Synthesis, crystal structure and oxidation of (R)-(+)-8,9-dimethoxy-6,10b-dihydro-5H-thiazolo[2,3-a]isoquinolin-3-one

Article abstract of DOI:10.1016/S0957-4166(02)00633-X

(R)-(+)-8,9-Dimethoxy-6,10b-dihydro-5H-thiazolo[2,3-a]isoquinolin-3-one 1 has been synthesized from 6,7-dimethoxy-3,4-dihydroisoquinoline and menthyl thioglycolate. Compound 1 was obtained in the enantiomerically pure form (mp 150-153°C, [α]_D +436) by a single crystallization of the crude reaction product (68% e.e.) from 96% ethanol. The absolute 10bR configuration was established by X-ray diffraction. Oxone oxidation of 1 resulted in a configurationally unstable dextrorotatory syn-sulfoxide 2 (mp 173-175°C, [α]_D +62.8).

Full text of DOI:10.1016/S0957-4166(02)00633-X

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 2329–2333
Synthesis, crystal structure and oxidation of
(R)-(+)-8,9-dimethoxy-6,10b-dihydro-5H-thiazolo-
[2,3-a]isoquinolin-3-one
M. D. Rozwadowska,a,* A. Sulimaa and A. Gzellab
aFaculty of Chemistry, Adam Mickiewicz University, ul. Grunwaldzka 6, 60-780 Poznan´, Poland
bDepartment of Organic Chemistry, K. Marcinkowski University of Medical Sciences, ul. Grunwaldzka 6,
60-780 Poznan´, Poland
Received 21 August 2002; accepted 27 September 2002
Abstract—(R)-(+)-8,9-Dimethoxy-6,10b-dihydro-5H-thiazolo[2,3-a]isoquinolin-3-one 1 has been synthesized from 6,7-dimethoxy-
3,4-dihydroisoquinoline and menthyl thioglycolate. Compound 1 was obtained in the enantiomerically pure form (mp 150–153°C,
[h]D +436) by a single crystallization of the crude reaction product (68% e.e.) from 96% ethanol. The absolute 10bR configuration
was established by X-ray diffraction. Oxone oxidation of 1 resulted in a configurationally unstable dextrorotatory syn-sulfoxide
2 (mp 173–175°C, [h]D +62.8). © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
mercaptoacid halides,2–6 or ethylene sulfide.7,8 The reac-
tions of 3,4-dihydroisothiocarbostyril with a-haloacids,9
and of N-thioacylated b-phenylethylamine with a-
haloacid halides10,11 have also been successfully applied.
In connection with our study on sulfur-mediated syn-
theses of isoquinoline alkaloids we have used the dihy-
drothiazolo[2,3-a]isoquinolinone derivatives 1 and 2
(Fig. 1) in racemic form as intermediates in the synthe-
sis of ( )-salsolidine.1 Recently, we have undertaken the
synthesis of 1 and 2 in non-racemic form with a view to
developing routes for the asymmetric synthesis of iso-
quinoline alkaloids.
As far as we know, none of the above synthetic strate-
gies has been adapted for asymmetric synthesis of thia-
zolo[2,3-a]isoquinoline derivatives, neither has any
compound of this type been obtained in enantiomeri-
cally pure form. Herein, we describe our investigations
into the asymmetric synthesis of compounds 1 and 2
from 6,7-dimethoxy-3,4-dihydroisoquinoline and (−)-
menthyl thioglycolate 3, resulting in enantiomerically
Several synthetic methods for the construction of the
partially-hydrogenated, racemic thiazolo[2,3-a]iso-
quinoline heterocyclic system, of the type 1, have been
developed. Most usually, they involve cyclocondensa-
tion reactions between 3,4-dihydroisoquinoline deriva-
tives and a-mercaptoacids,2–5 their esters2 or b-
pure
(R)-(+)-8,9-dimethoxy-6,10b-dihydro-5H-thia-
zolo[2,3-a]isoquinolin-3-one 1. The absolute configura-
tion of 1 was also established by X-ray crystallography.
Enantiomerically pure or enriched sulfoxides can be
conveniently prepared by a variety of procedures
involving asymmetric oxidation of the corresponding
sulfide.12 In our case, the chiral sulfide 1 was used as a
substrate to give (+)-8,9-dimethoxy-6,10b-dihydro-5H-
thiazolo[2,3-a]isoquinolin-3-one S-oxide 2 on oxidation
with oxone.
Figure 1.
2. Results and discussion
For asymmetric synthesis of 1, cyclocondensation of
3,4-dihydroisoquinoline with thioglycolic acid deriva-
* Corresponding author. Tel.: +48-61-829-13-22; fax: +48-61-8658-
008; e-mail: mdroz@amu.edu.pl
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00633-X

2330
M. D. Rozwadowska et al. / Tetrahedron: Asymmetry 13 (2002) 2329–2333
tives seemed to us to be the method of choice (Scheme
1).
1H NMR spectrum of amide 5, the CH3CHN group
protons appeared as a doublet and multiplet at 1.52
and 5.12 ppm, respectively, with J=6.9 Hz, along with
a characteristic absorption of protons within the –CH2-
SH substituent in the form a triplet at 1.87 ppm and a
doublet at 3.24 ppm with J=9.3 Hz. The carbonyl
group absorption was found at 1728 and 1730 cm−1 in
the IR spectra of esters 3, 4, and of the amide 5 at 1640
cm−1. The molecular formula of the three compounds
was confirmed by high resolution mass spectrometry.
This synthetic pathway offers the possibility of carrying
out both diastereoselective and enantioselective synthe-
ses. We assumed that the synthesis of 1 could be
realized by using chiral thioglycolic acid derivatives,
e.g. esters or amides, prepared with chiral alcohols or
amines. On the other hand, the use of external chiral
controllers might also effect the enantioselective synthe-
sis. The corresponding S-oxides, of the type 2, could
be prepared either from racemic 1 by asymmetric
oxidation,12 or from chiral nonracemic 1 by achiral
oxidants.
The Lewis acid-catalyzed cyclocondensation of 6,7-
dimethoxy-3,4-dihydroisoquinoline with the three chiral
derivatives of thioglycolic acid, 3, 4 and 5 was then
investigated. To optimize the reaction conditions, sev-
eral parameters, including the solvent, the temperature
and nature of the Lewis acid, were varied. The best
results, as to the yield (77%) and enantioselectivity
(68% e.e.), were achieved, when menthyl thioglycolate 3
was used and the reaction was carried out in isopropyl
ether, at rt, in the presence of titanium(IV) isopropox-
ide, under an argon atmosphere. To our surprise, the
use of ester 4, derived from 8-phenylmenthol, recom-
mended as a more powerful inductor of chirality,13
resulted in the formation of a racemic product in only
27% yield. The possible reasons for this failure could be
steric hindrance which could also account for the lack
of reactivity of 1-methyl-3,4-dihydroisoquinoline with
menthyl thioglycolate 3. Amide 5, also turned out to be
unreactive in the addition at rt, whereas at elevated
temperature it decomposed spontaneously.
In the initial step of the diastereoselective synthesis,
enantiomerically pure esters 3 and 4 and amide 5 were
first synthesized (Fig. 2). Esters 3 (oil, [h]D −76) and 4
(mp 43–47°C, [h]D +21) were obtained in high yield (96
and 89%, respectively) by condensing thioglycolic acid
with (−)-menthol and (−)-8-phenylmenthol, respec-
tively, in refluxing toluene under Dean–Stark condi-
tions, followed by chromatographic separation. In an
analogous reaction between thioglycolic acid and (+)-a-
phenylethylamine, amide 5 (65%, mp 70–75°C, [h]D
+72), accompanied by the corresponding dimeric
disulfide (19%, mp 136–139°C, [h]D +156), were formed.
1
The H NMR spectra of esters 3 and 4, revealed the
characteristic bands assigned to the two methylene
group protons of the methylthio substituent and the
methine -CHOCO- proton. In the spectrum of ester 3
the –CH2-S- group protons appeared as two singlets at
3.22 and 3.25 ppm, whereas in the spectrum of 4, they
Enantiomerically pure 1 (mp 150–153°C, [h]D +436),
was obtained by a single crystallization of the crude
reaction product from 96% ethanol. It was identical,
both spectroscopically and chromatographically, with a
sample of racemic 1,9 and its configurational integrity
2
gave rise to a doublet of AB quartet with J=15 Hz
3
and J=8 Hz, at 2.55 ppm. The -CHOCO- methine
proton multiplet was shifted downfield, to 4.71 (in 3)
and to 4.82 ppm (in 4), relative to its absorption
observed in the spectra of the parent alcohols, e.g. 3.40
ppm (menthol) and 3.48 ppm (phenylmenthol). In the
1
was confirmed by H NMR spectra measured in the
presence of DNBA14 and TADDOL15 as well as by
HPLC analysis, applying Chiracel OD-H column. The
Scheme 1.
Figure 2.

M. D. Rozwadowska et al. / Tetrahedron: Asymmetry 13 (2002) 2329–2333
2331
Oxazolines have already been reported to be efficient
chiral ligands in additions of organometallic reagents to
imines,19,20
absolute R configuration was then established by single-
crystal X-ray analysis; the ORTEP presentation of (+)-1
is shown in Fig. 3.
whereas TADDOL–titanate proved very
useful in additions to carbonyl compounds.21
In our experiments, however, these compounds exhib-
ited poor catalytic activity (yields 5–28%) and asymmet-
ric induction properties. Only in one experiment, in
which 6,7-dimethoxy-3,4-dihydroisoquinoline reacted
with thioglycolic acid in the presence of TADDOL–
titanate, ent-1 was formed in 38% yield and 8% e.e. (by
1H NMR).
As a direct route for the synthesis of sulfoxide 2
asymmetric oxidation of racemic thiazoloisoquinoline 1
was preferred. Several methods based on the Sharpless
epoxidation procedures adapted for oxidation of
sulfides to chiral sulfoxides, including the protocols
presented by Kagan,22,23 Modena24 and Uemura,25 were
applied and were unsuccessful. The C-1-methyl deriva-
tive was resistant to oxidation, while 1 was converted
into optically inactive sulfoxide 2 in yields ranging
between 9 and 46%. In several reactions, the unreacted
starting material was isolated and its enantiomeric com-
position was investigated by specific rotation and NMR
spectra measurements, in the hope that a kinetic resolu-
tion process was taking place. Unfortunately, only opti-
cally inactive 1 was found, indicating a lack of
selectivity in the oxidation of the heterocyclic system.
Figure 3.
The hydrogen atom at the stereogenic C10b centre
exhibits a b-orientation and occupies a pseudo-axial
position with respect to the partially saturated pyridine
ring and the five-membered ring. In the solid state, the
five-membered thiazolinone ring has an envelope con-
formation {Cremer and Pople16 puckering parameters:
,
Q=0.344(2) A, €=354.8(4)°}, whereas the partially
hydrogenated pyridine moiety has a conformation
intermediate between a half-chair and envelope, but
nearer to the envelope one {Cremer and Pople16 puck-
,
ering parameters: Q=0.445(2) A, q=52.1(3)°, €=
Since we had enantiopure 1 in hand, we decided to
carry out oxidation with an achiral oxidizing agent.
Thus, enantiomerically enriched (91% e.e.) thiazoloiso-
quinoline 1 was oxidized with Oxone, resulting in the
formation of two diastereomeric sulfoxides (TLC). The
initially formed less polar diastereomer was isolated in
68% yield from the reaction mixture by extraction with
carbon tetrachloride. It was characterized by mp (173–
48.0(4)°}. The dihedral angles between the best-fit
planes of the central ring of the tricyclic skeleton and
the outer six- and five-membered rings are 7.66(10) and
38.17(7)°. The angle between the outer rings is
40.19(7)°. Both methoxy groups on the fused aromatic
ring are inclined at 2.3(3)° (C8ꢀOCH3) and 2.2(3)°
(C9ꢀOCH3) out of the plane of the ring. The majority
of the bond lengths and angles in the structure of (+)-1
are comparable with those observed in the correspond-
ing S-oxides.17 In the five-membered thiazolinone ring,
1
175°C), the specific rotation value ([h]D +62.8) and H
1
NMR spectroscopy. The H NMR spectrum was iden-
tical with that of racemic syn-sulfoxide 2, but differed
from that of the anti- diastereomer, (whose configura-
tion was established by X-ray analysis).17 We were
unable to determine the enantiomeric purity of the
sulfoxide, because the spectral (1H NMR with shift
reagents) and chromatographic (HPLC with chiral Chi-
ralcel OD-H column) methods failed.
,
the C3ꢀN4 bond distance, 1.353(3) A, is typical of a
18
,
tertiary amide CꢀN bond length, 1.346(5) A. Along
the b axis, the screw-related molecules are linked by
CꢀH···O intermolecular three-centre hydrogen bonds
i
i
,
,
{C2···O2 , 3.378(4) A, C2···O3 , 3.249(3) A; (i): 1−x,
1/2+y, 2−z} to form an infinite one-dimensional chain.
In the attempted enantioselective synthesis of com-
pound 1, we used chiral oxazolines 6, 7, TADDOL 8
and BINOL as external inductors of chirality (Fig. 4).
The syn-diastereomer isomerized easily to the anti one
on attempted crystallization, or in the NMR tube in
CHCl3, to give a mixture of syn/anti isomers at a
Figure 4.

2332
M. D. Rozwadowska et al. / Tetrahedron: Asymmetry 13 (2002) 2329–2333
constant ratio 1:3.3. This process was accompanied by
loss of configuration at the stereogenic centres, which
also took place in the solid state, after a few weeks,
even at 0°C, the anti isomer so formed was optically
inactive. We have observed a similar syn/anti isomer-
ization in the case of racemic 1.
4.3. (+)-8-Phenylmenthyl thioglycolate, 4
Compound 4 was prepared in the same way as ester 3.
Yield: 89%; mp 43–47°C; [h]D +21 (c 1, CHCl3); IR
1
(KBr) cm−1: 1728; H NMR (CDCl3) l: 0.79–1.27 (m,
3H), 0.88 (d, J=6.6 Hz, 3H, CH3), 1.19 (s, 3H, CH3),
1.30 (s, 3H, CH3), 1.38–1.54 (m, 1H), 1.62–1.73 (m,
2H), 1.80–1.88 (m, 2H), 2.02–2.11 (m, 1H), 2.50 (dABq,
2J=15.4, J=8.4 Hz, 2H, CH2S), 4.82 (dt, J=10.7, 10.7,
4,4 Hz, 1H, CHOCO), 7.11–7.21 (m, 1H), 7.22–7.37 (m,
4H). EI MS m/z (%): 306 (M+, 1), 215 (21), 119 (100),
91 (21). HR MS calcd for C18H26O2S (M+): 306.16534,
found: 306.16343.
3. Conclusion
In conclusion, we have reported a facile and stereoselec-
tive approach to chiral, non-racemic dihydro-5H-thia-
zolo[2,3-a]isoquinolinone derivatives from readily
available 3,4-dihydroisoquinolines and the menthyl
ester of a thioglycolic acid, and its oxidation to an
optically active sulfoxide. The configurational instabil-
ity of the sulfoxide may discourage the use of such
compounds as intermediates in asymmetric synthesis. It
should be added that this study represents the first
reported preparation and characterization of chiral
non-racemic derivatives containing the thiazolo[2,3-
a]isoquinoline heterocyclic ring system.
4.4. (+)-Thioglycolic acid N-[(R)-a-methylbenzyl]
amide, 5
Compound 5 was prepared in the same way as ester 3.
Yield: 65%; mp 70–75°C (ethyl ether); [h]D +72 (c 0.21,
CHCl3); IR (KBr) cm−1: 1640, 2560, 3277; H NMR
1
(CDCl3) l: 1.52 (d, J=6.9 Hz, 3H, CH3), 1.87 (t,
J=9.3 Hz, 1H, SH), 3.24 (d, J=9.3 Hz, 2H, CH2), 5.12
(m, 1H, ArCHC), 6.92 (s, 1H, NH), 7.26–7.39 (m, 5H,
ArH). EI MS m/z (%): 195 (M+, 6), 162 (74), 120 (19),
105 (100), 91 (11), 79 (20), 77 (28). HR MS calcd for
C10H13NOS (M+): 195.07179, found: 195.07065.
4. Experimental
4.1. General
4.5. (+)-Thioglycolic acid N-[(R)-a-methylbenzyl] amide
Melting points were determined on a Koffler block and
are not corrected. IR spectra were recorded on Perkin–
Elmer 180, in KBr pellets. NMR spectra were taken in
CDCl3 and in DMSO-d6 on Varian Gemini 300 with
TMS as internal standard. Mass spectra (EI) and FAB
techniques were obtained by using Joel D-100 75 eV.
For FAB-mass spectra, 3-nitrobenzyl alcohol was used
as a matrix. Merck silica gel 60 (70–230 mesh) was used
for column chromatography and Merck DC-alufolien
silica gel 60254 for TLC. High performance liquid chro-
matographic data (HPLC) were obtained using a
Waters HPLC system with Mallinkrodt–Baker Chiracel
OD-H column.
dimmer
Yield: 19%; mp 136–139°C; [h]D1 +155.7 (c 0.53,
CHCl3); IR (KBr) cm−1:1646, 3275. H NMR (CDCl3)
l: 1.52 (d, J=6.9 Hz, 3H, CH3), 3.30 (s, 2H, CH2), 5.12
(m, 1H, ArCHC), 6.96 (d, J=7.1 Hz, 1H, NH), 7.24–
7.35 (m, 5H, ArH). EI MS m/z: 388 (M+, 1), 162 (86),
120 (22), 105 (100), 77 (19). HR MS calcd for
C20H24N2O2S2 (M+): 388.14358, found: 388.14362.
4.6. (R)-(+)-8,9-Dimethoxy-6,10b-dihydro-5H-thia-
zolo[2,3-a]isoquinolin-3-one, 1
4.2. (−)-Menthyl thioglycolate, 3
(−)-Menthyl thioglycolate (0.506 g, 2.2 mmol) and tita-
nium isopropoxide (0.66 ml, 2.2 mmol) in dry isopropyl
ether (20 ml) was stirred at rt for 0.5 h under the argon
A mixture of thioglycolic acid (0.45 g, 8.64 mmol),
(−)-menthol (1.3 g, 8.3 mmol) and p-toluenesulfonic
acid (0.2 g) in toluene (80 ml) was heated under reflux
with azeotropic removal of water for 10 h. After cool-
ing to rt, the reaction mixture was washed with 1%
aqueous sodium hydroxide and water, and then dried.
The solvent was then removed and the residue was
purified by column chromatography (silica gel 1:10)
with hexane/ethyl acetate (100:1) as eluent, to give 3 as
colorless oil. Yield: 96%; [h]D −75.5 (c 0.5, CHCl3); IR
atmosphere.
A
solution of 6,7-dimethoxy-3,4-
dihydroisoquinoline26 (0.382 g, 2 mmol) in isopropyl
ether (15 ml) was then added and the mixture stirred
for 48 h at rt, after that time the precipitated product 1
was filtered off (0.408 g, 77%, 68% e.e.) and recrystal-
lized from ethanol to deposit racemic 1 (0.192 g, 47%),
while enantiomerically pure (R)-(+)-1 (0.2 g, 49%) was
obtained from the mother liquors. Mp 150–153°C, [h]D
+436 (c 1, CHCl3). IR (KBr) cm−1: 1670. 1H NMR
1
2
(KBr) cm−1: 1730; H NMR (CDCl3) l: 0.76 (d, J=6.9
(CDCl3) l: 2.68–2.73 (m, 1H, H-6ce), 2.96 (ddd, J=
Hz, 3H, CH3), 0.99 (d, J=3.4 Hz, 3H, CH3), 0.92 (d,
J=3.4 Hz, 3H, CH3), 0.92–1.09 (m, 3H), 1.36–1.48 (m,
2H), 1.61–1.72 (m, 2H), 1.88–2.03 (m, 3H), 3.22 and
3.25 (2s, 2H, CH2S), 4.71 (dt, J=10.9, 10.9, 4.4 Hz, 1H,
CHOCO). EI MS m/z (%): 230 (M+, 0.14), 139 (56), 95
(26), 83 (100), 69 (41), 55 (58), 47 (31), 41 (42). HR MS
calcd for C12H22O2S (M+): 388.15826; found:
388.16087.
13.7 Hz, 3J=12,2 and 5.6 Hz, 1H, H-6ca), 3.11 (dt,
3
2J=12.2 Hz, J=12.2 and 3.8 Hz, 1H, H-5a), 3.61 (d,
J=15.4 Hz, 1H, H-2a), 3.83 (d, J=15.4 Hz, 1H, H-2b),
2
3.87 and 3.88 (2×s, 6H, 2×OCH3), 4.45 (ddd, J=12.2
3
Hz, J=5.6 and 1.8 Hz, 1H, H-5e), 6.01 (s, 1H, H-10b),
6.61 (s, 2H, ArH). EI MS m/z (%): 265 (M+, 100), 232
(14), 190 (76), 176 (16). HR MS (M+) calcd for:
C13H15NO3S (M+): 265.07727; found: 265.07770.

M. D. Rozwadowska et al. / Tetrahedron: Asymmetry 13 (2002) 2329–2333
2333
4.7. (+)-(2R,10bR)-8,9-Dimethoxy-6,10b-dihydro-5H-
thiazolo[2,3-a]isoquinolin-3-one S-oxide, 2
3. Nair, M. D.; Malik, S. R.; Mehta, S. R. Indian J. Chem.
1967, 5, 221–223.
4. Menendez, J. C.; Delgado-Iribarren, A.; Sollhuber, M.
M. An. Real Acad. Farm. 1987, 53, 238–248.
5. Menendez, J. C.; Sollhuber, M. M. Heterocycles 1990, 31,
2065–2071.
6. Wimmer, T. L.; Day, F. H.; Bradsher, C. K. J. Org.
Chem. 1974, 40, 1198–1201.
7. Potekhim, A. A.; Sokolov, W. W.; Ogloblin, K. A.;
Esacov, S. M. Khim. Geterocycl. Soedin. 1983, 6, 776–785.
8. Sokolov, W. W.; Salfetnikova, N.; Potekhin, A. A. Zh.
Org. Khim. 1996, 32, 870–878.
9. Rozwadowska, M. D.; Sulima, A. Tetrahedron 2001, 57,
3499–3506.
10. Sheehan, S. M.; Beall, L. S.; Padwa, A. Tetrahedron Lett.
1998, 39, 4761–4764.
11. Padwa, A.; Beall, L. S.; Heidelbaugh, T. M.; Liu, B.;
Sheehan, S. M. J. Org. Chem. 2000, 65, 2684–2695.
12. Kagan, H. B. Catalytic Asymmetric Synthesis; 2nd ed.;
Wiley-VCH, 2000; Vol. 6C, pp. 329–356.
13. Seyden-Penne, J. Chiral Auxiliaries and Ligands in Asym-
metric Synthesis; Wiley: New York, 1995.
14. Kagan, H. B.; Deshmukh, M.; Dunach, E. Tetrahedron
Lett. 1984, 25, 3467–3470.
15. Seebach, D.; Beck, A. K.; Imwinkelried, R.; Roggo, S.;
Wonnacott, A. Helv. Chim. Acta 1987, 70, 954–974.
16. Cremer, D.; Pople, J. A. J. Am. Chem. Soc. 1975, 97,
1354–1358.
17. Gzella, A.; Rozwadowska, M. D.; Sulima, A. Acta Crys-
tallogr. 2001, C57, 1454–1456.
18. Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.;
Orpen, A. G.; Taylor, R. J. Chem. Soc., Perkin Trans. 2
1987, S1–19.
19. Arrasate, S.; Lete, E.; Sotomayor, N. Tetrahedron: Asym-
metry 2001, 12, 2077–2082 and references cited therein.
20. Głuszyn´ska, A.; Rozwadowska, M. D. Tetrahedron:
Asymmetry 2000, 11, 2359–2366.
21. Seebach, D.; Plattner, D. A.; Beck, A. K.; Wang, Y. M.;
Hunziker, D. Helv. Chim. Acta 1992, 75, 2171–2209.
22. Brunel, J. M.; Diter, P.; Deutsch, M.; Kagan, H. B. J.
Org. Chem. 1995, 60, 8086–8088.
23. Brunel, J. M.; Kagan, H. B. Bull. Chem. Soc. Fr. 1996,
133, 1109–1115.
24. Di Furia, F.; Licini, G.; Modena, G. Gazz. Chim. Ital.
1990, 120, 165–169.
To a solution of (+)-(R)-1 (91% e.e., 0.10 g, 0.38 mmol)
in a mixture (2:1) of chloroform/methanol (30 ml)
Oxone (0.123 g, 0.4 mmol) in water (3 ml) was added at
0°C. After 0.5 h, water (30 ml) was added and the
reaction mixture was extracted with carbon tetra-
chloride. Sulfoxide 2 was obtained after work-up in
yield 68%, mp 173–175°C [h]D +62.8 (c 0.35, CHCl3).
1
IR (KBr) cm−1: 1711; H NMR (DMSO-d6) l: 2.68–
2
3
2.72 (m, 2H, H-6), 2.97 (dt, J=12.3 Hz, J=12.3 and
3.9 Hz, 1H, H-5a), 3.75 and 3.77 (2×s, 6H, 2×OCH3),
3.98 (d, J=14.5 Hz, 1H, H-2b), 4.15 (d, J=14.5 Hz,
2
3
1H, H-2a), 4.26 (ddd, J=12.3 Hz, J=4.6 and 2.1 Hz,
1H, H-5e), 5.61 (s, 1H, H-10b), 6.87 and 6.95 (2×s, 2H,
ArH). EI MS m/z (%): 281 (M+, 45), 233 (22), 191
(100), 176 (47), 133 (9). HR MS (M+) calcd for
C13H15NO4S (M+): 281.07309; found: 281.07219.
4.8. X-Ray crystallography
4.8.1. General. Intensity data were collected using
Kuma Diffraction KM-4 diffractometer with graphite
,
monochromated Cu-Ka radiation (u=1.54178 A). The
data were measured using ꢀ˜ 2q scan method. The psi-
scan absorption correction was applied.27 The absolute
configuration of (+)-1 was established by the structure
refinement using Bijvoet-pair reflections.28 The pro-
grams used were KM-4 Software,29 SHELXS-97,30
SHELXL-97,30 PLATON,31 and ORTEP-3 for
Windows.32
4.8.2. Crystal data for (+)-(R)-1. C13H15NO3S, M=
265.33, monoclinic, space group P21, a=4.3530(10),
,
b=19.534(4), c=7.516(2) A, i=95.30(3)°; V=636.4(3)
3
−1
,
A , T=293(2) K, Z=2, v(Cu-Ka)=2.27 mm , 2498
data measured of which 2313 were unique, Rint=0.037,
qmax=70.1°, all unique data used in refinement against
F2 values to give final wR=0.1085 (on F2 for all data),
R=0.0374 {for 2276 data with F2>4|(F2)}, S=1.075
(on F2 for all data), minimum and maximum transmis-
sion:
parameter
constrained.
T
min=0.055,
T
max=0.204, absolute structure
x=−0.005(19), H-atom parameters
25. Komatsu, N.; Hashizume, M.; Sugita, T.; Uemura, S. J.
Org. Chem. 1993, 58, 4529–4533.
26. Whaley, W. M.; Meadow, M. J. J. Chem. Soc. 1953,
1067–1070.
27. North, A. C. T.; Phillips, D. C.; Mathews, F. S. Acta
Crystallogr. 1968, A24, 351–359.
Acknowledgements
This work was financially supported by KBN grant no.
3 T09A 026 17 and 3 T09A 027 17.
28. Flack, H. D. Acta Crystallogr. 1983, A39, 876–881.
29. Kuma Diffraction 1991; Version 1991t; Kuma KM-4
User’s Guide; Wrocław, Poland.
References
30. Sheldrick, G. M. SHELXS-97 and SHELXL-97; 1997;
Release 97-2; University Go¨ttingen, Germany.
31. Spek, A. L. Acta Crystallogr. 1990, A46, C34.
32. Farrugia, L. J. J. Appl. Cryst. 1997, 30, 565.
1. Rozwadowska, M. D.; Sulima, A. Polish J. Chem. 2001,
75, 1847–1852.
2. Schneider, W.; Kammerer, E. Arch. Pharm. 1966, 299,
847–857.