Metal catalyzed multicomponent syntheses of secondary propargylamides and oxazoles from silylimines, acid chlorides, and alkynes

Article abstract of DOI:10.1016/j.tet.2005.09.096

Copper(I) and zinc(II) catalyzed routes to construct secondary propargylamides in one-pot procedures from aldehydes, LiN(TMS)₂, acid chlorides, and alkynes are described. This reaction has been subsequently used to provide a one-pot synthesis o

Full text of DOI:10.1016/j.tet.2005.09.096

Tetrahedron 61 (2005) 11317–11321
Metal catalyzed multicomponent syntheses of secondary
propargylamides and oxazoles from silylimines, acid chlorides,
and alkynes
*
Daniel A. Black and Bruce A. Arndtsen
Department of Chemistry, McGill University, 801 Sherbrooke St. West, Montreal, Quebec H3A 2K6, Canada
Received 19 August 2005; accepted 21 September 2005
Available online 10 October 2005
Abstract—Copper(I) and zinc(II) catalyzed routes to construct secondary propargylamides in one-pot procedures from aldehydes,
LiN(TMS)2, acid chlorides, and alkynes are described. This reaction has been subsequently used to provide a one-pot synthesis of oxazoles
from four simple building blocks.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
tertiary amides, and do not provide direct access to the
secondary propargylamide core.16 We describe herein, our
studies towards the development of a route to construct
secondary propargylamides, via the copper or zinc catalyzed
coupling of imines, acid chlorides, and terminal alkynes.
This process has been subsequently employed to provide a
novel route to construct tri-substituted oxazoles from four
readily available building blocks in a single pot reaction.
Multicomponent coupling reactions (MCRs) represent
efficient methods of rapidly increasing molecular
complexity in a modular fashion.1 From early examples,
such as the Strecker,2 Hantsch,3 and Mannich4 reactions, to
more recent reports,5 this approach has been used to prepare
a wide range of important chemical structures. In principle,
transition metal catalysis can provide a useful tool in the
design of new MCRs, through the ability to both induce and
control reactivity. Overall, this can allow the use of more
readily available, easily diversified, and less complex
building blocks, coupled together all at once via a metal-
based mechanism.6
2. Results and discussion
We have previously reported that tertiary propargylamides
(1) can be prepared through the copper catalyzed three-
component coupling of imines, acid chlorides, and alkynes
(Scheme 1).7
One class of molecules towards which metal catalyzed
multicomponent coupling has recently been applied are
propargylamides. We7 and others8,9 have shown that these
compounds, and their amine derivatives, can be assembled
from available building blocks, such as imines, aldehydes,
amines, acid chlorides, alkynes, using a range of metal
catalysts. Of the many propargylamides used in synthesis,
secondary amides have found particular utility. These core
structures are present in a variety of biologically active
molecules (e.g., oxotremorine10 and a range of fungicides
and herbicides).11 In addition, they are useful synthons in
the formation of heterocycles12–14 and biomimetic poly-
mers.15 Despite this utility, the current metal catalyzed
multicomponent routes to propargylamides all generate
Keywords: Alkynes; Oxazoles; Multicomponent.
*
Corresponding author. Tel.: C1 514 398 6903; fax: C1 514 398 2382;
e-mail: bruce.arndtsen@mcgill.ca
Scheme 1. Three-component synthesis of tertiary propargylamides.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.096

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D. A. Black, B. A. Arndtsen / Tetrahedron 61 (2005) 11317–11321
Table 1. Copper(I) and zinc(II) catalyzed multicomponent syntheses of
secondary propargylamides (Fig. 3)a
This reaction is considered to proceed through the attack of
a copper-acetylide on an in situ generated N-acyl iminium
salt. In order to extend this approach to secondary
propargylamides, N–H substituted imines would be required
as substrates, which are typically unstable.17 However,
trimethylsilyl-substituted imines (2) have been used as N–H
imine equivalents for nucleophilic addition chemistry,18
suggesting their potential utility in this system. Not
surprisingly, however, our initial attempt to employ these
imines in the copper catalyzed multicomponent coupling
with benzoyl chloride and phenylacetylene led instead to the
formation of N-acyl imines 3,19 eliminating TMSCl in the
process (Fig. 1).
Compound R1
R2
R3
Catalystb
Yield
(%)
4a
4b
4c
4d
4e
4f
4g
4h
4i
p-Tol
tBu
p-Tol
p-An
tBu
p-An
tBu
p-Tol
Ph
Ph
Ph
Ph
Vinyl
iPr
p-An
tBu
Ph
CuI/BF3
CuI/BF3
CuI/BF3
CuI/BF3
CuI/BF3
Zn(OTf)2
Zn(OTf)2
80
88
57
92
87
73
67
62c
91
89
nBu
Ph
Ph
nBu
Ph
p-I–6H4
Ph
Ph
CH2OTMS Zn(OTf)2
Ph
Ph
iBu
Ph
Zn(OTf)2
Zn(OTf)2
4j
a Aldehyde (0.63 mmol), 0.63 mmol LHMDS, and 0.83 mmol acid chloride
in hexanes, followed by 0.83 mmol alkyne 0.63 mmol EtiPr2N and
catalyst in CH3CN (7 ml).
b With 10% CuI with 20% BF3 diethyletherate at 65 8C for 14 h, or 10%
Zn(OTf)2 at ambient temperature for 10 h.
c Product isolated as the deprotected hydroxy-propargylamide.
Figure 1. Reaction of trimethylsilyl-substituted imine 2a with acid chloride
and alkyne.
In addition to the use of Lewis acids to increase the
electrophilicity of 3, an alternative approach to this reaction
involves increasing the nucleophilicity of the metal-
acetylide. In particular, zinc(II) salts have been shown by
Carreira to form zinc-acetylides in a similar manner to
copper acetylides, and have a higher propensity for addition
to such substrates as aldehydes,21a imines,21b,c and
enones.21d Indeed, 10% Zn(OTf)2 can be employed as a
catalyst for this same multicomponent reaction, in this case
under more mild conditions than that with copper, leading to
the formation of secondary propargylamide products after
only 10 h at ambient temperature (Table 1, 4f–j).
While in principle 3a could react with an in situ generated
copper-acetylide to form a propargylamide, even upon
prolonged heating at 105 8C, no reaction was observed. The
lack of alkyne addition to the N-acyl imine is likely the
result of its lower electrophilicity relative to N-acyl iminium
salts (e.g., in Scheme 1). Considering that Lewis acids have
been shown to catalyze addition reactions to aldehydes and
imines,20 Lewis acid co-catalysts were examined in concert
with copper salts. As was hoped, the reaction of 3a and
phenylacetylene in the presence of 10% CuI and 20%
BF3$Et2O leads to the formation of the desired propargyl-
amide 4a in 83% yield. This reaction can also be performed
in a multicomponent fashion, allowing the genertion of 4a in
similar yield directly from N-trimethylsilyl imine 2a, acid
chloride, and alkyne (Fig. 2). Alternatively, the construction
of the TMS-substituted imine can be performed in the same
reaction pot, eliminating the need to isolate these sensitive
substrates (Fig. 3, Table 1, 4a).† The latter provides a
modular method to construct secondary propargylamides
directly from aldehydes, silylamide, acid chlorides, and
alkynes.
As shown in Table 1, these reactions can be readily
diversified, allowing the formation of secondary amides
with a range of aldehyde, acid chloride, and alkyne
substrates. This includes aryl and non-enolizable alkyl
aldehydes,22 as well as aryl, alkyl, a,b-unsaturated, and
functionalized acid chlorides. Aryl, alkyl, and function-
alized alkynes can also be successfully incorporated into the
propargylamide product. In general, both catalyst systems
provide the products in similarly high yields.
Considering the utility of secondary propargylamides as
synthetic building blocks, their generation by this multi-
component reaction provides the opportunity to consider the
synthesis of other products in a similar modular fashion. As
an illustration of this feature, we have probed the coupling
of this reaction with the synthesis of oxazoles.23 It has been
reported that secondary propargylamides undergo cycliza-
tion to form oxazoles in the presence of base,12 palladium,13
or silica gel catalysts.14 Thus, performing the catalytic
synthesis of 4a followed by the addition of catalytic NaH to
the same reaction pot leads to the overall construction of
oxazole 5a in 76% yield (Scheme 2). This cycloisomeriza-
tion can be coupled with several of the propargylamide
syntheses (5a–d),‡ providing a one pot method to assemble
oxazoles from four separate units.
Figure 2. CuI/BF3 catalyzed synthesis of 4a.
Figure 3. A one-pot synthesis of propargylamides from aldehydes, acid
chlorides, silylamide, and alkynes.
† The hexane solvent and other volatile byproducts were removed in vacuo
prior to the addition of the alkyne, catalyst, and base in acetonitrile.
‡ In the case of oxazole 5c, the 5-benzylic position spontaneously oxidizes
in air giving a 5-aroyloxazole.

D. A. Black, B. A. Arndtsen / Tetrahedron 61 (2005) 11317–11321
11319
was stirred at 65 8C for 14 h, the solvent was removed in
vacuo, and the crude product was purified with column
chromatography using ethyl acetate/hexanes as eluent.
4.2.1. N-(3-phenyl-1-p-tolyl-prop-2-ynyl)-benzamide 4a.
Isolated yield: 80%. H NMR (300 MHz, 25 8C, CDCl3): d
1
7.80 (d, 2H, JZ7.8 Hz), 7.58–7.37 (m, 7H), 7.30 (d, 3H, JZ
8.7 Hz), 7.23–7.17 (d, 2H, JZ11.7 Hz), 6.84 (d, 1H, JZ
8.4 Hz), 6.45 (d, 1H, JZ8.4 Hz), 2.40 (s, 3H). 13C NMR
(75.5 MHz, 25 8C, CDCl3): d 166.3, 138.2, 136.4, 134.1,
132.1, 132.0, 129.7, 128.8, 128.7, 128.5, 127.4, 127.3,
122.8, 87.5, 85.1, 45.8, 21.6. nmax (KBr): 3236 (N–H), 1631
(C]O). HRMS for C23H19NO, calculated: 325.1467,
found: 325.1458.
Scheme 2. Four-component synthesis of oxazoles.
3. Conclusions
In conclusion, we have developed a metal catalyzed
multicomponent synthesis of secondary propargylamides
from trimethylsilyl-substituted imines, alkynes, and acid
chlorides. These processes rely upon the in situ generation
of N-acylimines and metal-acetylides, which in the presence
of either BF3 (with copper-acetylides), or with the use of
nucleophilic zinc(II)-acetylides, couple in a catalytic
fashion. By combining this process with the cyclo-
isomerization of the secondary propargylamide product, a
modular method to assemble oxazoles in a single pot can be
generated. The application of this chemistry to other
secondary propargylamide targets is currently underway.
4.2.2. N-(1-tert-butyl-hept-2-ynyl)-benzamide 4b. Iso-
lated yield: 88%. H NMR (300 MHz, 25 8C, CDCl3): d
1
7.80–7.72 (m, 2H), 7.49–7.36 (m, 3H), 6.20 (d, 1H, JZ
8.7 Hz), 4.80 (dd, 1H, JZ1.5, 8.7 Hz), 2.18 (t, 2H, JZ
6.6 Hz), 1.55–1.37 (m, 4H), 1.06 (s, 9H), 0.92 (t, 3H,
JZ6.6 Hz). 13C NMR (75.5 MHz, 60 8C, CDCl3): d 166.7,
134.8, 131.7, 128.8, 127.2, 84.5, 78.3, 51.4, 36.4, 31.2, 26.4,
22.3, 18.7, 14.0. nmax (KBr): 3267 (N–H), 1634 (C]O).
HRMS for C18H25NO, calculated: 271.1936, found:
271.1932.
4.2.3. N-(3-phenyl-1-p-tolyl-prop-2-ynyl)-acrylamide 4c.
Isolated yield: 57%. H NMR (300 MHz, 25 8C, CDCl3): d
1
7.48–7.43 (m, 4H), 7.39–7.28 (m, 3H), 7.18 (d, 2H, JZ
7.8 Hz), 6.43–6.29 (m, 2H), 6.21–6.07 (m, 2H), 5.69 (dd,
1H, JZ1.5, 8.7 Hz), 2.39 (s, 3H). 13C NMR (75.5 MHz,
25 8C, CDCl3): d 164.1, 138.0, 136.0, 131.8, 130.3, 129.4,
128.5, 128.3, 127.4, 127.1, 122.5, 87.0, 84.8, 44.9, 21.1.
nmax (KBr): 3274 (N–H), 1656 (C]O). HRMS for
C19H17NO, calculated: 275.1310, found: 275.1304.
4. Experimental
4.1. General
Unless otherwise noted, all manipulations were performed
under an inert atmosphere in a vacuum atmospheres 553-2
dry box or by using standard Schlenk or vacuum line
techniques. All reagents were purchased from Aldrichw and
used as received. Acetonitrile was distilled from CaH2 under
nitrogen. Deuterated acetonitrile was dried as its protonated
analogue, but was transferred under vacuum from the drying
agent, and stored over 4 A molecular sieves. H and 13C
˚
NMR spectra were recorded on JEOL 270, Varian Mercury
300 MHz, and Mercury 400 MHz spectrometers. Mass
spectra were obtained from the McGill University mass
spectral facilities.
4.2.4. N-[1-(4-methoxy-phenyl)-3-phenyl-prop-2-ynyl]-
isobutyramide 4d. Isolated yield: 92%. 1H NMR
(300 MHz, 25 8C, CDCl3): d 7.53–7.41 (m, 4H), 7.36–7.29
(m, 3H), 6.90 (d, 2H, JZ8.4 Hz), 6.22 (d, 1H, JZ8.4 Hz),
6.07 (d, 1H, JZ8.4 Hz), 3.82 (s, 3H), 2.49–2.35 (m, 1H),
1.24–1.17 (m, 6H). 13C NMR (75.5 MHz, 25 8C, CDCl3): d
175.6, 159.5, 132.0, 131.7, 128.7, 128.5, 128.5, 122.8,
114.3, 87.7, 84.8, 55.6, 44.7, 35.9, 19.9, 19.7. nmax (KBr):
3304 (N–H), 1640 (C]O). HRMS for C20H21NO2,
calculated: 307.1572, found: 307.1581.
1
4.2. Representative procedure for preparation of 4a–e
4.2.5. N-(1-tert-butyl-hept-2-ynyl)-4-methoxy-benzamide
4e. Isolated yield: 87%. 1H NMR (270 MHz, 25 8C, CDCl3):
d 7.70 (d, 2H, JZ8.7 Hz), 6.86 (d, 2H, JZ8.7 Hz), 6.19 (d,
1H, JZ9.6 Hz), 4.78 (d, 1H, JZ9.6 Hz), 3.82 (s, 3H), 2.18
(t, 3H, JZ6.6 Hz), 1.56–1.30 (m, 4H), 1.05 (s, 9H), 0.92 (t,
3H, JZ6.6 Hz). 13C NMR (75.5 MHz, 25 8C, CDCl3): d
170.9, 158.7, 137.5, 136.7, 136.6, 131.5, 129.4, 128.4,
128.3, 127.9, 127.7, 125.5, 113.4, 63.4, 54.5, 39.4, 19.4,
12.8. nmax (KBr): 3318 (N–H), 1629 (C]O). HRMS for
C19H27NO2, calculated: 301.2042, found: 301.2031.
To 1,1,1,3,3,3-hexamethyldisilazane (0.14 mL, 0.66 mmol)
in a 25 mL reaction bomb equipped with a stir bar in a 0 8C
ice bath, was added a 2.5 M solution of BuLi in hexanes
(0.25 mL, 0.66 mmol) over 10 min, under nitrogen.
Tolualdehyde (77 mg, 0.63 mmol) was then added over
1 h. The reaction was allowed to warm to ambient
temperature, acryloyl chloride (75 mg, 0.83 mmol) in
acetonitrile (3 mL) was added, and the mixture stirred for
30 min. The solvents and (TMS)2O were removed in vacuo,
the residue dissolved in acetonitrile (2 mL), and phenyl-
acetylene (65 mg, 0.63 mmol) in acetonitrile (1 mL),
copper(I) iodide (12 mg, 0.063 mmol) in acetonitrile
(2 mL), boron trifluoride diethyl etherate (18 mg,
0.126 mmol), and diisopropylethylamine (110 mL,
0.63 mmol) in acetonitrile (2 mL) were added. The mixture
4.3. Procedure for the preparation of 4f–j
An analogous procedure to the formation of 4a–e was
followed, except instead of adding CuI and boron
trifluoride, zinc(II) triflate (24 mg, 0.063 mmol) was added

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D. A. Black, B. A. Arndtsen / Tetrahedron 61 (2005) 11317–11321
as catalyst, and the mixture was stirred at ambient
temperature for 10 h. The solvent was removed in vacuo,
and the crude product purified by column chromatography
using ethyl acetate/hexanes as eluent.
was then quenched with 5 mL of methanol, the solvent
removed in vacuo, and the product purified by column
chromatography using ethyl acetate/hexanes as eluent.
4.4.1. 5-Benzyl-2-phenyl-4-p-tolyl-oxazole 5a. Isolated
yield: 76%. H NMR (300 MHz, 25 8C, CDCl3): d 8.11 (d,
4.3.1. N-[1-(4-methoxy-phenyl)-3-phenyl-prop-2-ynyl]-
2,2-dimethyl-propionamide 4f. Isolated yield: 73%. 1H
NMR (300 MHz, 25 8C, CDCl3): d 7.47 (d, 4H, JZ6.9 Hz),
7.36–7.31 (m, 3H), 6.89 (d, 2H, JZ8.7 Hz), 6.22 (s, 2H),
3.80 (s, 3H), 1.26 (s, 9H). 13C NMR (75.5 MHz, 25 8C,
CDCl3): d 177.2, 159.5, 132.0, 131.7, 128.7, 128.5, 128.4,
122.8, 114.2, 87.9, 84.8, 55.6, 44.9, 39.1, 27.8. nmax (KBr):
3409 (N–H), 1648 (C]O). HRMS for C21H23NO2,
calculated: 321.1729, found: 321.1739.
1
2H, JZ6.6 Hz), 7.68 (d, 2H, JZ8.4 Hz), 7.52–7.21 (m,
10H), 4.36 (s, 2H), 2.42 (s, 3H). 13C NMR (75.5 MHz,
25 8C, CDCl3): d 160.2, 145.4, 137.7, 137.6, 137.5, 130.3,
129.6, 129.4, 129.0, 128.9, 128.5, 127.9, 127.1, 127.0,
126.5, 32.4, 21.7. nmax (KBr): 2964, 1604, 1555, 1495, 1262,
1100. HRMS calculated for C23H19NO, calculated:
325.1467, found: 325.1457.
4.3.2. N-(1-tert-butyl-3-phenyl-prop-2-ynyl)-4-iodo-
benzamide 4g. Isolated yield: 67%. H NMR (300 MHz,
4.4.2. 5-Benzyl-2-isopropyl-4-p-tolyl-oxazole 5b. Isolated
yield: 82%. H NMR (300 MHz, 25 8C, CDCl3): d 7.57 (d,
1
1
25 8C, CDCl3): d 7.80 (d, 2H, JZ8.4 Hz), 7.51 (d, 2H, JZ
8.4 Hz), 7.45–7.38 (m, 2H), 7.33–7.25 (m, 3H), 6.23 (d, 1H,
JZ9.6 Hz), 5.06 (dd, 1H, JZ3.6, 6.0 Hz), 1.17 (s, 9H).
13C NMR (75.5 MHz, 25 8C, CDCl3): d 165.9, 137.8,
133.8, 131.7, 128.6, 128.4, 128.3, 122.6, 98.6, 87.2, 84.0,
51.4, 36.3, 26.1. nmax (KBr): 3296 (N–H), 1645 (C]O).
HRMS for C20H20NOI, calculated: 417.0590, found:
417.0580.
2H, JZ8.4 Hz), 7.36–7.17 (m, 7H), 4.21 (s, 2H), 3.20–3.04
(m, 1H), 2.39 (s, 3H), 1.40 (d, 6H, JZ6.9 Hz). 13C NMR
(75.5 MHz, 25 8C, CDCl3): d 167.6, 144.4, 137.8, 137.3,
135.6, 129.7, 129.5, 128.9, 128.4, 127.0, 126.8, 32.2, 28.9,
21.7, 21.0. nmax (KBr): 2972, 1659, 1611, 1413, 1286, 1178.
HRMS for C20H21NO, calculated: 291.1623, found:
291.1627.
4.4.3. (2-Isobutyl-4-phenyl-oxazol-5-yl)-phenyl-metha-
none 5c. Isolated yield: 79%. H NMR (300 MHz, 25 8C,
4.3.3. N-(4-hydroxy-1-p-tolyl-but-2-ynyl)-benzamide 4h.
Isolated yield: 62%. H NMR (270 MHz, 20 8C, CDCl3): d
1
1
7.71 (d, 2H, JZ6.3 Hz), 7.50–7.29 (m, 5H), 7.11 (d, 2H, JZ
6.3 Hz), 6.62 (d, 1H, JZ9.4 Hz), 6.51 (d, 1H, JZ9.4 Hz),
4.33 (dd, 2H, JZ3.2, 13.4 Hz), 2.37–2.22 (m, 4H). 13C
NMR (68.0 MHz, 20 8C, CDCl3): d 167.2, 138.5, 135.8,
133.6, 132.0, 129.3, 128.6, 127.1, 125.9, 80.0, 79.7, 74.4,
56.2, 21.1. nmax (KBr): 3272 (N–H), 1648 (C]O). HRMS
for, calculated: 279.1259, found: 279.1265.
CDCl3): d 8.00–7.92 (m, 2H), 7.85 (d, 2H, JZ8.4 Hz),
7.56–7.48 (m, 1H), 7.44–7.34 (m, 5H), 2.80 (d, 2H, JZ
7.2 Hz), 2.38–2.23 (m, 1H), 1.08 (d, 6H, JZ4.2 Hz). 13C
NMR (75.5 MHz, 25 8C, CDCl3): d 183.4, 165.9, 147.7,
143.7, 137.6, 133.0, 130.9, 129.8, 129.7, 129.4, 128.5,
128.4, 37.6, 28.0, 22.8. nmax (KBr): 2959, 1651, 1557, 1486,
1447, 1232, 1145. HRMS calculated for C20H19NO2,
calculated: 305.1416, found: 305.1408.
4.3.4. N-(1,3-diphenyl-prop-2-ynyl)-3-methyl-butyr-
amide 4i. Isolated yield: 91%. H NMR (300 MHz, 25 8C,
1
4.4.4. 5-Benzyl-2-isopropyl-4-(4-methoxy-phenyl)-oxa-
zole 5d. Isolated yield: 85%. H NMR (300 MHz, 25 8C,
CDCl3): d 7.57 (d, 2H, JZ6.3 Hz), 7.50–7.39 (m, 2H),
7.38–7.23 (m, 6H), 6.51 (d, 1H, JZ8.4 Hz), 6.29 (d, 1H, JZ
8.4 Hz), 2.30–2.08 (m, 3H), 1.00 (m, 6H). 13C NMR (75.5
MHz, 25 8C, CDCl3): d 171.6, 139.4, 132.0, 128.9, 128.7,
128.5, 128.2, 127.3, 122.8, 87.6, 84.9, 46.1, 45.3, 26.7, 22.9.
nmax (KBr): 3308 (N–H), 1641 (C]O). HRMS for
C20H21NO, calculated: 291.1623, found: 291.1621.
1
CDCl3): d 7.56 (d, 2H, JZ8.4 Hz), 7.36–7.18 (m, 5H), 6.91
(d, 2H, JZ8.4 Hz), 4.20 (s, 2H), 3.81 (s, 3H), 3.18–3.03 (m,
1H), 1.40 (d, 6H, JZ6.9 Hz). 13C NMR (75.5 MHz, 25 8C,
CDCl3): d 167.5, 159.1, 143.9, 137.9, 135.4, 128.9, 128.4,
126.8, 125.2, 114.3, 55.6, 32.1, 28.9, 21.0. nmax (KBr): 2971,
1605, 1583, 1512, 1495, 1454, 1303, 1251, 1174. HRMS
calculated forC20H21NO2, calculated: 307.1572, found:
307.1570.
4.3.5. N-(1,3-diphenyl-prop-2-ynyl)-benzamide 4j.
Isolated yield: 89%. H NMR (300 MHz, 80 8C, CD3CN):
1
d 7.83 (d, 2H, JZ8.4 Hz), 7.66 (d, 2H, JZ8.4 Hz), 7.52–
7.30 (m, 11H), 6.76 (d, 1H, JZ8.4 Hz), 6.50 (d, 1H, JZ
8.4 Hz). 13C NMR (75.5 MHz, 25 8C, CDCl3): d 166.3,
139.4, 134.2, 132.0, 131.9, 129.0, 128.8, 128.7, 128.5,
128.3, 127.4, 127.3, 122.8, 87.4, 85.4, 46.1. nmax (KBr):
3290 (N–H), 1633 (C]O). HRMS for C22H17NO,
calculated: 311.1310, found: 311.1302.
Supplementary material
1H and 13C NMR spectra of compounds 4a–j and 5a–d.
Supplementary data associated with this article can be found
in the online version at doi:10.1016/j.tet.2005.09.096.
4.4. Representative procedure for the preparation of
oxazoles 5a–c
Acknowledgements
Upon completion of either the copper or zinc catalyzed
synthesis of the propargylamides, before removal of solvent,
NaH (7.2 mg, 0.31 mmol) in 2 mL of acetonitrile was added
and the reaction mixture was stirred for 30 min. The mixture
We thank NSERC and FQRNT for funding. D. A. B. thanks
McGill for postgraduate funding.

D. A. Black, B. A. Arndtsen / Tetrahedron 61 (2005) 11317–11321
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