Asymmetric synthesis of stereodefined 7-(alk-1-enyl)-5,6,7,8- tetrahydronaphthalene-2-carboxylic acids and their precursors, bearing a polar group in the 8-position, by the 3-sulfonyl-1,3-oxazolidine method

Article abstract of DOI:10.1055/s-2000-7119

7-Bromo-1-(trimethylsilyloxy)-naphthalene 2 was subjected to asymmetric formylation by means of (R)-4-ethyl-2-methoxy-3-tosyl-1,3-oxazolidine (1). The enantiomerically pure 1-tetralones u-3 and l-3, bearing a masked formyl group, were elaborated diastereoselectively to achieve the title compounds 11, 13 and 23 by transformation of the l-oxo group to a tertiary methyl carbinol moiety or a hydroxymethyl group. Subsequently, the formyl group was converted to a long-chain alkene moiety and, finally, the carboxyl group was introduced via bromine-lithium exchange and carboxylation. Difficulties arose from the high dehydration tendencies of the intermediate tertiary alcohols and by facile epimerisation of the free hydroxyaldehydes. With examples for further application of similar strategies it is demonstrated how these problems could be solved.

Full text of DOI:10.1055/s-2000-7119

PAPER
1391
Asymmetric Synthesis of Stereodefined 7-(Alk-1-enyl)-5,6,7,8-
tetrahydronaphthalene-2-carboxylic Acids and Their Precursors, Bearing a
Polar Group in the 8-Position, by the 3-Sulfonyl-1,3-oxazolidine Method
Antje Kreier, Roland Fröhlich,# Elina Wegelius,# Dieter Hoppe*
Institut für Organische Chemie der Westfälischen Wilhelms-Universität Münster, Corrensstraße 40, D-48149 Münster, Germany
Fax +49(251)83 39772; E-mail: dhoppe@uni-muenster.de
Received 28 March 2000; revised 19 May 2000
Dedicated to Professor H. J. Bestmann on the occasion of his 75th birthday
verted to 15:85 by refluxing the original mixture with
Abstract: 7-Bromo-1-(trimethylsilyloxy)-naphthalene 2 was sub-
K2CO3 in acetone via the corresponding enolate.8a The
jected to asymmetric formylation by means of (R)-4-ethyl-2-
methoxy-3-tosyl-1,3-oxazolidine (1). The enantiomerically pure
1-tetralones u-3 and l-3, bearing a masked formyl group, were
same ratio was achieved by TMS triflate-mediated
epimerisation,5a,5e although severe decomposition was ob-
elaborated diastereoselectively to achieve the title compounds 11, served. Separation of the pure major diastereomer u-3 or
13 and 23 by transformation of the 1-oxo group to a tertiary methyl
l-3 was possible by LC on silica gel.
carbinol moiety or a hydroxymethyl group. Subsequently, the
formyl group was converted to a long-chain alkene moiety and, fi-
nally, the carboxyl group was introduced via bromine-lithium ex-
change and carboxylation. Difficulties arose from the high
dehydration tendencies of the intermediate tertiary alcohols and by
facile epimerisation of the free hydroxyaldehydes. With examples
for further application of similar strategies it is demonstrated how
these problems could be solved.
HX R1
*
7
6
1
4
CO2H
8
5
*
2
3
H
R2
A
Key words: asymmetric electrophilic formylation, chiral b-oxo al-
dehydes, 3-arenesulfonyl-1,3-oxazolidines, chiral tetrahydro-naph-
thalenes
HX R1
O
H
Br
Br
*
*
H
B
In the search for structurally simple inhibitors of protein
phosphatases PP1 and PP2A we became interested in a
flexible synthesis of structurally defined 5,6,7,8-tetrahy-
dronaphthalene-2-carboxylic acids A, bearing a polar
group XH (OH or CH2OH) in position 8 and possessing a
long-chain 1-alkenyl residue in the 7-position.1 7-Bromo-
1,2,3,4-tetrahydronaphthalene-2-carbaldehydes B were
aimed as intermediates which should be accessible from
the protected b-ketoaldehydes C via diastereoselective
nucleophilic attack at the oxo group, directed by the chiral
auxiliary in 2-position,2-4 and a subsequent reductive bro-
mo-carboxyl exchange. Compounds C are expected to be
formed by our method of asymmetric electrophilic
formylation5 of silyl enol ether 2 by means of a readily
available, enantiomerically pure N-arenesulfonyl-2-meth-
oxy-1,3-oxazolidine such as 1.3a,4,5
Silyl enol ether 2 was prepared from 7-bromo-1-tetralone6
by the usual method7 (LDA, Me3SiCl) and condensed
with oxazolidine 15e,8 under the influence of ZnCl2·OEt2 to
give the epimeric mixture u-3 and l-3 in a ratio of 70:30
and in 50% yield (Scheme 2). The diastereomeric ratio
(d.r.) could be improved to 87:13, and yield to 63%, when
TiCl4 was used and the trichlorotitanium enolate was
allowed to be formed before 1 was added.9 The d.r. is in-
O
H
O
H
8
5
2'
*
1
N
2
7
6
3
Ts
4
C
OSiMe3
O
N
Br
OMe
+
Ts
1
2
Scheme 1
An X-ray crystal structure analysis of u-3/l-310 (Figures 1
and 211) confirmed their [2S,2(2R,4R)]- and
[2R,2(2R,4R)]-configuration, respectively. Since u-3 al-
ready has the thermodynamically favoured 2,4-cis-con-
figuration at the oxazolidine ring, it is converted to an
even more stable diastereomer under Lewis acidic and
basic conditions, this one must differ in the ketone part of
the molecule and, thus, was assigned to be l-3.
Synthesis 2000, No. 10, 1391–1402 ISSN 0039-7881 © Thieme Stuttgart · New York

1392
A. Kreier et al.
PAPER
OSiMe3
O
N
Br
OMe
+
a or b
Ts
1
2
O
O
O
O
H
H
Br
Br
N
N
H
H
Ts
Ts
+
u-3
l-3
c
d
O
H
HOMe
O
H
Me OH
H
H
Figure 2 X-ray crystal structure of l-3.11
Br
+
Br
N
N
Ts
Ts
(1R)-4
(1S)-4
was isolated in good yields. Interestingly, when heating
the tertiary alcohol (1R)-4 with acetic anhydride/4-(N,N-
dimethylamino)pyridine (DMAP) in triethylamine,13 an
elimination to form the 1-methylene-2-decaline 6 with
90% yield occurred. Most probably, the reaction proceeds
through the tertiary acetate which undergoes ester pyroly-
sis at heating to 100 °C. In such a pericyclic reaction, due
to steric reasons, proton removal at the exocyclic methyl
group is predicted.14
e
f
O
H
CH2
S
Me
H
Br
Br
N
S
Ts
5
6
Reagents and conditions: a) ZnCl2∑OEt2 (1.15 equiv)/CH2Cl2, 0 °C, 2
h, 50%, d.r. 70:30; b) i. 2+TiCl4 (1.0 equiv)/CH2Cl2, -78 °C to r.t., 1
h, ii. 1 (1.1 equiv)/CH2Cl2, -90 °C to 0 °C, 14 h, 63%, d.r. 87:13; c)
K2CO3 (7.2 equiv)/acetone, reflux, 24 h, 80%, d.r. 15:85; d) MeMgCl
(3 equiv)/THF, -78 °C to r.t., 24 h, 89%, d.r. 80:20; e) HS(CH2)3SH
(2.1 equiv), MeSO3H (0.4 equiv)/CH2Cl2, r.t., 24 h, 93%; f) DMAP
(0.5 equiv), Ac2O, Et3N, 100 °C, 24 h, 90%.
It turned out that cleavage of the oxazolidine ring in tetra-
lols (1R)-4 and (1S)-4 could not be accomplished without
dehydration. Thus, the aldehyde protecting group had to
be exchanged at the stage of ketone u-3.15 Thiolysis with
1,3-propanedithiol gave the 1,3-dithiane R-7 without de-
tectable racemisation (Scheme 3). The absolute configu-
ration of R-7 was confirmed by anomalous X-ray
dispersion of suitable crystals16 (Figure 3).
Scheme 2
Figure 1 X-ray crystal structure of u-3.11
Figure 3 X-ray crystal structure of R-7.
Addition of methylmagnesium chloride in THF furnished
the epimeric tertiary alcohols (1R)-8 and (1S)-8 in a d.r. of
79:21 (yield 80%). As expected, the dithiane ring occu-
pies a pseudoequatorial position in the tetralone R-7
shielding the Re-face of the carbonyl group and directing
the nucleophile to enter predominantly from the Si-face
(at the rear) leading to the major diastereomer (1R)-8.
Here, the analysis of the g-effects12 in the 13C NMR spec-
The addition of methylmagnesium chloride to ketone u-3
gave rise to the formation of two epimeric tertiary alco-
hols (1R)-4 and (1S)-4 (ratio 80:20, yield 89%). The as-
signment of the relative configurations is based on the
g-effect in the 13C NMR spectra12 (Scheme 2).
All attempts of deblocking the masked hydroxy aldehydes
led to elimination reactions. When using 1,3-pro-
panedithiol the achiral dihydronaphth-2-yl-1,3-dithiane 5
Synthesis 2000, No. 10, 1391–1402 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Asymmetric Synthesis of Stereodefined 7-(Alk-1-enyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic Acids
1393
u-3
O
H
CH2
H
Br
a
N
a
b
u-3
Ts
S
H
O
Br
6
OH
OR
S
S
O
H
H
Br
Br
N
S
R-7
H
f
Ts
16
14 R = H
15 R = SiMe2tBu
b
c
S
H
HOMe
S
H
Me OH
h
d
Br
g
Br
S
S
OSiMe2tBu
Br
OH
+
S
H
(1R)-8
(1S)-8
R1
R2
Br
S
c
c
17
cis-19
R1 = CHO, R2 = H
O
H
HOMe
O
H
Me OH
trans-19 R1 = H, R2 = CHO
Br
Br
e
H
H
+
OSiMe2tBu
Br
O
(1R)-9
(1S)-9
R1
R2
Br
Br
HO
d
d
HOMe
Me OH
R1 = CHO, R2 = H
20
cis-18
trans-18 R1 = H, R2 = CHO
C5H11
X
C5H11
X
i
H
e
H
O
10 X = Bra
11 X = CO2Ha
12 X = Brb
13 X = CO2Hb
O
e
O
21
a Mixture of 3 isomers, only the main product is shown.
b The product was only prepared as the racemate.
Reagents and conditions: a) HS(CH2)3SH (1.5 equiv), BF3∑OEt2 (1.5
equiv)/CH2Cl2, 0 °C, 5 h, 88%, ee >90%; b) MeMgCl (3 equiv)/THF,
-78 °C to r.t., 24 h, 80%, d.r. 79:21; c) MeI (20 equiv), CaCO3 (15
equiv)/acetone:H2O (4:1), 60 °C, 24 h, (1R)-9: 98%; (1S)-9: 95%; d)
n-C6H13PPh3Br (2.10 equiv), n-BuLi (2.05 equiv)/THF, 0 °C, 4 h, 10:
50%, E-cis:Z-cis:E-trans:Z-trans = 57:31:12:0; 12: 52%, E only; e) i.
MeLi·LiBr (1.0 equiv)/THF, -78 °C, 30 min, ii. tert-BuLi (2.5
equiv)/THF, -78 °C, 10 min, iii. CO2, -78 °C to r.t., 30 min, 11:
91%, E-cis:Z-cis:E-trans:Z-trans = 56:28:16:0; 13: 29%, E only.
Br
Reagents and conditions: a) Tebbe reagent (1.06 equiv)/THF, r.t., 4
h, 75%; b) i. BH3·THF (5.0 equiv)/THF, r.t. 3 h, ii. H2O2, NaOH/H2O,
r.t., 3 h, 82%, d.r. > 95:5; c) i. NaH (1.5 equiv)/THF, r.t., 2 h, ii. TB-
DMSCl (2.5 equiv)/THF, r.t., 24 h, 90%; d) HS(CH2)3SH (1.5 equiv),
MeSO3H (0.3 equiv)/CH2Cl2, r.t., 3 h, 29%; e) MeI (20 equiv),
CaCO3 (15 equiv)/acetone:H2O (4:1), 60 °C, 24 h, 84%, d.r. 85:15; f)
14, HS(CH2)3SH (2 equiv), BF3∑OEt2 (2 equiv)/CH2Cl2, 0 °C, 2 h,
87%; g) i. NaH (2 equiv)/THF, r.t. 2 h, ii. TBDMSCl (2 equiv)/THF,
r.t., 24 h, 80%; h) MeI (20 equiv), CaCO3 (15 equiv)/acetone:H2O
(4:1), 60 °C, 24 h, 19: 43%, d.r. 23:77, and 20 (only from cis-19),
36%; i) crystallization, Et2O/petroleum ether, r.t., 5 d.
Scheme 3
Scheme 4
tra supports a (pseudo)equatorial position of the 1-CH3
group in (1R)-8.
The deprotection of separated epimers (1R)-8 and (1S)-8
to form the corresponding labile b-hydroxy aldehydes
(1R)-9 and (1S)-9 was accomplished without epimerisa-
tion or competing elimination of water by refluxing the
1,3-dithianes with a large excess of methyl iodide/calcium
carbonate in acetone/water.4,5d,5f Almost quantitative
yields (98% and 95%) resulted, when a special, non-aque-
ous work-up was applied (see Experimental).
of n-hexylidenetriphenylphosphorane. Surprisingly, a
mixture of (E)-(1R)-10, the corresponding (Z)-alkene and
the 1-epimer (E)-(1S)-10 (50%, 57:31:12) was isolated.
Obviously, an epimerisation of the aldehyde (1R)-9 takes
place under the basic reaction conditions. From another
experiment, a pure sample of racemic (E)-(1R*)-10 could
be separated, the vicinal coupling constants of the olefinic
protons (15.5 Hz and 10.9 Hz) support the E- and Z-as-
signment, respectively. A racemic sample of (1S*)-9 pro-
vided the racemic diastereomerically pure (E)-12.
A (Z)-1-heptenyl side chain, taken as a model for structur-
ally more complicated alkenyl residues, was elaborated
from the formyl groups. Aldehyde (1R)-9, without protec-
tion of the hydroxy group, was reacted with 2 equivalents
Synthesis 2000, No. 10, 1391–1402 ISSN 0039-7881 © Thieme Stuttgart · New York

1394
A. Kreier et al.
PAPER
Table 1 Prepared Compounds 3-5, 7-13.
Producta
Yield [%]
50c, 63d
Ratio (dr)
Mp [°C]b
[a]2D0 (c, CH2Cl2)
Configuration
u-3 +
l-3
R-7
(1R)-8 +
(1S)-8
(1R)-9
(1S)-9
10
rac-12
11
rac-13
(1R)-4 +
(1S)-4i
5
70:30c, 87:13d
180-182
199-201
131-132
118-120
105-106
oil
oil
oil
oil
wax
+97.4 (0.92)
+37.3 (1.00)
–23.6 (1.96)
–77.4 (0.95)
+30.1 (0.76)
2S,2(2R,4R)
2R,2(2R,4R)
2R
1R,2R
1S,2R
1R,2R
1S,2R
(1R,2RS)-2EZ
trans-(1RS,2RS)-2E
(7RS,8R)-7EZ
trans-(7RS,8RS)-7E
1R,2R,2(2R,4R)
1S,2R,2(2R,4R)
-
88
80
–
79:21
e
98
95
50f
52
91f
29
89
>95:5
>95:5
g
E-trans
h
-
-
e
-15.3 (0.79)
-
-6.8 (0.65)
-
E-trans
80:20
wax
172-173
+37.1 (0.63)
e
e
-
-
-
93
–
oil
a Satisfactory microanalysis, C 0.4, H 0.4, N 0.4, or HRMS were obtained.
b From Et2O/petroleum ether.
c Method A.
d Method B.
e Not determined.
f Diastereomeric mixture, which was not separable by flash chromatography.
g E(1R,2S):Z(1R,2S):E(1R,2R) = 57:31:12.
h E(7S,8R):Z(7S,8R):E(7R,8R) = 56:28:16.
i (1S)-4 could not be obtained as a diastereomerically pure sample by flash chromatography.
After reductive lithiation of the mixture of (E)- and (Z)-10
and carboxylation, a mixture of the carboxylic acids (1R)-
and (1S)-11 were formed in a ratio, which corresponds to
the starting material. Similarly, (E)-12 provided pure
(E)-13. Although the conditions have not been fully opti-
mised, it is evident, that the double bond and the stereo-
genic centers at C-1 and C-2 are not attacked during the
lithiation-carboxylation process.
The alkene 6 was also produced directly from ketone u-3
by the action of Tebbe reagent,17 yield 75% (Scheme 4).
Figure 4 X-ray crystal structure of 14.
Hydroboration of the exo-methylene derivative 6 (with
BH3 in THF) and the usual work-up gave the crystalline,
diastereomerically pure primary alcohol 14. The crystal
structure analysis of 1418 (Figure 4) reveals, as expected,
that borane had approached from the less hindered rear-
face. Cleavage of the oxazolidine ring in the O-TBDMS
ether 15 to form the dithiane 17 proceeded only with low
yield (29%). It turned out to be more advantageous to con-
vert the alcohol 14 directly to dithiane 16 (yield 87%), fol-
lowed by O-silylation to produce 17 (80%).
Dethioacetalisation of 17 (MeI/CaCO3 in wet acetone)
was accompanied by partial epimerisation in 2-position of
the aldehyde 18, a cis-18/trans-18 ratio of 85:15 was ob-
served. The dethioacetalisation of the free alcohol 16 by
the same method delivered, besides an inseparable mix-
ture of the cis, trans-aldehydes 19 (cis-19/trans-19, ratio
23:77), the cis-lactol 20. After having kept a sample for
several weeks, from a solution of 20 in Et2O, crystals sep-
Figure 5 X-ray crystal structure of 21.
Similarly, the protected enantiomeric hydroxyaldehyde
ent-17 was prepared from the ketone l-3 via the methylene
compound epi-6 and the alcohol epi-14 (Scheme 5).
arated which proved to consist of the stereohomogeneous From the Wittig reaction of cis-18/trans-18 (ratio 85:15)
“dimeric” acetal 21, formed by connecting two identical with n-hexyltriphenylphosphonium bromide,20 a homoge-
moieties by an exo,exo-oxygen bridge (Figure 5).19
neous pure sample21 (33%) of Z-alkene 22 was isolated
(Scheme 6). Fluoride-induced deprotection of 22 led to
Synthesis 2000, No. 10, 1391–1402 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Asymmetric Synthesis of Stereodefined 7-(Alk-1-enyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic Acids
1395
OR
O
H
CH2
H
Br
Br
N
b
a
H
c
l-3
a
Ts
cis/trans-18
C5H11
epi-6
22 R = SiMe2tBu
23 R = H
b
OR
OH
S
H
O
H
OH
H
Br
Br
N
S
CO2H
c
Ts
H
C5H11
epi-14
ent-16 R = H
ent-17 R = SiMe2tBu
d
24
Reagents and conditions: a) Tebbe reagent (1.06 equiv)/THF, r.t., 4 h,
74%; b) i. BH3·THF (5.0 equiv)/THF, r.t. 3 h, ii. H2O2, NaOH/H2O,
r.t., 3 h, 60%, d.r. > 95:5; c) HS(CH2)3SH (2.8 equiv), BF3∑OEt2 (2.8
equiv)/CH2Cl2, 0 °C, 3 h, 83%; d) i. NaH (2 equiv)/THF, r.t., 2 h, ii.
TBDMSCl (2 equiv)/THF, r.t., 24 h, 83%.
d
e
f
g
ent-17
ent-cis/trans-18
OH
ent-23
ent-22
CO2H
Scheme 5
H
C5H11
ent-24
the free alcohol 23.22 Starting from ent-17, the identical
sequence gave the enantiomer ent-23. Nearly identical
specific rotations of opposite sense give evidence that no
uncontrolled epimerisation reactions are involved in the
final steps. A (racemic) sample of lactol rac-20 was di-
rectly converted to pure alkene rac-23, illustrating that
two protecting group manipulations could be saved. Final-
ly, 23 and ent-23, via bromine-lithium exchange, followed
by carboxylation, provided the carboxylic acids 24 and
ent-24, respectively.
h
rac-20
rac-23
Reagents and conditions: a) n-C6H13PPh3Br (1.10 equiv), n-BuLi
(1.08 equiv)/THF, 0 °C, 4 h, 33%; b) TBAF (2 equiv)/THF, r.t., 24
h, 57%; c) i. MeLi·LiBr (1.0 equiv)/THF, -78 °C, 30 min, ii. tert-
BuLi (2.5 equiv)/THF, -78 °C, 10 min, iii. CO2, -78 °C to r.t., 30
min, 37%; d) MeI (20 equiv), CaCO3 (15 equiv)/acetone:H2O (4:1),
60 °C, 24 h, 92%, d.r. 70:30; e) n-C6H13PPh3Br (1.10 equiv), n-BuLi
(1.08 equiv)/THF, 0 °C, 4 h; f) TBAF (2 equiv)/THF, r.t., 24 h, 78%
(over 2 steps); g) i. MeLi·LiBr (1.0 equiv)/THF, -78 °C, 30 min, ii.
tert-BuLi (2.5 equiv)/THF, -78 °C, 10 min, iii. CO2, -78 °C to r.t.,
30 min, 54%; h) n-C6H13PPh3Br (2.10 equiv), n-BuLi (2.05 equiv)/
THF, 0 °C, 4 h, 34%.
We have demonstrated that the asymmetric formylation
by means of chiral N-arenesulfonyl-2-alkoxy-1,3-oxazo-
lidines provides a powerful and versatile tool for the
asymmetric introduction of vicinal carbon substituents,
starting from ketones. Even in problematic situations,
such as the presence of reactive benzylic positions, which
can give rise to side reactions, the method can be applied
advantageously. In addition, the high tendency of the in-
termediate sulfonyloxazolidines for crystallisation facili-
tates structure determinations during the synthesis.
Scheme 6
the mixture was stirred for 2 h at -78 °C, and Me3SiCl (5.56 mL,
44.0 mmol) slowly added. After stirring at -78 °C for 1 h, the reac-
tion mixture was allowed to warm to r.t. (approx. 1 h). The solvents
were evaporated in vacuo, light petroleum ether (PE) (50 mL) was
added to the remaining residue, the solids were filtered off, and the
solvents again removed. Distillation afforded 2 (10.0 g, 92%), as a
slightly yellow oil.
All reactions, which are sensitive to moisture, were carried out un-
der Ar. All solvents were purified by distillation and dried, if neces-
sary, prior to use. 1H and 13C NMR spectra were recorded on Bruker
WM300, AM360 or U600 spectrometers. HRMS was recorded on a
Finnigan MAT 8230 mass spectrometer (EI, 70 eV). Optical rota-
tions were recorded on a Perkin-Elmer polarimeter 241 at 20 °C.
Mps were obtained on Gallenkamp melting point apparatus MFB-
595 and are uncorrected. Microanalyses were performed at the Or-
ganisch-Chemisches Institut der WWU Münster with a Perkin-
Elmer Analyser 240. Products were purified by flash column chro-
matography on silica gel (40-63 µm). Tebbe reagent was purchased
from Fluka.
Rf 0.71 (Et2O/PE, 1:4); bp 115-117 °C, 0.05 Torr.
IR (film): v = 2860, 2810, 1615, 1580, 1545, 1410, 1230, 1175, 830,
750 cm-1.
1H NMR (300 MHz, CDCl3): d = 0.25 (s, 9H), 2.25-2.32 (m, 2H),
2.65-2.73 (m, 2H), 5.15-5.21 (m, 1H), 6.92-6.96 (m, 1H), 7.23
(dd, 1H, 4J = 2.13 Hz, 3J = 7.86 Hz), 7.50 (d, 1H, 4J = 2.13 Hz).
13C NMR (75 MHz, CDCl3): d = 0.2, 22.0, 27.6, 106.1, 120.0,
124.9, 128.5, 130.0, 135.5, 135.8, 147.1.
[2S,2(2R,4R)]- and [2R,2(2R,4R)]-7-Bromo-2-{4-ethyl-3-[(4-me-
thylbenzene)sulfonyl-1,3-oxazolidin-2-yl}-1,2,3,4-tetrahydro-1-
naphthalenone (u-3 and l-3)
Method A: To a solution of silyl enol ether 2 (2.97 g, 10.0 mmol)
and 2-methoxy-1,3-oxazolidine5e,23 1 (3.14 g, 11.0 mmol) in anhyd
CH2Cl2 (20 mL) at 0 °C was added 2.2 M ZnCl2·OEt2 in CH2Cl2
(5.23 mL, 11.5 mmol). The mixture was stirred at 0 °C for 2 h. After
addition of sat. NaCl (10 mL), the aqueous layer was separated, ex-
tracted with CH2Cl2 (3 ¥ 50 mL) and the combined organic extracts
7-Bromo-3,4-dihydro-1-trimethylsilyloxynaphthalene (2)
According to the general method7 a solution of LDA (38.4 mmol)
in THF (50 mL) was prepared from diisopropylamine (5.74 mL,
40.3 mmol) and 1.6 M n-BuLi in hexane (24.0 mL, 38.4 mmol). 7-
Bromo-1-tetralone6 (8.24 g, 36.6 mmol), dissolved in anhyd THF
(30 mL), was added dropwise during a period of 20 min at -78 °C,
Synthesis 2000, No. 10, 1391–1402 ISSN 0039-7881 © Thieme Stuttgart · New York

1396
A. Kreier et al.
PAPER
Table 2 Prepared Compounds 6, 14–24.
Producta
Yield [%]
Ratio (dr)
Mp [°C]b
[a]2D0 (c, CH2Cl2)
Configuration
6
90c, 75d
74
82
60
90
87
83
80
>95:5
>95:5
>95:5
>95:5
>95:5
-
-
-
-
137-138
138-140
159-161
142-144
oil
51-53
51-53
81-82
81-82
oil
-7.1 (0.54)
+108.0 (0.48)
+50.9 (0.51)
+45.3 (0.23)
+48.7 (0.46)
+60.7 (110)
-64.4 (0.95)
+51.3 (1.42)
-52.1 (1.05)
2R,2(2R),4R
2R,2(2S),4R
1R,2R,2(2R,4R)
1S,2S,2(2R,4R)
2R,2(1R,2R),4R
1R,2R
1S,2S
1R,2R
1S,2S
1R,2R
1R,2S
3R,3aR,9bR
1R,2R
1R,2S
1S,2S
epi-6
14
epi-14
15
16
ent-16
17
ent-17
cis-19 +
trans-19
20
cis-18 +
trans-18
ent-cis-18
ent-trans-18
22
ent-22
23
ent-23
24
83
43e
23:77
-
f
36
>95:5
85:15
127-129
oil
-108.0 (0.64)
84e
-
f
92e
70:30
oil
-
f
1S,2R
33
>95:5
>95:5
>95:5
>95:5
>95:5
>95:5
oil
oil
oil
oil
wax
wax
+61.8 (0.82)
1R,2S,2Z
1S,2R,2Z
1R,2S,2Z
1S,2R,2Z
7S,8R,7Z
7R,8S,7Z
f
f
-
-
57
78g
37
54
+65.2 (0.33)
-66.1 (0.12)
+70.6 (0.17)
150.0 (0.40)h
ent-24
a Satisfactory microanalysis, C 0.4, H 0.4, N 0.4, or HRMS were obtained.
b From Et2O/petroleum ether.
c Method A.
d Method B.
e Diastereomeric mixture, which was not separable by flash chromatography.
f Not determined.
g Yield over 2 steps.
h In CDCl3.
dried (Na2SO4). The solvent was removed in vacuo and the residue
(u-3:l-3, 70:30) purified on silica gel by flash chromatography with
Et2O/PE (1:4 to 1:2) to afford pure oxazolidine u-3 (0.36 g, 7%) and
a mixture of u-3:l-3 (2.06 g, 43%, d.r. 65:35); combined yield 50%.
Isomerization of u-3 into l-3
A mixture of ketones u-3 and l-3 (478 mg, 1.00 mmol, d.r. 70:30)
and K2CO3 (1.0 g, 7.2 mmol) in acetone (10 mL) was refluxed for
24 h. The salt was filtered off, the solvent removed in vacuo and the
residue (u-3:l-3, d.r. 15:85) separated by flash chromatography on
silica gel (Et2O/PE, 1:4) to afford pure l-3 (287 mg, 60%) and a mix-
ture of u-3:l-3 (96 mg, 20%, d.r. 60:40); combined yield 80%.
Method B: To a solution of silyl enol ether 2 (2.97 g, 10.0 mmol),
dissolved in anhyd CH2Cl2 (80 mL), TiCl4 (1.09 mL, 10.0 mmol)
was added dropwise below -78 °C. The mixture was stirred at
-78 °C (15 min) and at r.t. (25 min), chilled to -90 °C and 2-meth-
oxy-1,3-oxazolidine 1 (2.58 g, 10.9 mmol) in anhyd CH2Cl2
(20 mL) was slowly added during 1.5 h. The reaction mixture was
first allowed to warm slowly to -50 °C during 5 h and then to 0 °C
during 9 h. After addition of aq 2N HCl (10 mL) and sat. NaCl (10
mL), the aqueous layer was separated, extracted with CH2Cl2 (3 ¥
50 mL) and the combined organic extracts dried (Na2SO4). The sol-
vent was removed in vacuo and the residue (u-3:l-3, d.r. 87:13) pu-
rified on silica gel by flash chromatography with Et2O/PE (1:4 to
1:2) to afford pure oxazolidine u-3 (1.91 g, 40%) and a mixture of
u-3:l-3 (1.12 g, 23%, d.r. 70:30); combined yield 63%.
Compound l-3
Colourless crystals; Rf 0.38 (Et2O/PE, 1:1); mp 199-201 °C (Et2O/
PE).
[a]D = +37.3 (c 1.00, CH2Cl2).
1H, 13C NMR and IR data: see Tables 3 and 4.
(2R)-7-Bromo-2-(1,3-dithian-2-yl)-1,2,3,4-tetrahydro-1-naph-
thalenone [R-7]
To a solution of oxazolidine u-3 (1.23 g, 2.56 mmol) in anhyd
CH2Cl2 (20 mL) at 0 °C was added 1,3-propanedithiol (0.29 mL,
3.84 mmol) and BF3∑OEt2 (0.48 mL, 3.84 mmol). After stirring for
5 h, sat. NaHCO3 (20 mL) was introduced and the reaction mixture
was stirred for 20 min. The two phases were separated and the aque-
ous layer was extracted with CH2Cl2 (2 ¥ 30 mL). The combined or-
ganic phases were dried (Na2SO4) and the solvent was removed in
vacuo. The residue was flash chromatographed on silica gel (Et2O/
PE, 1:19 to 1:4) to give dithiane R-7 (774 mg, 88%).
An attempt to separate the epimers by crystallisation from Et2O/PE,
resulted in twin crystals of l-3 and u-3 (50:50).
Compound u-3
Colourless crystals; Rf 0.35 (Et2O/PE, 1:1); mp 180-182 °C (Et2O/
PE); [a]D = +97.4 (c 0.92, CH2Cl2).
Anal. Calcd for C22H24BrNO4S (478.4): C, 55.23; H, 5.06; N, 2.93.
Found: C, 55.51; H, 5.05; N, 2.98.
1H, 13C NMR and IR data: Tables 3 and 4.
Colourless crystals; Rf 0.33 (Et2O/PE, 1:4); mp 131-132 °C (Et2O/
PE).
[a]D = -23.6 (c 1.96, CH2Cl2).
HRMS (EI): m/z calcd for (M+): 341.97476. Found: 341.97555.
Synthesis 2000, No. 10, 1391–1402 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Asymmetric Synthesis of Stereodefined 7-(Alk-1-enyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic Acids
1397
Table 3 Selected Data of Compounds 3, 4, 7-9 (IR, 1H NMR).
Product
IR (KBr/film) n [cm–1]
1H-NMR (300 MHz, CDCl3), d, J (Hz)a
2¢-H (3J2′,2
)
2-H
1-CH3
1-OH
2-CHO
u-3
l-3
R-7
(1R)-8
(1S)-8
(1R)-9
(1S)-9
(1R)-4
(1S)-4
1685, 1340, 1160
1685, 1340, 1160
1670
5.57 (d, 4.53)
5.56 (d, 2.13)
4.95 (d, 3.33)
4.50 (d, 4.26)
4.42 (d, 4.47)
2.77–3.02 (m)
3.30 (ddd)
–
–
–
–
–
–
–
–
–
–
2.31–2.40 (m)
2.15–2.20 (m)
2.29–2.37 (m)
2.69–2.77 (m)
2.64–2.88 (m)
2.01–2.07 (m)
3490, 1580, 1260
3490, 1580, 1260
3400, 1700, 1340
3450, 1705, 1345
3482, 1165
1.49 (s)
1.49 (s)
1.60 (s)
1.46 (s)
1.46 (s)
3.23 (s)
2.75–3.01 (m)
2.69–2.77 (m)
2.64–2.88 (m)
4.17 (s)
–
9.82 (d)
10.01 (s)
–
–
5.22 (d, 10.26)
5.47 (d, 9.99)
b
b
b
b
b
–
–
–
–
–
a s = singlet, d = doublet, t = triplet, m = multiplet.
b Not determined. (1S)-4 could not be obtained as a diastereomerically pure sample by flash chromatography.
1H, 13C NMR and IR data: Tables 3 and 4.
(1R,2R,2(2R,4R)) and (1S,2R,2(2R,4R))-7-Bromo-2-{4-ethyl-3-
[(4-methylbenzene)sulfonyl]-1,3-oxazolidin-2-yl}-1-methyl-
1,2,3,4-tetrahydro-1-naphthol [(1R)-4 and (1S)-4]
(1R,2R)- and (1S,2R)-7-Bromo-2-(1,3-dithian-2-yl)-1-methyl-
1,2,3,4-tetrahydro-1-naphthol [(1R)-8 and (1S)-8]
MeMgCl (3 M) in THF (0.6 mL, 1.8 mmol) in anhyd THF (10 mL)
was cooled to -78 °C and oxazolidine u-3 (287 mg, 0.60 mmol),
dissolved in anhyd THF (10 mL) was added dropwise. The reaction
mixture was allowed to warm up to r.t. overnight and then hydroly-
sed with sat. NaCl (10 mL). The aqueous layer was separated and
extracted with Et2O (3 ¥ 25 mL). The combined organic phases
MeMgCl (3 M) in THF (2.4 mL, 7.13 mmol) in anhyd THF (5 mL)
was cooled to -78 °C and dithiane R-7 (816 mg, 2.38 mmol), dis-
solved in anhyd THF (15 mL), was added dropwise. The reaction
mixture was allowed to warm up to r.t. overnight and then hydro-
lysed with sat. NaCl (5 mL). The aqueous layer was separated and
extracted with Et2O (3 ¥ 30 mL). The combined organic phases
were dried (Na2SO4) and concentrated in vacuo. Purification of the
residue by flash chromatography (Et2O/PE, 1:9) afforded the dia-
stereomers (1R)-8 (535 mg, 63%) and (1S)-8 (140 mg, 17%) in a ra-
tio of 79:21 and some starting material R-7 (42 mg, 5%).
were dried (Na2SO4) and evaporated to leave
a residue
(1R)-4:(1S)-4 (80:20) whose purification by flash chromatography
(Et2O/PE, 1:2 to 1:1) furnished diastereomerically pure (1R)-4 as
a white foam (158 mg, 53%) and a mixture of (1R)-4 and (1S)-4
(82 mg, 28%) as a white solid, d.r. 41:59.
Compound (1R)-4
Compound (1R)-8
White foam; Rf 0.29 (Et2O/PE, 1:1); mp 171-172 °C (Et2O/PE).
White solid; Rf 0.15 (Et2O/PE, 1:9); mp 118-120 °C (Et2O/PE).
[a]D = +37.1 (c 0.63, CH2Cl2).
[a]D = -77.4 (c 0.95, CH2Cl2).
HRMS (EI): m/z calcd for (M+): 358.00607. Found: 358.00652.
Anal. Calcd for C23H28BrNO4S (494.44): C, 55.87; H, 5.71; N, 2.83.
Found: C, 55.97; H, 5.88; N, 2.99.
1H, 13C NMR and IR data of (1R)-4: Tables 3 and 4.
Compound (1S)-8
White solid; Rf 0.12 (Et2O/PE, 1:9); mp 105-106 °C (Et2O/PE).
2-(7-Bromo-3,4-dihydro-1-methyl-2-naphthyl)-1,3-dithiane (5)
To a solution of Grignard adduct (1R)-4 (340 mg, 0.69 mmol) in an-
hyd CH2Cl2 (15 mL) were added 1,3-propanedithiol (0.15 mL, 1.50
mmol) and MeSO3H (0.02 mL, 0.30 mmol). After stirring for 24 h
at r.t., solid K2CO3 (100 mg, 0.72 mmol) was added and the mixture
was stirred for 10 min. The solid materials were filtered off and
washed with CH2Cl2 (10 mL). The filtrate was concentrated in vac-
uo. The crude product was purified by flash chromatography (Et2O/
PE, 1:9) to give 5 (240 mg, 93%).
[a]D = +30.1 (c 0.76, CH2Cl2).
1H, 13C NMR and IR data of (1R)-8 and (1S)-8: Tables 3 and 4.
Table 4 Selected Data of Compounds 3, 4, 7–9 (13C NMR).
Colourless oil; Rf 0.23 (Et2O/PE, 1:9);
IR (film): v = 2920, 2890, 1580, 1475 cm-1.
Product
13C-NMR (75 MHz, CDCl3), d
C-1 C-3 1-CH3 2-CHO
1H NMR (300 MHz, CDCl3): d = 1.84-1.94 (m, 1H), 2.09-2.15 (m,
1H), 2.18 (s, 3H), 2.44-2.48 (m, 2H), 2.74-2.79 (m, 2H), 2.85-
3.00 (m, 4H), 4.74 (s, 1H), 6.98 (d, 1H, 3J = 7.80 Hz), 7.22 (dd, 1H,
4J = 1.98 Hz, 3J = 7.80 Hz), 7.40 (d, 1H, 4J = 1.98 Hz).
13C NMR (75 MHz, CDCl3): d = 14.6, 24.7, 25.2, 26.5, 31.1, 51.0,
120.0, 126.7, 128.5, 129.5, 130.7, 133.5, 135.0, 138.4.
C-2¢
C-2
u-3
l-3
R-7
(1R)-8
(1S)-8
(1R)-9
(1S)-9
(1R)-4
(1S)-4
90.7
91.0
52.5
49.9
47.7
–
51.4
51.3
48.0
49.0
51.0
56.6
57.4
46.2
49.1
194.9 24.1
195.7 21.2
193.9 25.1
72.2 22.5
74.5 23.9
70.9 20.3
72.6 20.4
72.6 20.9
73.1 23.0
–
–
–
31.7
26.9
30.9
27.4
32.7
27.0
–
–
–
–
–
204.6
204.4
–
(2R,2(2R),4R) and (2R,2(2S),4R)-2-[7-Bromo-1-methylene-
1,2,3,4-tetrahydro-2-naphthyl]-4-ethyl-3-[(4-ethyl-3-[(4-meth-
ylbenzene)sulfonyl]-1,3-oxazolidine (6 and epi-6)
Method A: A mixture of Grignard adduct (1R)-4 (2.00 g,
4.04 mmol), DMAP (240 mg, 2.00 mmol) acetic anhydride (20
–
93.4
a
–
–
a Not determined.
Synthesis 2000, No. 10, 1391–1402 ISSN 0039-7881 © Thieme Stuttgart · New York

1398
A. Kreier et al.
PAPER
mL), and Et3N (40 mL) was refluxed at 100 °C for 24 h. The reac-
tion mixture was cooled to r.t. and poured into a mixture of ice (200
g) and 2N HCl (200 mL). The aqueous layer was separated and ex-
tracted with CH2Cl2 (5 ¥ 50 mL) and the combined organic phases
were washed with sat. NaHCO3, dried (Na2SO4) and evaporated in
vacuo. Flash chromatography of the residue on silica gel (Et2O/PE,
1:2) afforded 6 (1.73 g, 90%) as a white solid.
(2R,2(1R,2R),4R)-2-{7-Bromo-1-[(tert-butyl-dimethylsilyloxy)-
methyl]-1,2,3,4-tetrahydro-2-naphthyl}-4-ethyl-3-[(4-methyl-
benzene)sulfonyl]-1,3-oxazolidine (15)
To a suspension of NaH (60% in mineral oil, 6.0 mg, 0.15 mmol) in
THF (1 mL) was added dropwise a solution of alcohol 14 (50 mg,
0.10 mmol) in THF (5 mL) at 0 °C. After stirring for 2 h at r.t. TB-
DMSCl (38 mg, 0.25 mmol) in THF (1 mL) was introduced with a
syringe and the reaction mixture was stirred at r.t. for 24 h. After hy-
drolysis with H2O (2 mL) the aqueous layer was separated and ex-
tracted with Et2O (3 ¥ 10 mL). The combined organic phases were
dried (Na2SO4) and the solvents were evaporated in vacuo. Purifi-
cation of the residue by flash chromatography (Et2O/PE, 1:4) af-
forded the silyl ether 15 (55 mg, 90%) as a colourless oil.
Method B: A solution of ketone u-3 (5.63 g, 11.8 mmol) in anhyd
THF (40 mL) was cooled to 0 °C and treated dropwise with Tebbe
reagent (0.5 M) in toluene (25.0 mL, 12.5 mmol), stirred at r.t. for
4 h and hydrolysed with 0.1 N NaOH (1 mL). The reaction mixture
was dried (Na2SO4) and filtered using Celite. The resulting filter
cake was washed with CH2Cl2 (3 ¥ 50 mL), and the filtrate was con-
centrated in vacuo. Purification of the residue by flash chromato-
graphy (Et2O/PE, 1:9 to 1:4) yielded analytically pure alkene 6
(4.15 g, 75%).
Rf 0.32 (Et2O/PE, 1:4); [a]D = +48.7 (c 1.46, CH2Cl2).
1H, 13C NMR and IR data of 15: Tables 5 and 6.
(1R,2R)- and (1S,2S)-[7-Bromo-2-(1,3-dithian-2-yl)-1,2,3,4-tet-
rahydro-1-naphthyl]methanol (16 and ent-16)
Compound 6
White solid; Rf 0.35 (Et2O/PE, 1:2); mp 137-138 °C (Et2O/PE).
To a solution of alcohol 14 (314 mg, 0.64 mmol) in CH2Cl2 (20 mL)
were added 1,3-propanedithiol (0.12 mL, 1.2 mmol) and BF3∑OEt2
(0.15 mL, 1.2 mmol) at 0 °C. After stirring for 2 h, sat. NaHCO3
(20 mL) was introduced and the mixture was stirred at r.t. for 20
min. The aqueous layer was separated and extracted with CH2Cl2 (3
¥ 20 mL). The combined organic phases were dried (Na2SO4) and
concentrated in vacuo. Purification of the residue by flash chroma-
tography (Et2O/PE, 1:99 to 1:1) afforded 16 (197 mg, 87%).
[a]D = -7.1 (c 0.54, CH2Cl2).
Anal. Calcd for C23H26BrNO3S (476.43): C, 57.98; H, 5.50; N, 2.94.
Found: C, 57.93; H, 5.39; N, 3.05.
Compound epi-6
Method B, from l-3 (134 mg, 0.30 mmol); yield 105 mg (74%).
Colourless crystals; Rf 0.32 (Et2O/PE, 1:2); mp 138-140 °C (Et2O/
White foam; Rf 0.32 (Et2O/PE, 1:1); mp 51-53 °C (Et2O/PE).
[a]D = +60.7 (c 1.10, CH2Cl2).
HRMS (EI): m/z calcd for (M+): 358.006068. Found: 358.00510.
PE)
[a]D = +108.0 (c 0.48, CH2Cl2).
1H, 13C NMR and IR data of 6 and epi-6: Tables 5 and 6.
Compound ent-16
From epi-14 (353 mg, 0.72 mmol); yield 214 mg (83%).
(1R,2R,2(2R,4R))- and (1S,2S,2(2R,4R))-7-Bromo-2-{4-ethyl-3-
[(4-methylbenzene)sulfonyl]-1,3-oxazolidin-2-yl}-1,2,3,4-tetra-
hydro-1-naphthyl)methanol (14 and epi-14)
[a]D = -64.4 (c 0.95, CH2Cl2).
1H, 13C NMR and IR data of 16 and ent-16: Tables 5 and 6.
To a solution of alkene 6 (1.50 g, 3.15 mmol) in anhyd THF (20 mL)
was added dropwise 1 M BH3·THF in THF (16.0 mL, 16.00 mmol)
at 0 °C. The solution was stirred for 3 h at r.t. and then cooled again
to 0 °C. NaOH (1.2 g), dissolved in H2O (6 mL), and H2O2 (30%,
4.5 mL) were added to the mixture and stirring was continued for
3 h at r.t. The two layers were separated and the aqueous phase was
extracted with Et2O (3 ¥ 50 mL). The combined organic layers were
washed with sat. FeSO4 , dried (Na2SO4) and concentrated in vacuo.
The residue was purified by flash chromatography (Et2O/PE, 1:3) to
yield diastereomerically pure 14 (1.27 g, 82%).
(1R,2R)- and (1S,2S)-{7-Bromo-1-[(tert-butyl-dimethylsilyl-
oxy)-methyl]-2-(1,3-dithian-2-yl)}-1,2,3,4-tetrahydronaphtha-
lene (17 and ent-17)
To a suspension of NaH (60% in mineral oil, 104 mg, 2.60 mmol)
in anhyd THF (10 mL) at r.t. was added dropwise a solution of al-
cohol 16 (462 mg, 1.30 mmol) in THF (5 mL). After stirring for 2 h
at r.t. TBDMSCl (392 mg, 2.60 mmol) in THF (5 mL) was intro-
duced with a syringe and the reaction mixture was stirred for 24 h.
After hydrolysis with H2O (3 mL) the aqueous layer was separated
and extracted with Et2O (3 ¥ 25 mL). The combined organic phases
were dried (Na2SO4) and concentrated in vacuo. Purification of
the residue by flash chromatography (Et2O/PE, 1:19) afforded 17
(491 mg, 80%).
Compound 14
Colourless crystals; Rf 0.16 (Et2O/PE, 1:1); mp 159-161 °C (Et2O/
PE).
[a]D = +50.9 (c 0.51, CH2Cl2).
White solid; Rf 0.68 (Et2O/PE, 1:1); mp 81-82 °C (Et2O/PE).
[a]D = +51.3 (c 1.42, CH2Cl2).
Anal. Calcd for C23H28BrNO4S (494.44): C, 55.87; H, 5.71; N, 2.83.
Found: C, 56.02; H, 5.89; N, 3.12.
HRMS (EI): m/z calcd for (M+-tert-butyl):. 415.02213. Found:
415.02160.
Compound epi-14
From epi-6 (100 mg, 0.21 mmol); yield 62 mg (60%).
Colourless crystals; Rf 0.19 (Et2O/PE, 1:1); mp 142-144 °C (Et2O/
PE).
Compound ent-17
From ent-16 (214 mg, 0.60 mmol); yield 236 mg (83%).
[a]D = +45.3 (c 0.23, CH2Cl2).
1H, 13C NMR and IR data of 14 and epi-14: Tables 5 and 6.
[a]D = -52.1 (c 1.05, CH2Cl2).
1H, 13C NMR and IR data of 17 and ent-17: Tables 5 and 6.
Preparation of 17 from 15
To a solution of silyl ether 15 (609 mg, 1.00 mmol) in anhyd CH2Cl2
(10 mL) were added 1,3-propanedithiol (0.15 mL, 1.50 mmol) and
MeSO3H (0.02 mL, 0.3 mmol). After stirring for 3 h at r.t., solid
Synthesis 2000, No. 10, 1391–1402 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Asymmetric Synthesis of Stereodefined 7-(Alk-1-enyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic Acids
1399
Table 5 Selected Data of Compounds 6, 14-18 (IR, 1H NMR)
Product
IR (KBr/film), v [cm–1]
1H-NMR (300 MHz, CDCl3), d, J (Hz)a
2¢-H (3J2′,2
)
2-H
1-H
11-H
2-CHO
6
1595, 1340, 1160
1595, 1340, 1160
3410, 1590, 1165
3410, 1590, 1165
2920, 1590, 1345, 1160
5.14 (d, 7.41)
5.09 (d, 5.25)
5.53 (d, 9.78)
5.21 (d, 3.57)
5.39 (d, 9.54)
4.31 (d, 9.30)
4.16 (d, 10.36) 2.22–2.31 (m)
–
–
2.87–2.93 (m)
2.82–2.92 (m)
2.60–2.80 (m)
2.71–2.75 (m)
3.42–3.60 (m)
2.25–2.32 (m)
-
-
5.14 (s), 5.57 (s)
5.16 (s), 5.59 (s)
–
–
–
–
–
–
epi-6
14
epi-14
15
2.91–2.99 (m)
2.71–2.57 (m)
1.66–1.95 (m)
3.29–3.35 (m)
3.19–3.24 (m)
3.53–3.67 (m)
3.53–3.67 (m)
3.67 (dd), 3.96 (dd)
3.85–3.92 (m)
3.68 (dd), 3.85 (dd)
3.72–3.78 (m), 3.92–3.98 (m)
3.76 (dd), 3.93 (dd)
3.53–3.67 (m)
16, ent-16 3400, 1585, 1270
17, ent-17 1585, 1250
-–
9.83 (s)
9.71 (d)
cis-18 +
1715, 1450, 1245
–
2.53–2.57 (m)
2.65–2.70 (m)
trans-18b
3.53–3.67 (m)
a s = singlet, d = doublet, t = triplet, m = multiplet.
b Diastereomeric mixture of cis-16 and trans-16 (85:15), which was not separable by flash chromatography; IR and NMR data from the mixture.
K2CO3 (100 mg, 0.73 mmol) was added and the mixture was stirred
for 10 min. The solid materials were filtered off, washed with
CH2Cl2 (10 mL), and the filtrate was concentrated in vacuo. The
crude product was purified by flash chromatography (Et2O/PE,
1:19) to give 17 (137 mg, 29%, data see above).
(1R,2RS)- and (1S,2RS)-7-Bromo-1-[(tert-butyldimethylsilyl-
oxy)-methyl]-1,2,3,4-tetrahydro-naphthalene-2-carbaldehyde
(18 and ent-18)
Compound 18
From 17 (491 mg, 1.04 mmol); yield 335 mg (84%).
Colourless oil; cis-18:trans-18 d.r. 85:15; Rf 0.55 (Et2O/PE, 1:4).
Preparation of Aldehydes; General Procedure
To dithiane (1.0 mmol) and CaCO3 (1.5 g, 15 mmol), suspended in
acetone (16 mL) and H2O (4 mL), MeI (1.25 mL, 20.0 mmol) was
added. The reaction mixture was heated at 60 °C for 24 h, cooled to
r.t. and diluted with CH2Cl2 (10 mL). The mixture was dried
(Na2SO4), the solid materials were filtered off and washed with
CH2Cl2 (10 mL). The filtrate was concentrated in vacuo (T <
35 °C). All aldehydes were used in the following Wittig reactions
without further purification because of their lability.
Compound ent-18
From ent-17 (236 mg, 0.50 mmol); yield 176 mg (92%).
Ent-cis-18:ent-trans-18 d.r. 70:30.
1H, 13C NMR and IR data of 18 and ent-18: Tables 5 and 6.
(1R,2RS)-7-Bromo-1-(hydroxymethyl)-1,2,3,4-tetrahydro-
naphthalene-2-carbaldehyde (19) and (3R,3aR,9bR)-
1,3,3a,4,5,9b-Hexahydrobenzo[e]isobenzofuran-3-ol (20)
As described above, dithiane 16 (186 mg, 0.52 mmol) was treated
with MeI and CaCO3. The work up, followed by flash chromato-
graphy on silica gel (Et2O/PE, 1:1) gave lactol 20 (51 mg, 36%) and
a mixture of aldehydes 19 (60 mg, 43%, d.r. 23:77).
(1R,2R)- and (1S,2R)-7-Bromo-1-hydroxy-1-methyl-1,2,3,4-tet-
rahydro-naphthalene-2-carbaldehyde [(1R)-9 and (1S)-9]
Compound (1R)-9
From (1R)-8 (359 mg, 1.00 mmol); yield 264 mg (98%).
Light yellow oil; Rf 0.32 (Et2O/PE, 1:1).
Compound 19
Colourless oil; cis-19:trans-19 d.r. 23:77; Rf 0.53 and 0.56 (Et2O/
PE, 1:1).
IR (film): v = 3450, 2920, 2870, 1700, 1585, 1475, 1070 cm-1.
Compound (1S)-9
From (1S)-8 (140 mg, 0.39 mmol); yield 100 mg (95%).
Light yellow oil; Rf 0.11 (Et2O/PE, 1:4).
1H, 13C NMR and IR data of (1R)-9 and (1S)-9: Tables 3 and 4.
Compound 20
Colourless crystals; Rf 0.24 (Et2O/PE, 1:9); mp 127-129 °C (Et2O/
PE); [a]D = -108.0 (c 0.64, CH2Cl2).
IR (KBr): v = 3380, 2930, 2870, 1585, 1470, 1070 cm-1.
Table 6 Selected Data of Compounds 6, 14–18 (13C NMR)
1H NMR (300 MHz, CDCl3): d = 1.48-1.65 (m, 1H), 1.86-1.95 (m,
1H), 2.39-2.46 (m, 1H), 2.50-2.75 (m, 2H), 3.20 (s, 1H), 3.62-
3.75 (m, 2H), 4.44-4.52 (m, 1H), 5.34 (s, 1H), 6.97 (d, 1H,
3J = 8.10 Hz), 7.20-7.26 (m, 2H).
Product
13C-NMR (75 MHz, CDCl3), d
C-2¢
C-2
C-1
C-3
C-11
2-CHO
13C NMR (75 MHz, CDCl3): d =22.6, 27.8, 39.3, 44.5, 73.8, 103.9,
6
93.2
94.2
93.7
94.0
93.7
51.3
50.3
–
45.0
44.3
41.8a
44.4
41.3a
43.2a
42.0a
42.5
39.9
136.4 24.7
137.2 22.1
41.9a 20.2
41.4 16.9
41.8a 20.5
41.7a 22.1
41.1a 22.5
49.2 16.7
47.8 14.2
113.8
112.6
64.8
65.1
64.7
64.7
64.2
–
–
–
–
–
–
–
epi-6
14
119.6, 129.2, 130.4, 131.8, 135.4, 138.2.
HRMS (EI): m/z calcd for (M+): 268.00989. Found: 268.00676.
epi-14
15
16, ent-16
17, ent-17
cis-18 +
trans-18a
3,3‘-Oxido-bi-[(3R,3aR,9bR)-1,3,3a,4,5,9b-hexahydrobenzo[e-
isobenzofuran] (21)
Crystallisation of 20 from Et2O/PE afforded colourless crystals of
the acetal 21.
65.8 201.4
67.0 203.6
–
Rf 0.50 (Et2O/PE, 1:1); mp 135-136 °C (Et2O/PE).
IR (KBr): v = 2920, 2860, 1580, 1475 cm-1.
a NMR data are interchangeable.
b Diastereomeric mixture of cis-16 and trans-16 (85:15), which was
not separable by flash chromatography; data from the mixture.
Synthesis 2000, No. 10, 1391–1402 ISSN 0039-7881 © Thieme Stuttgart · New York

1400
A. Kreier et al.
PAPER
Wittig Reaction of Aldehydes 18 and ent-18 (1R,2S)- and
(1S,2R)-{7-Bromo-1-(tert-butyldimethylsilyloxy)-methyl-2-[(Z)-
1-heptenyl]-1,2,3,4-tetrahydronaphthalene (22 and ent-22)
1H NMR (300 MHz, CDCl3): d = 1.48-1.65 (m, 2H), 1.86-1.95 (m,
2H), 2.39-2.46 (m, 2H), 2.50-2.75 (m, 4H), 3.62-3.75 (m, 4H),
4.44-4.52 (m, 2H), 5.34 (s, 2H), 6.97 (d, 2H, 3J = 8.10 Hz), 7.20-
7.26 (m, 4H).
To
a suspension of n-hexyltriphenylphosphonium bromide
(342 mg, 0.80 mmol) in THF (10 mL) was added dropwise n-BuLi
(1.6 M) in hexane (0.49 mL, 0.79 mmol) at -78 °C. After stirring
for 10 min at 0 °C, the mixture was cooled again to -78 °C and al-
dehyde 18 (203 mg, 0.53 mmol) in THF (7 mL) was added. The re-
action mixture was stirred for 4 h at 0 °C and then hydrolysed with
sat. NH4Cl (10 mL). The two layers were separated and the aqueous
phase was extracted with Et2O (3 ¥ 25 mL). The combined organic
layers were dried (Na2SO4) and concentrated in vacuo. The residue
was purified by flash chromatography (Et2O/PE, 1:99) to afford 22
(79 mg, 33%).
13C NMR (75 MHz, CDCl3): d = 22.6, 27.8, 39.3, 44.5, 73.8, 103.9,
119.6, 129.2, 130.4, 131.8, 135.4, 138.2.
Wittig Reaction of Aldehydes 9
(1R,2RS)-7-Bromo-2-[(EZ)-1-heptenyl]-1-methyl-1,2,3,4-tetra-
hydro-1-naphthol (10)
To a suspension of n-hexyltriphenylphosphonium bromide
(855 mg, 2.00 mmol) in THF (10 mL) was added dropwise n-BuLi
(1.6 M) in hexane (1.12 mL, 1.80 mmol) at -78 °C. After stirring
for 10 min at 0 °C, the mixture was cooled again to -78 °C and al-
dehyde (1R)-9 (183 mg, 0.68 mmol) in THF (8 mL) was introduced
slowly with a syringe. The reaction mixture was stirred for 4 h at
0 °C and then hydrolyzed with sat. NH4Cl (10 mL). The two layers
were separated and the aqueous phase was extracted with Et2O
(3 ¥ 25 mL). The combined organic layers were dried (Na2SO4) and
concentrated in vacuo. The residue was purified by flash chroma-
tography (Et2O/PE, 1:19) to afford a mixture of three diastereomers
10 (101 mg, 50%); d.r. [E-(1R,2S)]:[Z-(1R,2S)]:[E-(1R,2R)]:[Z-
(1R,2R)] = 57:31:12:0.
Colourless oil; Rf 0.29 (Et2O/PE, 1:99).
[a]D = +61.8 (c 0.82, CH2Cl2).
HRMS (EI): m/z calcd for (M+-tert-butyl): 393.124926. Found:
393.1236.
1H, 13C NMR and IR data of 22: Tables 7 and 8.
Compound ent-22
The crude product ent-22 (40 mg, 89%) obtained from ent-18
(38 mg, 0.10 mmol) was desilylated without further purification
(see below).
Colourless oil; Rf 0.26 (Et2O/PE, 1:19).
[a]D = -15.3 (c 0.79, CH2Cl2).
HRMS (EI): m/z for calcd (M+): 336.10889. Found: 336.10954.
(1R,2S)- and (1S,2R)-{7-Bromo-2-[(Z)-1-heptenyl]-1,2,3,4-
tetrahydro-1-naphthyl}methanol (23 and ent-23)
trans-(1RS,2RS)-7-Bromo-2-[(E)-1-heptenyl]-1-methyl-1,2,3,4-
tetrahydro-1-naphthol (12)
From rac-(1S*)-9 (46 mg, 0.17 mmol); yield 30 mg (52%).
To a solution of silyl ether 22 (79 mg, 0.18 mmol) in THF (3 mL)
was added 1 M TBAF in THF (0.4 mL, 0.40 mmol). The mixture
was stirred for 24 h at r.t. and then hydrolysed with H2O (1 mL). The
aqueous layer was separated and extracted with Et2O (3 ¥ 10 mL).
The combined organic phases were dried (Na2SO4) and concentrat-
ed in vacuo. Purification of the residue by flash chromatography
(Et2O/PE, 1:9) afforded alcohol 23 (27 mg, 57%).
Colourless oil; Rf 0.21 (Et2O/PE, 1:19); only 1 diastereomer
(E-trans) was detected.
1H, 13C NMR and IR data of 10 and 12: Tables 7 and 8.
Colourless oil; Rf 0.25 (Et2O/PE, 1:9).
Wittig Reaction of Lactol rac-20
(1RS,2SR)-{7-Bromo-2-[(Z)-1-heptenyl]-1,2,3,4-tetrahydro-1-
naphthyl}methanol (rac-23)
[a]D = +65.2 (c 0.33, CH2Cl2).
HRMS (EI): m/z calcd for (M+): 336.10889. Found: 336.10749.
As described above, lactol rac-20 (50 mg, 0.19 mmol) was treated
with 2 equiv n-hexyltriphenylphosphonium bromide/n-BuLi. The
work-up (as above), followed by flash chromatography on silica gel
(Et2O/PE, 1:9) gave pure Z-cis alkene rac-23 (22 mg, 34%; data Ta-
bles 7, 8) besides some starting material rac-20 (20 mg, 40%).
Compound ent-23
From crude ent-22 (40 mg, 0.09 mmol); yield 23 mg (78% over two
steps).
[a]D = -66.1 (c 0.12, CH2Cl2).
1H, 13C NMR and IR data of 23 and ent-23: Tables 7 and 8.
Table 7 Selected Data of Compounds 10–13, 22–24 (IR, 1H NMR)
Product
IR (KBr/film), n [cm–1]
1H-NMR (300 MHz, CDCl3), d, J (Hz)a
1-H
2-H
11-H
21-H (3J21,22
)
22-H
10b
3430, 1580, 1460
3250, 1580
3700, 1680
3400, 1685
1585, 1090
–
–
–
–
2.42–2.48 (m)
2.31–2.43 (m)
2.45–2.51 (m)
2.42–2.48 (m)
2.67–2.90 (m)
2.69–3.60 (m)
2.84–3.07 (m)
1.50 (s)
1.32 (s)
1.56 (s)
1.26–1.42 (m)
3.74–3.86 (m)
5.40 (ddt, 15.49)
5.49 (dd, 15.49)
5.40 (ddt, 15.52)
5.49–5.67 (m, 15.20)
5.32–5.42 (m, 10.90)
5.71 (dt)
5.60 (dt)
5.69, (dt)
5.49–5.67 (m)
5.32–5.42 (m)
5.39–5.55 (m)
5.43–5.57 (m)
rac-12
11c,d
rac-13d
22, ent-22
23, ent-23
2.67–2.90 (m)
2.69–3.00 (m)
2.84–3.07 (m)
3320, 1580, 1470
3.82 (dd), 3.92 (dd) 5.39–5.55 (m, 11.94)
3.91 (dd), 3.99 (dd) 5.43–5.57 (m, 8.78)
24, ent-24d 3360, 1665, 1600
as = singlet, d = doublet, t = triplet, m = multiplet.
bData of E(1R,2S)-10 from the diastereomeric mixture of E(1R,2S):Z(1R,2S):E(1R,2R) (57:31:12), which was not separable by flash chroma-
tography.
cData of E(7S,8R)-11 from the diastereomeric mixture of E(7S,8R):Z(7S,8R):E(7R,8R) (56:28:16), which was not separable by flash chroma-
tography.
dThe numbering is not following the IUPAC nomenclature.
Synthesis 2000, No. 10, 1391–1402 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Asymmetric Synthesis of Stereodefined 7-(Alk-1-enyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic Acids
1401
Table 8 Selected Data of Compounds 10–13, 22–24 (13C NMR)
[a]D = -105.0 (c 0.40, CDCl3).
1H, 13C NMR and IR data of 24 and ent-24: Tables 7 and 8.
Product
13C-NMR (75 MHz, CDCl3), d
1-C
2-C
11-C 21-C 22-C 7-C
71-C
Acknowledgement
10a
71.1 49.1 30.5 127.9 136.3 119.9
–
–
rac-12b
11c,d
–
–
–
–
–
–
The work was supported by the Fonds der Chemischen Industrie, by
the Deutsche Forschungsgemeinschaft, and the Bayer AG. E. W.
thanks the Academy of Finland for financial support.
71.2 49.1 32.7 127.7 136.0 129.2 171.9
71.7 43.2 27.8 127.7 136.0 129.2 171.9
rac-13d
22, ent-22 44.8 34.3 64.9 130.7 130.8 118.7
23, ent-23 44.9 34.1 64.9 130.7 131.7 119.2
–
–
24, ent-24d 44.8 34.1 65.0 131.0 132.1 126.7 171.3
References
a Data of E(1R,2S)-10 from the diastereomeric mixture of E(1R,2S):
Z(1R,2S):E(1R,2R) (57:31:12), which was not separable by flash
chromatography.
# X-ray structure analysis.
(1) MacKintosh, C.; MacKintosh, R. W. Trends Biochem. Sci.
1994, 19, 444.
bNot determined.
Rinehart, K. L.; Harada, K.; Namikoshi, M.; Chen, C.; Harvis,
C. A.; Munro, M. H. G.; Blunt, J. W.; Mulligan, P. E.;
Beasley, V. R.; Dahlem, A. M.; Carmichael, W. W. J. Am.
Chem. Soc. 1988, 110, 8557.
c Data of E(7S,8R)-11 from the diastereomeric mixture of E(1R,2S):
Z(1R,2S):E(1R,2R) (56:28:16), which was not separable by flash
chromatography.
d The numbering is not following the IUPAC nomenclature.
(2) First reports: Hoppe, I.; Hoppe, D.; Wolff, C.; Egert, E.;
Herbst, R. Angew. Chem., Int. Ed. Engl. 1989, 28, 67.
Scolastico, C. Pure Appl. Chem. 1988, 60, 1689.
(3) a) Hoppe, I.; Hoppe, D.; Herbst-Irmer, R.; Egert, E.
Tetrahedron Lett. 1990, 31, 6859.
Conversion of Bromides into Carboxylic Acids; General Proce-
dure
b) Pasquarello, A.; Poli, G.; Scolastico, C. Synlett 1992, 93.
c) Hoffmann, H.; Bolte, M.; Berger, B.; Hoppe, D.
Tetrahedron Lett. 1993, 34, 6537.
To a solution of bromoarene (1.0 mmol) in THF (10 mL) was added
dropwise 1.5 M MeLi·LiBr in Et2O (1.0 mL, 1.5 mmol) at -78 °C.
Stirring was continued for 30 min and then 1.5 M tert-BuLi in pen-
tane (1.66 mL, 2.50 mmol) was added dropwise to the mixture. Af-
ter stirring for 10 min, anhyd CO2 was bubbled through the reaction
mixture with a stainless steel needle and the mixture was allowed to
warm up to r.t. over 30 min. After addition of 2N HCl (4 mL) the
aqueous layer was separated and extracted with EtOAc (5 ¥ 10 mL).
The combined organic phases were dried (Na2SO4) and concentrat-
ed in vacuo. Purification of the residue by flash chromatography
(Et2O/PE, 1:1 to 1:1+5% MeOH) afforded the carboxylic acid.
(4) Hoppe, I.; Hoffmann, H.; Gärtner, I.; Krettek, T.; Hoppe, D.
Synthesis 1991, 1157.
(5) a) Conde-Frieboes, K.; Hoppe, D. Synlett 1990, 99.
b) Bernardi, A.; Cardani, S.; Carugo, O.; Colombo, L.;
Scolastico, C.; Villa, R. Tetrahedron Lett. 1990, 31, 2779.
c) Bernardi, A.; Piarulli, U.; Poli, G.; Scolastico, C.; Villa, R.
Bull. Soc. Chim. Fr. 1990, 127, 751.
d) Bernardi, A.; Cavicchioli, M.; Poli, G.; Scolastico, C.;
Sidjimov, A. Tetrahedron 1991, 47, 7925.
e) Conde-Frieboes, K.; Hoppe, D.; Tetrahedron 1992, 48,
6011.
f) Bernardi, A.; Cardani, S.; Poli, G.; Potenza, D.; Scolastico,
C. Tetrahedron 1992, 48, 1343.
(7RS,8R)-7-[(EZ)-1-Heptenyl]-8-hydroxy-8-methyl-5,6,7,8-tet-
rahydro-naphthalene-2-carboxylic Acid (11)
From 10 (101 mg, 0.30 mmol); yield 83 mg (91%).
g) Steif, F.; Wibbeling, B.; Meyer, O.; Hoppe, D. Synthesis
2000, 743.
(6) Cornelius, L. A. M.; Combs, D. W. Synth. Commun. 1994, 24,
2777.
(7) Fleming, I.; Patterson, I. Synthesis 1979, 736.
(8) a) Prien, O.; Hoffmann, H.; Conde-Frieboes, K.; Krettek, T.;
Berger, B.; Wagner, K.; Bolte, M.; Hoppe, D. Synthesis 1994,
1313.
b) Conde-Frieboes, K.; Harder, T.; Aulbert, D.; Strahringer,
C.; Bolte, M.; Hoppe, D. Synlett 1993, 921.
(9) Nakamura, E.; Kuwajima, I. Tetrahedron Lett. 1983, 24,
3343.
Brüggemann, M.; Hoppe, D. unpublished results.
(10) X-ray crystal structure analysis of 3: formula C22H24BrNO4S,
M = 478.39, colourless crystal 0.40 ¥ 0.30 ¥ 0.20 mm,
a = 12.135(1), b = 12.575(1), c = 13.829(2) Å, V = 2110.3(4)
Å3, rcalcd = 1.506 gcm-1, µ = 38.20 cm-1, empirical absorption
correction via y scan data (0.879 £ C £ 0.999), Z = 4,
orthorhombic, space group P212121 (No. 19), l = 1.54178 Å,
T = 223 K, w/2 q scans, 4682 reflections collected (+h, +k,
l), [(sin q)/l] = 0.62 Å-1, 4289 independent and 4089
observed reflections [I ≥ 2 s(I)], 301 refined parameters,
R = 0.038, Rw2 = 0.103, max. residual electron density 0.41
(-0.56) eÅ-3, Flack parameter 0.14(2), hydrogens calculated
and refined as riding atoms, disorder with 50/50%
distribution.
Colourless wax; d.r. [E-(7S,8R)]:[Z-(7S,8R)]:[E-(7R,8R)]:[Z-
(7R,8R)] = 56:28:16:0; Rf 0.51 (Et2O/PE; 1:1+5% MeOH).
[a]D = -6.8 (c 0.65, CH2Cl2).
HRMS (EI): m/z calcd for (M+): 302.18820. Found: 302.18923.
1H, 13C NMR and IR data: Tables 7 and 8.
trans-(7RS,8RS)-7-[(E)-1-Heptenyl]-8-hydroxy-8-methyl-
5,6,7,8-tetrahydro-naphthalene-2-carboxylic Acid (13)
From 12 (30 mg, 0.09 mmol); yield 8 mg (29%).
Colourless wax; Rf 0.22 (Et2O/PE, 1:1+5% MeOH).
HRMS (EI): m/z calcd for (M+): 302.18820. Found: 302.18607.
1H, 13C NMR and IR data: Tables 7 and 8.
(7S,8R)- and (7R,8S)-8-(Hydroxymethyl)-7-[(Z)-1-heptenyl]-
5,6,7,8-tetrahydro-naphthalene-2-carboxylic Acid (24 and ent-
24)
From 23 (27 mg, 0.08 mmol); yield 9 mg (37%).
Colourless wax; Rf 0.41 (Et2O/PE, 1:1+5% MeOH); [a]D = +70.6
(c = 0.17, CH2Cl2).
HRMS (EI): m/z calcd for (M+): 302.18820. Found: 302.18822.
Compound ent-24
From ent-23 (23 mg, 0.07 mmol); yield 11 mg (54%).
Synthesis 2000, No. 10, 1391–1402 ISSN 0039-7881 © Thieme Stuttgart · New York

1402
A. Kreier et al.
PAPER
(11) In the crystal structure both compounds are co-crystallised in
a 50:50 ratio. For clarity, the structures are shown in two
separate figures.
(12) Roberts, J. D.; Weigert, F. J.; Kroschwitz, H. J. J. Am. Chem.
Soc. 1970, 92, 1338.
electron density 0.64 (-0.48) eÅ-3, Flack parameter 0.03(2),
hydrogens calculated and refined as riding atoms.
(19) X-ray crystal structure analysis of 21: formula C24H24Br2O3,
M = 520.25, colourless crystal 0.30 ¥ 0.30 ¥ 0.10 mm,
a = 12.398(1), b = 6.662(1), c = 13.092(1) Å, b = 99.70(1)°,
V = 1065.9(2) Å3, rcalcd = 1.621 gcm-1, µ = 50.07 cm-1,
empirical absorption correction via y scan data (0.796 £ C £
1.000), Z = 2, monoclinic, space group P21 (No. 4),
l = 1.54178 Å, T = RT, w/2 q scans, 2487 reflections
collected (-h, +k, l), [(sin q)/l] = 0.62 Å-1, 2377
independent and 2332 observed reflections [I ≥ 2 s(I)], 263
refined parameters, R = 0.036, Rw2 = 0.105, max. residual
electron density 0.84 (-0.42) eÅ-3, Flack parameter 0.03(3),
hydrogens calculated and refined as riding atoms.
Data sets were collected with an Enraf Nonius CAD4
diffractometer. Programs used: data reduction MolEN,
stucture solution SHELXS-97, structure refinement
SHELXL-97, graphics SCHAKAL-92.
Crystallographic data (excluding structure factors) for the
structures reported in this paper have been deposited with the
Cambridge Crystallographic Data Centre as supplementary
publication no. CCSD-141914 (3), CCSD 141915 (R-7),
CCSD 141916 (14) and CCSD 141917 (21). Copies of the
data can be obtained free of charge on application to The
Director CCDC, 12 Union Road, CambridgeCB2 1EZ, UK
[fax:+44(1223)336033, e-mail: deposit@ccdc.cam.ac.uk].
(20) Schlosser, M.; Christmann, K. F. Liebigs Ann. Chem. 1967,
708, 1.
Whitesell, J. K.; Minton, M. A. Stereochemical Analysis of
Alicyclic Compounds by C-13 NMR Spectroscopy; Chapman
and Hall: Cambridge, 1987.
(13) Steglich, W.; Höfle, G. Angew. Chem. 1969, 81, 1001.
(14) DePuy, C. H.; King, R. W. Chem. Rev. 1969, 60, 431.
(15) Winter, E.; Hoppe, D. Tetrahedron 1998, 54, 10329.
(16) X-ray crystal structure analysis of (R)-7: formula
C14H15BrOS2, M = 343.29, colourless crystal
0.20 ¥ 0.15 ¥ 0.10 mm, a = 6.606(1), b = 9.120(2),
c = 23.968(4) Å, V = 1444.0(5) Å3, rcalcd = 1.579 gcm-1,
µ = 64.58 cm-1, empirical absorption correction via y scan
data (0.942 £ C £ 0.999), Z = 4, orthorhombic, space group
P212121 (No. 19), l = 1.54178 Å, T = 223 K, w/2 q scans,
1717 reflections collected (+h, +k, +l), [(sin q)/l] = 0.62 Å-1,
1717 independent and 1620 observed reflections [I ≥ 2 s(I)],
164 refined parameters, R = 0.02, Rw2 = 0.069, max. residual
electron density 0.47 (-0.54) eÅ-3, Flack parameter -0.01(3),
hydrogens calculated and refined as riding atoms.
(17) Review: Pine, S. H. Org. React. 1993, 43, 1.
Tebbe, F. N.; Parshall, G. W.; Reddy, G. S. J. Am. Chem. Soc.
1978, 100, 3611.
(18) X-ray crystal structure analysis of 14: formula C23H28BrNO4S,
M = 494.43, colourless crystal 0.3 ¥ 0.25 ¥ 0.20 mm,
a = 9.099(1), b = 10.236(1), c = 12.653(1) Å, b = 102.25(1)°,
V = 1151.6(2) Å3, rcalcd = 1.426 gcm-1, µ = 35.16 cm-1,
empirical absorption correction via y scan data (0.758 £ C £
0.999), Z = 2, monoclinic, space group P21 (No. 4),
l = 1.54178 Å, T = 223 K, w/2 q scans, 4961 reflections
collected ( h, -k, l), [(sin q)/l] = 0.62 Å-1, 2484
independent and 2437 observed reflections [I ≥ 2 s(I)], 275
refined parameters, R = 0.032, Rw2 = 0.086, max. residual
(21) The further fractions were not investigated.
(22) Corey, E. J.; Venkateswarlu, A. J. Am. Chem. Soc. 1972, 94,
6190.
(23) Wilkinson R. G.; Shepherd, R. G.; Thomas, J. P.; Baughn, C.
J. Am. Chem. Soc. 1961, 83, 2212.
Article Identifier:
1437-210X,E;2000,0,10,1391,1402,ftx,en;Z02100SS.pdf
Synthesis 2000, No. 10, 1391–1402 ISSN 0039-7881 © Thieme Stuttgart · New York