Synthesis of (3S,4R)-(+)-hydroxymethyl-3-(trifluoromethyl)-4,5,5-trimethylcyclopentene - a trifluoromethyl analogue of necrodols

Article abstract of DOI:10.1016/S0022-1139(00)00283-9

New trifluoromethyl group containing enantiomerically pure monoterpene derivatives, methyl (1S,3R,4S)-(+)-4-(trifluoromethyl)-2,2,3-trimethylcyclopentanecarboxylate (6); methyl (3S,4R)-(+)-3-(trifluoromethyl)-4,5,5-trimethylcyclopentenecarboxylate (10) and (3S,4R)-(+)-hydroxymethyl-3-(trifluoromethyl)-4,5,5-trimethylcyclopentene (1), were prepared using camphoric anhydride as the starting material and sulphur tetrafluoride as the fluorinating agent. Compound 1 is a trifluoromethyl analogue of an unknown isomer of necrodols.

Full text of DOI:10.1016/S0022-1139(00)00283-9

Journal of Fluorine Chemistry 105 (2000) 77±82
Synthesis of (3S,4R)-(‡)-hydroxymethyl-3-(tri¯uoromethyl)-4,5,5-
trimethylcyclopentene Ð a tri¯uoromethyl analogue of necrodols
Wojciech Dmowski*, Krystyna Piasecka-Maciejewska
Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warsaw, Poland
Received 28 February 2000; accepted 31 March 2000
Abstract
New tri¯uoromethyl group containing enantiomerically pure monoterpene derivatives, methyl (1S,3R,4S)-(‡)-4-(tri¯uoromethyl)-2,2,3-
trimethylcyclopentanecarboxylate (6); methyl (3S,4R)-(‡)-3-(tri¯uoromethyl)-4,5,5-trimethylcyclopentenecarboxylate (10) and (3S,4R)-
(‡)-hydroxymethyl-3-(tri¯uoromethyl)-4,5,5-trimethylcyclopentene (1), were prepared using camphoric anhydride as the starting material
and sulphur tetra¯uoride as the ¯uorinating agent. Compound 1 is a tri¯uoromethyl analogue of an unknown isomer of necrodols.
# 2000 Elsevier Science S.A. All rights reserved.
Keywords: Fluorination; Sulphur tetra¯uoride; Fluoroterpenoids; Fluoronecrodol; Methyl (1S,3R,4S)-4-(tri¯uoromethyl)-2,2,3-trimethylcyclopentanecar-
boxylate; Methyl (3S,4R)-3-(tri¯uoromethyl)-4,5,5-trimethylcyclopentenecarboxylate; (3S,4R)-Hydroxymethyl-3-(tri¯uoromethyl)-4,5,5-trimethylcyclopen-
tene
1. Introduction
Speci®c properties of the tri¯uoromethyl group [1±4] that
cause its introduction into biologically important molecules,
especially in place of the methyl group, is of considerable
importance. The access to compounds bearing the CF3 group
in an appropriate position remains, however, a dif®cult
Two terpene alcohols, ( )-a-necrodol and ( )-b-necro-
dol, were isolated by Meinwald et al. [9] from the defensive
spray of the red-lined carrion beetle (Necrodes surinamen-
sis). Syntheses of both compounds as well as of closely
related (but not known from natural sources) (‡)-epi-a-
necrodol, (‡)-epi-b-necrodol and (‡)-g-necrodol, were
reported by this same research group [10].
synthetic problem. In the preceding papers we reported
syntheses of a number of tri¯uoromethyl containing terpe-
noids by treatment of carboxylic derivatives of camphor
with sulphur tetra¯uoride [5±8]. The present paper aims in
describing the synthesis of (3S,4R)-(‡)-hydroxymethyl-3-
(tri¯uoromethyl)-4,5,5-trimethylcyclopentene (1), a tri¯uor-
omethyl analogue of non-naturally occurring d-necrodol.
The key intermediates in the syntheses of a-necrodols
were 3-(carbomethoxy)-4,4,5-trimethyl-cyclopentanecar-
boxylic acid (5) and its epimer, both obtained from cam-
phoric anhydride (2) via phenylcamphoric acid (3a) and
* Corresponding author.
E-mail address: dmowski@icho.edu.pl (W. Dmowski).
0022-1139/00/$ ± see front matter # 2000 Elsevier Science S.A. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 0 0 ) 0 0 2 8 3 - 9

78
W. Dmowski, K. Piasecka-Maciejewska / Journal of Fluorine Chemistry 105 (2000) 77±82
1
its trans-epimer was established 33 years later from H
epimeric ester (4a) and (4b). Further steps on the way to a-
and epi-a-necrodol involved reduction of the ester group
into hydroxymethyl group, introduction of the double bond
via selenylation/de-selenylation and ®nally, conversion of
the carboxylic group into the methyl group. Looking at the
Meinwald's synthetic scheme, we realized that, instead of
one of the methyl groups, the tri¯uoromethyl group may be
easily introduced into a necrodol molecule, simply by
NMR and X-ray crystallographic data [12]. Optically inac-
tive (Æ)-phenylcamphoric acid (3b) (mp 117±1198C) was
prepared from isolauronic acid [13] and from (Æ)-campho-
ric anhydride [14]. It has been reported that acylation of
benzene with ( )-camphoric anhydride, which is formed by
dehydration of (‡)-camphoric acid, a commercial reagent,
gives exclusively (‡)-phenylcamphoric acid (3a) [14].
treatment of acid 5 with sulphur tetra¯uoride. Our synthetic
pathway is shown in the scheme.
In our hands, however, a mixture of both (‡)- and (Æ)-
phenylcamphoric acids (3a) and (3b) was formed from
which enantiomer (3a) having a correct melting point was
isolated by repeated crystallisation.
2. Results and discussion
A rather large scale esteri®cation of acid (3a), for the sake
of safety was carried out via treatment with SOCl2 followed
by methanol instead of using diazomethane, and resulted in
partial epimerisation to give a ca. 1:1 mixture of cis and
trans esters (4a) and (4b) which were separated by crystal-
lisation. These two esters, and also the respective acid
chlorides, were easily distinguished by H NMR spectro-
scopy: signals of the geminal methyl groups showed che-
mical shifts characteristically different for both epimers
The ®rst intermediate in our synthetic scheme was (‡)-
phenylcamphoric acid (3a) (mp 1398C). This acid was ®rst
synthesised 50 years ago as a product of the Friedel±Crafts
acylation of benzene with camphoric anhydride but an
incorrect structure was assigned [11]. The correct structure
of acid 3a, in which the carboxylic group and the C-3 methyl
group are in the cis con®guration, as well as the structure of
1

W. Dmowski, K. Piasecka-Maciejewska / Journal of Fluorine Chemistry 105 (2000) 77±82
79
[10,14]. The sharpless oxidation of (4a) with NaIO4 and
RuCl3Á(H2O)n catalyst [15] afforded (1S,3S,5R)-(‡)-3-car-
boxymethyl-4,4,5-trimethylcyclopentanecarboxylic acid (5)
of which melting point and optical rotation coef®cient were
in agreement with the literature data [10].
a Shimadzu GC-14A chromatograph using a 3.5 mÂ2 mm
column packed with 5% silicone oil SE-52 on Chromosorb
G. The GC-MS analyses were performed with a Hewlett-
Packard 5890 apparatus using a 30 m capillary column
coated with a 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.
A crucial step in our synthesis, the ¯uorination of acid 5
with SF4, proceeded smoothly at 35±408C (at higher tem-
perature considerable charring occurred) to give the required
tri¯uoromethyl containing ester 6 as the main product (79
GLC%) together with acid ¯uoride 7 and penta¯uoroether 8
as side products. Distillation of the crude reaction mixture
afforded compound 6 in ca. 40% yield and of 96% purity
which showed a high optical rotation coef®cient. Since
reactions of carboxylic acids with SF4 do not affect the
con®guration of the adjacent carbon atom, the con®guration
of tri¯uoromethylated compound 6 should be identical with
the con®guration of its precursor 5; this was con®rmed by
the similarity of the chemical shifts of geminal methyl group
3.1. Cis-(‡)-phenylcamphoric acid (3a)
Acid 3a was synthesized by a Friedel±Crafts condensa-
tion of camphoric anhydride with benzene using a modi®ed
literature procedure [11].
Camphoric anhydride (2) [30 g, 0.165 mol, prepared by
re¯uxing commercial (1R,3S)-(‡)-camphoric acid and
acetic anhydride in the presence of ZnCl2 [mp 221±
2228C] was dissolved in dry benzene (500 ml) then anhy-
drous AlCl3 (46 g, 0.32 mol) was added portionwise under
an atmosphere of nitrogen. A slightly exothermic reaction
occurred with evolution of carbon monoxide which ceased
in ca. 30 min. The reaction mixture was stirred at 308C for an
additional 30 min, then water (500 ml) and concentrated
hydrochloric acid (70 ml) were added and the stirring was
continued until inorganic salts fully dissolved. The benzene
layer was separated, washed with water and extracted with
5% KOH (2 mlÂ200 ml‡100 ml). The combined alkaline
extracts were strongly acidi®ed with concentrated hydro-
chloric acid (residual benzene was ®rst removed on a rotary
evaporator), warmed up to 808C then 96% ethanol was
added in such amount (ca. 500 ml) to cause total dissolution
of the solid material and the solution was left overnight at
ambient temperature for crystallisation. A crystalline pro-
duct (36 g) showed correct elemental analysis and 1H NMR
spectrum but a wide range of melting point (110±1258C)
suggested a mixture of (‡)- and (Æ)-phenylcamphoric acids.
A double recrystallisation from hexanes gave pure cis-(‡)-
1
in the H NMR spectra of both compounds. Interestingly,
¯uorination of trans-epimer of 5 with SF4, even for much
longer time, gave mostly the respective acid ¯uoride.
Further synthetic steps were carried out as follows
using, in general, Meinwald's procedures [10]. Consecutive
treatment of 6 with n-BuLi, Me3SiCl and PhSeCl (one
pot reaction) gave selenylated compound 9 as a ca. 19:1
mixture of epimers which could not be distinguished
from their NMR spectra. Oxidation of compounds 9 with
m-chloroperbenzoic acid afforded unsaturated ester, methyl
(3S,4R)-( ‡ )-3-(tri¯uoromethyl)-4,5,5-trimethylcyclo-pen-
tenecarboxylate (10), in excellent yield. The two last pro-
cesses, i.e. selenylation and oxidation/deselenylation,
produced also ca. 20% of diphenyl diselenide as side product
which was effectively removed by column chromatography
on silica gel. Reduction of ester 10 with LiAlH4 afforded
®nal compound, (3R,4R)-(‡)-hydroxymethyl-3-(tri¯uoro-
methyl)-4,5,5-trimethylcyclopentene (1), contaminated with
ca. 5% of the respective saturated alcohol. Careful chroma-
tography on silica gel gave pure unsaturated terpenic alcohol
1 which may be considered as a tri¯uorinated analogue of an
unknown necrodol isomer.
enantiomer 3a as a cotton wool-like needles. Yield: 14.3 g
20
D
(37%). The mp 140±1428C (Lit. 139±1408C [16]). ‰aŠ ˆ
1
‡4.5 (cˆ5, CHCl3) (Lit. ‡5.5 [14]). H NMR (CDCl3) d:
0.77 (d, 3Jˆ6.8 Hz, CH3); 0.86 (s, CH3); 1.23 (s, CH3); 1.71
3
The present and the former [5±8] investigations lead to a
conclusion that ¯uorination of carboxylic derivatives of
terpenoids with SF4 seems to be a promising technique
for the synthesis of a variety of CF3-group containing
and, in most cases, enantiopure compounds, including tri-
¯uoromethyl analogues of naturally occurring terpenes.
(dq, Jˆ10.7 and 6.8 Hz, 1H); 1.92 (ddd, Jˆ13.4, 9.6 and
6.5, 1H), 2.53±2.90 (m, 3H); 7.25 (m, 5H) ppm. A signal of
the carboxylic group proton was not found. Analysis: Found:
C, 77.6; H, 8.7%. Calculated for C15H29O2 (232.32): C,
77.6; H, 8.7%.
Multiple crystallisation of the residue remaining after
separation of cis-(‡)-phenylcamphoric acid allowed isola-
tion of a sample of cis-(Æ)-phenylcamphoric (3b) acid as
large prisms: mp 116±1188C (Lit. 1178C [14]). Elemental
3. Experimental
1
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
Gemini 200 spectrometer at 200 and 188 MHz, respectively.
Chemical shifts are quoted in ppm from internal TMS for 1H
(positive down®eld) and from internal CFCl3 (positive
up®eld). Crude mixtures of products were analysed with
analysis and H NMR spectrum identical with those of the
(‡)-isomer.
3.2. Esterification of cis-(‡)-phenylcamphoric acid (3a)
Acid 3a (29 g, 0.125 mol) and thionyl chloride (40 ml)
were stirred together overnight at room temperature then an

80
W. Dmowski, K. Piasecka-Maciejewska / Journal of Fluorine Chemistry 105 (2000) 77±82
excess of SOCl2 was distilled off and the residue was
distilled under reduced pressure to give a crystalline product
(29.5 g, bp 140±1418C/3 Torr, solidi®ed in the refrigerator)
0.98 (d, 3Jˆ6.8 Hz, CH3); 1.14 (s, CH3); 1.91 (dq, 3Jˆ10.4
and 6.8 Hz, 1H); 2.04±2.18 (m, 1H), 2.32±2.85 (m, 3H);
3.70 (s, OCH3) ppm. A signal of the carboxylic group proton
was not found. Analysis: Found: C, 61.5; H, 8.6%. Calcu-
lated for C11H18O4 (214.26): C, 61.7; H, 8.5%.
1
which was found by H NMR as a 1:1 mixture of phenyl-
camphoroyl chloride (cis) and epi-phenylcamphoroyl chlor-
ide (trans) (CH3 groups signals: d (cis): 0.77 (d, 3Jˆ7.6 Hz);
3
0.92 (s); 1.32 (s) ppm. d (trans): 0.74 (d, Jˆ6.6 Hz); 1.12
3.4. Reaction of acid 5 with sulphur tetrafluoride
(s); 1.21 (s) ppm.). These acid chlorides were dissolved in
methanol (150 ml) pre-cooled to 58C, dry pyridine (10 ml)
was added (a precipitate began to form immediately) and the
reaction mixture was left overnight at room temperature. An
excess of methanol was removed on a rotary evaporator and
the residue was agitated with water (100 ml) and ether
(150 ml), the water and ether layers were separated, the
water layer was extracted with ether (50 ml) and the ether
layers were combined, washed with 2% hydrochloric acid
followed by water and dried over MgSO4. Evaporation of
ether gave ca. 1:1 mixture of methyl phenylcamphorate (4a)
Acid 5 (8.8 g, 41 mmol) was placed in a 30 ml capacity
stainless steel autoclave ®tted with a needle valve, the
autoclave was cooled in an acetone-dry ice bath, evacuated,
then sulphur tetra¯uoride (28 g, 260 mmol) was condensed
into it. The autoclave was mechanically agitated at 358C for
14 days. After completion of the reaction, gaseous products
were let off (excess SF4, SOF2, HF) and a dark residue was
dissolved in hexanes (50 ml). The GC-MS analysis showed
the presence of compound 6 (79%), acid ¯uoride 7 (18%)
and ¯uoroether 8 (2.3%). The solution was vigorously
stirred with saturated aqueous NaHCO3 for 1 h (removal
of the acid ¯uoride and HF), then washed with water and
dried over MgSO4. The solvent was removed on a rotary
evaporator and the residue was vacuum distilled to give a
1
and epi-phenylcamphorate (4b) (GLC and H NMR esti-
mate) as a soft crystalline material (27.8 g, yield 90%).
Recrystallisation from boiling methanol gave methyl cis-
(‡)-phenylcamphorate (4a) of 96.2% purity (GLC). Yield:
14 g (47.5%). The mp 89±918C (Lit. 918C [16], 948C [14]).
colourless oil containing 96% of 6, 0.8% of 7 and 2.9% of 8.
20
20
D
‰aŠ ˆ‡15.0 (cˆ5, CDCl3) (Lit. ‡10.6 [14]). 1H NMR
Yield: 4 g (ca. 41%). The bp 60±658C/7 Torr. ‰aŠ ˆ‡31.4
D
(CDCl3) d: 0.75 (d, 3Jˆ6.8 Hz, CH3); 0.77 (s, CH3);
(cˆ5, CHCl3). This material was used for further transfor-
3
1.17 (s, CH3); 1.68 (dq, Jˆ10.75 and 6.8 Hz, 1H); 1.81±
mations.
1.96 (m, 1H), 2.54±2.86 (m, 3H); 3.71 (s, OCH3); 7.23 (m,
5H) ppm.
3.4.1. Methyl (1S,3R,4S)-2,2,3-trimethyl-4-
(trifluoromethyl)cyclopentanecarboxylate (6)
Removal of methanol from a solution remaining after
isolation of 4a gave an oil (slowly crystallising on standing)
which consisted mostly (83%) of methyl epi-phenylcam-
phorate 4b. 1H NMR (CDCl3) d: 0.71 (d, 3Jˆ6.8 Hz, CH3);
0.98 (s, CH3); 1.01 (s, CH3); 1.86 (dq, 3Jˆ11.5 and 6.8 Hz,
1H); 2.20 (m, 2H), 2.63 (m, 2H); 3.71 (s, OCH3); 7.23 (m,
5H) ppm.
IR (CCl4) n (cm 1): 1724.1 (vs, COOMe). 1H NMR
(CDCl3) d: 0.68 (s, CH3); 1.00 (dd, 3Jˆ6.8 Hz, 4Jˆ0.6 Hz,
3
0.6 Hz, CH3); 1.14 (s, CH3); 1.82 (dq, Jˆ9.5 and 6.8 Hz,
1H); 1.91 (dd, Jˆca. 9.5 and 9.0 Hz, 1H); 2.25±2.45 (m,
3
2H), 2.58 (dd, Jˆ10.5 and 8.8 Hz, 1H); 3.70 (s, OCH3)
ppm. 19F NMR (CDCl3) d: 71.2 (d, 3JHFˆ9.1 Hz, CF3) ppm.
‡
The GC-MS m/z (rel. int., ion): 238 (2%, M ); 223 [5,
(M CH3) ]; 218 [30, (M HF) ]; 207 [15, (M CH3O) ];
‡ ‡ ‡
3.3. (1S,3S,5R)-3-Carboxymethyl-4,4,5-
trimethylcyclopentanecarboxylic acid (5)
‡ ‡
179 [10, (M CO2CH3) ]; 163 (18, C8H10F3 ); 152 (12,
‡
‡
‡
C7H111F3 ); 143 (18, C8H9F2 )]; 132 (30, C7H10F2 ); 113
(20, C7H10F ); 95 (18, C7H11 ); 87 (100, C4H7O2 ); 73 (15,
‡ ‡ ‡
A slightly modi®ed literature procedure was applied [10].
A solution of methyl phenylcamphorate 4a (6.75 g,
27 mmol) in CCl4 (100 ml) was added to a vigorously stirred
suspension of NaIO4 (71 g, 330 mmol) in acetonitrile
(100 ml) and water (150 ml), ®nally RuCl3ÁH2O (100 mg,
0.45 mmol) was added and the biphasic yellow mixture was
stirred at ambient temperature for 96 h. The mixture was
®ltered, the inorganic precipitate was separated and macer-
ated well with CH2Cl2 (3 mlÂ150 ml). The aqueous ®ltrate
was washed with CH2Cl2 (the black yellowish ruthenium
salts remained in the water layer) and the combined methy-
lene chloride solution (ca. 700 ml) was dried over MgSO4.
Evaporation of the solvent gave a solid material which was
‡
‡
‡
C3H5O2 ); 69 (30, CF3 ); 59 (28, CH3CO2 ); 55 (45,
‡
C4H7 ).
3.4.2. Methyl (1S,3R,4S)-2,2,3-trimethyl-4-
(fluoroformyl)cyclopentanecarboxylate (7)
‡
GC-MS m/z (rel. int., ion): 196 [5%, (M HF) ]; 185 [10,
‡
‡
(M CH3O) ]; 168 [10, (M CO HF) ]; 140 (25); 110 (70,
‡
‡
‡
‡
C8H14 ); 109 (80, C8H13 ); 108 (50, C8H12 ); 95 (40,
‡
‡
C7H11 ); 87 (45, C4H7O2 ); 69 (50, CF3 ); 59 (40,
‡
‡
‡
CH3CO2 ); 55 (80, C4H7 ); 41 (100, C3H5 ).
3.4.3. (1S,3R,4S)-1-(Methoxydifluoromethyl)-2,2,3-
trimethyl-4-(trifluoromethyl)cyclopentane (8)
recrystallised from hexanes. Yield: 8.8 g (75%). The mp 68±
20
‡
GC-MS m/z (rel. int., ion): 260 (2%, M ); 245 [10,
‡
708C (Lit. 70±718C [10]). ‰aŠ ˆ‡25.0 (cˆ3, CHCl3) (Lit.
D
‡
‡26.1 [10]). IR (neat) n (cm 1): 1734.9 (vs, COOMe);
(M CH3) ]; 225 [25, (M CH3 HF) ]; 179 [10, (M±
‡
1
‡
‡
CF2OCH3) ]; 149 (15, C7H8F3 ); 136 (50, C6H7F3 );
1704.7 (vs, COOH). H NMR (CDCl3) d: 0.68 (s, CH3);

W. Dmowski, K. Piasecka-Maciejewska / Journal of Fluorine Chemistry 105 (2000) 77±82
81
‡
‡
104 (80, C5H6F2 ); 89 (100, C4H4F2 ); 81 (60,
‡
(5.8 g of 60% purity, 20 mmol) was added portionwise over
15 min. The reaction mixture was agitated at 108C for 2 h
after which diisopropylamine (4 ml) was added and the
mixture was slowly warmed to room temperature and ®nally
re¯uxed for 30 min. The solvent was evaporated and the
residue was subjected to chromatography on silica±gel (40:1
hexanes/ether). A yellow fraction (2.7 g) was obtained
which was found by GS-MS to be a 5:1 mixture of ester
10 and diphenyl diselenide. Repeated chromatography using
neat CCl4 as an eluent gave pure ester 10 as colourless oil.
Yield: 1.9 g (84.2%). IR (CCl4) n (cm 1): 1726.0 (vs,
‡
‡
CH3OCF2 ); 77 (40, C3H3F2 ); 69 (40, CF3 ); 55 (18,
‡
C4H7 ).
3.5. Methyl (3R,4S)-1-(phenylseleno)-2,2,3-trimethyl-4-
(trifluoromethyl)cyclopentanecarboxylate (9)
The reaction was carried out by analogy to the literature
procedure [10]. A solution of dicyclohexylamine (3.55 g,
19.6 mmol) in dry THF (130 ml) was cooled to 788C then
n-butyllithium (7.7 ml of a 2.5 M solution in hexanes,
19.25 mmol) was added at such a rate to keep the tempera-
ture below 708C and the reaction mixture was stirred at
788C for 1 h. A solution of ester 6 (3.33 g, 14 mmol) in
THF (25 ml) was added with a syringe and the mixture was
allowed to warm up slowly to 208C (a clear yellowish
solution was formed). After 1 h at 208C, the solution was
20
1
COOMe); 1631.4 (s, C=C). ‰aŠ ˆ‡3.3 (cˆ5, CHCl3). H
D
NMR (CDCl3) d: 1.03 (s, CH3); 1.09 (dd, 3Jˆ7.0 Hz,
3
4Jˆ0.6 Hz, CH3); 1.26 (s, CH3); 2.11(dq, JHHˆ10.1 and
3
3
3
7.0 Hz, 1H); 2.99 (dqd, JHHˆ10.1, JHFˆ8.7 Hz, JHH
ˆ
2.0 Hz, 1H); 6.51 (d, 3Jˆ2.0 Hz, 1H); 3.75 (s, OCH3) ppm.
19F NMR (CDCl3) d: 69.3 (d, 3JHFˆ8.7 Hz, CF3) ppm. The
‡
cooled to
788C and trimethylsilyl chloride (2.78 g,
GC-MS m/z (rel. int., ion): 236 (5%, M ); 221 [44,
(M CH3) ]; 205 [25, (M CH3O) ]; 201 [44, (M CH3
‡ ‡
25.6 mmol) was added after which the temperature was
raised to 08C for 1 h then cooled again to 788C and a
solution of phenylselenyl chloride (3.9 g, 20.3 mmol) in
THF (25 ml) was added dropwise. The reaction mixture
was slowly warmed to room temperature and stirred over-
night; a dense slurry was formed. The solvents (THF,
hexanes) were removed on a rotary evaporator, the residue
was slurried with hexanes (150 ml), ®ltered and the inor-
ganic precipitate (LiCl) was washed with hexanes
(2 mlÂ150 ml). The combined ®ltrate was evaporated and
the residue was separated by column chromatography on
silica gel (40:1 hexanes/ether). The ®rst, intense yellow
fraction (1.5 g) was identi®ed as diphenyl diselenide GC-
‡
‡
‡
HF) ]; 189 (29, C9H8F3O ); 177 [100, (M CO2CH3) ];
‡
‡
‡
161 (42, C8H8F3 ); 141 (41, C8H7F2 ); 91 (15, C4H5F2 );
‡
‡
‡
77 (15, C3H3F2 ); 69 (16, CF3 ); 68 (20, C5H8 ); 59 (36,
‡
‡
‡
CH3CO2 ); 43 (24, C3H7 ); 41 (31, C3H5 ). Analysis:
Found: C, 55.8; H, 6.3; F, 24.1%. Calculated for
C11H15F3O2 (236.23): C, 55.9; H, 6.4; F, 24.1%.
3.7. (3S,4R)-Hydroxymethyl-3-(trifluoromethyl)-4,5,5-
trimethylcyclopentene (1)
A suspension of lithium aluminium chloride (0.28 g,
7.4 mmol) in ether (50 ml) was added dropwise (20 min)
to a stirred solution of ester 10 in ether (70 ml) at 08C. The
reaction was monitored by GLC; the reaction was completed
in 15 min after addition of LiAlH4. Hydrochloric acid (1%,
150 ml) was added, the organic layer was separated, water
layer was extracted with ether (2 mlÂ100 ml) and the
combined extract washed with water and dried over MgSO4.
Evaporation of the solvent gave compound 1 (1.22 g, yield
90%) contaminated with ca. 10% of saturated product (m/e
MS m/z: 316, 314, 312, 310 (314, 85% M 80Se); 234 (38%,
‡
Ph-Se80-Ph ); 157 (100%, PhSe80‡); 77 (97%, Ph ). The
second, slightly yellowish fraction was found by GC-MS to
be a ca. 19:1 mixture of epimers of selenide 9. Yield: 4.48 g
(81%). Recrystallisation from hexanes gave compound 9 as
‡
‡
white soft crystals with epimers ratio 67:1 (3.76 g). IR
20
(CCl4) n (cm 1): 1724 (vs, COOMe). ‰aŠ ˆ 66.0 (cˆ5,
D
1
3
CHCl3). H NMR (CDCl3) d: 0.83 (s, CH3); 1.04 (dd, Jˆ
6.6 Hz, 4Jˆ0.6 Hz, CH3); 1.37 (s, CH3); 2.09 (dd,
‡
JABˆ16.3 Hz, 3Jˆ5.1 Hz, 1H); 2.36 (ddqd, JHHˆ11.8
210, M ). Careful separation by column chromatography
(SiO2, 20:1 hexanes/ether) gave pure unsaturated alcohol 1
3
3
3
and 10.8 Hz, JHFˆ9.7 Hz, JHHˆ5.1 Hz, 1H); 2.68 (dd,
JABˆ16.3 Hz, 3Jˆ11.8 Hz, 1H); 2.70 (dq, 3Jˆ10.8 and
6.6 Hz, 1H); 3.70 (s, OCH3); 7.35 and 7.48 (m, 5H) ppm.
19F NMR (CDCl3) d: 68.5 (d, 3JHFˆ9.7 Hz, CF3) ppm. The
(0.75 g) as a colourless oil possessing a weak terpenic odour.
20
IR (®lm) n (cm 1): 3326 (vs, OH). ‰aŠ ˆ‡55.7 (cˆ2.5,
D
CHCl3). 1H NMR (CDCl3) d: 0.90 (s, CH3); 1.06 (s, CH3);
GC-MS m/z (rel. int., ion): 394 (11%, M 80Se); 335 [1,
1.07 (dd, Jˆ7.0 Hz, Jˆ0.65 Hz, CH3); 2.07 (dq, JHH
ˆ
‡
3
4
3
‡
‡
3
3
(M CO2CH3) ]; 237 [20, (M±PhSe) ]; 177 (100,
‡
9.6 and 7.0 Hz, 1H); 2.91 (dqm, JHHˆ8.7, JHFˆ9.6 Hz,
3JHHˆ1.7 Hz, 1H); 4.22 (m, CH2OH); 5.48 (q, 3J and
4Jˆ1.7 Hz, 1H) ppm. 19F NMR (CDCl3) d: 70.0 (d,
3JHFˆ8.7 Hz, CF3) ppm. The GC-MS m/z (rel. int., ion):
‡
‡
C9H12F3 ); 158 (15, C9H12F2 ); 77 (8, Ph ); 59 (10,
‡
CH3CO2 ). HRMS: found: 394.06564. C17H21F3O2Se80
requires: 394.06589.
‡
‡
208 (18%, M ); 193 [40, (M CH3) ]; 177 [100,
‡ ‡
3.6. Methyl (3S,4R)-3-(trifluoromethyl)-4,5,5-
trimethylcyclopentenecarboxylate (10)
(M CH2OH) ]; 175 [72, (M CH3 H2O) ]; 163 (16,
‡ ‡
C8H10F3 ); 155 (24, C9H9F2 ); 135 (12); 127 (18); 105
‡
‡
‡
(8, C8H9 ); 91 (13); 55 (9, C4H7 ); 41 (31, C3H5 ).
Analysis: Found: C, 57.9; H, 7.5; F, 27.3%. Calculated
for C10H15F3O (208.22): C, 57.8; H, 7.3; F, 27.4%.
A solution of 9 (3.76 g, 9.56 mmol) in methylene chloride
(100 ml) was cooled to 108C and m-chloroperbenzoic acid

82
W. Dmowski, K. Piasecka-Maciejewska / Journal of Fluorine Chemistry 105 (2000) 77±82
[7] W. Dmowski, K. Piasecka-Maciejewska, J. Fluorine Chem. 97 (1999)
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