Catalytic three-component domino reaction for the preparation of trisubstituted oxazoles

Article abstract of DOI:10.1002/chem.201300019

Multicomponent reactions are attractive for assembling functionalized heterocyclic compounds. To this end, an efficient gold-catalyzed three-component domino reaction to form oxazoles directly from imines, alkynes, and acid chlorides is presented. The reaction proceeds in a single synthetic step by using a gold(III)-N,N'-ethylenebis(salicylimine) (salen) catalyst to give trisubstituted oxazoles in up to 96 % yield. The substrate scope, a mechanistic study exploring the role of the gold catalyst, and the synthetic applications of the oxazole products are discussed. Copyright

Full text of DOI:10.1002/chem.201300019

FULL PAPER
DOI: 10.1002/chem.201300019
Catalytic Three-Component Domino Reaction for the Preparation of
Trisubstituted Oxazoles
Henrik v. Wachenfeldt, Philipp Rçse, Filip Paulsen, Nagarajan Loganathan, and
[
a]
Daniel Strand*
Abstract: Multicomponent reactions are attractive for assembling functionalized
heterocyclic compounds. To this end, an efficient gold-catalyzed three-component
domino reaction to form oxazoles directly from imines, alkynes, and acid chlorides
Keywords: gold
homogeneous catalysis · multicom-
ponent reactions · oxazoles
· heterocycles ·
is presented. The reaction proceeds in a single synthetic step by using a gold
A
H
U
G
R
N
U
G
ACHTUNGTRENNUNG
N,N’-ethylenebis(salicylimine) (salen) catalyst to give trisubstituted oxazoles in up
to 96% yield. The substrate scope, a mechanistic study exploring the role of the
gold catalyst, and the synthetic applications of the oxazole products are discussed.
Introduction
procedures rely on telescoping, in which the consecutive ad-
dition of reactants and/or reagents gives the oxazole product
[15]
Oxazoles constitute key structures in functional molecules
with diverse applications ranging from synthetic intermedi-
in one pot.
A convenient MCR to generate propargyl
amines with potential use as oxazole precursors is the cata-
[
1]
[2]
[3]
3
ates to fluorescent probes, peptidomimetics, and new
lytic addition of alkynes to imines formed in situ ( A cou-
[
4]
materials. They are represented in natural products with
pling). The reaction proceeds with a range of catalytic sys-
[
5,6]
[16a]
[16b]
[16c]
cytotoxic and antimicrobial properties,
as exemplified by
tems including the use of copper,
silver,
zinc,
An exten-
[7]
[16d]
[16e]
[16f]
[16g]
the nanomolar-active ajudazol. In medicinal chemistry, ox-
azoles are found in anti-inflammatory, antiviral, and analge-
iron,
indium,
iridium,
and gold salts.
sion of this methodology for the direct formation of prop-
argyl amides from alkynes and nonenolizable imines in the
presence of acyl chlorides was reported by Black and Arndt-
[8]
sic agents. Classical methods for oxazole synthesis include
dehydration of a-keto amides under forcing conditions.
Recent examples of oxazole synthesis by intermolecular re-
[
6,9]
[17]
sen. Conceptually, the bridging of complexity-generating
processes, such as catalytic acetylide addition to imines and
catalytic cycloisomerizations, in a single multicomponent
domino reaction is an attractive approach for the assembly
[
10a,b]
actions include the addition of a-isocyanates to imines,
[
10c]
cycloadditions of acyl azides to alkynes,
and transition-
Methods based on
[
10d,e]
metal-catalyzed [3+2] cycloadditions.
[18]
the cyclization/isomerization of propargyl amides have been
widely studied. Variations are plentiful and include the use
of multifunctionalized structures. The present art is, how-
ever, limited to processes that incorporate the substituents
on the imine nitrogen atom into the final product. This
limits the scope of the hetereocycles accessible through this
strategy, and consequently, it has not been used for oxazole
synthesis. Herein, we present a catalytic reaction that produ-
ces oxazoles directly from readily available N-benzylimines
and commercially available alkynes and acyl chlorides
(Scheme 1). Under optimized conditions, the reaction pro-
duces trisubstituted oxazoles displaying diverse functional
groups in up to 96% yield by using as little as 1 mol% of a
[11a]
[11b–d]
[11e–h]
of alkynyl alanes,
palladium salts,
gold salts,
Lewis acids,
[11i]
[11j]
[11k]
cerium salts,
Brçnsted acids.
oxazoles include the reaction of a-amino ketones and alde-
hypervalent iodine,
and
[
11l]
Additional cyclization reactions to form
[
12a]
hydes,
situ oxidation,
lyzed
the reaction of alkynes and amines followed by in
and oxidative gold- or copper-cata-
reactions between alkynes and nitriles.
[12b]
[
12c,d]
[13]
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
A powerful tool for the rapid generation of molecular
complexity is the multicomponent reaction (MCR). Domino
MCRs to form oxazoles are rare and are often based on the
Van Leusen oxazole synthesis or Ugi-like reactions with iso-
gold
15 min.
The essence of the title reaction is captured in Scheme 1.
ACHTUNGTRENNU(GN III)–salen catalyst and with a reaction time of only
[
14]
cyanates followed by in situ cyclization.
More common
At the outset, we envisioned that a single metal complex
would serve as a catalyst (or a precatalyst) to mediate three
consecutive processes: 1) an acyl iminium–alkyne coupling
to form a propargyl amide, 2) activation of the alkyne for
cyclization to form the penultimate five-membered ring, and
[
a] H. v. . Wachenfeldt, P. Rçse, F. Paulsen, Dr. N. Loganathan,
Dr. D. Strand
Centre for Analysis and Synthesis, Department of Chemistry
Lund University, PO Box 124, 22100 Lund (Sweden)
Fax : (+46)46-222-8209
3
) isomerization of the exo-alkene formed in the cyclization
E-mail: daniel.strand@chem.lu.se
step to give the desired oxazole. The overall process would
be enabled by the loss of the sacrificial imine benzyl group
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201300019.
Chem. Eur. J. 2013, 00, 0 – 0
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lene and benzoyl chloride with gold
alyst, the desired oxazole 4a was formed in moderate yield
Table 1, entry 1). In solvent (acetonitrile), the yield was im-
ACHTUNGERTNNUNG( III) chloride as the cat-
(
proved to 70%, but the reaction was accompanied by exten-
sive deposition of metallic gold. When the metal was stabi-
lized with a salen ligand in the form of [Au ACHTNUGTERNNN(UG salen)]PF , a
6
3
catalyst previously shown to efficiently catalyze A couplings
[21]
in water, oxazole 4a was obtained in essentially quantita-
tive yield by using as little as 1 mol% of the catalyst
[22]
(
entry 7).
The continuous removal of chloride ions from the reac-
tion mixture in the form of benzyl chloride is an important
feature of the reaction because it preserves the activity of
the gold catalyst. In a control experiment with gold ACHTUNGTRENNUNG( III)–
salen chloride as the catalyst, the yield was reduced to 50%
for the reaction between tBu-N-benzylimine, phenylacety-
lene, and benzoyl chloride. Solvents other than MeCN (di-
oxane, toluene, and dichloroethane) were screened, but all
Scheme 1. Transition-metal-catalyzed synthesis of oxazoles and their pre-
cursors. DIPEA=N,N-diisopropylethylamine.
resulted in a decreased yield. Additives like bases (Et N and
3
di-tert-butylpyridine) to promote the metal–acetylide forma-
tion led to decomposition, and a Lewis acid (Zn ACHTNUGERTNNUNG( OTf) )
2
[19]
[23]
in the form of benzyl chloride.
A conceptually related
procedure for the asymmetric synthesis of cyclic carbamimi-
dates was recently presented.
gave a decreased yield. Under the optimized conditions, the
reaction can be scaled by an order of magnitude without
loss of efficiency, and on over a gram scale, oxazole 4a was
crystallized directly from the reaction mixture in 80% yield
through addition of a small amount of water (Table 1,
entry 9). In contrast to phenylacetylene, methylpropiolate
(3b) failed to give the corresponding oxazole, 4b, with ben-
zoyl chloride under gold catalysis (entry 12). The high stabil-
ity of gold–propiolate complexes may be the reason for this
[20]
Results and Discussion
Optimization of the reaction was done with tert-butyl-N-
benzylimine (1a) as the imine component, and the results
are summarized in Table 1. In the presence of phenylacety-
[24]
I
failure, so we also evaluated Cu salts, which are
3
known to efficiently mediate
A
couplings.
Table 1. Optimization of the oxazole-forming reaction between N-ben
ACTHUNGTRNENUNGz yl CATHUNGTRENNGNUi mine 1a,
CuBr·DMS efficiently catalyzed the formation of
oxazole 4b from methylpropiolate (entry 13), but it
gave a lower yield than gold catalysis in the forma-
tion of 4a from phenylacetylene (entry 10).
acyl chloride 2a, and alkynes 3a and b.
To probe the role(s) of the gold–salen complex in
the catalytic cycle beyond the carbon–carbon bond-
forming step, two control reactions were designed
and the plausible intermediates 5 and 6 were syn-
thesized (Figure 1, see the Supporting Information
for details). In the first reaction, the cyclization
of propargyl amide 5 with various amounts of gold
catalyst was studied (Figure 1A). The HCl salt of
Entry
R
Cat.
Cat.
[mol%]
Solvent
T
[8C]
Product Yield
[
b]
A
H
U
G
R
N
U
G
[%]
[25]
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
CO
CO
AuCl
AuCl
3
30
30
20
20
5
5
1
1
1
–
150
190
150
190
190
170
190
190
170
150
150
170
150
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b
4b
49
70
51
83
87
89
96
80
3
MeCN
–
[Au
[Au(salen)]PF
[Au(salen)]PF
[Au(salen)]PF
[Au(salen)]PF
[Au(salen)]PF
[Au(salen)]PF
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(salen)]PF
6
6
6
6
6
6
6
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
–
2
,6-lutidine was used as the proton source in these
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
reactions because it is similar in pK value to the
a
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
protonated imine that is the putative proton source
under the regular reaction conditions. The forma-
tion of benzyl chloride (7), released in connection
with the formation of oxazoline 6, was used as a
measure of the reaction progress because oxazoline
[
[
c]
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
d]
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
91, 80
41
10
11
12
13
CuBr·DMS
CuCl
30
30
5
–
44
0
87
2
2
Me [Au
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(salen)]PF
6
MeCN
–
[
e]
Me CuBr·DMS
30
6
aromatizes into oxazole 4a. The amount of 4a
[
(
a] Reaction run on a 1.0 mmol scale (imine) with alkyne (2 equiv) and acyl chloride plus 6 formed in the reaction correlates within 5%
1 equiv) for 15 min with microwave heating. DMS=Di AHCTUNTGRENNUNGm eth CAHTUNGTRENNUNGy lsulfide. [b] Measured
to the amount of 7 at all time points studied. In the
second reaction, the isomerization of 6 into 4a was
studied with various amounts of gold or acid cata-
lyst (Figure 1B).
by NMR spectroscopy with mesitylene as an internal standard. [c] 1.1 equivalents of
alkyne were used. [d] Yield of isolated product. Reaction performed on a 2.4 g scale.
[
e] Yield of isolated product. [f] Thermal ellipsoid plot at 50% probability. Hydrogen
atoms are omitted.
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Domino Reaction for the Preparation of Trisubstituted Oxazoles
FULL PAPER
the gold-catalyst concentration,
the isomerization proceeds
faster. The isomerization of 6
into 4a is, however, cleaner
(
less byproduct formation) with
the lower gold-catalyst loading.
With 10 mol% of 2,6-luti-
dine·HCl, the acid-catalyzed cy-
clization is fast and gives oxa-
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
zole 4a quantitatively within
the allotted 16 min. A mixture
of [Au ACHTNUGTERNN(UGN salen)]PF and HCl·luti-
6
dine (5+5 mol%) was also tried
for the isomerization of 6. No
significant nonlinear effect was
observed in this experiment;
the reaction rate was equivalent
to that of the combined rates of
the individual catalysts. These
observations suggest that gold
is not involved to an apprecia-
ble extent in facilitating the
cyclization step but does con-
tribute to the isomerization of 6
into 4a, which led us to propose
the mechanism outlined in
Scheme 2: The oxazole-forming
process is initiated by the addi-
tion of metal acetylide II to the
activated N-acyl iminium salt V
1
Figure 1. Kinetic data obtained by H NMR spectroscopy for A) the cyclization of propargyl amide 5 into oxa-
[17]
zoline 6 and B) the isomerization of oxazoline 6 into oxazole 4a with various amounts of catalysts (*: no cata- to give propargyl amide VI.
&
6 6
lyst, : 5% [Au ACHTUNGTRENNUNG( salen)]PF ACHTUNGTNERNUNG( salen)]PF
, ~: 10% [Au , !: 5% 2,6-lutidine·HCl).
The proton released during
alkyne activation then activates
the triple bond of VI for attack
The following qualitative kinetic observations were made:
) The cyclization to generate oxazoline 6 is similar in rate
of the amide oxygen atom. The benzyl group of the resulting
iminium ion VII is released as benzyl chloride (VIII) by
1
in the presence and absence of
the gold catalyst. This observa-
tion is in line with the previous
III
observation that Au does not
catalyze cycloisomerization of
propargyl alkynes substituted at
[11-
the terminal alkyne position.
e–g]
The small rate differences
observed in the formation of 6
can be attributed to a less effi-
cient reaction (side-product for-
mation) at higher catalyst con-
centrations, rather than a lower
reaction rates. This is corrobo-
rated by the essentially full con-
version of starting material 5 in
all three experiments. 2) The
thermal isomerization of the
exo double bond of 6 to form
4
a is negligible under these
Scheme 2. Proposed mechanism for the gold-catalyzed formation of oxazoles from N-benzylimines, acyl chlor-
conditions. With an increase in ides, and alkynes.
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D. Strand et al.
attack of a chloride ion originating from the initial acylation
of imine IV. Finally, the isomerization of IX to produce oxa-
zole XI is mediated by a combination of Brçnsted acid and
Table 2. Oxazole formation with various alkynes.
[26]
metal catalysis.
The scope of the reaction was investigated by varying the
substrates corresponding to each position of the oxazole
ring. The study was conducted with gold catalysis because
the copper conditions are less general with respect to nonac-
ceptor alkynes. A catalyst loading of 5 mol% was beneficial
with most functionalized alkynes. Alkyl, aryl, and cycloprop-
yl-substituted alkynes all participate in the reaction to give
the corresponding oxazole products in moderate to good
yields (Table 2). Valuable handles for further derivatizations
like alkyl chlorides and silyl groups are also readily incorpo-
rated at this position, as shown by the formation of 4g and
4
e.
A variety of acid chlorides comprising aryl, heterocyclic,
and aliphatic structures all provided the corresponding oxa-
zoles in good to excellent yields (Table 3). Even the sterical-
ly encumbered pivaloyl chloride gave the corresponding bis-
[a] Reaction run on a 0.5 mmol scale (imine) with alkyne (2 equiv), acyl
chloride (1 equiv), and 5 mol% of [Au ACHTUGNTNERNU(GN salen)]PF with microwave heat-
6
ing (1708C).
2,4-tert-butyl-substituted oxazole product 4j, albeit at a
lower yield.
With multifunctionalized reagents, the reaction can be
used to assemble more than one heterocycle in a single op-
eration. An illustrative example is the reaction with triacid
chloride 2g (Scheme 3). In this transformation, a total of
seven components are assembled to form the final trioxazole
position (Table 4). In agreement with what would be expect-
[17]
ed from prior observations, enolizable (that is, aliphatic)
imines do not give oxazole formation. As is evident from
the isolation of N-benzyl enamides in these experiments,
this failure originates from the carbon–carbon bond-forming
step in the alkyne–iminium coupling. Aryl imines give poor
yields under gold catalysis. By using the Cu-catalyzed proce-
dure, 4s was isolated in 27% yield. Ethyl glyoxalate N-ben-
zylimine gave a trace of product (4%; not shown). Interest-
4
m through nine bond-forming events in 33% yield after
isolation. This result is also interesting in light of the possi-
ble pincer-ligand properties of this compound.
Various N-benzylimines with geminal substitution at the
imine a-position can participate in the reaction. Substituents
such as alkenes, ethers, and esters are compatible with this
Table 3. Oxazole formation with various acyl chlorides.
[
(
a] Reaction run on a 0.5 mmol scale (imine) with alkyne (2 equiv), acyl chloride (1 equiv), and 1 mol% of [Au
1708C). [b] Thermal ellipsoid plots at 50% probability. Hydrogen atoms are omitted.
6
ACHTUNGTNRENUNG( salen)]PF with microwave heating
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Domino Reaction for the Preparation of Trisubstituted Oxazoles
FULL PAPER
Scheme 3. Left-hand side: seven-component reaction to form trioxazole 4m. Right-hand side: the thermal ellipsoid plot at 50% probability and the rota-
tional distortions on two of the tert-butyl groups. Hydrogen atoms are omitted.
Table 4. Oxazole formation with various N-benzylimines.
use as ligands in asymmetric
[29]
catalysis.
Drawing from the
design elements of related suc-
[30]
cessful oxazoline systems, the
geminal dimethyl group that
enabled efficient oxazole for-
mation now conveniently serves
to preorganize the bidentate
structure for metal binding. The
short and modular nature of
this synthesis should be of
value in developing ligand li-
braries.
With the aim of circumvent-
ing the limitation of quaternary
substitution at the oxazole 4-
position, we explored rear-
rangement reactions. Access to
4
-vinyl oxazole 9 can be accom-
plished through a surprisingly
efficient thermal 1,2-rearrange-
ment of mesylate 8, readily
available from 4o in two steps
[31]
(
Scheme 4).
Vinyl oxazoles
[
[
a] Reaction run on a 0.5 mmol scale (imine) with alkyne (2 equiv), acyl chloride (1 equiv), and 1 mol% of
Au(salen)]PF with microwave heating (1708C, 15 min). [b] 5 mol% of [Au(salen)]PF was used. [c] Thermal
like 9 are valuable as masked
precursors to a range of func-
tional structures, including 4-
carboxy oxazoles, a motif prev-
alently found in bioactive mole-
cules including natural products
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
6
A
H
U
G
R
N
U
G
6
ellipsoid plot at 50% probability. Hydrogen atoms are omitted. [d] CuBr·DMS (20 mol%) was used as the cat-
alyst. [e] Measured by NMR spectroscopy with mesitylene as an internal standard.
ingly, methylene N-benzylimine gave 15% of the corre-
sponding 2,5-di-substituted oxazole 4r. The majority of the
material is lost as unspecific decomposition in the low yield-
ing entries. The side reactions that account for the low
yields with imines 1 f–h may be a result of the reduced steric
bulk in the imine a-position relative to that of the corre-
sponding trialkyl-substituted imines.
and pharmaceuticals. Rearrangement of 8 under kinetic con-
ditions (tBuOK, À788C) gave 4-(2-methylpropenyl)oxazole
10, with good selectivity (10/9=92:8) and yield. Whereas
similar rearrangements have been extensively studied with
[32]
aryl migrating groups and have been reported as side re-
[33]
actions for other heterocyclic migrating groups, the rear-
rangements of mesylate 8 constitute rare and distinctively
efficient examples of this type of reaction with an electron-
rich heterocycle as the migrating entity. Finally, direct decar-
boxylation of 4o under modified Krapcho conditions exem-
plifies a convenient entry to tertiary alkyl substitution at the
The synthetic utility of the reaction is highlighted by deri-
vatization of the oxazole product. Ester hydrolysis followed
[27]
[28]
by amide coupling and a dehydrative cyclization gives
rapid access to a new class of chiral oxazoline–oxazole struc-
tures, exemplified by oxazole 13 (Scheme 4), with potential
[34a]
oxazole 4-position.
To the best of our knowledge, this is
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D. Strand et al.
ent at the same position. Fur-
ther studies of this reaction and
extensions to related systems
are underway.
Experimental Section
Representative procedure: A micro-
wave vial was charged with [Au-
A
H
U
G
R
N
N
6
(3.04 mg,
5.00 mmol,
1
3
(
2
chloride (53 mL, 0.50 mmol, 1.0 equiv)
were added sequentially. The resulting
mixture was heated by microwave irra-
diation, with a ceiling temperature of
1
708C and the sample absorption set
to “very high” for 15 min. The crude
reaction mixture was dissolved in
2 2
CH Cl and a small amount of silica
Scheme 4. Application and post-MCR synthetic modifications of the oxazole products. DIBALH=diisobutyl-
ACHTUNGTRENNUNGa luminum hydride; 2,6-lut.=2,6-lutidine; TFFH=tetramethylfluoroformamidinium hexafluorophosphate.
was added to the mixture. The result-
ing slurry was concentrated under re-
duced pressure. The concentrate was
added to
eluted with CH
a
silica gel column and
Cl /heptane (1:3). The
2
2
product-containing fractions were pooled and concentrated under re-
duced pressure to give oxazole 4k (137 mg, 92%) as orange crystals.
the first example of a direct decarboxylation at this position
of an oxazole structure.
[34b]
Conclusion
Acknowledgements
An efficient gold-catalyzed multicomponent domino reac-
tion to form oxazoles by the bridging of catalytic acetylide
additions to imines and cycloisomerization of propargyl
amides is presented. Trisubstituted oxazoles displaying a
series of synthetically useful functional groups are formed in
a single step in up to 96% yield. The use of a sacrificial
benzyl group allows for product formation directly from
readily available N-benzylimines and feedstock reagents like
alkynes and acyl chlorides. The reaction also retains the effi-
ciency on over a gram scale. The role of the gold catalyst
was investigated, and in addition to catalyzing the carbon–
carbon bond-forming step, gold was shown to mediate the
isomerization of the intermediate oxazoline into the final
Financial support was provided by Lund University Faculty of Science,
the Royal Physiographical Society in Lund, and the Swedish Research
Council. We thank Professor Ola F. Wendt for assistance with the X-ray
analysis.
[
1] S. Reck, W. Friedrichsen, J. Org. Chem. 1998, 63, 7680–7686.
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[
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[
[
4] R. Hirohashi, Y. Hishiki, S. Ishikawa, Polymer 1970, 11, 297–308.
5] V. S. C. Yeh, Tetrahedron 2004, 60, 11995–12042.
[6] D. C. Palmer, S. Venkatraman in The Chemistry of Heterocyclic
Compounds: A Series of Monographs. Oxazoles: Synthesis, Reac-
tions, and Spectroscopy, Part A (Ed.: D. C. Palmer), John Wiley &
Sons, Hoboken, NJ, 2003.
aro ACHTUNGTRENNUNGm atic system, but not the preceding cyclization step. In-
[
[
[
7] a) B. Kunze, R. Jansen, G. Hofle, H. Reichenbach, J. Antibiot. 2004,
terestingly, the mechanism of the reaction would enable effi-
cient oxazole formation also through nonterminal alkynes.
The reaction was showcased in a highly modular and short
assembly of a new type of chiral oxazoline–oxazole structure
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vinyl- and allyl-substituted oxazoles, respectively. A decar-
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5
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Domino Reaction for the Preparation of Trisubstituted Oxazoles
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[
[
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[
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3
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Received: January 3, 2013
Revised: February 20, 2013
Published online: && &&, 0000
Chem. Eur. J. 2013, 00, 0 – 0
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
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D. Strand et al.
Multicomponent Reactions
H. v. . Wachenfeldt, P. Rçse, F. Paulsen,
N. Loganathan, D. Strand* . &&&& — &&&&
Catalytic Three-Component Domino
Reaction for the Preparation of
Trisubstituted Oxazoles
Crossing bridges: Oxazoles are gener-
ated in up to 96% yield from readily
available imines, acid chlorides, and
benzyl group enables the bridging of
an imine–alkyne coupling and a cyclo-
AHCTUNGTRENNUNGi somerization manifold to form the
alkynes by using a gold
A
H
U
G
R
N
N
(III) catalyst
oxazole products in a single domino
reaction.
(
see scheme). The use of a sacrificial
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ÝÝ
These are not the final page numbers!