,
J2 = 8 Hz, J3 = 3 Hz), 2.07–1.92 ppm (3H, m); 19F NMR
À90.6 (1F, dm, J = 50 Hz), À93.0 ppm (1F, dd, J1 = 50 Hz,
J2 = 25 Hz); 13C NMR 156.1 (t, J = 285 Hz), 78.2 (t,
J = 20 Hz), 37.1, 36.9, 33.1, 26.6, 23.3, 19.5 ppm; MS
(supersonic GC–MS) m/z 174 (M)+.
3.1.33. 1,1-Difluoro-2-butylhexene (5a)
This product was prepared from 2a as described above in
65% overall yield: oil; 1H NMR 1.97–1.90 (4H, m),
0.93 ppm (6H, t, J = 7 Hz); 19F NMR À97.2 ppm (s); 13C
NMR 153.2 (t, J = 282 Hz), 88.8 (t, J = 18 Hz), 29.6, 25.5,
22.5, 13.8 ppm; MS (supersonic GC–MS) m/z 176 (M)+.
3.1.40. 1,1-Difluoro-3-norbornylprop-1-ene (5h)
This product was prepared from 7h as described above in
70% overall yield: oil; 1H NMR 4.09 ppm (1H, dtd,
J1 = 25 Hz, J2 = 8 Hz, J3 = 3 Hz); 19F NMR À90.2 (1F, dm,
3.1.34. 1-[Difluoromethylene]-3,3,5,5-
tetramethylcyclohexane (5b) [15]
This product was prepared from 2b as described above in
J = 50 Hz), À92.5 ppm (1F, dd, J1 = 50 Hz, J2 = 25 Hz); 13
C
1
60% overall yield: oil; H NMR 1.83 (4H, s), 1.21 (2H, s),
NMR 156.5 (t, J = 285 Hz), 77.2 (t, J = 21 Hz), 42.2, 40.6,
37.6, 36.6, 35.0, 29.9, 29.0, 28.7 ppm; MS (supersonic GC–
MS) m/z 172 (M)+.
0.97 ppm (12H, s); 19F NMR À98.8 ppm (s); 13C NMR
152.3 (t, J = 281 Hz), 77.0 (t, J = 18 Hz), 52.4, 37.8, 32.5,
30.6 ppm; MS (supersonic GC–MS) m/z 188 (M)+.
3.1.41. 7-Chloro-1,1-difluorohept-1-ene (5i)
This product was prepared from 7i as described above in
72% overall yield: oil; H NMR 4.11 (1H, dtd, J1 = 25 Hz,
J2 = 8 Hz, J3 = 3 Hz), 3.51 ppm (2H, t, J = 7 Hz); 19F NMR
À89.8 (1F, dm, J = 48 Hz), À92.4 ppm (1F, dd, J1 = 48 Hz,
J2 = 25 Hz); 13C NMR 156.3 (t, J = 285 Hz), 77.6 (t, J =
21 Hz), 44.8, 32.5, 28.6, 26.1, 21.9 ppm; MS (supersonic
GC–MS) m/z 170 (M)+.
3.1.35. 3-[Difluoromethylene]cholestane (5c)
1
This product was prepared from 2c as described above in
70% overall yield: white solid; 19F NMR À99.5 (1F, dm,
J = 65 Hz), À100.1 ppm (1F, dm, J = 65 Hz); 13C NMR
(only the relevant peaks) 150.6 (t, J = 280 Hz), 87.7 ppm (t,
J = 18 Hz); HRMS (CI) (m/z) calcd for C28H47F2 421.3645
(MH)+, found: 421.3643; Anal. Calcd. for C28H46F2:

A. Hagooly, S. Rozen / Journal of Fluorine Chemistry 126 (2005) 1239–1245
1245
(b) A. Hagooly, R. Sasson, S. Rozen, J. Org. Chem. 68 (2003) 8287–
8289;
Acknowledgment
(c) S. Rozen, I. Ben-David, J. Org. Chem. 66 (2001) 496–500.
[9] R. Sasson, A. Hagooly, S. Rozen, Org. Lett. 5 (2003) 769–771.
[10] I. Ben-David, D. Rechavi, E. Mishani, S. Rozen, J. Fluorine Chem. 97
(1999) 75–78.
This work was supported by the USA Israel Binational
Science Foundation (BSF), Jerusalem, Israel.
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