Sodium dithionite initiated addition of 1-bromo-1-chloro-2,2,2-trifluoroethane to β-pinene. Synthesis of CF3-substituted terpenoids

Article abstract of DOI:10.1016/j.jfluchem.2004.03.001

Sodium dithionite effectively promotes the addition of 1-bromo-1-chloro -2,2,2-trifluoroethane to the exocyclic double bond of β-pinene. The reaction proceeded in an MeCN/H₂O system to give almost quantitatively a 1:1 mixture of diastereoisomers of 4-(2-bromoisopropyl) -1-(2-chloro-3,3,3-trifluoropropyl)-cyclohexene (1). Dehydrobromination of 1 with pyridine gave a mixture of regioisomeric dienes 2 and 3, while treatment with DBU at elevated temperature resulted in total dehydrohalogenation to give trienes 4 and 5. Reduction of 1 with Bu₃SnH gave 1-(2-chloro-3,3,3-trifluoropropyl)-4-(isopropyl) cyclohexene (6) which on dehydrochlorination with 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU) afforded conjugated diene, 4-isopropyl-1 -(trans-3,3,3-trifluoropropenyl)-cyclohexene (7), with 50% overall yield. All the transformations proceeded with the retention of configuration at the carbon atom C-4 and the final compound 7 exhibited high optical activity.

Full text of DOI:10.1016/j.jfluchem.2004.03.001

Journal of Fluorine Chemistry 125 (2004) 1147–1151
Sodium dithionite initiated addition of
1-bromo-1-chloro-2,2,2-trifluoroethane to b-pinene
Synthesis of CF3-substituted terpenoids
Wojciech Dmowski*, Jolanta Ignatowska, Krystyna Piasecka-Maciejewska
Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warsaw, Poland
Received 6 January 2004; received in revised form 25 February 2004; accepted 1 March 2004
Abstract
Sodium dithionite effectively promotes the addition of 1-bromo-1-chloro-2,2,2-trifluoroethane to the exocyclic double bond of b-pinene.
The reaction proceeded in an MeCN/H2O system to give almost quantitatively a 1:1 mixture of diastereoisomers of 4-(2-bromoisopropyl)-1-
(2-chloro-3,3,3-trifluoropropyl)-cyclohexene (1). Dehydrobromination of 1 with pyridine gave a mixture of regioisomeric dienes 2 and 3,
while treatment with DBU at elevated temperature resulted in total dehydrohalogenation to give trienes 4 and 5. Reduction of 1 with Bu3SnH
gave 1-(2-chloro-3,3,3-trifluoropropyl)-4-(isopropyl)cyclohexene (6) which on dehydrochlorination with 1,8-diazabicyclo[5.4.0]undec-7-
ene (DBU) afforded conjugated diene, 4-isopropyl-1-(trans-3,3,3-trifluoropropenyl)-cyclohexene (7), with 50% overall yield. All the
transformations proceeded with the retention of configuration at the carbon atom C-4 and the final compound 7 exhibited high optical activity.
# 2004 Elsevier B.V. All rights reserved.
Keywords: 1-Bromo-1-chloro-2,2,2-trifluoroethane; Sodium dithionite; Pinene; Trifluoromethyl terpenoids
1. Introduction
able as Halothane1 (inhalation anaesthetic), to generate
CF3CHCl. radicals which readily reacted with vinyl ethers
[6,7] and with pyrroles [8].
The reaction of perfluoroalkyl halides (RFI, RFBr) with
sodium dithionite in aqueous medium, known as ‘‘sulfina-
todehalogenation’’, provides an easy way of generating
perfluoroalkyl radicals [1,2]. These electron-deficient radi-
cals could be effectively trapped by electron-rich substrates
like alkenes, alkynes and arenes to give addition or sub-
stitution products. The addition of perfluoroalkyl iodides
to a-pinene was reported to proceed with ring opening to
give unstable (not isolated) adducts, 4-(2-iodoisopropyl)-1-
methyl-6-perfluoroalkylcyclohexenes, which after in situ
reduction of the iodine afforded 4-(isopropyl)-1-methyl-6-
perfluoroalkylcyclohexenesinreasonableyields[3,4].Asimi-
lar reaction of 1,1,1-tribromo-2,2,2-trifluoroethane with
b-pinene gave stable adduct, 4-(2-bromoisopropyl)-1-(1,
1-dibromo-3,3,3-trifluoroethyl)cyclohexeneina57%yield[5].
In the preceding papers [6–8], we reported that
sulfinatodehalogenation procedure could be applied to
1-bromo-1-chloro-2,2,2-trifluoroethane, commercially avail-
Presently, we report successful addition of 1-bromo-1-
chloro-trifluoroethane, to (1S,5S)-(ꢀ)-b-pinene and trans-
formations of the adduct 1 to new trifluoromethyl-substituted
terpenoids 2–7. The aim of this work was to verify applic-
ability of the CF3CHClBr/Na2S2O4 system for introduction
of the CF3 group into more complex molecules, e.g. terpenes.
2. Results and discussion
1-Bromo-1-chloro-2,2,2-trifluoroethane reacted sponta-
neously with b-pinene under typical sulfinatodehalogena-
tion conditions (Na2S2O4/NaHCO3/MeCN/H2O) to give
4-(2-bromoisopropyl)-1-(2-chloro-3,3,3-trifluoropropyl)-
cyclohexane (1) almost quantitatively (Scheme 1). Since the
reaction mixture formed a three-phase system (organic
phase, water phase saturated with inorganic salts and solid
phase of insoluble salts), vigorous agitation was essential for
the reaction to proceed and to give satisfactory yields. The
reaction started at 18–20 8C, as evidenced by evolution of
gaseous CO2 (formed by the reaction of SO2 with NaHCO3)
* Corresponding author. Tel.: þ48-22-632-32-21;
fax: þ48-22-632-66-81.
E-mail address: dmowski@icho.edu.pl (W. Dmowski).
0022-1139/$ – see front matter # 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2004.03.001

1148
W. Dmowski et al. / Journal of Fluorine Chemistry 125 (2004) 1147–1151
Cl
the present case, as little as 0.25 equivalent of Na2S2O4 was
found to be satisfactory. The reactions proceeded at similar
rates affording similar, high yields of products as with an
equivalent amount of the initiator. There are only two papers
[8,9] prior to the present work, reporting the use of a low
ratio of the initiator to a perhaloalkane. Low ratio of the
initiator to CF3CHClBr suggests a free radical chain
mechanism, possibly as depicted in Scheme 2. High yields
of 1 indicate that the attack of the CF3CHCl radicals on the
double bond of b-pinene and the bromine transfer, are much
faster processes than the termination reaction with the SO2
radical-anion leading to the sulfinate.
In spite of the thermal instability of 1, this compound was
found to be reasonably stable in alkaline media; no dehy-
drobromination occurred by stirring with 10% aqueous
KOH for 24 h at room temperature. However, treatment
of 1 with methanolic solution of KOH at ambient tempera-
ture resulted in dehydrobromination to give a mixture of
regioisomeric dienes, 1-(2-chloro-3,3,3-trifluoropropyl)-4-
(isopropenyl)cyclohexene (2) and 1-(2-chloro-3,3,3-tri-
CF3
Na2S2O4 , NaHCO3
CF3CHClBr
+
MeCN , H2O
18 - 25 oC , 1 h
Br
( > 82 %)
1
Scheme 1.
and a considerable exothermic effect (temperature rise to
30–32 8C), and was completed within about 15 min. Ele-
mental analysis of the crude product gave almost theoretical
values for all the elements indicating that it consisted
essentially of compound 1. The crude product crystallised
soon after removal of a solvent, which phenomenon also
confirmed high contents of 1. The 1H and 19F NMR spectra
disclosed, however, the presence of ca. 6–8% of dehydro-
brominated compound 2. Better results were obtained when
the reaction temperature was kept at 25 8C; the reaction time
was increased to about 1 h but the contents of 2 was reduced
to 2–3%. Pure compound 1 (ca. 99%) was obtained by
pressing out a liquid fraction from the crystalline row product
at room temperature under reduced pressure. As evidenced by
spectral data, compound 1 was always formed as a 1:1
mixture of two diastereoisomers (two signals for the CF3
and CHCl groups) but their attempted separation by crystal-
lisation failed; the isomer ratios in the crystals and in the
liquid phases were almost the same. We were also unable to
separate the isomers by TLC and GLC techniques. Compound
1 is stable at ambient temperature but the attempted distilla-
tion, even under low pressure (3.3 N/m2), resulted in evolu-
tion of copious amounts of HBr and tar formation.
fluoro-propyl)-4-(isopropylidene)cyclohexene (3), in
a
1:1.7 ratio. Compound 1 was also successfully dehydrobro-
minated with pyridine in refluxing toluene but in this case a
limonene-like diene 2 was the major product (2:3 ¼ 3.5:1).
In both cases, the reactions proceeded chemoselectively,
i.e. no dehydrochlorinated products were found (Scheme 3).
Compounds 2 and 3 are difficult to separate from one
another and therefore they were identified in their mixtures.
These mixtures gave correct elemental analyses, identical
GC–mass spectra for both components, structures of which
1
were unambiguously determined by the H and 19F NMR
spectra. Careful distillation allowed a fraction containing
90% of 2 to be obtained; this compound, as expected and
confirmed by two NMR signals of the CF3 and CHCl groups,
always was a mixture of two diastereoisomers in a 1:1 ratio.
Total dehydrohalogenation of 1 was achieved by 1,8-
diazabicyclo[5.4.0]undec-7-ene (DBU) in refluxing toluene
to give inseparable mixture of trienes, 4-isopropenyl-1-
In most of the published works, including our earlier
studies of the reactions of CF3CHClBr with enol ethers [6,7],
equimolar amounts of the initiator and a perhaloalkane were
reported to be necessary to achieve good yields. However, in
Initiation:
_
_
.
_
solvent
S2O4
2 SO2
.
.
_
_
SO2
CF3CHClBr +
Propagation:
CF3CHCl + Br
+ SO2
Cl
Cl
Cl
CF3
CF3
+
.
CF3
.
CF3CHClBr
CF3CHCl
.
Br
Termination:
_
.
.
SO2
_
CF3CHCl
CF3CHClSO2
+
Scheme 2.

W. Dmowski et al. / Journal of Fluorine Chemistry 125 (2004) 1147–1151
Cl
1149
Cl
Cl
Cl
CF3
CF3
CF3
CF3
CF3
CF3
DBU, toluene
reflux, 6 h
a) or b)
+
+
Br
Br
5
2
1
3
4
1
a) KOH, MeOH, 20oC, 20 h
2 : 3 = 1 : 1.7
2 : 3 = 3.5 : 1
overall yields > 90 %
b) pyridine, toluene, 110oC, 48 h
Scheme 4.
Scheme 3.
with the retention of absolute configuration at carbon atom
C-4. Compound 7 seems to be valuable intermediate to
numerous CF3-substituted bicyclic terpenenoids; its beha-
viour in the Diels–Alder cycloaddition reactions is under
investigation.
(trans-3,3,3-trifluoropropenyl)cyclohexene (4) and 3-iso-
propylidene-6-(3,3,3-trifluoropropylidene)-cyclohexene (5)
(Scheme 4) as the main components (total 68%) together
1
with numerous unidentified compounds. H and 19F NMR
spectra of this mixture were sufficiently clear to elucidate
structures of both compounds; the presence of the CH2CF3
moiety in 5 was clearly evidenced by the CF3 group signal
which appeared as a triplet. Formation of 5 should be
interpreted in terms of a base initiated proton abstraction
from the most acidic position 3 in 4, followed by p-electron
shift. After 1 week at room temperature, this mixture poly-
merised to form a viscous resin.
The most successful transformation of 1 was reduction of
the bromine atom with Bu3SnH to give the menthene-like
compound 6 which on dehydrochlorination afforded con-
jugated diene, 4-isopropyl-1-(trans-3,3,3-trifluoroprope-
nyl)cyclohexene (7) (Scheme 5). The reduction proceeded
cleanly to give, after double distillation, compound 6 of 95%
purity and with over 75% isolated yield. Removal of the HCl
molecule from 6 required prolonged treatment with DBU in
refluxing toluene and gave a mixture containing ca. 82% of 7
together with 1–2% of unchanged 6, 10–12% of 4 and 5 and
some unidentified compounds. Careful distillation allowed
diene 7 of 88% purity to be obtained. The presence of
conjugated double bonds in 7 has been confirmed by strong
IR absorption at 1656 cmꢀ1 and the trans configuration of
the exocyclic double bond by large coupling constant of the
vinylic protons. No cis isomer was found.
3. Experimental
Melting points were determined in capillaries and boiling
points were measured during distillation; both are uncor-
rected. 1H and 19F NMR spectra were recorded with a Varian
400 spectrometer, both in CDCl3 solutions. Chemical shifts
are quoted in ppm from internal TMS for 1H and from
internal CFCl3 for 19F nuclei. GLC analyses were performed
with a Shimadzu GC-14A chromatograph using a 3:5 mꢁ
2 mm column packed with 5% silicone oil SE-52 on Chro-
mosorb. GC–MS analyses were performed with a Hewlett-
Packard 5890 apparatus (30 m capillary column, HP-5 oil).
Mass spectra of pure compounds were obtained with an
AMD-604 spectrometer and IR spectra with a Perkin-Elmer
Spectrum 2000 instrument.
1-Bromo-1-chloro-2,2,2-trifluoroethane and (1S,5S)-(ꢀ)-
b-pinene [purity ꢂ 99%, a2D0 ¼ ꢀ21 ꢃ 1 (neat)] were com-
mercial reagents.
3.1. (4S)-4-(2-Bromoisopropyl)-1-(2-chloro-3,3,3-
trifluoropropyl)cyclohexene (1) (two diastereo isomers
in a 1:1 ratio)
Diene 7 exhibits high optical activity and the same sign of
the optical rotation coefficient as the starting b-pinene; this
suggests that all the transformations leading to 7 proceed
Sodium dithionite (1.0 g [85%], 5 mmol) and sodium
hydrogen carbonate (2.1 g, 25 mmol) were suspended in
Cl
Cl
CF3
CF3
CF3
Bu3SnH, Et2O
reflux, 2 h
DBU, toluene
reflux, 10 h
Br
(66 %)
(76 %)
7
6
1
Scheme 5.

1150
W. Dmowski et al. / Journal of Fluorine Chemistry 125 (2004) 1147–1151
an acetonitrile–water solution (2:1, 30 ml). The reaction
mixture was vigorously stirred and cooled to 15 8C, then
b-pinene (2.7 g, 20 mmol) and CF3CHClBr (4.15 g,
21 mmol) were added one by one. The cooling bath was
removed and the reaction mixture was allowed to warm
up. When the temperature reached 18–20 8C, gas evolution
(CO2) began and a noticeable exothermic effect occurred.
When the temperature reached 25 8C, it was kept at this
level, initially by cooling and then by warming with an
external water bath. The reaction ceased after about 1 h (no
more gas evolution) and most of inorganic salts dissolved.
Stirring was continued for another 15 min, while keeping the
temperature at 25 8C, then water (50 ml) was added. The
reaction mixture was extracted with diethyl ether (30 þ 2 ꢁ
20 ml), the combined extracts were washed with brine
(3 ꢁ 30 ml) and dried over MgSO4. Removal of the solvent
on a rotary evaporator gave colourless oil, which soon
solidified to form white, soft crystals (6.1 g, purity 92–
94%). Pure compound 1 (ca. 99%) was obtained by putting
the crude crystalline product on a Schott’s funnel and
sucking off an oily part under reduced pressure at room
temperature. Yield: 5.5 g (82.5%). mp 30–32 8C. Analysis:
Found: C, 43.3; H, 5.3; Br, 23.5; Cl, 10.7; F, 17.1%.
Calculated for C12H17BrClF3 (333.62): C, 43.2; H, 5.1;
Br, 23.95; Cl, 10.6; F, 17.1%. 1H NMR d: ca. 1.45 (complex,
1H); ca. 1.65 (complex, 1H); 1.75 (s, 3H, CH3); 1.81 (d,
4JHH ¼ 1:65 Hz, 3H, CH3); 1.9–2.2 (complex, 4H); 2.27 and
2.32 (m, 1H); 2.41 (ddd, JAB ¼ 14.7 Hz, 3JHH ¼ 11:14 and
C, 57.0; H, 6.4; Cl, 14.1; F, 22.55%. This liquid was shown by
integrated 1H and 19F NMR spectra and the GLC analysis to
contain ca. 34% of diene 2 and 58% of diene 3.
3.2.2. With pyridine in refluxing toluene
Compound 1 (6 g, 18 mmol) and pyridine (4.3 g,
54 mmol) were refluxed in dry toluene (50 ml) for 48 h.
The precipitate of pyridine hydrobromide was filtered off,
the solution was washed with 3% hydrochloric acid
(3 ꢁ 20 ml), followed with brine, until neutral, and dried
over anhydrous MgSO4. Evaporation of the solvent gave
4.3 g (17 mmol, yield: 95%) of colourless liquid composed
of diene 2 (78%) and diene 3 (22%) (estimated from the
integrated NMR spectra). Elemental analysis as above.
Careful distillation of the combined products of two
experiments (8 g) through a 10 cm long Vigreux column
gave a fraction containing 90% of 2 and 10% of 3 (3.2 g, bp
40–44 8C/13.3 N/m2) and a fraction containing 85% of 2 and
15% of 3 (3.7 g, bp 44–46 8C/0.1 Torr). The residue con-
tained mostly 3 (ca. 80%) and unknown impurities.
(4S)-1-(2-Chloro-3,3,3-trifluoropropyl)-4-(isopropenyl)-
cyclohexene (2) (diastereoisomers ratio 1:1): 1H NMR d: ca.
1.45 (complex, 1H); ca. 1.65 (complex, 1H); 1.75 (s, 3H,
4
CH3) and 1.81 (d, JHH ¼ 1:65 Hz, 3H, CH3); 1.9–2.2
(complex, 4H); 2.27 and 2.32 (m, 1H); 2.41 (ddd,
3
JAB ¼ 14.7 Hz, JHH ¼ 11:4 and ca. 3.3 Hz, 1H, HA,
CH2ꢀCHCl); 2.68 (d of narrow m, JAB ¼ 14.7 Hz, 1H,
3
HB, ꢀCH2ꢀCHCl); 4.18 (2ꢁ dqd, JHH ¼ ca: 11 Hz,
ca. 3.3 Hz, HA, ꢀCH2ꢀCHCl); 2.68 (d of narrow m, JAB
¼
3JHF ¼ ca: 6:6 and 3.3 Hz, 1H, CHCl); 4.72 (narrow m,
1H, CH2¼); 4.73 (sext, J ¼ ca. 1.5 Hz, 1H, CH2¼); 5.60
(narrow m, 1H, vinylic) ppm. 19F NMR d: 75.07 (d,
14.7 Hz, HB, ꢀCH2ꢀCHCl); ca. 4.18 (2ꢁ dqd,
3
3JHH ¼ ca: 11 Hz, JHF ¼ ca: 6:6 and 3.3 Hz, 1H, CHCl);
3
5.60 (narrow m, 1H, vinylic) ppm. 19F NMR d: 75.07 and
3JHF ¼ 6:8 Hz) and 75.16 (d, JHF ¼ 6:8 Hz) ppm. MS
75.16 (d, JHF ¼ 6:8 Hz, CF3, signal ratio ¼ 1:1) ppm. MS
(EI, 70 eV): m/z (rel. int., ion): 254, 252 (18, 47, Mþ);
239, 237 [13, 34, (M–CH3)þ]; 225, 223 [4, 12, (M–C2H5)þ];
212, 210 [10, 42, (M–C3H4)þ]; 211, 209 [45, 84, (M–
C3H5)þ]; 210, 208 [27, 34, (M–C3H6)þ]; 173 [36, (M–
HCl–C3H5)þ]; 169 (20); 153 (28); 135 (19); 121 (49); 93
(55); 91 (59); 79 (48, C6H5þ); 68 (100, C5H8þ); 67 (34,
C5H7þ). IR (neat): 1645 cmꢀ1 (m, exocyclic C¼C); 1676,
1717 cmꢀ1 (vw, ring C¼C).
3
(EI, 70 eV, 42 8C): m/z (rel. int., ion): 336, 334, 332 (1.5,
Mþ); 255, 253 [13, 39, (M–Br)þ]; 254, 252 [17, 36, (M–
HBr)þ]; 239, 237 [7, 20, (M–HBr–CH3)þ]; 213, 211 [7, 26,
(M–Br–C3H6)þ]; 199, 197 [32, 100, (M–Br–C4H8)þ]; 173
(9); 135 (18); 121 (25); 109 (20); 93 (30); 91 (941); 79 (43);
77 (20); 69 (29, CF3þ); 68 (42, C5H8þ); 67 (27, C5H7þ); 43
(37, C3H7þ); 41 (48, C3H5þ), 39 (20).
1-(2-Chloro-3,3,3-trifluoropropyl)-4-(isopropylidene)cy-
clohexene (3): 1H NMR d: 1.66 (narrow m, J ¼ ca. 0.4 Hz,
CH3); 1.70 (narrow m, J ¼ ca. 0.4 Hz, CH3); 1.8–2.4 (com-
3.2. Dehydrohalogenation of 1
2
3
3.2.1. With KOH in methanol
plex, 4H); 2.43 (dd, JAB ¼ 14:7 Hz, JHH ¼ 10:8 Hz, HA,
2
Compound 1 (6 g, 18 mmol), prepared as in Section 3.1,
was added to a 1.5 M solution of KOH in methanol (50 ml)
and stirred at ambient temperature overnight after which
time a large amount of KBr precipitated. Methanol was
removed on a rotary evaporator then water (80 ml) was
added and excess KOH was neutralised with hydrochloric
acid. The organic material was extracted with ether (30 þ 2
ꢁ 20 ml) and the extract was dried over anhydrous MgSO4.
Evaporation of the solvent on a rotary evaporator gave 4.1 g
(16.2 mmol, yield: 90%) of colourless liquid possessing a
mild terpenic smell. Elemental analysis: Found: C, 56.85; H,
6.45; Cl, 14.2; F, 22.8%. Calculated for C12H16ClF3 (252.70):
CH2ꢀCHCl); 2.68 (dm, JAB ¼ 14:7 Hz, HB, CH2ꢀCHCl)
3
3
2.80 (narrow m, 2H); 4.19 (dqd, JHH ¼ 10:8 Hz; JHF
¼
3
6:7 Hz; JHH ¼ 3:3 Hz, 1H, CHCl): 5.59 (narrow m, 1H,
vinylic) ppm. 19F NMR: 75.16 (d, JHF ¼ 6.7 Hz) ppm.
3.2.3. With 1,8-diazabicyclo[5.4.0]undec-7-ene in
refluxing toluene
Crude 1 (10.5 g, 31.5 mmol) and DBU (13.7 g, 90 mmol)
were refluxed in dry toluene (80 ml, distilled from sodium
wire) for 6 h. The precipitate of DBU hydrohalides (11.5 g)
was filtered off, washed with toluene, the combined solu-
tions were washed with 3% hydrochloric acid (3 ꢁ 20 ml),

W. Dmowski et al. / Journal of Fluorine Chemistry 125 (2004) 1147–1151
1151
followed with brine until neutral, and dried over anhydrous
MgSO4. Evaporation of the solvent under reduced pressure
(660 N/m2) gave 6.6 g (30.5 mmol, yield: 97%) of a brown
70.28 (d, 3JHF ¼ 6:5 Hz) ppm in a 1:1 ratio. MS (EI, 70 eV):
m/z (rel. int., ion): 256, 254 (8, 26, Mþ); 241, 239 [6, 18, (M–
CH3)þ]; 213, 211 [33, 100, (M–C3H7)þ]; 199, 197 [6, 18,
(M–C4H9)þ]; 175 [10, (M–C3H7–HCl)þ]; 135 (14); 123
(17); 81 (34, C6H9þ); 79 (45, C6H7þ); 69 (30, CF3þ); 67
(30, C5H7þ); 55 (29, C4H7þ); 43 (25, C3H7þ); 41 (38,
C3H5þ). IR (neat): 1676 and 1726 cmꢀ1 (vw, C¼C).
1
liquid which was shown by integrated H and 19F NMR
spectra to contain trienes 4 (30%) and 5 (38%), ca. 7% of
dienes 2 and 3 and ca. 25% of numerous unidentified
compounds containing the CF3 group.
Alike treatment of a mixture of dienes 2 (85%) and 3
(15%) (5.8 g, 23 mmol) with DBU (5.3 g, 35 mmol) resulted
in a mixture (4.9 g, 22.7 mmol, yield: 98%) containing 58%
of 4, 14% of 5, 13% of unreacted 2 and 3 and ca. 15% of
numerous minor components. Vacuum distillation (106.6 N/
m2) through a 10 cm long Vigreux column gave a colourless
fraction (3.5 g, bp 58–60 8C/0.8 Torr) containing ca. 40% of
4, 10% of 2 and 3, 50% of numerous minor components, but
not compound 5 was present.
3.4. (4S)-(ꢀ)-4-Isopropyl-1-(trans-3,3,3-
trifluoropropenyl)cyclohexene (7)
Compound 6 (6.8 g, 26.7 mmol, purity 95%) and DBU
(8.0 g, 53 mmol) were refluxed in dry toluene (60 ml) for
10 h and left overnight at ambient temperature. The pre-
cipitate of DBU hydrochloride was washed out with 3%
hydrochloric acid (3 ꢁ 20 ml), followed by brine until neu-
tral, and dried over anhydrous MgSO4. The solvent was
removed on a rotary evaporator and the residue was vacuum
distilled using a 5 cm long Vigreux column. A fraction
collected at 48–52 8C/0.4 Torr (4.7 g) was found by inte-
grated 19F NMR to contain ca. 82% of 7, 3% of 4, 8% of 5,
1% of 6 and 6% of a unknown compound. Yield of 7: 66%.
Re-distillation of the combined fractions from three experi-
ments (12.5 g) gave compound 7 of 88% purity (9.6 g); a
colourless liquid possessing a weak irritating smell. bp 50–
52 8C/0.4 mmHg. Analysis: Found: C, 65.5; H, 7.7; F, 25.9%
and trace amount of Cl. Calculated for C12H17F3 (218.16):
C, 66.0; H, 7.85; F, 26.1%. 1H NMR: 0.90 (d, 3JHH ¼ 6:8 Hz,
(4S)-4-Isopropenyl-1-(trans-3,3,3-trifluoropropenyl)-
cyclohexene (4): 1H NMR d: 1.75 (narrow q, J ¼ ca. 0.6 Hz,
CH3); 1.92 (dm, J ¼ ca. 12 Hz, 1H); 2.1–2.4 (6H); 4.73 (qn,
J ¼ ca. 0.9 Hz, 1H, ¼CH2); 4.76 (qn, J ¼ ca. 1.5 Hz, 1H,
3
3
¼CH2); 5.54 (dq, JHH ¼ 16:0 Hz, JHF ¼ 6:8 Hz, 1H,
¼CH–CF3); 6.07 (narrow m, 1H, ¼CH–); 6.75 (dq,
4
3JHH ¼ 16:0 Hz, JHF ¼ 2:0 Hz, exocyclic –CH¼) ppm.
3
19F NMR d: 63.15 (broad d, JHF ¼ 6:8 Hz) ppm.
3-Isopropylidene-6-(3,3,3-trifluoropropylidene)cyclo-
1
hexene (5): H NMR d: 1.78 (s, CH3); 1.82 (s, CH3); 2.38
(broad s, 2H, H-4); 2.39 (broad s, 2H, H-5); 2.91 (qd,
3
3JHF ¼ 10:9 Hz, JHH ¼ 7:5 Hz, 2H, CH2CF3); 5.29 (br t,
3
3
3JHH ¼ 7:5 Hz, 1H, H-7), 6.05 (d, JHH ¼ 10:0 Hz, 1H, H-
3H, CH3); 0.92 (d, JHH ¼ 6:8 Hz, 3H, CH3); 1.2–1.4 (m,
2); 6.49 (d, 3JHH ¼ 10:0 Hz, 1H, H-1) ppm. 19F NMR d: 66.6
2H); 1.51 (oct, 3J ¼ 6:8 Hz, 1H): 1.8–1.9 (m, 2H); 2.08 (m,
3
(t, JHF ¼ 10:9 Hz, CF3) ppm.
1H); 2.20 (narrow m, 1H); 2.21 (narrow m, 1H): 5.52(dd,
3
3JHH ¼ 15:8 Hz, JHF ¼ 6:9 Hz, 1H, ¼¼CHꢀCF3); 6.05
3
3.3. (4S)-1-(2-Chloro-3,3,3-trifluoropropyl)-4-
(isopropyl)cyclohexene (6)
(narrow m, 1H, H-2): 6.94 (dd, JHH ¼ 15:8 and 1.7 Hz,
3
1H, exocycle ꢀCH¼¼) ppm. 19F NMR: 63.1(d, JHF
¼
6:9 Hz) ppm. GC–MS: 218 (40, Mþ); 203 [10, (M–
CH3)þ]; 189 [10, (M–C2H5)þ]; 175 [70, (M–C3H7)þ];
161 [75, (M–C4H9)þ]; 127 (30); 91 (35, C7H7þ); 79 (85,
C6H7þ); 77 (45, C6H5þ); 69 (50, CF3þ); 55 (60, C4H7þ); 43
(60, C3H7þ); 41 (100, C3H5þ). HRMS: Found: 218.12747.
Calculated for C12H17F3: 218.12824. IR (film): 1656 cmꢀ1
(s) (C¼C–C¼C). a3D0 ¼ ꢀ89:7 (5% w EtOH).
Compound 1 (12 g, 36 mmol, 99% purity) and HSnBu3
(12 g, 41 mmol) were refluxed in dry ether (80 ml) under
atmosphere of argon for 2 h then left overnight at ambient
temperature while stirring. The reaction mixture was sub-
jected to a vacuum distillation using a 5 cm long Vigreux
column. A fraction collected at 50–58 8C/53.3 N/m2 (9.6 g)
was found by GLC to contain ca. 90% of 6 and some
unidentified components. Re-distillation gave compound 6
of 95% purity (by integrated 19F NMR contains ca. 3% of 2)
as colourless liquid with a mild terpenic smell. Yield: 7.0 g
(76.4%). bp 54–56 8C/53.3 N/m2. Analysis: Found: C, 56.4;
H, 7.2; Cl, 13.7; F, 22.2%. Calculated for C12H18ClF3
References
[1] W.Y. Huang, J. Fluorine Chem. 58 (1992) 1–8.
[2] W.Y. Huang, F.H. Wu, Isr. J. Chem. 39 (1999) 167–170.
[3] W.Y. Huang, W. Wang, B.N. Huang, Acta Chim. Sinica (Engl. Ed.)
(1986) 178–184.
1
(254.72): C, 56.6; H, 7.1; Cl, 13.9; F, 22.4%. H NMR d:
[4] B.N. Huang, J.T. Liu, Chin. J. Chem. (1990) 358–361.
[5] W.Y. Huang, W. Wang, Acta Chim. Sinica (Chin. Ed.) 47 (1986)
141–146.
(400Mz, CDCl3): 0.89 (d, 3JHH ¼ 6:6 Hz, 3H, CH3); 0.90 (d,
3JHH ¼ 6:6 Hz, 3H, CH3); 1.28 (m, 2H); 1.48 (oct d,
3J ¼ 6:8 and ca. 1.1 Hz, 1H): ca. 1.8 (m, 2H); 1.9–2.1
´
[6] H. Plenkiewicz, W. Dmowski, M. Lipinski, J. Fluorine Chem. 111
2
3
(2001) 227–232.
[7] W. Dmowski, J. Ignatowska, J. Fluorine Chem. 123 (2003) 37–42.
´
[8] W. Dmowski, K. Piasecka-Maciejewska, Z. Urbanczyk-Lipkowska,
(complex, 3H); 2.40 (dd, JAB ¼ 14:6 Hz, JHH
¼
2
11:0 Hz, 1H, CH2); 2.66 (dm, JAB ¼ 14:6 Hz, 1H, CH2);
3
3
3
4.18 (2ꢁ dqd, JHH ¼ 11:0 Hz; JHF ¼ 6:6 Hz; JHH
¼
Synthesis (2003) 841–844.
ca: 3:3 Hz, 1H, CHCl–); 5.59 (narrow m, 1H, H-2) ppm.
19F NMR d: (400Mz, CDCl3): 70.20 (d, 3JHF ¼ 6:7 Hz) and
[9] C. Amato, C. Naud, P. Calas, A. Commeyras, J. Fluorine Chem. 113
(2002) 55–63.