Synthesis of diastereomerically pure [1,3]thiazolo[3,2-α]azepane derivatives from D-hexoses

Article abstract of DOI:10.1055/s-1999-3474

Reaction of cysteamine with protected D-hexoses yielded the corresponding thiazolidines. The thiazolidine derived from 2,3;5,6-di-O- isopropylidene-D-mannofuranose was obtained stereoselectively and a subsequent N-heterocyclisation led to a diastereomeric

Full text of DOI:10.1055/s-1999-3474

PAPER
839
Synthesis of Diastereomerically Pure [1,3]Thiazolo[3,2-a]azepane Derivatives
from D-Hexoses
Delphine Marek, Anne Wadouachi, Daniel Beaupère*
Laboratoire de Chimie Organique, Université de Picardie Jules Verne, 33 rue Saint-Leu F- 80039 Amiens, France
Fax +33(03)22827562; E-mail: daniel.Beaupère@sc.u-picardie.fr
Received 30 September 1998; revised 15 December 1998
Abstract: Reaction of cysteamine with protected D-hexoses yielded
the corresponding thiazolidines. The thiazolidine derived from
2,3;5,6-di-O-isopropylidene-D-mannofuranose was obtained stere-
oselectively and a subsequent N-heterocyclisation led to a dia-
stereomerically pure analogue of pyrrolizidine. Alternatively, a
“one-pot” procedure for synthesis of pure [1,3]thiazolo[3,2-
a]azepane derivatives was realized from 6-O-sulfonyl-D-hexoses.
Key words: 2-aminoethanethiol, 6-O-sulfonyl-D-hexoses, N-het-
erocyclisation, [1,3]thiazolo[3,2-a]azepane, stereoselectivity
Polyhydroxylated alkaloids such as castanospermine 1
and australine 2 have aroused much interest as a result of
their potent inhibitory action against glycosidases.1
In preceding papers,2,3 we reported the synthesis of dias-
tereomerically pure analogues of castanospermine 3 and
australine 4 from D-pentoses, in which the C-1 atom is re-
placed by a sulfur atom (Scheme 1). In a two steps strate-
gy, partially protected D-pentoses were stereoselectively
transformed into the corresponding thiazolidines by the
action of cysteamine (2-aminoethanethiol). Then a cycli-
Scheme 1
sation with BuLi/TsCl or Bu3P/DIAD led to indolizidine
or pyrrolizidine analogues. Alternatively a one-pot strate-
gy was realized from 5-O-tosyl-D-pentose derivatives. In
yl group in compound 12 did not improve the stereoselec-
order to obtain new pyrrolizidines 5 and thiazolo[3,2-
tivity and the corresponding thiazolidine 13 was obtained
a]azepanes 6 (Scheme 1), we describe herein these strate-
in the same epimeric ratio.
gies applied to D-hexose derivatives.
A more contrasting and interesting result was obtained
In the first method, condensation of unprotected D-glu-
cose, D-mannose and D-galactose with cysteamine gave
highly hydrophilic thiazolidines derivatives without any
with the 2,3;5,6-di-O-isopropylidene-D-mannofuranose
14,7 in which the C-1'–C-2' and C-4'–C-5' rotations were
inhibited. The thiazolidine derivative 15 was obtained as
stereoselectivity. So, by analogy with results concerning
a single epimer.8 Compound 15 was subjected to X-ray
D-pentoses,3 we have synthesized partially protected D-
analysis to determine the 2S absolute configuration at the
glucose and D-mannose derivatives. The structure of thia-
zolidines obtained and their stereochemistry are reported
new chiral center.9
For such reactions, the imine intermediate was not isol-
able. On our assumption,3 the more probable isomer E
could adopt two preferred “cis” and “gauche” conforma-
tions and the cyclisation should proceed by a nucleophilic
attack of the sulfur atom anti to the C-1'–O-1' linkage.10
The two preferred conformations are represented in Table
2 for compounds 10 and 14. Following a kinetic explana-
tion, for the “gauche” and “cis” conformations of the imi-
ne derived from 2,3-O-isopropylidene-D-mannofuranose
(10a and 10b), the two epimers of the corresponding thia-
zolidine were obtained. In contrast, for the imine interme-
diate of compound 14, a repulsion between the N atom
and the terminal isopropylidene group should prevent the
in Table 1. The treatment of 3,5,6-tri-O-benzyl-D-gluco-
furanose 74 with cysteamine (1.5 equiv) in refluxed meth-
anol gave the thiazolidine derivative 7a in a C-2 epimeric
mixture 2R:2S = 1:1. Any selectivity has also been ob-
served for the thiazolidine 9 derived from the 4,6-O-ben-
zylidene-D-glucopyranose 8.5 In a previous paper, we
have observed that the 2,3-O-isopropylidene-D-ribofura-
nose led to the corresponding thiazolidine derivative in a
C-2 epimeric mixture (2R:2S = 8:92).2 In contrast with
this previous result, the condensation of this compound 10
with cysteamine in refluxed methanol gave the thiazoli-
dine derivative 118 as a mixture of C-2 epimers (2R:2S =
1:1). The introduction of a trityl group6 at the C-6 hydrox-
Synthesis 1999, No. 5, 839–843 ISSN 0039-7881 © Thieme Stuttgart · New York

840
D. Marek et al.
PAPER
Table 2 Imine intermediate in the formation of thiazolidine
derivatives.
formation of the “cis” conformation of the imine 14b. So,
the formation of the epimer 2S of thiazolidine 15 should
occur via the “gauche” conformation 14b.
Sub-
strate
Imine intermediate
« gauche » conformation
Imine intermediate
« cis » conformation
To obtain an analogue of pyrrolizidine, the thiazolidine 15
was cyclised using the system BuLi/ TsCl11 (Scheme 2).
A chemoselective sulfonylation and a subsequent cyclisa-
tion by the nucleophilic attack of the amino group led to
the (5S,6S,7S,7aS)-6,7-dihydroxy-6,7-O-isopropylidene-
5-(8,9-O-isopropylidene-8,9-dihydroxyethyl)perhy-
dro[1,3]thiazolo[3,2-a]pyrrole (16) in 55% yield. The
structure of compound 16 was elucidated by its 1H and 13C
spectrum. The 13C NMR spectrum indicated characteristic
data of carbons C-2, C-3 and C-5 at respectively d = 28.1,
54.7 and 66.5. The 1H NMR spectrum showed a multiplet
10
14
Table 1 Thiazolidines derived from D-hexoses
Substrat
Thiazolidine derivatives
resonating at d = 2.8 assigned to H-5 which was character-
istic of the formation of a C–N linkage.
(i) BuLi (1 eq), THF, 0 °C; (ii) TsCl (1.2 eq), THF, 0 °C, 30 min, 70
°C, 4 h
Scheme 2
The second way to access these N-heterocycles com-
pounds was a “one-pot” procedure from 6-O-sulfonyl-D-
hexose derivatives and cysteamine. This method was now
applied to the 6-O-mesyl-D-glucopyranose 17 prepared by
treatment of D-glucose with methanesulfonyl chloride
(1.2 equiv) in pyridine (Scheme 3). The treatment of this
compound 17 with cysteamine hydrochloride and sodium
methoxide in refluxed methanol led only to the single C-
9aS epimer of [1,3]thiazolo[3,2-a]azepane derivative 18.
This product 18 was a highly hydrophilic compound and
was separated from excess of cysteamine with difficulty
and isolated in 35% yield. The13C NMR spectrum indicat-
ed data characteristic of carbons C-2, C-5 and C-3 at re-
spectively d = 30.3, 53.9 and 63.2 ppm. The configuration
of the carbon C-9a of compound 18 was first established
from its 1H NMR spectrum. The doublet signal at d = 4.77
ppm with a J9–9a of 8.6 Hz indicated a trans configuration
for H-9 and H-9a. Obtaining compound 18 in crystalline
form provided an opportunity to unequivocally confirm
Synthesis 1999, No. 5, 839–843 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
Synthesis of Diastereomerically Pure [1,3]Thiazolo[3,2-a]azepane Derivatives
841
its bicyclic structure and the configuration of the C-9aS signed to H-9a, indicated a trans configuration for H-9 and
epimer by RX spectroscopy.12
H-9a.
In summary, the first method allowed the synthesis of a
diastereomerically pure thiazolidine derived from the
2,3;5,6-di-O-isopropylidene-D-mannofuranose stereose-
lectively. The N-heterocyclisation of this intermediate led
to a diastereomerically pure analogue of polyhydroxylat-
ed pyrrolizidine. More interesting was the second method,
a ”one-pot” procedure in which 6-O-sulfonyl-D-hexoses
reacted with cysteamine. This method only led to new bi-
cyclic compounds stereoselectively: the [1,3]-thiazolo-
[3,2-a]azepane derivatives. Tests for activity against gly-
cosidases will be reported elsewhere.
Melting points were determined with a Buchi 535 apparatus and are
uncorrected. TLC was performed on silica gel Merck 60 F254 plates
with visualization by charring with a phosphomolybdic acid–H2SO4
reagent. Preparative column chromatography was performed using
230–400 mesh Merck silica gel. Optical rotations were determined
with a Jasco-DIP-370 electronic micropolarimeter. NMR spectra
were recorded on a Bruker 300 WB spectrometer. Chemical shifts
are expressed in ppm downfield from TMS. Coupling constants are
in Hz and splitting pattern abbreviations are: s, singlet; d, doublet;
m, multiplet; t, triplet; q, quadruplet. Elemental analyses were per-
formed by the “Service Central de Microanalyse du CNRS” of Ver-
naison (69-Rhône-France). All solvents were distilled before use.
All reactions were performed under Ar atmosphere.
Preparation of Thiazolidines Derivatives from Reducing D-hex-
oses; General Procedure
To a solution of 2-aminoethanethiol hydrochloride (1 eq.) in MeOH
was added sodium methoxide (1 equiv). The mixture was stirred un-
der Ar at r.t. for 30 min, then salts were removed by filtration and
D-hexose derivative (0.5 equiv) was added to the filtrate. The mix-
ture was heated to reflux 2 h. The MeOH was removed under re-
duced pressure to give a crude product which was purified on silica
gel column.
HSCH2CH2NH2.HCl (2 eq), MeONa (2 eq), MeOH, reflux; (ii) Ac2O
(12 eq), pyridine, r.t.
Scheme 3
The reaction ”one-pot” applied to the 6-O-mesyl-D-man-
nose 19 led to the formation of the product 20 isolated in
63% yield in an epimeric mixture 9aR:9aS = 9:1 (Scheme
2-(2’,4’,5’-Tri-O-benzyl-D-gluco-tetrahydroxypentyl)thiazoli-
dine (7a)
Yield: 66%, syrup, column eluant: hexane/EtOAc 6:4 then EtOAc.
13C NMR (CDCl3): d = 33.6, 34.2 (C-5, 2R, 2S), 50.3, 50.6 (C-4, 2R,
2S), 69.2, 70.8 (C-5’, 2R, 2S), 72.6, 73.3, 74.0 (CH2Ph, 2R, 2S),
69.6, 70.5, 71.2, 76.6, 77.1, 78.9 (C-2, C-1’, C-2’, C-3’, C-4’, 2R,
2S), 126.3, 126.8, 127.3 (Ph, 2R, 2S), 137.2 (Cipso, 2R, 2S).
13
3). The C spectrum of the 9aR major product indicated
data characteristic of a [1,3]-thiazolo-[3,2-a]azepane (C-
2, C-5 and C-3 at respectively d = 30.9, 53.2 and 63.7
ppm). The compound 20 was converted to the correspond-
1
ing tetraacetate derivative 21 for H NMR (Ac2O, pyri-
C29H35O5NS calcd
(509) found
C
68.37
68.44
H
6.87 N 2.75 S 6.28
6.88 2.70 6.34
dine). The configuration of the carbon C-9a of compound
1
21 was established from its H NMR and by comparison
2-(3’,5’-O-Benzylidene-D-gluco-pentahydroxypentyl)thiazoli-
dine (9)
with the one of compound 18. The downfield resonances
were assigned to H-9aR of majority epimer: d 4.56 (d, J
9a–9 = 9,4 Hz), H-9aS of minority epimer: d = 4.50 (d, J
Yield: 78%, powder, column eluant: EtOAc then EtOAc/MeOH
9:1.
13C NMR (DMSO-d6): d = 33.9, 34.4 (C-5, 2R, 2S), 51.6, 52.1 (C-
4, 2R, 2S), 59.8, 60.2 (C-4’, 2R, 2S), 70.9 (C-5’, 2R, 2S), 69.8, 70.4,
72.1 (C-2, C-1’, C-2’, C-3’, 2R, 2S), 99.7 (CHPh, 2R, 2S), 125.8,
126.0, 128.4 (Ph, 2R, 2S), 138.2 (Cipso, 2R, 2S).
= 2,5 Hz). To obtain a pure [1,3]-thiazolo-[3,2-
9a–9
a]azepane derived from D-mannose, the ”one-pot” reac-
tion was applied to the 6-O-tosyl-2,3-O-isopropylidene-
D-mannofuranose 22 (Scheme 3). The treatment of the
compound 22 with cysteamine hydrochloride and sodium
methoxide in refluxed methanol gave the compound 23 in
78% yield with a pure C-9a (R) configuration. The struc-
ture and configuration of compound 23 were established
from its 1H NMR spectrum obtained in deuterated DMSO.
The doublet signal at d = 3.64 with a J9,9a of 9.4 Hz, as-
C15H21O5NS calcd
(327) found
C
45.87
45.92
H
6.42 N 4.28 S 9.78
6.35 4.18 9.85
2-(2,3-O-Isopropylidene-6-O-trityl-D-manno-pentahydroxy-
pentyl)thiazolidine (13)
Yield: 83%, powder, column eluant: hexane/EtOAc 6:4.
Synthesis 1999, No. 5, 839–843 ISSN 0039-7881 © Thieme Stuttgart · New York

842
D. Marek et al.
PAPER
13C NMR (CDCl3): d = 23.2, 24.3, 25.3, 26.7 (2 CH3, 2R, 2S), 33.7,
34.2 (C-5, 2R, 2S), 50.6, 50.9 (C-4, 2R, 2S), 64.3 (C-5’, 2R, 2S),
67.0, 67.6, 68.6, 70.4, 71.4, 74.77, 75.5, 75.8, 76.8, 78.9 (C-2, C-1’,
C-2’, C-3’, C-4’, 2R, 2S), 85.9 (CPh3, 2R, 2S), 107.0, 107.6 (CIV,
2R, 2S), 126.2, 126.9, 127.8 (Ph, 2R, 2S), 142.9 (Cipso, 2R, 2S).
13C NMR (CDCl3): d = 19.8 (CH3), 29.9 (C-2), 49.8 (C-5), 60.9 (C-
3), 69.5 (C-6), 69.7, 69.9, 72.2 (C-7, C-8, C-9), 71.5 (C-9a), 168.3,
168.7, 168.9 (C=O).
C16H23O8NS calcd
(389) found
C
49.35 H
49.56
5.91
6.22
N
3.59 S 8.22
3.15 8.76
C30H35O5NS calcd
(521) found
C
69.09
69.01
H
6.71 N 2.68 S 6.14
6.83 2.81 6.08
2,3-O-Isopropylidene-6-O-tosyl-a-D-mannofuranose (22)
To a solution of 10 (1.4 g, 6.36 mM) in pyridine (30 mL) cooled to
0 °C was added tosyl chloride (1.45 g, 7.63 mM). The mixture was
stirred at 0 °C for 1 h under Ar, then 16 h at r.t. The pyridine was
removed under reduced pressure to give a crude product which was
purified on silica gel column (hexane/EtOAc = 6:4, then 5:5) to give
the compound 22 as a powder (1.6 g, 67%).
(5S,6S,7S,7aS)-6,7-Dihydroxy-6,7-O-isopropylidene-5-(8,9-O-
isopropylidene-8,9-dihydroxyethyl)perhydro[1,3]thiazolo[3,2-
a]pyrrole (16)
To a solution of thiazolidine 15 (1 g, 3.13 mM) in 10 mL of THF,
cooled at 0 °C, was added BuLi 2,5 M in THF (1.3 mL, 3.13 mM).
After stirring at 0 °C under Ar for 15 min, tosyl chloride (712 mg,
3.75 mM) was added and the mixture was stirred 30 min at this tem-
perature, then was heated at 70°C for 4h. The mixture was concen-
trated and the residue was chromatographed on silica gel (hexane/
EtOAc 85: 15 and 7: 3) to give the pure compound 16 as syrup (520
mg, 55%).
1H NMR (CDCl3): d= 1.21, 1.24, 1.27, 1.51 (4s, 12H, 4 CH3), 2.76-
2.97 (m, 4H, H-2a, H-2b, H-3a, H-5), 3.72 (dd, 1H, H-9a, J = 9 Hz,
J = 5.7 Hz), 3.85 (m, 1H, H-3b), 3.98–4.08 (m, 2H, H-9b, H-8), 4.29
(t, 1H, H-6, J = 4.6 Hz), 4.82–4.86 (m, 2H, H-7, H-7a).
Rf = 0.45 (hexane/EtOAc = 1:1), mp = 160–161°C, [a]21D = +19 (c
= 1, EtOAc).
1H NMR (DMSO): d = 1.21, 1.25 (2s, 6H, 2 CH3), 2.39 (s, 3H, CH3
(OTs), 3.84–3.90 (m, 3H, H-6, H-6’, H-5), 4.1 (dd, 1H, H-4, J = 2.7
Hz, J = 5.8 Hz), 4.84 (d, 1H, H-2, J = 5.8 Hz), 4.69 (dd, 1H, H-3, J
= 5.8 Hz, J = 2.7 Hz), 5.06 (s, 1H, H-1, J = 0 Hz), 7.46–7.76 (2d,
4H Ph).
13C NMR (DMSO): d = 20.9 (CH3 (OTs)), 24.4, 25.7 (2 CH3), 65.7
(C-5), 73.1 (C-6), 78.4 (C-4), 79.1 (C-3), 85.0 (C-2), 100.1 (C-1),
111.2 (C iso), 127.5, 130.0 (C Ph), 132.1 (C ipso), 144.7 (C ipso).
13C NMR (CDCl3): d = 24.3, 24.8, 25.7 (4 CH3), 28.1 (C-2), 54.7
(C-3), 65.6 (C-9), 66.5 (C-5), 77.2 (C-8), 78.4, 78.7, 81.3 (C-6, C-
7, C-7a), 108.8, 114.3 (2C iso).
C16H22O8S
(374)
calcd
C
51.33
51.47
H
5.88
6.01
found
C14H23O4NS calcd C
(301) found
55.81 H
55.75
7.64
7.69
N
4.65 S 10.63
4.70 10.58
(6R,7R,8S,9S,9aR)-6,7,8,9-Tetrahydroxy-8,9-O-isopropy-
lidene[1,3]thiazolo[3,2-a]azepane (23)
Yield: 78%, powder, mp = 130–131 °C, [a]20 –12 (c = 0.36,
D
CH2Cl2).
”One-Pot” Preparation of [1,3]Thiazolo[3,2-a]azepane Deriva-
tives from 6-O-Sulfonyl-D-hexoses; General Procedure
The procedure was identical to the preparation of thiazolidine deriv-
atives but from the 6-O-sulfonyl-D-hexose derivative and the mix-
ture was stirred in refuxed MeOH for 7 h.
1H NMR (DMSO): d = 1.23, 1.31 (2s, 6H, 2 CH3), 2.47 (m, 1H, H-
5a), 2.61–2.70 (m, 2H, H-2a, H-3a), 2.81 (m, 1H, H-2b), 3.08 (dd,
1H, H-5b, J = 12.9 Hz, J = 5 Hz), 3.30 (dd, 1H, H-3b, J = 8.4 Hz, J
= 5.3 Hz), 3.64–3.74 (m, 3H, H-9a, H-7, H-6), 4.02 (dd, 1H, H-9, J
= 9.4 Hz, J = 7 Hz), 4.22 (t, 1H, H-8, J = 7,0 Hz).
13C NMR (DMSO): d = 24.5, 27.5 (2 CH3), 27.1 (C-2), 58.1 (C-5),
61.3 (C-3), 69.8 (C-9a), 71.8, 73.0 (C-6, C-7), 79.1 (C-9), 80.7 (C-
8), 106.7 (C iso).
(6R,7R,8S,9R,9aS)-6,7,8,9-Tetrahydroxy[1,3]thiazolo[(3,2-
a]azepane (18)
Yield: 35%, powder, mp = 139–140 °C, [a]24 –98.8 (c = 0.7,
D
MeOH).
1H NMR (C5D5N): d = 2.64 (dd, 1H, H-5a, J = 13.5 Hz, J = 2.7 Hz),
2.76 (m, 1H, H-3a), 2.80–2.91 (m, 2H, H-2a, H-2b), 3.13 (dd, 1H,
H-5b, J = 5.2 Hz), 3.29 (m, 1H, H-3b), 3.96 (dd, 1H, H-7, J = 3.3
Hz), 4.05 (t, 1H, H-9, J = 8.8 Hz), 4.34 (m, 1H, H-6), 4.44 (t, 1H,
H-8, J = 8.8 Hz), 4.77 (d, 1H, H-9a, J = 8.6 Hz).
13C NMR (C5D5N): d = 30.3 (C-2), 53.9 (C-5), 63.2 (C-3), 70.2 (C-
6), 73.3 (C-8), 77.2 (C-7), 77.9 (C-9), 78.2 (C-9a).
C11H19O4NS calcd
(261) found
C
50.50 H
49.88
7.28 N 5.36 S 12.26
7.47 4.96 11.76
Acknowledgement
We thank Professor Guy Nowogrocki (E.N.S.C. de Lille) for the X-
ray analyses.
C8H15O4NS calcd
(221) found
C
43.43
43.46
H
6.78 N 6.33 S 14.48
6.57 6.07 14.75
References
(1) Burgess, K.; Henderson, I. Tetrahedron 1992, 48, 4045.
(2) Marek, D.; Wadouachi, A.; Uzan, R.; Beaupère, D. Tetrahe-
dron Lett. 1996, 37, 49.
(3) Marek, D.; Wadouachi, A.; Beaupère D. Tetrahedron: Asym-
metry 1997, 8, 3223.
(4) Lu, Y.; Kong, F. J. Carbohydr. Chem. 1996, 15, 797.
(5) Clissod D. W., UK Patent Application 1987, 2188626A.
(6) Helferich, B. Adv. Carbohydr. Chem. 1948, 3, 79. Introduc-
tion of trityl group at C-6 hydroxyl group was realized by tre-
atment of hexose (1 equiv) with trityl chloride (1.4 equiv) in
pyridine under Ar atmosphere. The mixture was stirred for 24
h, then concentrated under reduced pressure and the crude pro-
duct chromatographed on silica gel (hexane/ EtOAc = 6:4).
(7) Regnault, I.; Ronco, G. L., Villa, P., Brevet Générale Su-
crière, 1989, 8915995.
(6R,7R,8S,9S,9aR)-6,7,8,9-Tetraacetoxy[1,3]thiazolo[3,2-
a]azepane (21)
To a solution of 20 (170 mg, 0.77 mM) in pyridine (10 mL) was
added Ac2O (723 mL, 7.7 mM). The solution was stirred at r.t. for
24 h. The pyridine was removed under reduced pressure to give a
crude product which was purified on silica gel column eluting with
hexane/EtOAc (8:2, 7:3 then 6:4) to give the compound 21 (230 mg,
77%) as syrup.
[a]24D –5.0 (c = 1.4, CH2Cl2).
1H NMR (CDCl3): d = 1.93, 1.97, 1.98, 2.00 (4s, 12 H, 4 CH3), 2.65
(dd, 1H, H-5a, J = 13.9 Hz, J = 6.5 Hz), 2.77–2.84 (m, 2H, H-2a, H-
2b), 2.87–2.97 (m, 2H, H-3a, H-5b), 3.34 (dd, 1H, H-3b, J = 10.7
Hz, J = 4.6 Hz), 4.56 (d, 1H, H-9a, J = 9.4 Hz), 5.25 (m, 1H, H-6),
5.37–5.42 (m, 3H, H-7, H-8, H-9).
Synthesis 1999, No. 5, 839–843 ISSN 0039-7881 © Thieme Stuttgart · New York

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Synthesis of Diastereomerically Pure [1,3]Thiazolo[3,2-a]azepane Derivatives
843
(8) Wadouachi, A.; Beaupère, D.; Uzan, R.; Stasik, I.; Ewing, D.
F.; Mackenzie, G. Carbohydr. Res. 1994, 262, 147.
(9) X-ray Data: 15: Empirical formula C14H25O5NS, 1/2 H2O, M
= 328.44. Monoclinic space group C2 (#5), a =19.56 (1), b =
6.263 (5), c =13.69 (1) Å, b = 93.3 (1), V = 1679 (2) Å3, Z =
4, D0 = 1.30 g/cm3, m = 2.2 cm–1, F(000) = 708. Data collected
at 295 K on a Phillips PW 1100 diffractometer with graphite
monochromated Mo Ka radiation and q/2q scans to a 2q max
of 50°, –23<h<23, –7<k<7, 0<1<16. Reflections measured:
3089; number of unique reflections with I>3s(I): 1383; Solu-
tion by direct methods; hydrogen atoms localized on diffe-
rence Fourier maps. Last least-square with 48 atoms and 273
parameters gave Rf = 0.035, RW = 0.036 and GoF = 0.036. The
enantiomorph configuration gave GoF = 1.02.
(12) X-ray Data: 18: Empirical formula C8H15O4NS, M = 273.35.
Orthorhombic space group P212121 (#19), a = 22.42 (5), b =
12.04 (2), c = 7.25 (1) Å, V=1957 (6) Å3, Z = 8 Dc = 1.51 g/
cm3, m = 3.2 cm–1, F(000) = 824. Data collected at 295 K on a
Phillips PW 1100 diffractometer with graphite monochroma-
ted Mo Ka radiation and q/2q scans to a 2q max of 40°,
–21<h<21, –11<k<11, 0<1<6. Reflections measured: 4031;
number of unique reflections with I>3s(I): 1526; Solution by
direct methods; hydrogen atoms localized on difference Fou-
rier maps. Last least square with 58 atoms (two independant
molecules) and 344 parameters gave Rf = 0.029, RW = 0.029
and GoF = 1.26. The enantiomorph configuration gave GoF
=1 .29.
(10) Eliel, E. L.; Wilen, S. H. in Stéréochimie des Composés Orga-
niques, Ed. Lavoisier, 1996, 628.
(11) Martin, O. R.; Saavedra, O. M., Tetrahedron Lett. 1995, 36,
799.
Article Identifier:
1437-210X,E;1999,0,05,0839,0843,ftx,en;P04998SS.pdf
Synthesis 1999, No. 5, 839–843 ISSN 0039-7881 © Thieme Stuttgart · New York