Intermolecular dipolar cycloaddition reactions of 5H,7H-thiazolo[3,4- c]oxazol-4-ium-1-olates

Article abstract of DOI:10.1016/S0040-4020(00)00243-X

(5R)-3-Methyl-5-phenyl-5H, 7H-thiazolo[3,4-c]oxazol-4-ium-1-olate was generated in the presence of a range of dipolarophiles. The intermolecular 1,3-dipolar cycloaddition of this mesoionic species led to the synthesis of chiral 1H-pyrrolo[1,2-c]thiazole derivatives 7a, 7b, 8, 14, 18, 19 and 20. In the reaction with methyl and ethyl vinyl ketone, spiro compounds 9 and 15 were also obtained. The structure of compound 15 was determined by X-ray crystallography. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00243-X

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 3419±3424
Intermolecular Dipolar Cycloaddition Reactions of
5
H,7H-Thiazolo[3,4-c]oxazol-4-ium-1-olates
a,* a
a
Teresa M. V. D. Pinho e Melo, Maria I. L. Soares, D a lia M. Barbosa,
a
Ant o nio M. d'A. Rocha Gonsalves, Ana Matos Beja, Jos e A. Paix aÄ o, Manuela Ramos Silva
b
b
b
b
and Luiz Alte da Veiga
a
Departamento de Qu Âõ mica, Faculdade de Ci eà ncias e Tecnologia, Universidade de Coimbra, 3000 Coimbra, Portugal
b
Departamento de F Âõ sica, Faculdade de Ci eà ncias e Tecnologia, Universidade de Coimbra, 3000 Coimbra, Portugal
Received 6 December 1999; revised 29 February 2000; accepted 16 March 2000
AbstractÐ(5R)-3-Methyl-5-phenyl-5H,7H-thiazolo[3,4-c]oxazol-4-ium-1-olate was generated in the presence of a range of dipolarophiles.
The intermolecular 1,3-dipolar cycloaddition of this mesoionic species led to the synthesis of chiral 1H-pyrrolo[1,2-c]thiazole derivatives 7a,
7b, 8, 14, 18, 19 and 20. In the reaction with methyl and ethyl vinyl ketone, spiro compounds 9 and 15 were also obtained. The structure of
compound 15 was determined by X-ray crystallography. q 2000 Published by Elsevier Science Ltd.
Introduction
the reaction of diastereoisomerically pure 2-substituted-N-
acetyl-1,3-thiazolidine-4-carboxylic acids with acetylenic
dicarboxylates. The chirality at C-4 of the thiazolidine is
lost and the chirality at C-2 (C-3 in the product) is retained.
We have recently described the use of N-acyl-2-phenyl-
(2R,4R)-thiazolidine-4-carboxylic acids to generate 5H,7H-
thiazolo[3,4-c]oxazol-4-ium-1-olates with internal dipolaro-
1
philes. The intramolecular 1,3-dipolar cycloaddition of
Dipolar cycloaddition reactions of 5H,7H-thiazolo-
[3,4-c]oxazol-4-ium-1-olate 6
these mesoionic species led to the synthesis of new chiral
3,4-dihydro-1H-pyrrolo[1,2-c]thiazole derivatives (1 and
2). The study was now extended to include intermolecular
cycloaddition of this type of dipoles.
In our work we observed that starting from 2-phenylthiazo-
lidine-4-carboxylic acid (4) as a mixture of 2R,4R- and
2
S,4R-diastereoisomers, chiral 3,4-dihydro-1H-pyrrolo[1,2-
c]thiazole derivatives were obtained (Scheme 1).
Compound 4 was heated in a solution of acetic anhydride
in the presence of a dipolarophile. Under these reaction
conditions the N-acylation occurs in situ, followed by an
intermolecular dipolar cycloaddition via a mesoionic oxazo-
lone intermediate. With dimethyl acetylenedicarboxylate
compound 7a was obtained in an overall yield of 75.5%
2
D
5
(
R con®guration at C-3; [a] ˆ1160 and ee of 97.9%).
Compound 7a was known in the literature and was prepared
from (2R,4R)-2-phenyl-N-acetyl-1,3-thiazolidine-4-car-
2
boxylic acid. According to our procedure the compound
was obtained without requiring a diastereoisomerically
pure compound as starting material. This result allowed us
to conclude that the in situ acylation involved is a stereo-
selective synthesis of (2R,4R)-2-phenyl-N-acetyl-1,3-
thiazolidine-4-carboxylic acid (5).
2
Gy oÈ rgyde a k et al. have previously shown that chiral 3-substi-
tuted 3,4-dihydropyrrolo[1,2-c]thiazole-6,7-dicarboxylates
(
3) can be obtained with high enantiomeric excess from
The intermolecular dipolar cycloaddition was also
performed with the dipolarophile methyl propiolate giving
exclusively the regioisomer 7b (Scheme 1). The observed
regioselectivity is consistent with that of other mesoionic
Keywords: dipolar cycloadditions; pyrrolo[1,2-c]thiazole; mesoionic
species.
* Corresponding author. Tel.: 1351-239-826-6068; fax: 1351-239-85-
2080; e-mail: tmelo@lyra.ci.uc.pt
0040±4020/00/$ - see front matter q 2000 Published by Elsevier Science Ltd.
PII: S0040-4020(00)00243-X

3
420
T. M. V. D. Pinho e Melo et al. / Tetrahedron 56 (2000) 3419±3424
Scheme 1.
Scheme 2.
3
compounds of this type. The product 7b was obtained with
In order to evaluate the above proposal, the reaction of 4
with ethyl vinyl ketone was performed. As expected, we
obtained two products: the 3,4-dihydro-1H-pyrrolo[1,2-c]-
thiazole derivative 14 in 10% yield and a spiro compound
(15) in 8% yield (Scheme 5).
2
5
R con®guration at C-3 in 55% yield ([a] ˆ1305).
D
2-Phenylthiazolidine-4-carboxylic acid 4 was heated in
acetic anhydride and methyl vinyl ketone was used as the
dipolarophile (Scheme 2). In this case two products were
obtained, the expected methyl (3R)-7-acetyl-3-phenyl-5-
methyl-3,4-dihydro-1H-pyrrolo[1,2-c]thiazole 8 in 25%
yield, and the spiro compound 9 in 7% yield. The structure
The structure of 15 was con®rmed by X-ray crystallography
(Fig. 1 and Table 1). The absolute structure was determined
6
by a Flack analysis that assigns the R,R,R,S con®guration to
4
0
0
of 9 was established by X-ray crystallography.
the four chiral centers C2, C3 a, C5 and C6 a, respectively.
The two furan rings are fused cis, the dihedral angle
between the least-squares planes of these rings is
57.86(8)8. Both the dihydrofuran ring and the saturated
furan ring deviate signi®cantly from planarity, being
5
It was observed by Texier et al. that, in the cycloaddition of
m uÈ nchnone 10 with acrylates, the initially formed cyclo-
adduct 11 does not lose CO but instead undergoes a
2
0
rearrangement giving product 12 (Scheme 3). If a similar
rearrangement occurred in the reaction of mesoionic species
slightly puckered towards C6 a- and C5-envelope confor-
mations, respectively. The puckering parameters for the two
7
Ê
6
with methyl vinyl ketone, the analogous adduct would be
rings as de®ned by Cremer et al. are q ˆ0.152(2) A,
2
Ê
compound 13 (Scheme 4). The observed product 9 could
then be obtained by cleavage of 13 followed by a deacyla-
tion reaction whereby the acetyl group from methyl vinyl
ketone would be lost.
f ˆ140.6(7)8 and q ˆ0.125 A, f ˆ65.78, the f angles
2
2
2
2
for the pure envelope forms being 144 and 728, respectively.
3
The two Csp ±O bonds in the furan ring system C6a ±O6
0
0
and C6a ±O1 have practically identical values which are
0
5
Scheme 3.

T. M. V. D. Pinho e Melo et al. / Tetrahedron 56 (2000) 3419±3424
3421
9
Figure 1. ORTEPII plot of the molecule of compound 15. Displacement ellipsoids are drawn at the 50% level.
Ê
Table 1. Selected bond lengths and angles (A, 8) for compound 15
0
0
S1±C4
S1±C2
O1±C2
1.810(2)
1.8273(17)
1.340(2)
1.452(2)
1.390(2)
1.438(2)
1.491(3)
C4 ±C5
1.313(3)
89.10(8)
N1±C5±C4
0
105.26(14)
103.49(14)
110.91(14)
101.17(14)
110.06(17)
113.53(17)
106.09(15)
0
C4±S1±C2
C12±N1±C5
C12±N1±C2
C2 ±C5±C3a
0
0
118.53(14)
124.78(14)
111.97(14)
106.67(14)
103.97(11)
O1±C2 ±C5
0
0
0
0
0
O1±C6a
0
C4 ±C3a ±C6a
0
0
0
0
0
0
0
0
O6 ±C5
0
C2 ±O1±C6a
0
C5 ±C4 ±C3a
0
0
0
0
O6 ±C6a
0
C5 ±O6 ±C6a
N1±C2±S1
C4 ±C5 ±O6
0
0
0
C3a ±C4
O6 ±C6a ±C3a
3
slightly shorter than the tabulated Csp ±O(2) bonds in ring
The thiazolidine ring has a twisted conformation with a
local pseudo two-fold axis running through N1 and the
middle of the C4±S1 bond. The two-fold asymmetry para-
8
systems. Comparing the lengths of the two C sp ±O bonds
2
0
0
1.368 A], there is a lengthening of the C5 ±O6 bond
0
C5 ±O6 and C2 ±O1 with the tabulated value in furan
0
0
1.395(3) A] and a shortening of the C2 ±O1 bond
1
0
Ê
[
[
[
meter DC [S1±C4] is 3.94(14)8. The puckering para-
2
0
7
meters q2 and f2 are 0.509(2) A and 344.8(2)8. The
Ê
Ê
Ê
1.351(3) A].
phase angle f of the pure twisted conformation is 3428.
2
Scheme 4.
Scheme 5.

3
422
T. M. V. D. Pinho e Melo et al. / Tetrahedron 56 (2000) 3419±3424
Scheme 6.
S1 and C4 are on opposite sides of the plane passing through
Ê
C2, N1 and C5 at 20.500(5) and 0.370(5) A, respectively.
and acetic anhydride to give the intermediate 16 which leads
to the spiro compound on eliminating acetic acid (Scheme 6).
The values of the bond lengths S±C are in good agreement
with tabulated value and the bond angle C±S±C is close to
the values observed in other thiazolidine compounds. The
exocyclic angles around the N1 atom show some asymmetry.
However, the sum of the valence angles around N1 is
8
The intermolecular dipolar cycloaddition of 5H,7H-thiazolo-
[3,4-c]oxazol-4-ium-1-oxide with acrylonitrile was also
studied (Scheme 7). A 1:1 mixture of compounds 18 and
19 was obtained in low yield. In this case the initially
formed dipolar cycloadduct does not lead to the aromati-
zation to the pyrrole ring, which requires oxidation with
DDQ to give the 3,4-dihydro-1H-pyrrolo[1,2-c]thiazole
derivative 20.
359.8(3)8, indicating no signi®cant pyramidalization of
this atom. The environment of the spiro C5 atom is nearly
tetrahedral, with bond angles in the range 105.23(15)±
1
15.31(15)8. The phenyl ring has an axial position with
respect to the thiazolidine ring with torsion angles
105.67(15)8 [C5±N1±C2±C6] and 89.80(14)8 [C4±C2±
2
S1±C6]. The dihedral angle between the least-squares
planes of the phenyl and thiazolidine rings is 81.19(7)8.
The geometry of the acetyl group is normal. It is almost co-
planar with the thiazolidine group, the angle between the
least-squares plane of the N1-acetyl group and that de®ned
by N1 C2 and C5 is only 6.35(16)8. The short carboxyl
C12vO2 bond is in agreement with an O atom not involved
in hydrogen-bonding. In fact, cohesion of the crystal is
mainly due to van der Waals interactions, with no classical
hydrogen bonds present in the structure. Inspection of close
contact distances shows that C7±H7´´´N1 [2.88(3) A] and
Ê
C15±H15C´´´O1 [2.893(3) A] may correspond to weak
intermolecular interactions which are probably relevant in
determining the crystal packing.
In the intermolecular dipolar cycloaddition of m uÈ nchnones
the primary cycloadducts are not usually isolable, because
the carbon dioxide is easily eliminated, giving products with
higher unsaturation with loss of information concerning
the mechanism. However, Maryanoff et al. described
the dipolar cycloaddition of 1,2-dicyanocyclobutene with
m uÈ nchones and showed that the extrusion of carbon dioxide
from the primary adducts is not a concerted process, giving
carboxylic acid derivatives as intermediates. Thus, the
elimination of carbon dioxide does not need to be a
concerted process, allowing a mechanism of formation of
compound 18 and 19 as described in Scheme 7. The initially
Ê
1
1
These results rule out the mechanism outlined in Scheme 4,
because it should lead to a product without an ethyl group.
Taking into account this new observation it seems more
likely that the mechanism involves the formation of the
mesoionic species 6 which reacts with ethyl vinyl ketone
formed cycloadduct can lose CO either by a concerted
2
process or by a stepwise process, giving azomethine ylide
17 which is converted into the ®nal products.
Scheme 7.

T. M. V. D. Pinho e Melo et al. / Tetrahedron 56 (2000) 3419±3424
3423
Conclusions
then ethyl acetate] giving compound 7b (55%); mp 87±
98C (from ethyl ether±hexane) (Found; C, 66.3; H, 5.7;
N, 5.1; S, 11.5. C H NO S requires C, 65.9; H, 5.5; N,
8
The study of the intermolecular 1,3-dipolar cycloaddition of
(5R)-3-methyl-5-phenyl-5H,7H-thiazolo[3,4-c]oxazol-4-ium-
-olate led to the synthesis of 1H-pyrrolo[1,2-c]thiazole
derivatives as single enantiomers. The results showed
that it is necessary to use strongly activated dipolar-
ophiles in order to obtain ef®cient cycloadditions.
From this study the synthesis of new spiro compounds
was also achieved.
1
5
15
2
5.1; S, 11.7); dH 2.17 (3H, s), 3.78 (3H, s), 4.01 (1H, d,
Jˆ13.1 Hz), 4.26 (1H, d, Jˆ13.1 Hz), 6.25 (1H, s), 6.32
(1H, s) 6.97±7.02 (2H, m, ArH) and 7.28±7.35 (3H, m,
ArH); dC 11.80, 28.13, 50.78, 63.87, 101.60, 116.53,
125.33, 128.57, 129.06, 131.90, 133.08, 141.06 and
1
2
D
5
165.77; [a] ˆ1305 (cˆ1, CHCl ).
3
(
[
3R)-7-Acetyl-5-methyl-3-phenyl-3,4-dihydro-1H-pyrrolo-
1,2-c]thiazole 8 and (R)-spiro[(2R)-N-acetyl-2-phenyl-
0
0
0
0
0
0
0
Experimental
1,3-thiazolidine-5,3 -(3a R,6a S)-5 ,6a -dimethyl-3a 6a -
dihydro-3H-furo[2,3-b]furan-2-one] 9. 2-Phenylthiazo-
lidine-4-carboxylic acid 4 (0.52 g, 2.5 mmol), methyl
General
vinyl ketone (1 mL, 12.5 mmol) and Ac O (10 mL) were
2
heated at 95±1008C for 12 h. The reaction was cooled to
1
H NMR spectra were recorded on a Brucker ACE200
spectrometer operating at 200 MHz (where indicated) or
on a Brucker AMX300 instrument operating at 300 MHz.
C NMR spectra were recorded on a Brucker AMX300
room temperature and was diluted with CH
The organic phase was washed with saturated aqueous
solution of NaHCO and with water, dried (Na SO ) and
2 2
Cl (25 mL).
1
3
3
2
4
instrument operating at 75.5 MHz. The solvent is deuterio-
chloroform. IR spectra were recorded on a Perkin±Elmer
evaporated off. The products were isolated by ¯ash chroma-
tography [hexane±ethyl acetate (3:1), hexane±ethyl acetate
(1:1) then ethyl acetate]: compound 8 was obtained in 25%
yield and compound 9 in 7% yield.
1
720X FTIR spectrometer. Mass spectra were recorded
under electron impact at 70 eV on a VG Micromass
070E instrument. Optical rotations were measured on an
7
Optical Activity AA-5 electrical polarimeter. Mp were
recorded on a Reichert hot stage and are uncorrected.
Flash column chromatography was performed with Merck
Compound 8 was an oil: IR 2924, 1717, 1686, 1653 and
1.83 (3H, s), 2.38 (3H, s), 4.38 (1H, d,
H
2
1240 cm ; d
1
Jˆ15.0 Hz), 4.54 (1H, dd, Jˆ15.0 and 1.9 Hz), 6.27 (1H,
9385 silica as the stationary phase. Methyl 2-phenylthiazo-
lidine-4-carboxylate 4 was prepared as described in the
d, Jˆ1.9 Hz), 6.33 (1H, s), 7.05±7.1 (2H, m, ArH) and
25
7.31±7.38 (3H, m, ArH); HRMS (EI1): found 257.0874.
1
2
literature and was isolated as a mixture of the (2R,4R)
and (2S,4R) diastereoisomers.
C
CHCl ).
15
H
15NOS requires 257.0874; [a] ˆ1192.3 cˆ0.1,
D
3
Dimethyl (3R)-5-methyl-3-phenyl-3,4-dihydro-1H-pyrrolo-
[
4
Compound 9. Mp 202±2058C (from hexane±ethyl acetate)
(Found; C, 62.62; H, 5.67; N, 4.02; S, 9.30. C18
requires C, 62.59; H, 5.54; N, 4.06; S, 9.28); IR (KBr) 3020,
1,2-c]thiazole-6,7-dicarboxylate 7a. 2-Phenylthiazolidine-
-carboxylic acid 4 (1.045 g, 5 mmol), dimethylacetylene
dicarboxylate (0.9 mL, 7.5 mmol) and Ac O (20 mL) were
H19NO S
4
2
1
2940, 1788 and 1655 cm ; d
CH CHv), 1.90 (3H, s, CH
3
1.87 (6H, m, CH
), 3.09 (1H, d, Jˆ12.1 Hz,
CO and
3
2
H
heated at 95±1008C for 4 h. The reaction was cooled to
room temperature and was diluted with CH Cl (50 mL).
3
H-4), 3.37 (1H, d, Jˆ12.1 Hz, H-4), 3.47 (1H, m,
2
2
0
0
The organic phase was washed with saturated aqueous
solution of NaHCO and with water, dried (Na SO ) and
H-3a ), 4.93 (1H, m, H-4 ), 5.99 (1H, s, H-2), 7.30±
7.35 (1H, m, ArH), 7.40±7.47 (2H, m, ArH) and
7.63±7.66 (2H, m, ArH); m/z 345 (M , 23%), 302 (25),
3
2
4
1
evaporated off. The crude product was puri®ed by ¯ash
chromatography [hexane±ethyl acetate (3:1)] giving
compound 7a as a white solid (75.5%); mp 149±1518C
179 (48) and 148 (53).
2
(
mp 163±1658C) (Found; C, 61.2; H, 5.2; N, 3.9. Calcd
for C H NO S C, 61.6; H, 5.2; N, 4.6); d 2.01 (3 H, s),
(3R)-7-Propionyl-5-methyl-3-phenyl-3,4-dihydro-1H-
pyrrolo[1,2-c]thiazole 14 and (R)-spiro[(2R)-N-acetyl-2-
1
7
17
4
H
0 0 0 0 0
phenyl-1,3-thiazolidine-5,3 -(3a R,6a S)-5 -methyl-6a -
3
.83 (3H, s), 4.31 (1H, d, Jˆ15.0 Hz), 4.48 (1H, dd, Jˆ15.0
0
0
and 1.5 Hz), 6.28 (1H, d, Jˆ1.5 Hz), 7.04±7.07 (2H, m,
phenyl-3a ,6a -dihydro-3H-furo[2,3-b]furan-2-one] 15.
2-Phenylthiazolidine-4-carboxylic acid 4 (2.09 g, 10 mmol),
ArH) and 7.26±7.36 (3H, m, ArH); d 11.44, 30.01,
C
5
1
1.41, 51.58, 64.90, 106.77, 125.58, 128.99, 129.25,
30.73, 140.08, 140.51, 164.30 and 165.30; [a] 1160
ethyl vinyl ketone (5.5 mL, 50 mmol) and Ac
were heated at 95±1008C for 12 h. The reaction was cooled
to room temperature and was diluted with CH Cl (25 mL).
The organic phase was washed with saturated aqueous
solution of NaHCO and with water, dried (Na SO ) and
2
O (40 mL)
2
D
5
(
cˆ1, CHCl3).
2
2
Methyl (3R)-5-methyl-3-phenyl-3,4-dihydro-1H-pyrrolo-
3
2
4
[
1,2-c]thiazole-7-carboxylate 7b. 2-Phenylthiazolidine-4-
carboxylic acid 4 (1.045 g, 5 mmol), methyl propiolate
0.75 mL, 7.5 mmol) and Ac O (20 mL) were heated at
evaporated off. The products were isolated by ¯ash chroma-
tography [hexane-ethyl acetate (3:1), hexane-ethyl acetate
(1:1) then ethyl acetate]: compound 14 was obtained in 10%
yield and compound 15 in 8% yield.
(
2
95±1008C for 4 h. The reaction was cooled to room
temperature and was diluted with CH Cl (50 mL). The
2
2
organic phase was washed with saturated aqueous solution
of NaHCO and with water, dried (Na SO ) and evaporated
Compound 14 was an oil: d
H
1.19 (3H, t, Jˆ7.2 Hz), 1.84
(3H, s), 2.75 (2H, q, Jˆ7.2 Hz), 4.39 (1H, d, Jˆ15.1 Hz),
4.56 (1H, d, Jˆ15.1 Hz), 6.26 (1H, s), 6.34 (1H, s), 7.05±
7.08 (2H, m, ArH), 7.30±7.36 (3H, m, ArH); HRMS (EI1):
3
2
4
off. The crude product was puri®ed by ¯ash chromatography
hexane±ethyl acetate (3:1), hexane±ethyl acetate(1:1),
[

3
424
T. M. V. D. Pinho e Melo et al. / Tetrahedron 56 (2000) 3419±3424
2
D
5
found 271.1028. C H NOS requires 271.1031; [a] ˆ
used in the re®nement and 230 variable parameters.
H-Atoms were placed at calculated positions except those
of the methyl groups which were determined from a Fourier
difference synthesis and re®ned as riding on their parent
atoms. X-Ray measurements were performed on a Enraf±
Nonius CAD-4 diffractometer using v ±2u scans up to
umaxˆ25.078. Atomic coordinates, bond lengths and angles
and displacement parameters have been deposited at the
Cambridge Crystallographic Data Centre.
1
6
17
1
300.0 (cˆ0.1, CHCl ).
3
Compound 15. Mp 189.8±191.98C. dH 1.02 (3H, t,
Jˆ7.4 Hz), 1.89 (6H, m, CH CO and CH CHv), 2.24
3
3
1
4
(
2H, m, CH CH ), 3.10 (1H, d, Jˆ12.1 Hz, H-4), 3.37
2
3
0
m, H-4 ), 5.98 (1H, s, H-2), 7.30±7.35 (1H, m, ArH),
(
1H, d, Jˆ12.1 Hz, H-4), 3.49 (1H, m, H-3a ), 4.94 (1H,
0
.40±7.45 (2H, m, ArH) and 7.63±7.66 (2H, m, ArH); dC
7
1
1
2
3.6, 22.8, 29.7, 35.6, 55.8, 65.7, 74.4, 94.4, 117.1, 125.4,
28.3, 129.3, 141.5, 156.8, 168.9 and 173.2; m/z 360 (MH ,
%), 148 (44), 122 (100), 110 (47) and 77 (8).
1
Acknowledgements
(
1
7
3R,5S)-7-Cyano-5-methyl-3-phenyl-3,4,5,6-tetrahydro-
H-pyrrolo[1,2-c]thiazole-7-carboxylate 18 and (3R,5R)-
-cyano-5-methyl-3-phenyl-3,4,5,6-tetrahydro-1H-pyrrolo-
The authors wish to thank Dr T. L. Gilchrist and Dr R. Storr
(
University of Liverpool) for very useful discussions
concerning this project. They also thank Chymiotechnon
for ®nancial support.
[
1,2-c]thiazole-7-carboxylate 19. 2-Phenylthiazolidine-4-
carboxylic acid 4 (6.0 g, 28.7 mmol), acrylonitrile (9.5 mL,
43.5 mmol) and Ac O (120 mL) were heated at 95±1008C
1
2
for 16 h. The reaction was cooled to room temperature and
was diluted with CH Cl (200 mL). The organic phase was
washed with saturated aqueous solution of NaHCO and
References
2
2
3
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2
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J. A.; Silva, M. R.; Alte da Veiga, L. J. Chem. Soc., Perkin Trans. 1
1999, 1219±1223.
4
product was puri®ed by ¯ash chromatography [hexane±
ethyl acetate (1:1), hexane±ethyl acetate (1:2) then ethyl
acetate] giving a mixture (56:44) of compounds 18 and 19
(
6
5
3%). mp 96±998C (from hexane±ethyl acetate). (Found; C,
2. Gy oÈ rgyde a k, Z.; Szil a gyi, L.; Kajt a r, J.; Argay, G.; K a lm a n, A.
Monatsh. Chem. 1994, 125, 189±208.
9.03; H, 5.78; N, 11.34. C H N S requires C, 69.39; H,
14 14 2
2
.82; N, 11.56); IR (Nujol) 2190 and 1620 cm ; d (major
1
3. Coppola, B. P.; Noe, M. C.; Hong, S. S.-K. Tetrahedron Lett.
1997, 38, 7159±7162.
4. Silva, M. R.; Beja, A. M.; Paix aÄ o, J. A.; Alte da Veiga, L.;
Barbosa, D. M.; Soares, M. I. L.; Pinho e Melo, T. M. V. D.;
Rocha Gonsalves, A. M. d'A. Acta Crystallogr. C 1999, 55,
1094±1096.
H
component) 1.14 (3H, d, J6.3 Hz), 2.67±2.77 (1H, m),
.25±3.34 (1H, m), 3.55±3.64 (1H, m), 3.77±3.99 (2H,
m), 5.57 (1H, s, CHPh) and 7.26±7.47 (5H, m, ArH); dH
minor component) 0.84 (3H, d, Jˆ6.3 Hz), 2.67±2.77 (1H,
m), 3.14 (1H, approx. dd, Jˆ9.6 and 14.4 Hz), 3.66±3.74
1H, m), 3.77±3.99 (2H m), 5.14 (1H, s, CHPh) and 7.26±
3
(
(
7
1
5. Texier, F.; Yebdri, O.; Laidoudi, A.; Talbi, B.; Balegroune, F.;
Germain, G. Tetrahedron Lett. 1983, 24, 189±192.
6. Flack, H. D. Acta Crystallogr. A 1983, 39, 876±881.
1
.47 (5H, m, ArH); m/z 242 (M , 60%), 165 (26), 121 (100),
05 (31) and 77 (20).
7
1358.
. Cremer, D.; Pople, J. A. J. Am. Chem. Soc. 1975, 97, 1354±
Oxidation of the mixture (18 and 19) with DDQ led to the
formation of (3R)-7-cyano-5-methyl-3-phenyl-3,4-dihydro-
8. Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.; Orpen,
A. G.; Taylor, R. J. Chem. Soc., Perkin Trans. 2 1987, S1±19.
9. Johnson, C. K. ORTEPII. Report ORNL-5138. Oak Ridge
National Laboratory, Tennessee, USA, 1976.
1H-pyrrolo[1,2-c]thiazole 20. dH 1.81 (3H, s, CH ), 4.21
3
(
1H, d, Jˆ14.1 Hz), 4.42 (1H, d, Jˆ14.1 Hz), 6.20 (1H, s,
CHPh), 6.29 (1H, s), 7.06±7.08 (2H, m, ArH), 7.35±7.37
3H, m, ArH).
(
10. Duax, W.; Weeks, C. M.; Roher, D. C. In Topics in Stereo-
chemistry, Eliel, E. L., Allinger, N., Eds.; Wiley: New York, 1976;
vol. 9, pp 271±383.
Crystal data for C H NO S 15. Mˆ359.44, orthorhombic,
19
21
4
space group P2 2 2 (# 19), aˆ5.944(2), bˆ16.251(2),
11. Maryanoff, E. A.; Karash, C. B.; Turchi, I. J.; Corey, E. R.;
Maryanoff, B. E. J. Org. Chem. 1989, 54, 3790±3792.
12. Gilchrist, T. L.; Rocha Gonsalves, A. M. d'A.; Pinho e Melo,
T. M. V. D. Tetrahedron 1994, 50, 13709±13724.
13. Sheldrick, G. M. shelxs97, a program for the solution crystal
structures. University of G oÈ ttingen, Germany, 1997.
14. Enraf Nonius, CAD4 Software, Version 5.0, Enraf Nonius,
Delft, The Netherlands, 1989.
1
1 1
3
23
Ê
Ê
cˆ18.664(3) A, Vˆ1802.8(8) A , Zˆ4, D ˆ1.324 g cm ,
c
2
1
F
ˆ460, mˆ0.20 cm , Tˆ296 K. Number of inde-
0
00
pendent intensities 3033 from colourless prism, 0.32£
3
0
.37£0.59 mm . No absorption correction was applied and
no signi®cant crystal decay was detected. Structure solution
1
3
by direct methods using shelxs97. Rˆ0.0271 for 2836
re¯ections with I.2s, R ˆ0.0803 for 3033 re¯ections
w