Stereoselective synthesis of substituted bicyclo-[3.3.1]-nonan-9-ones by additions of enamines of cyclohexanones to 4-Ethoxy-1,1,1-trifluorobut-3-ene-2-one

Article abstract of DOI:10.1016/S0040-4020(00)00596-2

Addition of the pyrrolidine enamine of cyclohexanone to 4-ethoxy-1,1,1-trifluorobut-3-ene-2-one affords a single diastereoisomer of 4-ethoxy-2-hydroxy-2-trifluoromethylbicyclo[3.3.1]nonan-9-one. Similarly the pyrrolidine enamine of 4-methylcyclohexanone a

Full text of DOI:10.1016/S0040-4020(00)00596-2

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 7255–7260
Stereoselective Synthesis of Substituted
Bicyclo-[3.3.1]-nonan-9-ones by Additions of Enamines of
Cyclohexanones to 4-Ethoxy-1,1,1-trifluorobut-3-ene-2-one
*
Rebecca J. Andrew, John M. Mellor and Gillian Reid
Department of Chemistry, University of Southampton, Southampton SO17 1BJ, UK
Received 22 March 2000; revised 8 June 2000; accepted 22 June 2000
Abstract—Addition of the pyrrolidine enamine of cyclohexanone to 4-ethoxy-1,1,1-trifluorobut-3-ene-2-one affords a single diastereo-
isomer of 4-ethoxy-2-hydroxy-2-trifluoromethylbicyclo[3.3.1]nonan-9-one. Similarly the pyrrolidine enamine of 4-methylcyclohexanone
also in a highly diastereoselective manner affords a single bicyclic ketone. In the latter case a single crystal X-ray diffraction analysis permits
unambiguous determination of all stereochemical detail. Other examples of addition to 4-ethoxy-1,1,1-trifluorobut-3-ene-2-one are
discussed. The mechanistic explanation of the unusually high selectivity is discussed. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Introduction
ketones have been described. A rather specific route, lacking
generality, is the reaction of trifluoroacetic anhydride with
tertiary amines. Discovered in Russia9 and developed by
Schreiber10 the reaction is limited in utility to triethylamine,
but has been used11 in the synthesis of fluorinated hetero-
cycles. A more general route developed by Hojo et al.12 is
based on nucleophilic substitutions of other b-substituted
unsaturated ketones. A third route13 is based on the reaction
of lithium derivatives of enamines with electrophiles such
as ethyl trifluoroacetate, or on the direct acylation14 of
enamines. The progress in preparation of b-substituted
unsaturated trifluoromethylketones is further illustrated by
the preparation15 of b-tellurium substituted ketones. With a
ready access to this broad range of b-substituted unsaturated
trifluoromethylketones it is surprising that their use as
building blocks has been relatively less investigated. Here
we describe their first use in the synthesis of fluorinated
alicyclics. We were interested to explore the chemistry of
the more readily available 4-alkoxy-1,1,1-trifluorobut-3-
ene-2-ones (2) and 4-dialkylamino-1,1,1-trifluorobut-3-
ene-2-ones (3) as building blocks with other nucleophilic
reagents such as enamines. We discuss here the products of
reaction with enamines of cyclic ketones and in particular we
describe the highly stereo- and regio-selective addition of
pyrrolidine enamines of cyclohexanones to 4-ethoxy-1,1,1-
trifluorobut-3-ene-2-one (4). The resulting high selectivity
permits an efficient route to be established to fluorinated
bicyclo[3.3.1]nonanones. With enamines of acyclic ketones
fluorinated monocyclic products can be obtained.
The present importance of organofluorine compounds,
whether they be aromatic, aliphatic or alicyclic,1 has
stimulated the development of new synthetic routes. The
problems of direct introduction of fluorine witnessed by
the comment2 ‘difficulties in the synthesis of C–F bonds
persist—even for experts’ have encouraged the synthesis
of building blocks incorporating the desired fluorinated sub-
groups. There has been extensive recent interest in the use of
4-substituted-1,1,1-trifluorobut-3-ene-2-ones (1) as building
blocks. In other papers3,4 we describe their use in a general
synthesis of aliphatic unsaturated ketones and in the
synthesis of fluorinated aromatics. In this paper we describe
their use in the synthesis of fluorinated alicyclic ketones.
There have been earlier studies with substituted 1,1,1-
trifluorobut-3-ene-2-ones (1) having chlorine, oxygen,
sulfur or nitrogen substituted at the 4-position. The chlori-
nated derivatives have been prepared and used to permit the
synthesis5 of a wide series of enaminoketones via nucleo-
philic displacements. The access to the 4-alkoxy series has
been well developed based on Friedel and Crafts acylation6
of the appropriate vinyl ether. A similar route from vinyl
sulfides has been used7 to prepare sulfur substituted
derivatives.
With subsequent oxidation to afford intermediate sulfones a
new route8 to heteroaryl substituted trifluoromethyl ketones
has been established. A number of routes to the enamino-
Keywords: addition; enamines; organofluorine; phenols; X-ray diffraction.
* Corresponding author. Tel.: ϩ44-(0)23-8059-2392; fax: ϩ44-(0)23-
8059-6805; e-mail: jmm4@soton.ac.uk
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00596-2

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R. J. Andrew et al. / Tetrahedron 56 (2000) 7255–7260
Scheme 1.
Results and Discussion
was maintained in the reaction of the enamine (9) of
4-methylcyclohexanone, which gave the bicyclic ketone
(10) in 90% yield. Additions to other enamines of cyclic
and acyclic ketones were illustrated by synthesis of the
bicyclic ketone (11) from the enamine of cycloheptanone
(12) in 44% yield and of the cyclohexenone (13) from the
enamine of 3-pentanone (14) in 39% yield. Most of the
structural features of the products can be understood by
analysis of the likely course of the reactions. In the most
complex case, addition to the enamine of 4-methylcyclo-
hexanone can be rationalised mechanistically, but the
outcome was also confirmed by a single crystal X-ray analy-
sis of the structure of the hydroxyketone product (10). The
first step, a Michael addition, is followed by a proton
transfer to afford an intermediate enamino ketone (15)
(see Scheme 1). The initial carbon–carbon bond forming
step takes place from a pseudo-chair conformation with
the methyl group occupying an equatorial position and
with the addition occurring from the less hindered trans
face. A similar stereochemical outcome is observed16,17 in
other reactions of enamines of 4-methylcyclohexanone.
Reaction with acrolein16 affords a bicyclononanone having
the methyl group in the same exo, equatorial position. Simi-
larly only exo-7-methylbicyclononane-2,9-dione is
isolated17 following reaction with acrylolyl chloride. The
stereochemical outcome of the addition defining the stereo-
chemistry of the ethyloxy group follows from Newman
projections (A) and (B) (Fig. 1). In the former case leading
to the observed product, steric interactions are minimised. It
is probable that those steps leading to this intermediate (15)
are mainly kinetically controlled. In contrast the step which
determines the stereochemistry of the hydroxyl group, could
be kinetically or thermodynamically controlled. The
possibility of strong hydrogen bonding between the axial
The study of reaction of 4-substituted-1,1,1-trifluoro-3-
buten-2-ones (1) with enamines was initiated with the
4-dimethylaminobutenone (5). Attempted reaction of the
pyrrolidino enamine of cyclohexanone (6) with the ketone
(5) failed to afford products via carbon–carbon bond forma-
tion. Instead some exchange of the enamines was observed
affording mixtures containing the pyrrolidino enamino
ketone (7). To circumvent this exchange reaction the pyrro-
lidino enamino ketone (7) was reacted with the pyrrolidino
enamine of cyclohexanone (6). However, no addition
products were observed either by reaction in ether at room
temperature or under reflux in toluene.
However, the 4-alkoxy-1,1,1-trifluorobut-3-ene-2-ones (2)
are more reactive than their enamine analogues. Reaction
of 4-ethyloxy-1,1,1-trifluorobut-3-ene-2-one (4), used crude
from ethyl vinyl ether, with the pyrrolidino-enamine of
cyclohexanone gave the bicyclic ketone (8), after hydrolysis,
as a single diastereoisomer in 88% overall yield. The gener-
ality of the reaction was established by addition of other
enamines to the alkoxyketone (4). The high stereoselectivity
Figure 1. Newman projections of diastereoisomeric transition states A and B.

R. J. Andrew et al. / Tetrahedron 56 (2000) 7255–7260
7257
Figure 2. Structure of 4-(ethyloxy)-2-hydroxy-7-methyl-2-(trifluoro-
methyl)bicyclo[3.3.1]nonan-9-one (10).
hydroxy and ethyloxy groups could define the observed
stereochemistry of the product (10). The structure of the
product (10) from 4-methylcyclohexanone was established
by an X-ray study (see Fig. 2). This X-ray analysis both
supported the mechanistic commentary and showed
interesting structural features. Deformations of the more
substituted ring, associated with the reflex effect18 can be
observed. The pinching imposed by the bicyclic skeleton
leads to a splaying apart of the ethyloxy and hydroxy
groups. Based on the established structure of the hydroxy-
ketone (10) derived from 4-methylcyclohexanone, a similar
stereochemistry could be assigned to the products (8) and
(11) derived from cyclohexanone and cycloheptanone,
respectively. The three bicyclic hydroxyketones (8), (10)
and (11) have common NMR spectral features, notably
the position of the equatorial proton adjacent to the ethyloxy
group, which is observed at 4.03 ppm in the ketone (8), at
4.04 ppm in the methyl analogue (10) and at 3.97 ppm in the
bicyclododecanone (11). The monocyclic hydroxyketone
(13) is obtained as a mixture of diastereoisomers. The two
isomers can be efficiently dehydrated to give the fluorinated
phenol (16) in 73% yield. In the light of the present interest
in fluoroaromatics as pharmaceutical intermediates, this
novel entry to fluorinated phenols is noteworthy.
In summary these additions illustrate the utility of 4-alkoxy-
1,1,1-trifluorobut-3-ene-2-ones (2) as synthons. Whereas
with more reactive nucleophiles use3 of 4-dialkylamino-
1,1,1-trifluorobut-3-ene-2-ones (3) offers some advantage,
in reactions with enamines the greater reactivity of the
alkoxy substituted ketones is required to permit efficient
reaction.
Experimental
General techniques
Petroleum ether refers to the fraction boiling within the
range 40–60ЊC. Dimethylformamide was distilled from
molecular sieves, dichloromethane and triethylamine from
calcium hydride, diethyl ether and toluene from sodium, and
anhydrous ethanol by distilling over magnesium. Melting
points were determined using an electrothermal Gallenkamp
apparatus and are uncorrected. IR spectra were recorded on
a Perkin Elmer 1600 series FTIR spectrometer as Nujol
mulls, dichloromethane solutions or using sodium chloride
disks. Mass spectra were recorded on a VG Analytical
70-250-SE spectrometer for FAB and EI spectra and on a

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R. J. Andrew et al. / Tetrahedron 56 (2000) 7255–7260
Micromass Platform quadrupole mass analyser for APCI
distilled 1-(4-methyl-1-cyclohexenyl)tetrahydro-1H-pyrrole
(9) (0.40 g, 2.4 mmol) in anhydrous ether (2 ml). After stir-
ring for 72 h at room temperature, water (5 ml) and diethyl
ether (5 ml) were added, the reaction mixture was worked
up as described above and the resultant red oil was purified
by flash column chromatography (silica gel, petroleum
ether/ethyl acetate 7:3) to give the title compound (10) as
a solid (0.28 g, 90%) and (E)-1,1,1-trifluoro-4-tetrahydro-
1H-1-pyrrolyl-3-buten-2-one (7) (0.02 g, 9%) as colourless
crystals. Recrystallisation of the title compound (10) from
n-pentane afforded colourless crystals, mp 66–67ЊC; Found:
C, 55.7; H. 6.6. C13H19F3O3 requires C, 55.7; H, 6.8%; dH
4.14 (1H, s, OH), 4.04 (1H, br t, Jˆ4.0 Hz, Heq-4), 3.62 (1H,
dq, Jˆ9.0, 7.0 Hz, OCH2CH3), 3.42 (1H, dq, Jˆ9.0, 7.0 Hz,
OCH2CH3), 2.78 (2H, m, Heq-1, Heq-5), 2.68 (1H, dd,
Jˆ15.4, 4.0 Hz, Heq-3), 2.25 (3H, m, Hax-3, Hax-7, Heq-6
or Heq-8), 2.08 (1H, m, Heq-6 or Heq-8), 1.72 (1H, ddd,
Jˆ14.3, 12.1, 5.5 Hz, Hax-6 or Hax-8), 1.56 (1H, m, Hax-6
or Hax-8), 1.14 (3H, t, Jˆ7.0 Hz, OCH2CH3) and 0.88 (3H, t,
Jˆ7.0 Hz, CH3); dC 213.40 (C-9), 124.67 (q, JC–Fˆ284 Hz,
CF3), 81.31 (C-4), 79.34 (q, JC–Fˆ29 Hz, C-2), 65.18
(OCH2CH3), 54.18 (C-1), 49.98 (C-5), 39.28 and 38.62
(C-6 and C-8), 33.43 (C-3), 24.75 (C-7), 22.27 (CH3) and
15.37 (OCH2CH3); dF Ϫ81.57 (CF3); nmax (cmϪ1) 3458
(OH), 2961, 2875, 1728 (CO), 1460, 1276, 1160, 1118,
1021; found Mϩ 280.1278, C13H19F3O3 requires Mϩ
280.1286 m/z 280 (Mϩ, 20%), 262 (16), 234 (15), 218
(34), 169 (100), 151 (7), 141 (74) and 112 (36).
1
and ES spectra. H and 13C NMR spectra were recorded
on a Bruker WH-300 spectrometer and chemical shifts,
expressed in ppm, are relative to the internal reference,
tetramethylsilane. Coupling constants are quoted in Hz.
19F NMR spectra were recorded using hexafluorobenzene
as an internal standard. Analytical thin layer chromato-
graphy (TLC) was performed on precoated Macherey-
Nagel ALUGRAM SIL G/UV254 aluminium backed plates
and compounds were visualised by UV light, iodine or
sulfuric acid. Flash column chromatography was performed
using silica gel 60 (Macherey-Nagel, 230–400 mesh).
Elemental analyses were undertaken at University College,
London.
4-(Ethyloxy)-2-hydroxy-2-(trifluoromethyl)bicyclo[3.3.1]-
nonan-9-one (8). To a stirred solution of 4-dimethylamino-
pyridine (1 mg, 8×10Ϫ3 mmol) and trifluoroacetic
anhydride (0.27 g, 1.3 mmol) in anhydrous dichloro-
methane (1.5 ml) was added dropwise at Ϫ10ЊC ethyl
vinyl ether (0.08 g, 1.1 mmol). After stirring for 19 h at
0ЊC the mixture was allowed to warm to room temperature
and the solvent removed in vacuo. To the stirred resulting
oil was added dropwise at room temperature a solution of
freshly distilled 1-(1-cyclohexenyl)tetrahydro-1H-pyrrole
(6) (0.36 g, 2.4 mmol) in anhydrous ether (2 ml). After stir-
ring for 77 h at room temperature, water (5 ml) and diethyl
ether (5 ml) were added. The two phases were separated and
the aqueous phase extracted with diethyl ether (5×5 ml).
The combined organic phases were dried (MgSO4) and the
solvent removed in vacuo. The resultant orange oil was
purified by flash column chromatography (silica gel,
petroleum ether/ethyl acetate 1:1) to give the title compound
(8) as a solid (0.26 g, 88%) and (E)-1,1,1-trifluoro-4-tetra-
hydro-1H-1-pyrrolyl-3-buten-2-one (7) (0.02 g, 9%) as
colourless crystals. Recrystallisation of the title compound
(8) from diethyl ether afforded colourless crystals, mp 75–
76ЊC; Found: C, 54.3; H. 6.1. C12H17F3O3 requires C, 54.1;
H, 6.4%; dH 4.21 (1H, s, OH), 4.03 (1H, br t, Jˆ4.0 Hz, Heq-
4), 3.63 (1H, dq, Jˆ9.0 Hz, 7.0, OCH2CH3), 3.42 (1H, dq,
Jˆ9.0, 7.0 Hz, OCH2CH3), 2.82 (2H, br s Heq-1, Heq-5), 2.63
(1H, dd, Jˆ15.4, 4.0 Hz, Heq-3), 2.29 (2H, m, Hax-3, Heq-6
or Heq-8), 2.00 (4H, m, Heq-7, Hax-6, Hax-8 and Heq-6 or
Heq-8), 1.58 (1H, m, Hax-7), 1.15 (3H, t, Jˆ7.0 Hz,
OCH2CH3); dC 213.09 (C-9), 124.68 (q, JC–Fˆ284 Hz,
CF3), 81.40 (C-4), 79.36 (q, JC–Fˆ29 Hz, C-2), 65.19
(OCH2CH3), 54.39 (C-1), 50.08 (C-5), 33.17 (C-3), 30.82
and 30.29 (C-6 and C-8), 18.29 (C-7) and 15.37
(OCH2CH3); dF Ϫ81.57 (CF3); nmax (cmϪ1) 3345 (OH),
2975, 2862, 1718 (CO), 1462, 1281, 1155, 1138, 1023,
972, 873; Found Mϩ 266.1115, C12H17F3O3 requires Mϩ
266.1130 m/z 266 (Mϩ,17%), 248 (27), 220 (20), 204
(45), 169 (97), 151 (17), 141 (100) and 98 (33).
9-(Ethyloxy)-7-hydroxy-7-(trifluoromethyl)bicyclo[4.3.1]-
decan-10-one (11). To a stirred solution of 4-dimethyl-
aminopyridine (1 mg, 8×10Ϫ3 mmol) and trifluoroacetic
anhydride (0.27 g, 1.3 mmol) in anhydrous dichloro-
methane (1.5 ml) was added dropwise at Ϫ10ЊC ethyl
vinyl ether (0.08 g, 1.1 mmol). After stirring for 19 h at
0ЊC the mixture was allowed to warm to room temperature
and the solvent removed in vacuo. To the stirred resulting
oil was added dropwise at room temperature a solution of
freshly distilled 1-(1-cycloheptenyl)tetrahydro-1H-pyrrole
(12) (0.40 g, 2.4 mmol) in anhydrous ether (2 ml). After
stirring for 76 h at room temperature, 5% aqueous acetic
acid (20 ml) was added and the mixture was heated under
reflux for 90 min. The mixture was cooled to room tempera-
ture, worked up as described above and the resultant brown
oil was purified by flash column chromatography (silica gel,
petroleum ether/ethyl acetate 3:2) to give the title compound
(11) as a solid (0.14 g, 44%) and (E)-1,1,1-trifluoro-4-tetra-
hydro-1H-1-pyrrolyl-3-buten-2-one (7) (0.03 g, 14%) as a
colourless solid. Recrystallisation of the title compound (11)
from n-pentane afforded colourless needles, mp 82–83ЊC;
Found: C, 55.7; H. 6.6. C13H19F3O3 requires C, 55.7; H,
6.8%; dH 3.97 (1H, dt, Jˆ10.2, 6.0 Hz, Hax-9), 3.53 (1H,
dq, Jˆ9.0, 7.0 Hz, OCH2CH3), 3.49 (1H, s, OH), 3.41 (1H,
dq, Jˆ9.0, 7.0 Hz, OCH2CH3), 3.19 (1H, dt, Jˆ9.8, 4.9 Hz,
Heq-1), 2.76 (1H, br t, Jˆ5.1 Hz, Heq-6), 2.18 (1H, d,
Jˆ5.2 Hz, Heq-8), 2.17 (1H, d, Jˆ10.7 Hz, Hax-8), 1.65
(8H, m, H-2, H-3, H-4, H-5), 1.18 (3H, t, Jˆ7.0 Hz,
OCH2CH3; dC 211.63 (C-10), 125.21 (q, JC–Fˆ286 Hz,
CF3, 75.54 (q, JC–Fˆ29 Hz, C-7), 73.16 (C-9), 64.13
(OCH2CH3), 55.99 (C-6), 51.83 (C-1), 30.12 (C-8), 25.78,
25.04 and 21.54 (C-2, C-3, C-4 and C-5), and 15.49
(OCH2CH3); dF Ϫ81.98 (CF3); nmax (cmϪ1) 3422 (OH),
2936, 2873, 1703 (CO), 1456, 1280, 1164, 1109, 1076;
4-(Ethyloxy)-2-hydroxy-7-methyl-2-(trifluoromethyl)bi-
cyclo[3.3.1]nonan-9-one (10). To a stirred solution of 4-
dimethylaminopyridine (1 mg, 8×10Ϫ3 mmol) and trifluoro-
acetic anhydride (0.27 g, 1.3 mmol) in anhydrous dichloro-
methane (1.5 ml) was added dropwise at Ϫ10ЊC ethyl vinyl
ether (0.08 g, 1.1 mmol). After stirring for 19 h at 0ЊC the
mixture was allowed to warm to room temperature and the
solvent removed in vacuo. To the stirred resulting oil was
added dropwise at room temperature a solution of freshly

R. J. Andrew et al. / Tetrahedron 56 (2000) 7255–7260
7259
Found Mϩ 280.1283, C13H19F3O3 requires Mϩ 280.1286 m/z
280 (Mϩ, 29%), 262 (26), 234 (16), 218 (25), 169 (100), 141
(78) and 112 (32).
The combined organic phases were washed with 2 M
sodium hydroxide solution (5 ml) and the aqueous phase
extracted with dichloromethane (2×5 ml). The combined
organic phases were dried (MgSO4) and the solvent
removed in vacuo. The resultant brown oil was purified by
flash column chromatography (silica gel, petroleum ether/
ethyl acetate 88:12) to give the title compound (16) as a
colourless oil (0.04 g, 73%); dH 7.14 (1H, d, Jˆ8.1 Hz,
H-5), 7.05 (1H, d, Jˆ8.1 Hz, H-4), 4.25 (1H, br s, OH),
2.35 (3H, d, Jˆ1.1 Hz, C-6-CH3), 2.30 (3H, s, C-2-CH3);
dC 152.99 (C-1), 127.87 (C-5), 127.13 (C-2), 124.65 (q,
JC–Fˆ273 Hz, CF3), 121.92 (C-6), 117.82 (q, JC–Fˆ6 Hz,
C-4), 16.36 (C-6-CH3) and 11.76 (C-2-CH3); dF Ϫ94.92
(CF3); nmax (cmϪ1) 3780 (OH), 2985, 2935, 1320, 1241,
1173, 1119, 1013; m/z 190 (Mϩ, 75%), 121 (34), 86 (100).
5-Hydroxy-2,6-dimethyl-5-(trifluoromethyl)-2-cyclo-
hexen-1-one (13). To a stirred solution of 4-dimethylamino-
pyridine (1 mg, 8×10Ϫ3 mmol) and trifluoroacetic
anhydride (0.27 g, 1.3 mmol) in anhydrous dichloro-
methane (1.5 ml) was added dropwise at Ϫ10ЊC ethyl
vinyl ether (0.08 g, 1.1 mmol). After stirring for 19 h at
0ЊC the mixture was allowed to warm to room temperature
and the solvent removed in vacuo. To the stirred resulting
oil was added dropwise at room temperature a solution of
freshly distilled 1-(Z-1-ethyl-1-propenyl)tetrahydro-1H-
pyrrole (14) (0.33 g, 2.4 mmol) in anhydrous ether (2 ml).
After stirring for 74 h at room temperature, 5% aqueous
acetic acid (20 ml) was added and the mixture was heated
under reflux for 90 min. The mixture was allowed to cool to
room temperature, worked up as described above and the
resultant brown oil was purified by flash column chromato-
graphy (silica gel, petroleum ether/ethyl acetate 7:3) to give
the title compound (13) as a yellow oil (0.09 g, 39%) and
(E)-1,1,1-trifluoro-4-tetrahydro-1H-1-pyrrolyl-3-buten-2-one
(7) (0.03 g, 14%) as a colourless solid. The title compound
(13) was isolated as a mixture (3:2) of diastereoisomers, dH
6.52 (1H, br s, H-3), 3.50 (0.6H, br s, OH), 3.18 (0.4H, br s
OH) 2.69 (3H, m, H-4, H-6), 1.79 (3H, s, C-2-CH3), 1.25
(1.2H, dd, Jˆ7.0, 1.1 Hz, C-6-CH3), 1.17 (1.8H, dd, Jˆ7.4,
1.5 Hz, C-6-CH3); dC 200.15 (C-1), 198.17 (C-1), 137.57
(C-3), 137.38 (C-3), 134.92 (C-2), 133.87 (C-2), 125.43 (q,
JC–Fˆ287 Hz, CF3), 125.16 (q, JC–Fˆ286 Hz, CF3), 76.65
(q, JC–Fˆ28 Hz, C-5), 76.58 (q, JC–Fˆ28 Hz, C-5), 48.25
(C-6), 46.16 (C-6), 32.34 (C-4), 29.34 (C-4), 15.93 (C-2-
CH3), 15.87 (C-2-CH3), 13.33 (C-6-CH3) and 8.77 (C-6-
CH3); dF Ϫ82.40 (CF3); nmax (cmϪ1) 3426 (OH), 2983,
2928, 1673 (CO), 1303, 1172, 1130; Found Mϩ 208.0720,
C9H11F3O2 requires Mϩ 208.0711 m/z 208 (Mϩ, 39%), 191
(6), 163 (19), 139 (13), 82 (100). The minor fraction was
recrystallised from petroleum ether to afford (E)-1,1,1-
trifluoro-4-tetrahydro-1H-pyrrolyl-3-buten-2-one (7), mp
68–69ЊC; Found: C, 49.6; H, 5.0; N, 7.2. C8H10F3NO
requires C, 49.7; H, 5.2; N, 7.3%; dH 8.07 (1H, d,
Jˆ12.1 Hz, H-4), 5.23 (1H, d, Jˆ12.1 Hz, H-3), 3.62 (2H,
t, Jˆ6.6 Hz, NCH2), 3.31 (2H, t, Jˆ6.6 Hz, NCH2), 2.08
(2H, dquin, Jˆ1.5, 6.6 Hz, CH2), 1.99 (2H, dquin, Jˆ1.5,
6.6 Hz, CH2); dC 176.86 (q, JC–Fˆ33 Hz, C-2), 152.67
(C-4), 118.02 (q, JC–Fˆ291 Hz, C-1), 88.39 (C-3), 53.24
(NCH2), 47.70 (NCH2), 25.20 (CH2), 25.06 (CH2); dF
Ϫ84.67 (CF3); nmax (cmϪ1) 2984, 2884, 1654, 1572, 1256,
1173, 1090, 894 and 769; Found Mϩ 193.0714, C8H10F3NO
requires Mϩ 193.0714 m/z 193 (Mϩ, 29%), 124 (100), and
96 (5).
X-Ray structural analysis of 4-(ethyloxy)-2-hydroxy-7-
methyl-2-(trifluoromethyl)bicyclo[3.3.1]nonan-9-one (10).
A rather weakly diffracting crystal (0.35×0.22×0.18 mm)
was obtained by recrystallisation from n-pentane. Crystal
data: C13H19F3O3, Mˆ280.29, triclinic space group P-1
˚
(#2), aˆ12.435(7), bˆ12.561(6), cˆ10.068(4) A, aˆ
3
˚
90.60(4), bˆ98.19(4), gˆ117.74(3)Њ, Vˆ1372(1) A ,
Zˆ4. Dcalcˆ1.356 g cmϪ3, mˆ1.20 cmϪ1, F(000)ˆ592.
Data collection used a Rigaku AFC7S four-circle diffract-
˚
ometer [l(Mo-Ka)ˆ0.71073 A] operating at 150 K. 2923
unique data were collected (Rintˆ0.034) of which 1913
with IϾ2.5s(I) were used in all calculations. The structure
was solved using shelxs-8619 and refined using texsan,20
which revealed two essentially indistinguishable indepen-
dent molecules in the asymmetric unit. The O and F atoms
were refined anisotropically and H atoms were included in
fixed calculated positions. Rˆ0.051, Rwˆ0.59, Goofˆ2.47,
wϪ1ˆs2(F).
Acknowledgements
We thank EPSRC for a Quota Award (R. J. A.).
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