Enantiopure 2-(Trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1,2-diols from a tartaric acid derived scaffold

Article abstract of DOI:10.1002/ejoc.200901153

The synthesis of the four stereoisomers of 2-(trifluoromethyl) tetrahydronaphthalene-1,2-diols and/or their 2-O-allyl derivatives is reported. Nucleophilic trifluoromethylation of a tar taric acid derived keto amide, and a one-pot hydrolysis/oxidative cleavage/intramolecular Friedel-Crafts transformation are the main features of this synthesis.

Full text of DOI:10.1002/ejoc.200901153

FULL PAPER
DOI: 10.1002/ejoc.200901153
Enantiopure 2-(Trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1,2-diols from a
Tartaric Acid Derived Scaffold
Fabien Massicot,[a] Jean Nonnenmacher,[a] Fabienne Grellepois,[a] and Charles Portella*[a]
Keywords: Aromatic substitution / Asymmetric synthesis / Chiral pool / Cyclization / Fluorine
The synthesis of the four stereoisomers of 2-(trifluoromethyl)
taric acid derived keto amide, and a one-pot hydrolysis/oxi-
tetrahydronaphthalene-1,2-diols and/or their 2-O-allyl deriv- dative cleavage/intramolecular Friedel–Crafts transforma-
atives is reported. Nucleophilic trifluoromethylation of a tar-
tion are the main features of this synthesis.
based on our recently reported methodology,[4] where the
key step is a nucleophilic trifluoromethylation of a tartaric
acid derived keto amide.
Introduction
Organofluorine compounds have many applications in
various fields, owing to their particular physicochemical
and biological properties induced by the presence of the
fluorine element.[1] Trifluoromethyl (Tfm) substituted com-
pounds are of particular interest, because of the size, the
high metabolic stability, and the hydrophobic character of
the trifluoromethyl group.[2] We have recently reported dia-
stereoselective methodologies to prepare enantiopure α-
Tfm-α-alkoxy aldehydes from tartaric acid derived diket-
ones[3] and keto amides[4] in only a few steps. The latter,
more general, enabled us to prepare both aliphatic and aro-
matic derivatives, the former being limited to aromatic ones.
On the other hand, several recent patents disclosed the
synthesis of Tfm-substituted tetrahydronaphthalene-1,2-
diol[5] and 1,2-amino alcohol[6] derivatives as anti-inflam-
matory compounds. The synthesis was performed in race-
mic series, some amino alcohols derivatives having been re-
solved by classical selective crystallization of salt dia-
stereomers. These naphthalenediols were prepared from α-
Tfm-α-hydroxy aldehydes.
Scheme 1. Retrosynthetic pathway.
O-Allyl trifluoromethylated intermediate 4 was first syn-
thesized from keto amide 2 prepared from the bis(dimethyl-
amide) of tartaric acid (1),[7] according to the one-pot pro-
cedure depicted in Scheme 2.[4] As previously observed, the
trifluoromethylation step with aliphatic ketones is less dia-
stereoselective than it was with aromatic ones, which is ad-
vantageous to have access to the whole set of stereoisomers.
Unfortunately, the separation of the diastereomers of 4
proved to be difficult and a stepwise procedure had to be
carried out. Thus, trifluoromethylation and subsequent de-
silylation led to carbinols 3, the diastereomers of which
were separated by silica gel chromatography (Scheme 3).
Each diastereomer was then protected as the corresponding
O-allyl ethers 4a and 4b. The R configuration was ascribed
to the major diastereomer according to 19F NMR spec-
troscopy correlation: the CF3 signal of the major R isomer
appears at upper field.[4]
Compounds 4a and 4b were then submitted to hydrolysis
of the ketal moiety and subsequent oxidative cleavage ac-
cording to the reported procedure.[4] Under these acidic
conditions, the intramolecular Friedel–Crafts reaction was
easily activated so that the intermediate aldehyde was di-
rectly converted into the final tetrahydronaphthalene deriv-
ative 5 as a mixture of easily separated diastereomers. As a
We report in this paper the synthesis of the enantiopure
stereoisomers of the 2-O-allyl derivative of 2-(trifluoro-
methyl)naphthalene-1,2-diols and that of the corresponding
diols.
Results and Discussion
The strategy for the asymmetric synthesis of the interme-
diate aldehydes and of the targeted compounds consists of
the retrosynthetic scheme depicted in Scheme 1, which is
[a] Université de Reims-Champagne-Ardenne, Institut de Chimie
Moléculaire de Reims, UMR CNRS 6229, UFR Sciences
Exactes et Naturelles,
B. P. 1039, 51687 Reims cedex 2, France
Fax: +33-3-26913166
E-mail: charles.portella@univ-reims.fr
Eur. J. Org. Chem. 2010, 275–279
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275

F. Massicot, J. Nonnenmacher, F. Grellepois, C. Portella
FULL PAPER
Finally, palladium-catalyzed deallylation[8] of (–)-cis-5
and (–)-trans-5 afforded the corresponding enantiopure 2-
Tfm-tetrahydronaphthalene-1,2-diols (–)-cis-6 and (–)-
trans-6 (Scheme 5).
Scheme 2. Direct synthesis of intermediate 4.
Scheme 5. Conversion of intermediates 5 into 2-Tfm-tetrahydro-
naphthalene-1,2-diols (–)-cis-6 and (–)-trans-6.
Conclusions
We have described the synthesis of enantiopure stereoiso-
mers of 2-(trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-
1,2-diol in a few steps from -tartaric acid, a simple chiral-
pool-derived starting material. The method is based on a
fairly diastereoselective nucleophilic trifluoromethylation
reaction with CF3TMS, the separation of the diastereomers,
and their subsequent one-pot transformation involving a se-
quential ketal hydrolysis/oxidative cleavage/intramolecular
Friedel Crafts reaction. Taking into account that -tartaric
acid is also commercially available, the choice of the start-
ing material may be adapted to the targeted stereoisomer.
Further applications of this strategy to the synthesis of
valuable enantiopure trifluoromethylated building blocks
are in progress and will be reported in a forthcoming paper.
Scheme 3. Stepwise synthesis and separation of intermediates 4.
result, the four stereoisomers of 2-O-allyl-2-(trifluorometh-
yl)-1,2,3,4-tetrahydronaphthalene-1,2-diol were prepared in
a one-pot process from intermediate 4 (Scheme 4).
Experimental Section
General Remarks: THF was distilled from sodium–benzophenone.
DCM (dichloromethane) was distilled from CaH2. Trifluorometh-
ylation reactions were carried out in extra-dry DMF. Phen-
ethylmagnesium chloride was titrated through the combined use of
(+)-menthol and (1,10)-phenanthroline as indicator.[9] (Trifluoro-
methyl)trimethylsilane was distilled (b.p. 56 °C) before use. Others
reagents and solvents were obtained from common commercial
sources and used as received. Thin-layer chromatography using pre-
coated aluminum-backed plates (Merck Kieselgel 60F254) were vis-
ualized by UV light and by an alcoholic solution of phosphomolyb-
dic acid or an aqueous solution of potassium permanganate. Silica
gel (Macherey–Nagel GmbH & Co KG, 40–63 µm, ASTM for col-
umn chromatography) was used for flash chromatography. Prepara-
tive centrifugal thin-layer chromatography was carried out on ro-
tors coated with silica gel 60 PF254 containing gypsum, the layer
thickness was 1 or 2 mm, depending on the amount of product to
purify. Melting points were determined with a Tottoli apparatus
and are uncorrected. Optical rotations were measured at room tem-
perature (ca. 20 °C). NMR spectra were recorded in CDCl3, at fre-
Scheme 4. One-pot, three-step conversion of intermediate 4 into
tetrahydronaphthalene derivatives 5.
276
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Enantiopure 2-(Trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1,2-diols
1
quencies of 250 MHz or 500 MHz for H, 235.3 MHz for 19F, and
aryl), 142.1 (CIV aryl), 170.5 (C=O) ppm. C18H24F3NO4 (375.38):
62.9 MHz or 125.8 MHz for 13C nuclei. Chemical shifts are re-
ported relative to TMS for 1H and 13C NMR spectra and to CFCl3
for 19F NMR spectra. In the 13C NMR spectroscopic data, re-
ported signal multiplicities are related to C-F coupling. The follow-
ing abbreviations are used to indicate the multiplicities: s (singlet),
d (doublet), t (triplet), q (quartet), m (multiplet), br. s (broad sing-
let). The diastereomeric ratios (dr) were determined by 19F NMR
spectroscopic analysis of the crude mixture. HRMS (ESI+) were
recorded with a spectrometer by using an electrospray source in
positive mode. Elemental analysis were performed with a Perkin–
Elmer CHN 2400 apparatus and analyses fell within Ϯ0.4% of the
calculated values. Isopropylidene-protected bis(amide) 1[7] was pre-
pared according to reported procedures from dimethyl 2,3-O-iso-
propylidenetartrate.[10]
calcd. C 57.60, H 6.40, N 3.73; found C 57.69, H 6.64, N 3.81.
(–)-(4R,5R)-5-[(S)-1-Hydroxy-3-phenyl-1-(trifluoromethyl)propyl]-
2,2-dimethyl-[1,3]-dioxolane-4-(dimethyl)carboxyl-amide (3b): M.p.
110–111 °C (PE/EtOAc). [α]D = –14 (c = 1.00, CHCl3). 19F NMR
(235.3 MHz, CDCl3): δ = –76.4 ppm. 1H NMR (250 MHz, CDCl3):
δ = 1.42 (s, 3 H, CH3), 1.46 (s, 3 H, CH3), 1.90–2.16 (m, 2 H, CH2),
2.70–2.94 (m, 2 H, CH2), 2.99 (s, 3 H, NCH3), 3.17 (s, 3 H, NCH3),
3
3
4.62 (d, JHH = 7.6 Hz, 1 H, CH), 4.66 (d, JHH = 8.5 Hz, 1 H,
CH), 5.37 (s, 1 H, OH), 7.19–7.31 (m, 5 H, H aryl) ppm. 13C NMR
(62.9 MHz, CDCl3): δ = 26.0 (CH3), 26.4 (CH3), 28.4 (CH2), 34.9
2
(CH2), 36.0 (NCH3), 37.4 (NCH3), 73.5 (q, JCF = 27.0 Hz, C-
CF3), 74.6 (CH), 77.8 (CH), 109.7 [C(CH3)2], 125.9 (q, JCF
1
=
288.0 Hz, CF3), 125.9, 128.3, 128.4 (CH aryl), 141.8 (CIV aryl),
168.9 (C=O) ppm. C18H24F3NO4 (375.38): calcd. C 57.60, H 6.40,
N 3.73; found C 57.52, H 6.67, N 3.92.
(+)-(4R,5R)-2,2-Dimethyl-5-(3-phenylpropanoyl)-[1,3]-dioxolane-4-
(dimethyl)carboxylamide (2): To a solution of amide 1 (9.77 g,
40.0 mmol) in THF (50 mL) was added, at –10 °C and under an
atmosphere of argon, phenethylmagnesium chloride (44 mL,
44 mmol, 1.1 equiv.). After complete conversion of the starting
amide (reaction monitored by GC), the reaction was quenched with
saturated aqueous NH4Cl and extracted with Et2O (2ϫ). The com-
bined organic layer was washed with brine, dried (MgSO4), and
concentrated under reduced pressure. Chromatography [petroleum
ether (PE)/EtOAc, 76:24] afforded keto amide 2 (6.95 g, 57%) as
white crystals. M.p. 52 °C (PE/Et2O). [α]D = +7 (c = 1.00, CHCl3).
1H NMR (250 MHz, CDCl3): δ = 1.39 (s, 3 H, CH3), 1.41 (s, 3 H,
CH3), 2.95 (m, 4 H, CH2CH2), 2.98 (s, 3 H, NCH3), 3.09 (s, 3 H,
Preparation of O-Allyl Ethers 4: To a solution of carbinol 3 in
DMF (≈1 mL/mmol) was added, at room temperature and under
an atmosphere of argon, potassium tert-butoxide (2.0 equiv.), tetra-
n-butylammonium iodide (TBAI, 0.10 equiv.), and allyl bromide
(AllBr, 2.0 equiv.). After 4 h, the reaction was quenched with satu-
rated aqueous NH4Cl and extracted with Et2O (3ϫ). The combined
organic layer was washed with brine, dried (MgSO4), and concen-
trated under reduced pressure. The residue was then purified by
preparative centrifugal thin-layer chromatography (PE/EtOAc,
90:10).
(–)-(4R,5R)-5-[(R)-1-Allyloxy-3-phenyl-1-(trifluoromethyl)propyl]-
2,2-dimethyl-[1,3]-dioxolane-4-(dimethyl)carboxylamide (4a): Ac-
cording to the general procedure, 3a (2.4 g, 6.4 mmol) was treated
with tBuOK (1.44 g, 12.8 mmol, 2.0 equiv.), TBAI (236 mg,
0.64 mmol, 0.1 equiv.), and AllBr (1.04 mL, 12.8 mmol, 2.0 equiv.)
in DMF (13 mL). Chromatography afforded 4a (2.60 g, 98%) as a
pale-yellow oil. [α]D = –17 (c = 1.00, CHCl3). 19F NMR
(235.3 MHz, CDCl3): δ = –73.6 ppm. 1H NMR (500 MHz, CDCl3):
δ = 1.37 (s, 3 H, CH3), 1.47 (s, 3 H, CH3), 2.24–2.31 (m, 2 H, CH2),
3
3
NCH3), 4.69 (d, JHH = 6.0 Hz, 1 H, CH), 5.16 (d, JHH = 6.0 Hz,
1 H, CH), 7.20 (m, 2 H, H aryl), 7.25–7.27 (m, 3 H, H aryl) ppm.
13C NMR (62.9 MHz, CDCl3): δ = 26.0 (CH3), 26.3 (CH3), 29.1
[C(O)CH2], 36.0 (NCH3), 37.1 (NCH3), 41.0 (CH2Ph), 74.9 (CH),
82.1 (CH), 112.2 [C(CH3)2], 126.1, 128.4, 128.5 (CH aryl), 140.9
(CIV aryl), 168.0 [C(O)N], 208.3 (C=O) ppm. HRMS (ESI+): calcd.
for [C17H23NO4 + Na]+ 328.1525; found 328.1515.
3
Preparation of (Trifluoromethyl)carbinols 3: To a solution of keto
amide 2 (4.50 g, 14.7 mmol) and CF3TMS (2.62 mL, 17.7 mmol,
1.2 equiv.) in DMF (30 mL) was added, at room temperature and
under an atmosphere of argon, potassium carbonate (203 mg,
1.47 mmol, 0.1 equiv.). After 1.5 h, the reaction was quenched with
saturated aqueous NH4Cl and extracted with Et2O (3ϫ). The com-
bined organic layer was washed with brine, dried (MgSO4), and
concentrated under reduced pressure. The crude product was di-
luted in CH2Cl2 and tetra n-butylammonium fluoride trihydrate
(6 g, 19.1 mmol, 1.3 equiv.) was added. After 3 h, the reaction mix-
ture was washed with water and dried (MgSO4), and the solvent
was removed under reduced pressure. Preparative centrifugal thin-
layer chromatography (PE/EtOAc, 90:10) afforded product 3a
(2.6 g, 48%), an intermediate fraction containing 3a + 3b (0.33 g,
6%), and product 3b (0.66 g, 12%) as white crystals.
2.83 (t, JHH = 8.5 Hz, 2 H, CH2), 2.99 (s, 3 H, NCH3), 3.15 (s, 3
2
3
H, NCH3), 4.23 (dd, JHH = 12.5 Hz, JHH = 5.0 Hz, 1 H, OCH-
2
3
aHb), 4.30 (dd, JHH = 12.5 Hz, JHH = 5.0 Hz, 1 H, OCHaHb),
4.94 (d, JHH = 6.0 Hz, 1 H, CH), 5.16 (dd, JHH = 1.5 Hz, JHH
= 10.5 Hz, 1 H, CH=CHcis), 5.28 (d, JHH = 6.0 Hz, 1 H, CH),
5.32 (dd, JHH = 1.5 Hz, JHH = 17.0 Hz, 1 H, CH=CHtrans), 5.88
(m, 1 H, CH=CH2), 7.20–7.23 (m, 3 H, H aryl), 7.29–7.32 (m, 2
H, H aryl) ppm. 13C NMR (125.8 MHz, CDCl3): δ = 25.5 (CH3),
3
2
3
3
2
3
26.6 (CH3), 29.3 (CH2), 31.2 (CH2), 35.9 (NCH3), 37.1 (NCH3),
2
65.4 (OCH2), 72.7 (CH-C-CF3), 77.8 (CH-C=O), 79.1 (q, JCF
=
25.0 Hz, C-CF3), 110.7 [C(CH3)2], 116.0 (CH=CH2), 125.4 (q, 1JCF
= 289.0 Hz, CF3), 126.1, 128.3, 128.5 (CH aryl), 134.3 (CH=CH2),
141.8 (CIV aryl), 168.9 (C=O) ppm. C21H28F3NO4 (415.45): calcd.
C 60.72, H 6.74, N 3.37; found C 60.43, H 6.84, N 3.59. HRMS
(ESI+): calcd. for [C21H28F3NO4 + Na]+ 438.1868; found 438.1875.
(–)-(4R,5R)-5-[(R)-1-Hydroxy-3-phenyl-1-(trifluoromethyl)propyl]-
2,2-dimethyl-[1,3]-dioxolane-4-(dimethyl)carboxyl-amide (3a): M.p.
98–99 °C (PE/EtOAc). [α]D = –20 (c = 1.00, CHCl3). 19F NMR
(–)-(4R,5R)-5-[(S)-1-Allyloxy-3-phenyl-1-(trifluoromethyl)propyl]-2,2-
dimethyl-[1,3]-dioxolane-4-(dimethyl)carboxylamide (4b): According
to the general procedure, 3b (0.80 g, 2.13 mmol) was treated with
(235.3 MHz, CDCl3): δ = –78.9 ppm. 1H NMR (250 MHz, CDCl3): tBuOK (0.48 g, 4.27 mmol, 2.0 equiv.), TBAI (78 mg, 0.21 mmol,
δ = 1.37 (s, 3 H, CH3), 1.47 (s, 3 H, CH3), 1.99 (m, 1 H, CH2),
0.1 equiv.), and AllBr (0.35 mL, 4.27 mmol, 2.0 equiv.).
Chromatography afforded 4b (0.85 g, 96%) as a pale-yellow oil.
3
2.17 (m, 1 H, CH2), 2.87 (t, JHH = 8.6 Hz, 2 H, CH2), 2.99 (s, 3
H, NCH3), 3.18 (s, 3 H, NCH3), 4.64 (d, 3JHH = 7.6 Hz, 1 H, CH), [α]D = –8 (c = 1.00, CHCl3). 19F NMR (235.3 MHz, CDCl3): δ =
4.82 (s, 1 H, OH), 4.88 (d, 3JHH = 7.5 Hz, 1 H, CH), 7.21–7.33 (m, –70.4 ppm. H NMR (500 MHz, CDCl3): δ = 1.40 (s, 3 H, CH3),
1
5 H, H aryl) ppm. 13C NMR (62.9 MHz, CDCl3): δ = 25.4 (CH3),
1.47 (s, 3 H, CH3), 1.98 (m, 1 H, CHaHb), 2.22 (m, 1 H, CHaHb),
26.6 (CH3), 28.9 (CH2), 33.1 (CH2), 36.3 (NCH3), 37.5 (NCH3), 2.77–2.81 (m, 2 H, CH2), 2.99 (s, 3 H, NCH3), 3.14 (s, 3 H, NCH3),
2
3
73.7 (q, JCF = 27.0 Hz, C-CF3), 74.9 (CH), 77.6 (CH), 111.1 4.22–4.23 (m, 2 H, OCH2), 4.95 (d, JHH = 6.0 Hz, 1 H, CH), 5.14
[C(CH3)2], 124.4 (q, 1JCF = 287.0 Hz, CF3), 126.0, 128.3, 128.4 (CH (dd, JHH = 1.5 Hz, JHH = 10.5 Hz, 1 H, CH=CHcis), 5.25 (d,
2
3
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F. Massicot, J. Nonnenmacher, F. Grellepois, C. Portella
FULL PAPER
3JHH = 6.0 Hz, 1 H, CH), 5.28 (dd, 2JHH = 1.5 Hz, 3JHH = 17.0 Hz, (+)-(1R,2S)-2-(Allyloxy)-2-(trifluoromethyl)-1,2,3,4-tetrahydro-
1 H, CH=CHtrans), 5.86 (m, 1 H, CH=CH2), 7.19–7.21 (m, 3 H, H naphthalen-1-ol [(+)-cis-5] and (+)-(1S,2S)-2-(Allyloxy)-2-(trifluoro-
aryl), 7.26–7.30 (m, 2 H, H aryl) ppm. 13C NMR (125.8 MHz,
methyl)-1,2,3,4-tetrahydronaphthalen-1-ol [(+)-trans-5]: According
CDCl3): δ = 25.8 (CH3), 26.5 (CH3), 28.7 (CH2), 32.3 (CH2), 36.0 to the general procedure, 4b (500 mg, 1.21 mmol) in a mixture TFA/
(NCH3), 37.1 (NCH3), 65.2 (OCH2), 72.9 (CH-C-CF3), 78.3 (CH- H2O (3.3 mL) was treated with periodic acid (384 mg, 1.69 mmol).
2
C=O), 79.2 (q, JCF = 25.0 Hz, C-CF3), 111.4 [C(CH3)2], 116.0
Chromatography afforded successively the products (+)-cis-5
(82 mg, 25%) as a pale-yellow oil and (+)-trans-5 (140 mg, 43%)
as white crystals. Data for (+)-cis-5: [α]D = +63 (c = 1.00, CHCl3).
Data for (+)-trans-5: M.p. 84–85 °C (PE/EtOAc). [α]D = +44 (c =
1.00, CHCl3).
1
(CH=CH2), 125.7 (q, JCF = 291.0 Hz, CF3), 126.1, 128.3, 128.5
(CH aryl), 134.3 (CH=CH2), 141.5 (CIV aryl), 169.1 (C=O) ppm.
C21H28F3NO4 (415.45): calcd. C 60.72, H 6.74, N 3.37; found C
60.81, H 6.86, N 3.59. HRMS (ESI+): calcd. for [C21H28F3NO4 +
Na]+ 438.1868; found 438.1863.
Preparation of Tetrahydronaphthalene-1,2-diol Derivatives 6: To a
solution of 2-(allyloxy)-tetrahydronaphthalenols 5 (300 mg,
1.1 mmol) in EtOH (20 mL) was added, at room temperature and
under an atmosphere of argon, tetrakis(triphenylphosphane)palla-
dium (64 mg, 0.055 mmol, 0.05 equiv.) and potassium carbonate
(453 mg, 3.3 mmol, 3 equiv.). The mixture was heated for 30 to
45 min, then cooled to room temperature. Et2O (20 mL) was added,
and the mixture was filtered through Celite. The filtrate was washed
with brine (2ϫ), dried (MgSO4), and concentrated under reduced
pressure. The residue was purified by preparative centrifugal thin-
layer chromatography (PE/EtOAc, 85:15).
Preparation of 2-O-Allyl Tetrahydronaphthalene Derivatives 5: To a
solution of trifluoromethyl ether 4 in a mixture TFA/H2O (10:1)
was added, at room temperature and under an atmosphere of ar-
gon, periodic acid (1.4 equiv.). After 6.5 h the reaction was diluted
with Et2O, quenched with saturated aqueous Na2CO3 and ex-
tracted with Et2O (3ϫ). The combined organic layer was washed
with brine, dried (MgSO4), and concentrated under reduced pres-
sure. The residue was then purified by preparative centrifugal thin-
layer chromatography (PE/Et2O, 97:3).
(–)-(1S,2R)-2-(Allyloxy)-2-(trifluoromethyl)-1,2,3,4-tetrahydronaph-
thalen-1-ol [(–)-cis-5] and (–)-(1R,2R)-2-(allyloxy)-2-(trifluoro-
methyl)-1,2,3,4-tetrahydronaphthalen-1-ol [(–)-trans-5]: According
to the general procedure, 4a (1.8 g, 4.35 mmol) in a mixture of
TFA/H2O (5.5 mL) was treated with periodic acid (1.38 g,
6.07 mmol). Chromatography afforded successively the products
(–)-cis-5 (370 mg, 31%) as a pale-yellow oil and (–)-trans-5 (365 mg,
31%) as white crystals.
(–)-(1S,2R)-2-(Trifluoromethyl)-1,2,3,4-tetrahydronaphthalene-1,2-
diol [(–)-cis-6]: Prepared from (–)-cis-5; reaction afforded (–)-cis-6
(237 mg, 93%) as white crystals. M.p. 90–91 °C (PE/EtOAc). [α]D
= –85 (c = 1.00, CHCl3). 19F NMR (235.3 MHz, CDCl3): δ =
–81.1 ppm. 1H NMR (250 MHz, CDCl3): δ = 1.93 (m, 1 H,
CHaHb-CH2Ar), 2.27 (m, 1 H, CHaHb-CH2Ar), 2.70 (m, 1 H,
CHaHb-Ar), 2.94 (s, 1 H, OH), 3.13 (m, 1 H, CHaHb-Ar), 3.66 (s,
1 H, OH), 5.08 (s, 1 H, CHOH), 7.13 (m, 1 H, H aryl), 7.25–7.28
(m, 2 H, H aryl), 7.53 (m, 1 H, H aryl) ppm. 13C NMR (62.9 MHz,
CDCl3): δ = 23.6 (CH2-Ar), 26.1 (CH2-CH2Ar), 66.6 (OCH), 72.4
(q, 2JCF = 26.0 Hz, C-CF3), 126.2 (q, 1JCF = 286.7 Hz, CF3), 126.7,
127.9, 128.1 and 128.4 (CH aryl), 134.4 and 135.8 (CIV aryl) ppm.
C11H11F3O2 (232.20): calcd. C 56.89, H 4.74; found C 56.51, H
4.47.
(–)-cis-5: [α]D = –66 (c = 1.00, CHCl3). 19F NMR (235.3 MHz,
CDCl3): δ = –73.5 ppm. 1H NMR (250 MHz, CDCl3): δ = 1.99
2
3
3
(ddd, JHH = 14.5 Hz, JHH = 11.0 Hz, JHH = 6.5 Hz, 1 H,
2
3
3
CHaHb-CH2Ar), 2.48 (ddd, JHH = 14.5 Hz, JHH = 5.0 Hz, JHH
= 4.0 Hz, 1 H, CHaHb-CH2Ar), 2.50 (br. s, 1 H, OH), 2.74–2.96
(m, 2 H, CH2Ar), 4.23 (d, JHH = 5.5 Hz, 2 H, OCH2), 4.94 (s, 1
H, CHOH), 5.10 (dd, JHH = 1.5 Hz, JHH = 10.5 Hz, 1 H,
CH=CHcis), 5.15 (dd, JHH = 1.5 Hz, JHH = 17.0 Hz, 1 H,
3
2
3
(–)-(1R,2R)-1,2,3,4-Tetrahydro-2-(trifluoromethyl)naphthalene-1,2-
diol [(–)-trans-6]: Prepared from (–)-trans-5; reaction afforded (–)-
trans-6 (229 mg, 90%) as white crystals. M.p. 128–129 °C (PE/
EtOAc). [α]D = –38 (c = 1.00, CHCl3). 19F NMR (235.3 MHz,
CDCl3): δ = –78.9 ppm. 1H NMR (250 MHz, CDCl3): δ = 1.96–
2.01 (m, 2 H, CHaHb-CH2Ar, OH), 2.28–2.35 (m, 2 H, CHaHb-
CH2Ar, OH), 2.92–2.98 (m, 2 H, CH2-Ar), 4.69 (s, 1 H, CHOH),
2
3
3
3
3
CH=CHtrans), 5.83 (tdd, JHH = 17.0 Hz, JHH = 10.5 Hz, JHH
=
5.0 Hz, 1 H, CH=CH2), 7.10 (d, 3JHH = 6.5 Hz, 1 H, H aryl), 7.18–
3
7.28 (m, 2 H, H aryl.), 7.64 (d, JHH = 6.5 Hz, 1 H, H aryl) ppm.
13C NMR (125.8 MHz, CDCl3): δ = 22.8 (CH2), 24.4 (CH2), 65.6
2
(OCH2), 69.7 (OCH), 77.1 (q, JCF = 25.0 Hz, C-CF3), 117.0
(CH=CH2), 125.9 (q, JCF = 290.5 Hz, CF3), 126.7, 127.5, 127.7,
1
7.15–7.35 (m, 4 H, H aryl) ppm. 13C NMR (62.9 MHz, CDCl3): δ
and 128.1 (CH aryl), 133.7 (CH=CH2), 134.5 and 136.8 (CIV aryl)
ppm. HRMS (ESI+): calcd. for [C14H15F3O2 + Na]+ 295.0922;
found 295.0930.
2
= 22.8 (CH2-Ar), 23.9 (CH2-CH2Ar), 70.5 (OCH), 74.2 (q, JCF
=
1
26.7 Hz, C-CF3), 125.9 (q, JCF = 285.4 Hz, CF3), 126.8, 128.6,
128.7 and 130.0 (CH aryl), 134.8 and 134.9 (CIV aryl) ppm.
C11H11F3O2 (232.20): calcd. C 56.89, H 4.74; found C 57.10, H
4.88.
(–)-trans-5: M.p. 82–83 °C (PE/EtOAc). [α]D = –41 (c = 1.00,
CHCl3). 19F NMR (235.3 MHz, CDCl3): δ = –73.3 ppm. 1H NMR
(250 MHz, CDCl3): δ = 1.90 (br. s, 1 H, OH), 2.18 (m, 1 H, CHaHb-
CH2Ar), 2.38 (m, 1 H, CHaHb-CH2Ar), 2.89–2.98 (m, 2 H,
Acknowledgments
2
3
CH2Ar), 4.12 (d, JHH = 13.0 Hz, JHH = 5.0 Hz, 1 H, OCHaHb),
2
3
4.19 (d, JHH = 13.0 Hz, JHH = 5.0 Hz, 1 H, OCHaHb), 4.91 (s, 1
H, CHOH), 5.00 (dd, JHH = 1.5 Hz, JHH = 10.5 Hz, 1 H,
CH=CHcis), 5.02 (dd, JHH = 1.5 Hz, JHH = 17.0 Hz, 1 H,
We thank the Centre National de la Recherche Scientifique
(CNRS) and Région Champagne-Ardenne for a PhD fellowship
(J.N.). This project was supported (programme GLYCOVAL) by
the Contrat de Plan Etat-Région. We thank Aurélien Lebrun for
the NMR spectroscopic analyses, Dominique Harakat for HRMS
analyses, and Sylvie Lanthony for elemental analyses.
2
3
2
3
3
3
3
CH=CHtrans), 5.69 (tdd, JHH = 17.0 Hz, JHH = 10.5 Hz, JHH
=
5.0 Hz, 1 H, CH=CH2), 7.13–7.38 (m, 4 H, H aryl) ppm. 13C NMR
4
(125.8 MHz, CDCl3): δ = 21.1 (CH2), 24.3 (CH2), 65.7 (d, JCF
=
2.0 Hz, OCH2), 69.1 (OCH), 78.1 (q, 2JCF = 25.0 Hz, C-CF3), 116.3
1
(CH=CH2), 126.4 (q, JCF = 290.0 Hz, CF3), 126.7, 128.4, 128.7,
130.0 (CH aryl), 134.1 (CH=CH2), 135.2 and 135.4 (CIV aryl) ppm.
HRMS (ESI+): calcd. for [C14H15F3O2 + Na]+ 295.0922; found
295.0921.
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Received: October 13, 2009
Published Online: December 3, 2009
Eur. J. Org. Chem. 2010, 275–279
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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