Tertiary amines as synthetic equivalents of vinyl cations: Zinc bromide promoted coupling of propargylamines with α-isocyanoacetamides to give 2,4,5-trisubstituted oxazoles initiated by an internal redox process

Article abstract of DOI:10.1002/chem.201302106

Crabee interrupted: Propargylamines 1 react with α-isocyanoacetamides 2 in the presence of zinc bromide to afford vinyl oxazoles 3. The transformation, wherein the propargylamine acts as a vinyl cation synthetic equivalent, involves a domino sequence incorporating a 1,5-hydride shift, intermolecular trapping/cyclization, and a 1,6-elimination (see scheme). Copyright

Full text of DOI:10.1002/chem.201302106

COMMUNICATION
DOI: 10.1002/chem.201302106
Tertiary Amines as Synthetic Equivalents of Vinyl Cations: Zinc Bromide
Promoted Coupling of Propargylamines with a-Isocyanoacetamides to Give
2,4,5-Trisubstituted Oxazoles Initiated by an Internal Redox Process
Yann Odabachian, Qian Wang, and Jieping Zhu*[a]
The Crabbꢀ homologation allows the synthesis of allenes
from in situ generated propargylamines through a 1,5-hy-
can interrupt the Crabbꢀ homologation leading to 2-vinyl
oxazoles 3 by an unprecedented domino 1,5-hydride shift/in-
dride
shift/1,2-elimination
sequence
(Equation (1),
termolecular
trapping/cyclization/elimination
sequence
Scheme 1).[1] Initially developed for the synthesis of mono-
substituted allenes, reaction conditions have now been es-
(Equation (3), Scheme 1). In this transformation, propargyl-
amine 1 acts formally as a synthetic equivalent of a vinyl
cation.[8] We note that a vinyl anion can be easily generated
from tosylhydrazone in the presence of a strong base and is
widely used in organic synthesis (the Shapiro reaction;
Equation (4), Scheme 1).[9] However, to the best of our
knowledge, the use of tertiary aliphatic amines as vinyl
cation synthetic equivalents has not yet been reported.[10]
We began our studies by investigating the reaction be-
tween N,N-diisopropylprop-2-yn-1-amine (1a) and a-isocya-
noacetamide 2a[11] in the presence of different metal salts. It
was found that neither CuI nor ZnACTHNUTRGNENUG(OTf)2 was able to pro-
mote the reaction. However, in the presence of a catalytic
amount of ZnBr2, the reaction produced a small amount of
unexpected 2-vinyl oxazole 3a (Table 1).[12] Intrigued by the
mechanism of this unprecedented reaction and the impor-
tance of oxazoles in natural product and medicinal chemis-
try,[13] the reaction conditions were optimized by varying the
amount of ZnBr2, the solvent, the temperature, and the ad-
ditives. Using the optimized reaction conditions—1a
(1.0 equiv, 0.1M), 2a (2.0 equiv), ZnBr2 (1.5 equiv), toluene,
reflux—oxazole 3a was isolated in 74% yield (Table 1). The
use of a stoichiometric amount of ZnBr2 was necessary for
the success of this transformation, the requirement originat-
Scheme 1. Tertiary propargylamine as a synthetic equivalent of a vinyl
cation: synthesis of 2-vinyl oxazoles.
tablished allowing access to di- and trisubstituted allenes.[2–3]
A recent important discovery came from the research group
of Nakamura who reported the first examples of intermolec-
ular nucleophilic trapping of incipient iminium intermediate
A for the synthesis of N-tethered 1,6-enynes C (Equa-
tion (2), Scheme 1).[4] Although there is recent interest in
the domino 1,5-hydride shift/cyclization of zwitterionic inter-
mediates,[5] examples of using an external nucleophile to
trap the cationic intermediate resulting from intramolecular
hydride shift are rare.[4,6–7] We report herein that isonitriles
ing from product inhibition, oxazoles being known to coor-
[14]
dinate strongly to Zn2+
.
Using 2a as the isocyanide component, the scope of the
tertiary amine was first examined (Table 1). In the case of
N-(pentan-3-yl)-N-(prop-2-yn-1-yl)pentan-3-amine (1b),
a
mixture of two stereoisomers was obtained in 74% yield in
favor of the Z isomer. With N-(sec-butyl)-N-(prop-2-yn-1-
yl)butan-2-amine (1c), less-substituted terminal olefin 3c
was formed together with a small amount of internal alkene
3c’ (3c/3c’, 10:1). Therefore, the regioselectivity of olefin
formation follows the Hofmann rule. Dicycloalkylpropargyl-
amines 1d–1g participated in this reaction without problems
to afford the corresponding products, namely, cyclopent-1-
en-1-yl, cyclohex-1-en-1-yl, cyclohept-1-en-1-yl, and cyclo-
oct-1-en-1-yl oxazoles (3d–g), respectively, in good yields.
Notably, the reaction also worked with N-methyl-propargyl-
amines 1h–1j. In accordance with the notion that a tertiary
[a] Dr. Y. Odabachian, Dr. Q. Wang, Prof. Dr. J. Zhu
Institute of Chemical Sciences and Engineering
Ecole Polytechnique Fꢀdꢀrale de Lausanne
EPFL-SB-ISIC-LSPN, BCH 5304, 1015 Lausanne (Switzerland)
Fax : (+41)21-6939740
E-mail: jieping.zhu@epfl.ch
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201302106.
À
À
C H bond is a better hydride donor than a primary C H
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Table 1. Scope of the propargylamine component.
Table 2. Scope of the a-isocyanoacetamide component.
[a] 1 (0.10 mmol, 0.1m),
1008C. [b] Reactions were carried out with 3.0 equiv of the isocyanoacet-
AHCTUNGTREaNGNUN mide, either 2i or 2j, and 1.5 equiv of ZnBr2.
2 (0.20 mmol), ZnBr2 (0.15 mmol), toluene,
The scope of a-isocyanoacetamides 2 was next examined
(Table 2). Benzyl, alkyl, and aryl substituents with different
electronic properties at the a position of a-isocyanoacet-
AHCTUNGTREGaNNNU mides 2 were well tolerated, thus affording oxazoles 3k–3r
in good yields. However, a large excess (3.0 equiv) of 2i and
2j was required owing to their facile ring-chain isomeriza-
tion leading to C-2 unsubstituted 5-aminooxazole 4. The re-
action was also attempted with methyl a-(4-nitrophenyl)-a-
isocyanoacetate,[16] but no desired product was isolated.
It is known that the structure of the secondary amine in-
fluences the efficiency of the Crabbꢀ homologation,[17] al-
though it was previously impossible to quantitatively evalu-
ate the hydride-donor capability of the two N-alkyl groups.
À
Because only one of the two N Calkyl groups in the propar-
gylamine component was cleaved in our reaction, it provid-
ed a unique opportunity for us to quantify the hydride-trans-
fer capability of the N-alkyl groups by an internal competi-
tion experiment. Two propargylamines bearing two different
a-tertiary alkyl groups (1k and 1l) were therefore prepared.
Whereas the reaction of 1k with 2a under the standard re-
action conditions afforded cyclohex-1-en-1-yl oxazole 3e
and isopropenyl oxazole 3a in a 6:1 ratio, the reaction of 1l
with 2a afforded 2-(cyclopent-1-en-1-yl)oxazole 3d and 2-
(cyclohex-1-en-1-yl) oxazole 3e in 60% and 14% yields
(3d/3e, 4.3:1), respectively (Scheme 2). Therefore, the hy-
dride-donor ability of a-tertiary alkyl groups was deter-
mined to be as follows: cyclopentyl>cyclohexyl>isopropyl.
To gain mechanistic insights on this transformation, deu-
terated substrates [D1]-5, [D2]-5, 6, and 7 were prepared.
Reaction of [D1]-5 with 2a followed by acylation produced
N-allyl-N-cyclohexyl acetamide 8a and 8a’ with 24% deute-
rium incorporation (KH/KD =3:1) at the terminal carbon of
olefin 8aꢀ (Equation (1), Scheme 3). No doubly deuterated
allylamine was detected by mass spectrometry, thus indicat-
[a] 1 (0.10 mmol, 0.1m), 2a (0.20 mmol), ZnBr2 (0.15 mmol), toluene
1008C. [b] Reactions were carried out with 3.0 equiv of the isocyanoacet-
ACHTUNGTRENNUNGamide 2a and 1.5 equiv of ZnBr2. [c] Reactions were carried out with
5.0 equiv of the isocyanoacetamide 2a and 5.0 equiv of ZnBr2. [d] Togeth-
er with an inseparable 3,4-unsaturated isomer (5:1).
bond, the a-hydrogen atom of the more substituted N-alkyl
group was transferred preferentially, thus providing more
functionalized alkenes 3h–3j exclusively. Notably, oxazoles
3i and 3j, which incorporate a steroid skeleton and are
known to be potent P45017a inhibitors, were prepared with
ease.[15]
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Tertiary Amines as Synthetic Equivalents of Vinyl Cations
COMMUNICATION
ment involving 1e and [D2]-5 with 2a provided a KIE of 2:1
(Equation (3), Scheme 3). This result indicated that the 1,5-
hydride shift was the rate-limiting step of the domino pro-
AHCTUNGTREGcNNNU ess. Finally, deuterium was lost to a great extent (95%)
when compound 6 was submitted to the above reaction con-
ditions and no deuterium transfer from a-d-a-isocyanoacet-
AHCTUNGTREGaNNNU mide 7 to propargylamine 1e was observed (reaction con-
ditions: i) 1e (1.0 equiv), ZnBr2 (1.5 equiv), toluene, reflux;
ii) Ac2O, Et3N, CH2Cl2).
Two additional control experiments were performed as
follows. Firstly, reaction of authentic 5-aminooxazole 4a
(R=Bn, X=morpholinyl) with 1e under standard reaction
conditions did not produce 3e. Secondly, heating a toluene
solution of 2a in the presence of ZnBr2 (1.0 equiv) followed
by addition of a solution of 1e and ZnBr2 (0.5 equiv) also
failed to produce vinyl oxazole 3a. These results indicated
that neither oxazole 4a nor the corresponding oxazol-2-yl
zinc bromide was involved in the formation of 2-vinyl
oxazole.
Scheme 2. Competitive hydride-transfer reactions.
Based on the results of these control experiments, a possi-
ble reaction pathway leading to vinyl oxazoles 3 from prop-
argylamines 1 and a-isocyano acetamides 2 was proposed as
shown in Scheme 4. Formation of alkyne–ZnBr2 p complex I
Scheme 4. Possible reaction pathway leading to 3.
could lead to zinc acetylide II, thus accounting for the loss
of deuterium in 6, as observed in the control experiment.
Alternatively, the formation of I could trigger the 1,5-hy-
dride shift, thus leading to iminium ion III. Coordination of
vinyl zinc bromide to isocyanoacetamide to give IV would
facilitate the nucleophilic addition of isocyanide to the imi-
nium ion, thus leading to a nitrilium intermediate that could
cyclize to V.[18] It is apparent that this step outpaced the
elimination of imine, which leads to allene and is the normal
Crabbꢀ reaction pathway. We assumed that the formation of
Scheme 3. Deuterium labeling experiments. Conditions: i) 2a (2.0 equiv),
ZnBr2 (1.5 equiv), toluene, reflux; ii) Ac2O, Et3N, CH2Cl2.
ing that the redox process occurred exclusively in an intra-
molecular fashion. Further evidence in line with this conclu-
sion was obtained by a crossover experiment involving
mixing equimolar amounts of [D1]-5 and 1 f with 2a (Equa-
tion (2), Scheme 3). An intermolecular competition experi-
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J. Zhu et al.
[2] For recent examples, see: a) J. Kuang, S. Ma, J. Am. Chem. Soc.
2010, 132, 1786–1787; b) S. Kitagaki, M. Komizu, C. Mukai, Synlett
2011, 1129–1132; c) J. Kuang, H. Luo, S. Ma, Adv. Synth. Catal.
2012, 354, 933–944; d) M. Periasamy, N. Sanjeevakumar, M. Dalai,
R. Gurubrahamam, P. O. Reddy, Org. Lett. 2012, 14, 2932–2935;
e) J. Ye, S. Li, B. Chen, W. Fan, J. Kuang, J. Liu, Y. Liu, B. Miao, B.
Wan, Y. Wang, X. Xie, Q. Yu, W. Yuan, S. Ma, Org. Lett. 2012, 14,
1346–1349; f) J. Ye, W. Fan, S. Ma, Chem. Eur. J. 2013, 19, 716–720;
for a review, see: g) S. Yu, S. Ma, Chem. Commun. 2011, 47, 5384–
5418.
[3] For variations of the Crabbꢀ homologation, see: a) H. Nakamura, T.
Kamakura, M. Ishikura, J.-F. Biellmann, J. Am. Chem. Soc. 2004,
126, 5958–5959; b) V. K.-Y. Lo, M.-K. Wong, C.-M. Che, Org. Lett.
2008, 10, 517–519; c) V. K.-Y. Lo, C.-Y. Zhou, M.-K. Wong, C.-M.
Che, Chem. Commun. 2010, 46, 213–215; d) B. Bolte, Y. Odaba-
chian, F. Gagosz, J. Am. Chem. Soc. 2010, 132, 7294–7296.
complex IV was important for the success of the reaction. In
fact, control experiments indicated that reaction of 2a with
cyclohexanone and allylcyclohexylamine under our opti-
mized reaction conditions failed to produce vinyl oxazole
3e. Aromatization of V could then afford zinc bromide che-
lated oxazole VI. The coordination of the tertiary allylamine
to zinc bromide could also make it a potentially good leav-
ing group. Assisted by the lone pair of the 5-dialkylamino
group, 1,6-elimination of allylamine could occur to provide
VII that, upon proton transfer and isomerization, would be
converted into 5-amino-2-vinyloxazole 3, most probably co-
ordinated to ZnBr2.
In summary, we developed a novel synthesis of 2-vinyl-5-
aminooxazoles by a ZnBr2-promoted reaction between ter-
[4] T. Sugiishi, H. Nakamura, J. Am. Chem. Soc. 2012, 134, 2504–2507.
[5] For selected recent examples, see: a) S. J. Pastine, K. M. McQuaid,
D. Sames, J. Am. Chem. Soc. 2005, 127, 12180–12181; b) C. Zhang,
C. K. De, R. Mak, D. Seidel, J. Am. Chem. Soc. 2008, 130, 416–417;
c) L. Zheng, F. Yang, Q. Dang, X. Bai, Org. Lett. 2008, 10, 889–892;
d) P. A. Vadola, D. Sames, J. Am. Chem. Soc. 2009, 131, 16525–
16528; e) Y. K. Kang, S. M. Kim, D. Y. Kim, J. Am. Chem. Soc.
2010, 132, 11847–11849; f) I. D. Jurberg, Y. Odabachian, F. Gagosz,
J. Am. Chem. Soc. 2010, 132, 3543–3552; g) K. Mori, T. Kawasaki,
S. Sueoka, T. Akiyama, Org. Lett. 2010, 12, 1732–1735; h) G. Zhou,
J. Zhang, Chem. Commun. 2010, 46, 6593–6595; i) M. Alajarin, M.
Marin-Luna, A. Vidal, Adv. Synth. Catal. 2011, 353, 557–562; j) B.
Bolte, F. Gagosz, J. Am. Chem. Soc. 2011, 133, 7696–7699; k) K.
Mori, S. Sueoka, T. Akiyama, J. Am. Chem. Soc. 2011, 133, 2424–
2426; l) J. Barluenga, R. Sigꢂeiro, R. Vicente, A. Ballesteros, M.
Tomꢃs, M. A. Rodrꢄguez, Angew. Chem. 2012, 124, 10523–10527;
Angew. Chem. Int. Ed. 2012, 51, 10377–10381; m) D.-F. Chen, Z.-Y.
Han, Y.-P. He, J. Yu, L.-Z. Gong, Angew. Chem. 2012, 124, 12473–
12476; Angew. Chem. Int. Ed. 2012, 51, 12307–12310; n) L. Chen, L.
Zhang, J. Lv, J.-P. Cheng, S. Luo, Chem. Eur. J. 2012, 18, 8891–8895;
o) X. Gao, V. Gaddam, E. Altenhofer, R. R. Tata, Z. Cai, N. Yong-
pruksa, A. K. Garimallaprabhakaran, M. Harmata, Angew. Chem.
2012, 124, 7122–7125; Angew. Chem. Int. Ed. 2012, 51, 7016–7019;
p) Z.-W. Jiao, S.-Y. Zhang, C. He, Y.-Q. Tu, S.-H. Wang, F.-M.
Zhang, Y.-Q. Zhang, H. Li, Angew. Chem. 2012, 124, 8941–8945;
Angew. Chem. Int. Ed. 2012, 51, 8811–8815; q) K. Mori, T. Kawasa-
ki, T. Akiyama, Org. Lett. 2012, 14, 1436–1439; r) P. A. Vadola, I.
Carrera, D. Sames, J. Org. Chem. 2012, 77, 6689–6702; s) X.-F. Xia,
X.-R. Song, N. Wang, H.-L. Wei, X.-Y. Liu, Y.-M. Liang, RSC Adv.
2012, 2, 560–565; t) C. Ma, Z.-J. Jia, J.-X. Liu, Q.-Q. Zhou, L.
Dong, Y.-C. Chen, Angew. Chem. 2013, 125, 982–985; Angew.
Chem. Int. Ed. 2013, 52, 948–951.
ACHTUNGTRENNUNGtiary propargylamines and a-isocyanoacetamides. The reac-
tion went through an unprecedented 1,5-hydride shift/inter-
molecular nucleophilic addition/cyclization/elimination se-
quence. The propargylamine formally serves as a synthetic
equivalent of a vinyl cation. The present domino process
represents a rare example of an interrupted Crabbꢀ reaction
wherein the in situ generated iminium salt is trapped by an
external nucleophile.
Experimental Section
General procedure:
A suspension of propargylamine 1a (0.1 mmol,
0.1m), isocyanoacetamide 2a (0.2 mmol, 2.0 equiv), and zinc bromide
(0.15 mmol, 1.5 equiv) in toluene (1 mL) was heated to reflux under Ar.
After being stirred for 6 h, the reaction mixture was cooled to room tem-
perature and was quenched by addition of aqueous K2CO3. The aqueous
phase was extracted with CH2Cl2. The combined organic layers were
washed with brine, dried over Na2SO4, and concentrated in vacuo. The
crude material was purified by flash chromatography (silica gel; petrole-
um ether/AcOEt, 93:7) to give desired oxazole 3a (21.0 mg, 74% yield).
1H NMR (400 MHz, CDCl3): d=7.35–7.24 (m, 4H), 7.23–7.16 (m, 1H),
5.80–5.75 (m, 1H), 5.27 (quintet, J=1.4 Hz, 1H), 3.87 (s, 2H), 3.74–3.69
(m, 4H), 3.05–2.97 (m, 4H), 2.12 (dd, J=1.4, 1.0 Hz, 3H); 13C NMR
(100 MHz, CDCl3): d=156.9, 151.6, 139.6, 131.9, 128.5, 128.3, 126.1,
˜
125.3, 116.3, 66.8, 50.8, 32.0, 18.7; IR (ATR-IR: n=2959, 2916, 2853,
1652, 1621, 1453, 1116, 917 cmÀ1
; HRMS (ESI): m/z calcd for
C17H21N2O2+: 285.1598 [M+H+]; found: 285.1595.
[6] For an example of intermolecular nucleophilic trapping of in situ
generated 1,3-dipoles, see: D. Das, A. X. Sun, D. Seidel, Angew.
Chem. 2013, 125, 3853–3857; Angew. Chem. Int. Ed. 2013, 52, 3765–
3769.
[7] For a sequence involving a 1,5-hydride shift, cyclization, and ring
opening by an external nucleophile, see: I. D. Jurberg, B. Peng, E.
Wçstefeld, M. Wasserloos, N. Maulide, Angew. Chem. 2012, 124,
1986–1989; Angew. Chem. Int. Ed. 2012, 51, 1950–1953.
Acknowledgements
We thank EPFL, Swiss National Science Foundation (SNSF) and Swiss
National Centers of Competence in Research (NCCR) for financial
support.
[8] For the development of propargylamine as a donor of acetylide, see:
T. Sugiishi, A. Kimura, H. Nakamura, J. Am. Chem. Soc. 2010, 132,
5332–5333.
Keywords: Crabbꢀ homologation
· domino processes ·
[9] R. H. Shapiro, Org. React. 1976, 23, 405.
isonitriles · oxazoles · redox processes
[10] For the development of intramolecular vinyl transfer of N-benzyl-
N’-alkenyl urea in the presence of a strong base, see: J. Lefranc,
A. M. Fournier, G. Mingat, S. Herbert, T. Marcelli, J. Clayden, J.
Am. Chem. Soc. 2012, 134, 7286–7289.
[11] a) J. Zhu, Eur. J. Org. Chem. 2003, 1133–1144; b) A. Dçmling,
Chem. Rev. 2006, 106, 17–89; c) L. El Kaim, L. Grimaud, Tetrahe-
dron 2009, 65, 2153–2171; d) A. V. Gulevich, A. G. Zhdanko, R. V.
Orru, V. G. Nenajdenko, Chem. Rev. 2010, 110, 5235–5331.
[1] a) P. Crabbꢀ, H. Fillion, D. Andrꢀ, J.-L. Luche, J. Chem. Soc. Chem.
Commun. 1979, 859–860; b) H. Fillion, D. Andrꢀ, J.-L. Luche, Tetra-
hedron Lett. 1980, 21, 929–930; c) S. Searles, Y. Li, B. Nassim, M.-
T. R. Lopes, P. T. Tran, P. Crabbꢀ, J. Chem. Soc. Perkin Trans. 1
1984, 747–751.
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Tertiary Amines as Synthetic Equivalents of Vinyl Cations
COMMUNICATION
[12] For recent examples of oxazole synthesis, see: a) S. X. Wang, M. X.
Wang, D. X. Wang, J. Zhu, Org. Lett. 2007, 9, 3615–3618; b) N.
Elders, E. Ruijter, F. J. J. de Kanter, R. V. A. Orru, Chem. Eur. J.
2008, 14, 4961–4973; c) T. Yue, M.-X. Wang, D.-X. Wang, G.
Masson, J. Zhu, J. Org. Chem. 2009, 74, 8396–8399; d) J. Zhang, P.-
Y. Coqueron, J.-P. Vors, M. A. Ciufolini, Org. Lett. 2010, 12, 3942–
3945; e) J. Wu, W. Chen, M. Hu, H. Zou, Y. Yu, Org. Lett. 2010, 12,
616–619; f) R. Mossetti, T. Pirali, G. C. Tron, J. Zhu, Org. Lett.
2010, 12, 820–823; g) J. P. Weyrauch, A. S. K. Hashmi, A. Schuster,
T. Hengst, S. Schetter, A. Littmann, M. Rudolph, M. Hamzic, J.
Visus, F. Rominger, W. Frey, J. W. Bats, Chem. Eur. J. 2010, 16, 956–
963; h) I. Cano, E. Alvarez, M. C. Nicasio, P. J. Pꢀrez, J. Am. Chem.
Soc. 2011, 133, 191–193; i) P. W. Davies, A. Cremonesi, L. Dumitres-
cu, Angew. Chem. 2011, 123, 9093–9097; Angew. Chem. Int. Ed.
2011, 50, 8931–8935; j) Y. Li, X. Xu, J. Tan, C. Xia, D. Zhang, Q.
Liu, J. Am. Chem. Soc. 2011, 133, 1775–1777; k) C. Lalli, M. J.
Bouma, D. Bonne, G. Masson, J. Zhu, Chem. Eur. J. 2011, 17, 880–
889; l) T. Lechel, M. Gerhard, D. Trawny, B. Brusilowskij, L. Schef-
zig, R. Zimmer, D. Lentz, C. A. Schalley, H.-U. Reissig, Chem. Eur.
J. 2011, 17, 7480–7491; m) S. V. Kumar, B. Saraiah, N. C. Misra, H.
Ila, J. Org. Chem. 2012, 77, 10752–10763; n) C. L. Zhong, B. Y.
Tang, P. Yin, Y. Chen, L. He, J. Org. Chem. 2012, 77, 4271–4277;
o) L. El Kaꢅm, L. Grimaud, P. Patil, Synlett 2012, 1361–1363; p) Y.
Luo, K. Ji, Y. Li, L. Zhang, J. Am. Chem. Soc. 2012, 134, 17412–
17415; q) X. Xu, P. Y. Zavalij, W. Hu, M. P. Doyle, Chem. Commun.
2012, 48, 11522–11524; r) A. Y. Shaw, Z. Xu, C. Hulme, Tetrahedron
Lett. 2012, 53, 1998–2000; s) Z. Xu, C. Zhang, N. Jiao, Angew.
Chem. 2012, 124, 11529–11532; Angew. Chem. Int. Ed. 2012, 51,
11367–11370; t) X. Li, L. Huang, H. Chen, W. Wu, H. Huang, H.
Jiang, Chem. Sci. 2012, 3, 3463–3467.
[13] a) P. Wipf, Chem. Rev. 1995, 95, 2115–2134; b) V. S. C. Yeh, Tetrahe-
dron 2004, 60, 11995–12042; c) Z. Jin, Nat. Prod. Rep. 2011, 28,
1143–1191; d) J. Zhang, P.-Y. Coqueron, M. A. Ciufolini, Heterocy-
cles 2011, 82, 949–980.
[14] a) R. C. Jones, M. W. Chojnacka, J. W. Quail, M. G. Gardiner, A.
Decken, B. F. Yates, R. A. Gossage, Dalton Trans. 2011, 40, 1594–
1600; b) M.-T. Chen, C.-T. Chen, Dalton Trans. 2011, 40, 12886–
12894.
[15] N. Zhu, Y. Ling, X. Lei, V. Handratta, A. M. H. Brodie, Steroids
2003, 68, 603–611.
[16] D. Bonne, M. Dekhane, J. Zhu, Angew. Chem. 2007, 119, 2537–
2540; Angew. Chem. Int. Ed. 2007, 46, 2485–2488.
[17] a) H. Nakamura, M. Ishikura, T. Sugiishi, T. Kamakura, J.-F. Biell-
mann, Org. Biomol. Chem. 2008, 6, 1471–1477; b) J. Kuang, S. Ma,
J. Org. Chem. 2009, 74, 1763–1765.
[18] a) P. Janvier, X. Sun, H. Bienaymꢀ, J. Zhu, J. Am. Chem. Soc. 2002,
124, 2560–2567; b) R. Gꢃmez-MontaÇo, E. Gonzꢃlez-Zamora, P.
Potier, J. Zhu, Tetrahedron 2002, 58, 6351–6358; c) A. Fayol, J. Zhu,
Org. Lett. 2004, 6, 115–118; d) A. Fayol, J. Zhu, Org. Lett. 2005, 7,
239–242; e) S. Wang, M.-X. Wang, D.-X. Wang, J. Zhu, Eur. J. Org.
Chem. 2007, 4076–4080.
Received: June 3, 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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J. Zhu et al.
Coupling Reactions
Y. Odabachian, Q. Wang,
J. Zhu* ......................... &&&& — &&&&
Tertiary Amines as Synthetic Equiva-
lents of Vinyl Cations: Zinc Bromide
Promoted Coupling of Propargyla-
mines with a-Isocyanoacetamides to
Give 2,4,5-Trisubstituted Oxazoles
Initiated by an Internal Redox Process
Crabꢁe interrupted: Propargylamines 1
react with a-isocyanoacetamides 2 in
the presence of zinc bromide to afford
vinyl oxazoles 3. The transformation,
wherein the propargylamine acts as a
vinyl cation synthetic equivalent,
involves a domino sequence incorpo-
rating a 1,5-hydride shift, intermolecu-
lar trapping/cyclization, and a 1,6-elim-
ination (see scheme).
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ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 0000, 00, 0 – 0
ÝÝ
These are not the final page numbers!