Organocatalytic strategies for the construction of optically active imidazoles, oxazoles, and thiazoles

Article abstract of DOI:10.1002/chem.201101817

This study demonstrates the first enantioselective synthesis of hydroxyalkyl- and aminoalkyl-substituted imidazoles, oxazoles, and thiazoles. The approach developed utilizes a highly effective one-pot reaction cascade that consists of either an organocatalytic epoxidation or aziridination of α,β-unsaturated aldehydes coupled with a [3+2]-annulation, in which amidines, ureas, or thioureas act as effective 1,3-dinucleophilic species. The methodology described benefits from low catalyst loadings, commercially and readily available starting materials, and mild reaction conditions.

Full text of DOI:10.1002/chem.201101817

DOI: 10.1002/chem.201101817
Organocatalytic Strategies for the Construction of Optically Active
Imidazoles, Oxazoles, and Thiazoles
Łukasz Albrecht, Lars Krogager Ransborg, Anna Albrecht, Lennart Lykke, and
Karl Anker Jørgensen*[a]
Abstract: This study demonstrates the first enantioselective synthesis of hydroxy-
ACHTUNGTRENNUNGalkyl- and aminoalkyl-substituted imidazoles, oxazoles, and thiazoles. The ap-
proach developed utilizes a highly effective one-pot reaction cascade that consists
of either an organocatalytic epoxidation or aziridination of a,b-unsaturated alde-
hydes coupled with a [3+2]-annulation, in which amidines, ureas, or thioureas act
as effective 1,3-dinucleophilic species. The methodology described benefits from
low catalyst loadings, commercially and readily available starting materials, and
mild reaction conditions.
Keywords: annulation · asymmetric
catalysis · azoles · heterocycles ·
one-pot reactions
Introduction
The increasing demand from the chemical community for
the development of cost- and time-effective, environmental-
ly benign synthetic methodologies has resulted in tremen-
dous expansion of the field of asymmetric catalysis.[1] Since
the turn of the millennium, the application of small, chiral
molecules as catalysts for a variety of enantioselective trans-
formations—termed organocatalysis—has attracted much at-
tention and has become a complementary method to the
classical approaches utilized in asymmetric synthesis.[2] In
particular, organocatalytic asymmetric one-pot strategies
have recently emerged as a very rapidly developing research
area and allow for facile and stereoselective assembly of
Scheme 1. Importance of 1,3-azole structural unit.
molecular and stereochemical complexity.[3]
Heteroaromatic compounds occupy a prominent position
among biologically relevant molecules.[4] The extraordinary
abundance of heteroaromatic frameworks, their remarkable
structural diversity, and specific chemical behavior, as well
as wide occurrence in nature, gives them a privileged posi-
tion in modern medicinal and synthetic organic chemistry.
1,3-Azoles, namely imidazoles, oxazoles, and thiazoles, con-
stitute a particularly important class of heteroaromatic
framework that occurs in many biologically active com-
pounds and natural products (Scheme 1).[5–7] For instance,
the imidazole ring is a constituent of the amino acid histi-
dine. 2-Acetyl-4-tetrahydroxybutylimidazole (THI) is a com-
ponent of caramel color III, a colorant commonly used in
foods and beverages.[8] It was also found to produce lympho-
penia without toxic effects in rats and mice.[8c,d] Girolline, a
natural isolate from Cymbastela cantharella collected
around New Caledonian, exhibits strong cytotoxicity and an-
titumor activity.[6a,g] Furthermore, 1,3-azoles constitute im-
portant synthetic intermediates that have found widespread
applications in target-oriented synthesis[9] and are also com-
monly utilized as precursors of N-heterocyclic carbenes[10]
and ionic liquids.[11]
Traditionally, the predominant strategy for the synthesis
of 1,3-azoles utilizes a condensation reaction between a-
halogenated carbonyl compounds and thioamides (Hantzsch
synthesis) or amidines (Scheme 2).[12] Alternatively, oxiranes
with a suitable leaving group on the epoxide ring can be ap-
plied instead of a-halogenated carbonyls in such annulation
strategies.[13] However, the utilization of 2,3-epoxy or 2,3-
aziridne aldehydes for the construction of 5-hydroxyalkyl-
or 5-aminoalkyl-substituted 1,3-azoles is, to the best of our
knowledge, unknown. So far, the only report on similar
[a] Dr. Ł. Albrecht, L. K. Ransborg, Dr. A. Albrecht, L. Lykke,
Prof. Dr. K. A. Jørgensen
Center for Catalysis, Department of Chemistry
Aarhus University
8000 Aarhus C (Denmark)
Fax : (+45)8619-6199
E-mail: kaj@chem.au.dk
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201101817.
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FULL PAPER
Scheme 4. Asymmetric organocatalytic strategy for the synthesis of imi-
dazoles, oxazoles, and thiazoles.
Scheme 2. Synthetic strategies for the synthesis of polysubstituted 1,3-
azoles.
2,3-aziridine aldehydes, easily accessed through enantiose-
lective aminocatalytic epoxidation/aziridination of a,b-unsa-
turated aldehydes, could undergo nucleophilic 1,2-addition
when treated with amidines, ureas, or thioureas. Subsequent
cyclization through an epoxide or aziridine ring-opening re-
action, followed by dehydrative aromatization, should afford
the 1,3-azole framework.
Herein, we report an organocatalytic, enantioselective
one-pot strategy for the preparation of hydroxyalkyl- or
aminoalkyl-substituted imidazoles, oxazoles, and thiazoles.
Practical aspects of the developed strategy are worth noting
(low catalyst loadings of 2.5–5 mol%, commercially avail-
able starting materials, and no necessity for inert conditions)
and may greatly enhance the applicability of the developed
protocol.
methodology deals with the application of 2,3-epoxy ketones
for the preparation of fully substituted racemic thiazoles
from the reaction with thiourea or thioamides.[14] Moreover,
methods for the preparation of hydroxyalkyl- or aminoalkyl-
substituted 1,3-azoles are scarcely recognized,[15] and no
enantioselective method for the preparation of 5-substituted
derivatives exists in the literature. Therefore, the develop-
ment of synthetic methods that lead to these essential struc-
tural motifs is of particular importance.
Recently we have developed new synthetic strategies to
provide optically active hydroxyalkyl- and aminoalkyl-sub-
stituted heteroaromatic compounds: electron-poor furans,
imidazoACHTUNGTRENNUNG
[1,2-a]pyridines, and indolizines (Scheme 3).[16] This
Results and Discussion
To find the optimal conditions for the preparation of hy-
droxyalkyl-substituted imidazoles, screening studies were in-
itiated by using trans-2-nonenal (1a) as a model carbonyl
compound and benzamidine (4a) as the 1,3-dinucleophilic
species in the presence of catalytic a,a-bisACTHNUTRGNEUGN[3,5-bis(trifluoro-
methyl)phenyl]-2-pyrrolidinemethanol trimethylsilyl ether
(2).[16,17] Preliminary results revealed that imidazole 5a can
be accessed from a one-pot, two-step epoxidation/annulation
reaction sequence. However, a moderate yield of 5a was ob-
tained when the epoxidation was performed under the con-
ditions previously developed (Table 1, entry 1). Further-
more, it was observed that the amount of 4a used had no
pronounced effect on the reaction outcome (Table 1,
entry 2). In both cases the annulation step was performed at
608C and was terminated within 1 h. Importantly, it was
found that excess H2O2 from the epoxidation step has a cru-
cial influence on the reaction outcome. When equimolar
amounts of 1a and H2O2 were used, the yield of the one-pot
reaction cascade increased to 70% (Table 1, entry 3), which
indicates that over-oxidation is a competitive process and re-
sults in yield deterioration. The reaction sequence could
also be performed at room temperature, however, a longer
reaction time (24 h) was required to achieve full conversion
(Table 1, entry 4). Gratifyingly, in both cases, 5a was formed
Scheme 3. Enantioselective organocatalytic [3+2]-annulation strategies
for the synthesis of electron-poor furans, imidazo
dolizines.
ACHTUNGERTN[NUNG 1,2-a]pyridines, and in-
approach is based on an efficient and highly enantioselective
one-pot reaction sequence that consists of asymmetric orga-
nocatalytic epoxidation or aziridination of a,b-unsaturated
aldehydes, followed by annulation with a 1,3-dinucleophilc
species, such as a 1,3-dicarbonyl compound, 2-aminopyri-
dine, or pyridylacetate.
Given the importance of functionalized imidazoles, oxa-
zoles, and thiazoles, as well as the absence of a general
enantioselective methodology for the preparation of
hydroxyACHTUNGTRENNUNGalkyl- or aminoalkyl-substituted 1,3-azoles, we envi-
sioned that a strategy utilizing amidines, ureas, or thioureas
as 1,3-dinucleophilic species in the annulation step could be
feasible (Scheme 4). It was anticipated that 2,3-epoxy- or
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K. A. Jørgensen et al.
Table 1. Optimization of the reaction conditions for the synthesis of
hydroxyalkyl-substituted imidazoles.[a]
Table 2. Aldehyde scope of the enantioselective synthesis of optically
active hydroxyalkyl-substituted imidazoles.[a]
Solvent Catalyst
loading [mol%]
H2O2
[equiv]
4a
A
T
Yield ee
1
R
Product
Yield
[%][b]
ee
G
[%][c]
1
2
3
toluene
toluene
toluene
5
1.3
1.3
1
1
1
1.05
1.5
60
60
60
RT
40
60
52
54
70
70
36
64
65
n.d.[e]
n.d.
93
93
n.d.
93
1
2
3
1a
1b
1c
1d
1e
1 f
1g
hexyl
Pr
iPr
Me
(E)-hex-3-enyl
CH2OBn
CH2CH2Ph
5a
5b
5c
5d
5e
5 f
5g
70
68
64
52
76
44
58
93
94
97
92
96
92
93
5
5
5
1.05
1.05
1.05
1.05
1.5
4[f] toluene
4[d]
5
5
CH2Cl2 2.5
6[g] toluene
toluene
5
5
1
1
6
7
7
60
93
[a] Reactions performed on a 0.2 mmol scale in 0.4 mL of the solvent
(see the Supporting Information for details). [b] Reaction temperature
for the second step. [c] Overall yield. [d] Determined by chiral stationary
phase HPLC. [e] Not determined. [f] Annulation step performed for 24 h.
[g] Annulation step performed in the presence of Na2SO4.
[a] Reactions performed on a 0.2 mmol scale in toluene (0.4 mL); see the
Supporting Information for details. [b] Overall yield. [c] Determined by
chiral stationary phase HPLC. [d] Epoxidation performed with catalyst 2
(10 mol%).
4a being optimal (Table 3, entry 3). Again, the annulation
step could be performed at elevated temperature (608C)
without detriment to the enantioselectivity of the one-pot
reaction cascade.
in a highly enantioselective manner—93% enantiomeric
excess (ee)—which indicated that the elevated temperature
of the annulation step did not lead to racemization of the in-
troduced stereogenic center. Further screening revealed that
a change of the solvent to CH2Cl2, or the presence of
Na2SO4 as additive to remove the water present in the reac-
tion mixture from the epoxidation step, did not improve the
results (Table 1, entries 5 and 6). Moreover, increasing the
amount of 4a used had no beneficial effect on the cascade
yield (Table 1, entry 7).
Table 3. Optimization of the reaction conditions for the synthesis of ami-
noalkyl-substituted imidazoles.[a]
With the optimized conditions for the enantioselective
formation of hydroxyalkyl-substituted imidazoles in hand,
attention was turned to the scope of the methodology
(Table 2). A range of optically active 2,5-disubstituted imi-
dazoles were readily and efficiently prepared in moderate to
good yields (44–76%) with excellent enantioselectivities
(92–97% ee). Linear and g-branched aldehydes 1a–d partici-
pated smoothly in the one-pot reaction sequence to afford
imidazoles 5a–d in good yields and with excellent ee values
(Table 2, entries 1–4). Furthermore, functional groups, such
as a double bond (1e), protected alcohol (1 f), and phenyl
ring (1g), present in the side-chain of the starting a,b-unsa-
turated aldehyde were well tolerated (Table 2, entries 5–7).
Notably, cinnamaldehyde and ethyl 4-oxobutenoate were
also applied in the reaction sequence under the optimized
reaction conditions. However, unsatisfactory results were
obtained in these instances.
4a
[equiv]
T
t
Yield
[%][d]
n.d.[g]
44
66
57
Conv.
[%][e]
ee
G
[8C][b]
[h][c]
[%][f]
1
2
3
4
5
1.05
1.05
1.50
2.00
1.60
RT
60
60
60
60
24
1
50
53
>95
>95
>95
n.d.
n.d.
96
n.d.
96
1.5
1
1.5
65
[a] Reactions performed on a 0.1 mmol scale in toluene (0.5 mL); see the
Supporting Information for details. [b] Reaction temperature for the
second step. [c] Reaction time for the second step. [d] Overall yield.
[e] Conversion of 6a in the second step, determined by 1H NMR spec-
troscopy. [f] Determined by chiral stationary phase HPLC. [g] Not deter-
mined.
Having accomplished the synthesis of the hydroxyalkyl-
substituted imidazoles 5, screening of the complementary
aziridination/annulation strategy was initiated (Table 3).
Preliminary experiments revealed that the amount of 4a
used is crucial to achieve full conversion of the intermediary
aziridine 6a into 7a in the annulation step, with 1.5 equiv of
The generality of the aziridination/annulation one-pot re-
action cascade was next evaluated. As presented in Table 4,
the established reaction conditions could be successfully ap-
plied with various a,b-unsaturated aldehydes 1, an indica-
tion of the high versatility of the reaction. Good yields and
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Optically Active Imidazoles
FULL PAPER
Table 4. Aldehyde scope in the enantioselective synthesis of optically
active aminoalkyl-substituted imidazoles.[a]
Table 5. Amidine scope in the enantioselective synthesis of optically
active imidazoles.
1
R
Product
Yield
[%][b]
ee
4
R
X
Product
Yield
[%][c]
ee
[%][c]
[%][d]
1
2
3
4
5
6
7
1a
1b
1c
1d
1e
1 f
1g
hexyl
Pr
iPr
Me
(E)-hex-3-enyl
CH2OBn
CH2CH2Ph
7a
7b
7c
7d
7e
7 f
7g
66
52
51
56
70
60
65
96
96
95
93
96
96
92
1[a]
4b
4b
4c
4c
4d
4d
4e
4e
4 f
4 f
4g
4g
cPr
cPr
tBu
tBu
4-CH3-C6H4-
4-CH3-C6H4-
4-Cl-C6H4-
4-Cl-C6H4-
3-NO2-C6H4-
3-NO2-C6H4-
3-pyridyl
3-pyridyl
O
NTs
O
NTs
O
NTs
O
NTs
O
NTs
O
5h
7h
5i
7i
5j
63
69
66
55
64
68
52
63
59
64
62
75
91[f]
96
2[b]
3[a]
n.d.[g]
94
4[b]
5[a]
94
96
93
95
93
96
92
92
6[b]
7[a,e]
8[b,e]
9[a]
7j
5k
7k
5l
7l
5m
7m
[a] Reactions performed on a 0.1 mmol scale in toluene (0.5 mL); see the
Supporting Information for details. [b] Overall yield. [c] Determined by
chiral stationary phase HPLC.
10[b]
11[a]
12[b]
NTs
enantioselectivities of 7a–ACTHNUTRGNEUGNd were obtained in the case of
[a] Reactions performed on a 0.2 mmol scale in toluene (0.4 mL); see the
Supporting Information for details. [b] Reactions performed on
a
linear and g-branched aldehydes 1a–d. Furthermore, the re-
action cascade proved to be unbiased towards additional
functional groups in the side chain of the starting a,b-unsa-
turated aldehyde. Aldehydes 1e–g afforded imidazoles 7e–g
in good yields and with excellent enantioselectivities. 6-Oxo-
hept-2-enal was also reacted under optimized reaction con-
ditions, but the target imidazole was obtained in only 28%
yield, probably due to side reactions taking place at the car-
bonyl side-chain functionality.
0.1 mmol scale in toluene (0.5 mL); see the Supporting Information for
details. [c] Overall yield. [d] Determined by chiral stationary phase
HPLC. [e] HI salt used. [f] Determined by chiral stationary phase HPLC
after the transformation of the products into the corresponding N-trity-
lated derivative (see the Supporting Information for details). [g] Not de-
termined—separation of the enantiomers by chiral stationary phase
HPLC could not be achieved. However, because the optical activity of 5i
originates from the same enantiodifferentiating process as for the other
imidazoles 5 obtained, it is reasonable to assume that the ee also exceeds
90% in this case.
With an established efficient and enantioselective meth-
odology for the preparation of hydroxyalkyl- or aminoalkyl-
substituted imidazoles 5 and 7 in place, the possibility of in-
troducing various substituents at the 2-position of the target
imidazole derivative was evaluated (Table 5). Therefore, dif-
ferently functionalized aliphatic, aromatic, and heteroaro-
matic amidines were employed. However, because commer-
cial amidines are available as hydrochloride or hydroiodide
salts, additional base had to be employed in the annulation
step. Initial experiments allowed us to identify K2CO3 as the
most suitable base for liberation of amidines from their
salts. Moreover, in the case of the aziridination/annulation
sequences it was found that the use of K2CO3 as a base in
both processes is beneficial for the overall reaction outcome.
To our delight aliphatic amidines 4b and c participated
smoothly in the reaction cascade, which allowed for facile
introduction of cyclic or acyclic aliphatic side chains in the
target imidazoles 5 or 7 (Table 5, entries 1–4). Various aro-
matic and heteroaromatic amidines were also evaluated
(Table 5, entries 5–12). Pleasingly, the nature and position of
the substituents on the aromatic ring of amidines 4 had no
major influence on the outcome of the one-pot cascade and
both electron-rich and electron-poor systems could be suc-
cessfully applied (Table 5, entries 5–10). The use of heteroar-
omatic 3-pyridyl-substituted amidine 4g is also worth men-
tioning; imidazoles 5m or 7m were afforded in high yields,
in an enantioselective manner (Table 5, entries 11 and 12).
Importantly, in all of the cases, excellent enantioselectivities
(92–96% ee) were obtained despite basic reaction conditions
and elevated temperatures.
The chemical and biological properties of the 2-amino-
1,3-azole subunit (a very potent pharmacophore, commonly
utilized in drug discovery process) have recently gained
much attention.[6a,g] Many natural products isolated from
marine sponges contain this moiety and have intriguing bio-
logical properties. Therefore, we questioned whether the de-
veloped strategy could be extended to these structural
motifs. In particular, a facile construction of oxazole and
thiazole rings seemed appealing. To access these two classes
of heteroaromatic compounds, the replacement of amidines
with ureas or thioureas in the annulation step was envi-
sioned (Scheme 5). The studies were performed by using 1a
as a model carbonyl compound and 1,1-diethyl-urea (4h) or
thiourea (4i) as the annulating reagent. We were pleased to
observe that this approach proved successful. 5-Hydroxy-
AHCTUNGTREGaNNNU lkyl- and aminoalkyl-substituted oxazoles 8a and 8b and
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K. A. Jørgensen et al.
this technique. In this context it is worth mentioning that
unusual signal broadening, especially pronounced for the C4
and C5 carbon atoms in all obtained imidazoles 5 and 7, was
observed by 13C NMR spectroscopy.
Similarly, the absolute stereochemistry of the thiazole 9b
was established as (R)-9b by single crystal X-ray analysis.[19]
This result also revealed that the sulfur atom is indeed in-
volved in the aziridine ring-opening reaction, which results
in a fully regioselective cascade. The absolute configuration
of all remaining imidazoles 5b–m and 7b–m, oxazoles 8a
and 8b, and thiazole 9a, as well as the regioselectivity of the
oxazole and thiazole annulations, were assigned by analogy.
These assignments are in accordance with the previous re-
sults for epoxidation and aziridination of enals 1 catalyzed
by 2 and their applications in the synthesis of heteroaromat-
ic compounds.[16,17a–d]
Scheme 5. Enantioselective synthesis of optically active oxazole and
thiazole derivatives.
thiazoles 9a and 9b were effectively accessed in a highly
enantioselective manner. Notably, higher yields were ob-
served for aziridination/annulation sequences relative to the
cascades initiated with organocatalytic epoxidations. A par-
ticularly remarkable feature of the developed cascades is
the complete regioselectivity. In all cases, the formation of
oxazoles 8 and thiazoles 9 arises from opening of the epox-
ide or aziridine ring by the oxygen or sulfur atom of 4h or
4i, respectively (see below and Figure 1 for further details).
Conclusion
The enantioselective organocatalytic strategy for the synthe-
sis of hydroxyalkyl- and aminoalkyl-substituted imidazoles
was established. This efficient one-pot protocol utilizes a
highly enantioselective aminocatalytic epoxidation or aziri-
dination of a,b-unsaturated aldehydes, followed by a ring-
closing step that uses amidines as 1,3-dinucleophilic species.
Various linear, branched, and functionalized a,b-unsaturated
aldehydes can be efficiently applied in these cascades. Fur-
thermore, the generality of the process was confirmed by
use of aromatic, heteroaromatic, and aliphatic amidines,
which allowed for the introduction of various substituents in
the 2-position of the target imidazoles. Finally, the estab-
lished protocol was extended to the synthesis of 2-diethyl-
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
complete regioselectivity of the reaction was observed and
5-substituted oxazoles and thiazoles were the only products.
Experimental Section
Figure 1. X-ray structures of 7a and 9b.
General procedure for the preparation of hydroxyalkyl-substituted imid-
AHCTUNGTRENNUNG
1
2
0.05 equiv), and toluene (0.4 mL). After briefly stirring at RT, H2O2
(35%w/w in water, 0.2 mmol, 1 equiv) was added. The stirring was main-
tained at ambient temperature for 24 h to achieve full conversion of 1.
Upon completion of the reaction, benzamidine 4a (0.21 mmol,
1.05 equiv) [or the corresponding amidine salt 4b–g (0.3 mmol, 1.5 equiv)
and K2CO3 (0.3 mmol, 1.5 equiv)] was added. The mixture was heated at
608C for 1 h and then directly subjected to flash column chromatography
on silica gel to afford imidazole 5.
Amides and thioamides were also investigated in the devel-
oped synthetic strategy. Benzamide was unreactive under
the present reaction conditions. Contrarily, thiobenzamide
underwent reaction with the intermediary 2,3-epoxy alde-
hyde, but the desired thiazole was not obtained.[18]
The absolute configuration of imidazole 7a was unambig-
uously assigned as (R)-7a by X-ray analysis.[19] Interestingly,
it was found that in the crystal unit, 7a exists as a mixture
of two tautomers. Notably, one main product was observed
General procedure for the preparation of aminoalkyl-substituted imid-
AHCTUNGTRENNUNG
1
2
1
0.025 equiv), and toluene (0.5 mL). After briefly stirring at RT,
TsNHOTs (0.1 mmol, 1 equiv) was added, followed by NaOAc
(0.3 mmol, 3 equiv) or K2CO3 (0.3 mmol, 3 equiv). The stirring was main-
tained at ambient temperature for 24 h to achieve full conversion of the
nucleophile. Upon completion of the reaction, benzamidine 4a
by H NMR spectroscopy, which indicates that the rate of
tautomeric proton shift is similar to, or faster, than the
NMR timescale. Therefore, two tautomers of imidazoles 5
or 7 exist in rapid equilibrium and are indistinguishable by
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Optically Active Imidazoles
FULL PAPER
(0.3 mmol, 1.5 equiv) [or the corresponding amidine salt 4b–g (0.3 mmol,
1.5 equiv) and K2CO3 (0.3 mmol, 1.5 equiv)] was added. The resulting
mixture was heated at 608C for 1.5 h and then directly subjected to flash
column chromatography on silica gel to afford imidazole 7.
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General procedure for the preparation of hydroxyalkyl-substituted oxa-
zoles and thiazoles: A glass vial equipped with a magnetic stirrer bar was
charged with aldehyde 1 (0.2 mmol, 1 equiv), aminocatalyst 2 (0.01 mmol,
0.05 equiv) and toluene (0.4 mL). After briefly stirring at RT, H2O2
(35%w/w in water, 0.2 mmol, 1 equiv) was added. The stirring was main-
tained at ambient temperature for 24 h to achieve full conversion of 1.
Upon completion of the reaction, urea 4h or thiourea 4i (0.21 mmol,
1.05 equiv) was added. The resulting mixture was heated at 608C for 1 h
and then directly subjected to flash column chromatography on silica gel
to afford oxazole 8a or thiazole 9a.
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charged with aldehyde 1 (0.12 mmol, 1.2 equiv), catalyst 2 (0.0025 mmol,
0.025 equiv), and toluene (0.5 mL). After briefly stirring at RT,
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flash column chromatography on silica gel to afford oxazole 8b or
ACHTUNGTRENNUNGthiazole 9b.
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Acknowledgements
This work was made possible by grants from OChemSchool, Carlsberg
Foundation, FNU and a scholarship from Foundation for Polish Science
(Kolumb Programme - ŁA). We thank Dr. Jacob Overgaard for perform-
ing X-ray analysis and Joachim Møllesøe Vinther for assistance with
NMR spectroscopic analysis.
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Received: June 14, 2011
Published online: October 20, 2011
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