Synthesis of Imidazoles and Pyrimidines Using Palladium-Catalyzed Decarboxylative Intramolecular Condensation of 1,2,4-Oxadiazol-5(4 H)-ones

Article abstract of DOI:10.1055/s-0034-1378320

We found that 1,2,4-oxadiazol-5(4H)-ones acted as iminonitrene equivalents in the presence of a palladium catalyst and a stoichiometric amount of phosphine and that aza-Wittig-type condensation with the internal carbonyl moiety occurred to afford the corresponding imidazoles and pyrimidines. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0034-1378320

1916▌
LETTER
lSetyternthesis of Imidazoles and Pyrimidines Using Palladium-Catalyzed Decar-
boxylative Intramolecular Condensation of 1,2,4-Oxadiazol-5(4H)-ones
Synthesis of Imidazoles and Pyrimidines
Takuya Shimbayashi, Kazuhiro Okamoto,* Kouichi Ohe*
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510,
Japan
Fax +81(75)3832499; E-mail: kokamoto@scl.kyoto-u.ac.jp; E-mail: ohe@scl.kyoto-u.ac.jp
Received: 07.05.2014; Accepted after revision: 13.05.2014
Abstract: We found that 1,2,4-oxadiazol-5(4H)-ones acted as imi-
nonitrene equivalents in the presence of a palladium catalyst and a
stoichiometric amount of phosphine and that aza-Wittig-type con-
densation with the internal carbonyl moiety occurred to afford the
corresponding imidazoles and pyrimidines.
Key words: imidazoles, palladium, decarboxylation, aza-Wittig re-
action
1,3-Diaza-heteroaromatic compounds, such as imidazoles
and pyrimidines, are known as one of the most important
classes of compounds, because they are commonly found
in a variety of natural products and pharmaceuticals. Be-
cause of the basicity and coordination ability of imidaz-
oles, they have been applied to functional materials, such
as chemical sensors and biologically active molecules.1
For several decades, much attention has been paid to the
development of transition-metal-catalyzed synthesis of
these heteroaromatics as novel or alternative methods.2
Recently, we have studied the transition-metal-catalyzed
reactions of nitrogen-containing heterocyclic compounds
involving nitrenoid species as intermediates. We have
found that isoxazol-5(4H)-ones (isoxazolones) act as
equivalents of vinylnitrene species under palladium catal-
ysis (Scheme 1). Alkene-tethered isoxazolones efficiently
underwent decarboxylative intramolecular aziridination
by a palladium–phosphine catalyst to afford the corre-
sponding fused aziridines (Scheme 1, a).3 Isoxazolones
Scheme 1 Palladium-catalyzed decarboxylative transformation of
nitrogen-containing five-membered molecules
also reacted with aldehydes in the presence of a palladium
catalyst and a stoichiometric amount of triphenylphos-
phine (Ph3P) to afford the 2-aza-1,3-dienes as products4
through intermolecular aza-Wittig-type condensation
(Scheme 1, b).5,6 We thus expected that 1,2,4-oxadiazol-
5(4H)-ones (oxadiazolones), possessing two nitrogen at-
oms in their heteroaromatic ring, would serve as iminoni-
trene precursors (Scheme 1, c).7 Herein, we report an
efficient synthetic method for imidazoles and pyrimidines
using palladium-catalyzed decarboxylative condensation
reactions of oxadiazolones bearing tethered carbonyl moi-
eties (Scheme 1, c).
N
N
2
PPh3
N
O
Pd(PPh3)4 (25 mol%)
Ph
Ph
N
dioxane, 100 °C, 4 h
O
Me
Me
1
detected by 1H and 31P NMR, MS.
Scheme 2
To confirm the generation of iminophosphorane species
from oxadiazolones, the reactivity of a simple oxadiazo-
lone toward a phosphine in the presence of a palladium
catalyst was examined as an initial attempt. When a solu-
tion of oxadiazolone 1 and Pd(PPh3)4 (25 mol%) in diox-
ane was reacted at 100 °C for 4 hours, 1 was almost fully
converted, and the generation of iminophosphorane 2 was
detected by NMR and mass spectrometry (Scheme 2). The
SYNLETT 2014, 25, 1916–1920
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DOI: 10.1055/s-0034-1378320; Art ID: st-2014-u0390-l
© Georg Thieme Verlag Stuttgart · New York

LETTER
Synthesis of Imidazoles and Pyrimidines
1917
formation of 2 did not occur at all either in the absence of on the meta or para position remains intact during the re-
Pd(PPh3)4 or in the presence of only Ph3P (without palla- action (4e and 4f). ortho-Substituted phenyl, 2-naphthyl,
dium), which indicates that iminophosphorane 2 was and 2-thienyl groups could be employed as substituent R1
formed by the initial palladium-catalyzed decarboxylation (4g–i). Oxadiazolones bearing various aromatic groups
of 1 followed by nitrene transfer from the generated ni- (4j–n) as well as primary, secondary, and tertiary alkyl
trene–palladium species to Ph3P.
groups (4o–q) attached on the R2 position are also appli-
cable to the present reaction. Secondary alkyl groups were
also compatible at the R1 position (4r and 4s). Triphenyl-
imidazole (4t; R1 = R2 = R3 = Ph) was also obtained in ex-
cellent yield.
N
N
R3
R2
Pd(PPh3)4 (3 mol%)
Ph3P (1.1 equiv)
O
O
R1
R2
N
R1
O
dioxane, 80 °C, 24–96 h
N
H
4
The present reaction was expanded successfully to the
gram-scale preparation of imidazoles, and the standard
palladium loading was enough for the formation of 1.05 g
of imidazole 4a in 88% yield (Scheme 4). Moreover, me-
ta- or para-phenylene-bridged bis(imidazole) derivatives
could be readily prepared using this method. Because tri-
phenylphosphine oxide (O=PPh3) was difficult to remove
from the reaction mixture, we applied the conditions with
the combination of CpPd(η3-C3H5) as a catalyst precursor
and triphenylphosphanemonosulfonic acid sodium salt
(tppms) as a condensation agent. The corresponding
bis(imidazole) derivatives 4u and 4v were obtained in
high yields (Scheme 5).
R3
3
Me
Ph
N
Ph
N
Ph
O
N
N
H
N
X
H
N
H
Me
4f 81%
4g 81%
4a X = H
99%
85%
97%
98%
95%
4b X = OMe
4c X = F
Ph
Ph
S
N
N
4d X = CO2Me
4e X = COMe
N
H
N
H
4h 95%
4i 67%a,b
X
N
N
Pd(PPh3)4 (3 mol%)
PPh3 (1.2 equiv)
O
Ph
N
N
Ph
Ph
Ph
O
dioxane, 80 °C, 67 h
N
N
O
N
H
N
H
Ph
Ph
O
F
4a 88% (1.05 g)
70%a,b
90%
N
N
H
4j X = OMe
4k X = Cl
Ph
H
3a (1.51 g, 5.4 mmol)
4m 92%a,b
4n 82%
4l X = CO2Et
97%
Scheme 4
Me
Cy
t-Bu
N
N
N
Ph
Ph
Ph
Ph
A proposed catalytic cycle for the present reaction is
shown in Scheme 6. First, oxadiazolone 3 oxidatively
adds to the low-valent palladium species to form pallada-
cycle A.9–11 Decarboxylation from A generates the palla-
dium–iminonitrene complex B.12 Another possible active
intermediate may be the four-membered diazapalladacy-
cle B′. When enough Ph3P exists in this system, imino-
phosphorane C is preferentially formed by fast nitrene
transfer from intermediate B or B′ to phosphine and un-
dergoes intramolecular aza-Wittig-type condensation ac-
companied with isomerization to afford imidazole 4 and
triphenylphosphine oxide (path a).13,14 Unlike the inter-
molecular condensation reaction starting from isoxazo-
lones, iminophosphorane species generated from the
combination of phosphine and more electron-deficient ni-
trene species are considered to be much more stable be-
cause the iminophosphorane species could be detected in
the reaction of simple oxadiazolone. Although the direct
intramolecular cyclization of intermediate B without the
formation of iminophosphorane C (path b) is also a possi-
ble alternative pathway, path a will be the major pathway
compared with path b for the above reason.15
N
N
H
N
H
H
4o 94%c
84%
4p
4q
80%
Ph
Ph
Ph
Ph
N
N
N
Cy
i-Pr
N
H
61%b
N
H
N
H
4r
4s 75%a,b
4t 93%
Scheme 3 Palladium-catalyzed decarboxylative intramolecular aza-
Wittig-type reaction of 1,2,4-oxadiazol-5-one 3 leading to imidazole
4. The reactions were carried out with oxadiazolones 3 (0.20 mmol),
Pd(PPh3)4 (3.0 mol%), and Ph3P (1.1 equiv) in 1,4-dioxane (1.5 mL).
a
Isolated yields are shown. Conditions: 5 mol% of Pd(PPh3)4 were
used. b At 100 °C. c CpPd(η3-C3H5) (3 mol%) and tppms (1.2 equiv)
were used instead of Pd(PPh3)4 and Ph3P.
As a result of various investigations of inter- and intramo-
lecular condensation reactions, we were pleased to find
that oxadiazolone bearing a ketone moiety (3a) underwent
intramolecular condensation in the presence of 3 mol% of
Pd(PPh3)4 and 1.1 equivalents of Ph3P to afford the corre-
sponding imidazole 4a quantitatively. This imidazole-
forming reaction also occurred effectively when oxadia-
zolones bearing various substituents were used (Scheme
3).8 para Substituents on the aromatic ring R1, such as me-
thoxy, fluoro, acetyl, and methoxycarbonyl groups, did
not affect the reaction efficiency (4b–e). A ketone moiety
When we examined the reactivity of substrate 5, in which
the oxadiazolone moiety and the ketone moiety are linked
with the vinylene tether, we found that the condensation
reaction proceeds under similar conditions to form the
© Georg Thieme Verlag Stuttgart · New York
Synlett 2014, 25, 1916–1920

1918
T. Shimbayashi et al.
LETTER
CpPd(η3-C3H5)
(6 mol%)
tppms
Ph
N
Ph
N
O
O
Ph
HN
Ph
NH
(2.4 equiv)
N
N
N
N
O
dioxane
80 °C, 90 h
O
4u 81%
O
O
3u
CpPd(η3-C3H5)
(6 mol%)
Ph
Ph
tppms
Ph
Ph
N
N
O
O
(2.4 equiv)
NH
HN
O
O
N
N
N
N
dioxane
80 °C, 90 h
O
O
3v
4v 96%
Scheme 5
R3
R2
N
N
O
R1
R1
R2
N
N
H
O
4
[Pd]
O
R3
PPh3
[Pd]
R3
N
3
oxidative
addition
R1
Ph3P
O
O
N
R2
N
N
[Pd]
O
R1
R2
Ph3P
O
[Pd]
O
O
N
R3
Ph3P
R1
O
R1
R3
N
O
decarboxylation
CO2
A
N
R2
R3
D
path b
N
R2
[Pd]
O
C
PPh3
N
N
N
N
R1
[Pd]
path a
R1
R3
O
R2
R2
B'
B
R3
Scheme 6 Proposed catalytic cycle for the palladium-catalyzed intramolecular condensation of oxadiazolone 3
corresponding pyrimidine 6 in 70% isolated yield ious functionalized imidazoles as well as bis(imidazole)
(Scheme 7). This result indicates the possibility that this derivatives could be obtained efficiently. Further investi-
reaction can be expanded to the general synthesis of vari- gations to improve efficiency in terms of catalytic activity
ous 1,3-diazaheterocyclic compounds.
and substrate scope are in progress.
Ph
N
Pd(PPh3)4 (5 mol%)
O
Acknowledgment
N
Ph
Ph3P (0.8 equiv)
Ph
N
This work was supported financially by Grant-in-Aid for Scientific
Research from JSPS, Japan. K. Okamoto also thanks Toray Award
in Synthetic Organic Chemistry, Japan.
O
dioxane, 80 °C, 96 h
N
6 70%
O
Ph
Supporting Information for this article is available online
5
at
http://www.thieme-connect.com/products/ejournals/journal/
Scheme 7
10.1055/s-00000083.SunogIpimrfiantoSuIpg
n
fonirtat
ori
In conclusion, we have developed a palladium-catalyzed
novel transformation reaction of readily available 1,2,4-
oxadiazol-5(4H)-ones as starting materials with triphe-
nylphosphine, leading to N-unprotected imidazole deriva-
tives and a pyrimidine derivative. Because the present
reaction proceeds under mild and neutral conditions, var-
References and Notes
(1) For selected examples on the material or medicinal
application of imidazoles, see: (a) Fabbrizzi, L.; Francese,
G.; Licchelli, M.; Perotti, A.; Taglietti, A. Chem. Commun.
1997, 581. (b) Zhang, Y.; Yang, R. H.; Liu, F.; Li, K. A.
Anal. Chem. 2004, 76, 7336. (c) Zeng, Q.; Cai, P.; Li, Z.;
Synlett 2014, 25, 1916–1920
© Georg Thieme Verlag Stuttgart · New York

LETTER
Qin, J.; Tang, B. Z. Chem. Commun. 2008, 1094.
(d) Berezin, M. Y.; Kao, J.; Achilefu, S. Chem. Eur. J. 2009,
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Geng, R.-X.; Zhou, C.-H. Med. Res. Rev. 2014, 34, 340.
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pyrimidines, see: (a) Xi, N.; Huang, Q.; Liu, L.
Synthesis of Imidazoles and Pyrimidines
1919
3.9 Hz, 1 H), 7.27 (t, J = 7.3 Hz, 1 H), 7.34 (d, J = 5.1 Hz, 1
H), 7.35 (s, 1 H), 7.39 (d, J = 8.1 Hz, 2 H), 7.41 (d, J = 3.7
Hz, 1 H), 7.72 (br s, 2 H). 13C NMR (100 MHz, acetone-d6):
δ = 116.4, 124.1, 125.2, 126.3, 127.0, 128.2, 129.0, 134.4,
135.2, 140.5, 143.1. HRMS–FAB: m/z calcd for C13H11N2S
[M + H]+: 227.0643; found: 227.0639.
Imidazole 4j
Pale yellow solid (35.0 mg, 0.14 mmol, 70% yield; mp
124.3–126.2 °C). 1H NMR (400 MHz, CDCl3): δ = 3.84 (s,
3 H), 6.93 (d, J = 8.8 Hz, 2 H), 7.27 (d, J = 8.5 Hz, 2 H), 7.35
(t, J = 7.6 Hz, 1 H), 7.42 (t, J = 7.8 Hz, 2 H), 7.67 (d, J = 8.5
Hz, 2 H), 7.87 (d, J = 7.1 Hz, 2 H). 13C NMR (100 MHz,
acetone-d6): δ = 55.3, 114.6, 125.7, 125.8, 126.6, 128.7,
129.3, 129.9, 131.1, 131.8, 146.9, 159.4. HRMS–FAB: m/z
calcd for C16H15N2O [M + H]+: 251.1184; found: 251.1181.
Imidazole 4o
Comprehensive Heterocyclic Chemistry III; Joule, J., Ed.;
Vol. 4, 281. (b) Rewcastle, G. W. Comprehensive
Heterocyclic Chemistry III; Aitken, R. A., Ed.; Vol. 8, 191.
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Int. Ed. 2011, 50, 11470.
(4) Okamoto, K.; Shimbayashi, T.; Tamura, E.; Ohe, K. Chem.
Eur. J. 2014, 20, 1490.
White solid (29.7 mg, 0.19 mmol, 94% yield; mp 180.5–
181.6 °C). 1H NMR (400 MHz, CDCl3): δ = 2.29 (s, 3 H),
6.82 (s, 1 H), 7.31 (t, J = 6.4 Hz, 1 H), 7.37 (t, J = 6.8 Hz, 2
H), 7.81 (d, J = 7.8 Hz, 2 H). 13C NMR (100 MHz, CDCl3):
δ = 12.0, 119.4, 125.0, 128.2, 128.8, 130.4, 132.1, 146.0.
HRMS–FAB: m/z calcd for C10H11N2 [M + H]+: 159.0922;
found: 159.0923.
(5) For reviews on aza-Wittig reactions, see: (a) Fresneda, P.
M.; Molina, P. Synlett 2004, 1. (b) Palacios, F.; Alonso, C.;
Aparicio, D.; Rubiales, G.; de los Santos, J. M. Tetrahedron
2007, 63, 523. (c) Palacios, F.; Alonso, C.; Aparicio, D.;
Rubiales, G.; de los Santos, J. M. Organic Azides: Syntheses
and Applications; Bräse, S.; Banert, K., Eds.; John Wiley
and Sons: Chichester, 2009, Chap. 15, 439-46.
(6) As a related chemistry, catalytic carbene transfer reactions
via phosphorus ylides have been reported by some groups.
See: (a) Mirafzal, G. A.; Cheng, G.; Woo, L. K. J. Am.
Chem. Soc. 2002, 124, 176. (b) Cheng, G.; Mirafzal, G. A.;
Woo, L. K. Organometallics 2003, 22, 1468; and references
cited therein. (c) Aggarwal, V. K.; Fulton, J. R.; Sheldon, C.
G.; de Vicente, J. J. Am. Chem. Soc. 2003, 125, 6034.
(d) Miki, K.; Washitake, Y.; Ohe, K.; Uemura, S. Angew.
Chem. Int. Ed. 2004, 43, 1857.
(7) Oxadiazolones are easily prepared in a few steps from
abundant molecules. See: (a) Takács, K.; Harádnyi, K.
Chem. Ber. 1970, 103, 2330. (b) Charton, J.; Cousaert, N.;
Bochu, C.; Willand, N.; Déprez, B.; Déprez-Poulain, R.
Tetrahedron Lett. 2007, 48, 1479.
(8) General Procedure for the Catalytic ReactionsA solution
of Pd(PPh3)4 (6.9 mg, 6.0 μmol) and oxadiazolone 3 (0.20
mmol) in 1,4-dioxane (1.5 mL) was stirred at 80 °C for 24 h.
The reaction mixture was filtered through a pad of Florisil®,
and the filtrate was concentrated under vacuum. The residue
was subjected to column chromatography on Florisil®
(hexane–EtOAc = 4:1) to afford imidazole 4.
(9) For reviews, see: (a) Kitamura, M.; Narasaka, K. Chem. Rec.
2002, 2, 268. (b) Narasaka, K.; Kitamura, M. Eur. J. Org.
Chem. 2005, 4505.
(10) For recent examples, see: (a) Zaman, S.; Kitamura, M.;
Abell, A. D. Org. Lett. 2005, 7, 609. (b) Gerfaud, T.;
Neuville, L.; Zhu, J. Angew. Chem. Int. Ed. 2009, 48, 572.
(c) Tan, Y.; Hartwig, J. F. J. Am. Chem. Soc. 2010, 132,
3676. (d) Kitamura, M.; Moriyasu, Y.; Okauchi, T. Synlett
2011, 643. (e) Faulkner, A.; Bower, J. F. Angew. Chem. Int.
Ed. 2012, 51, 1675. (f) Faulkner, A.; Scott, J. S.; Bower, J.
F. Chem. Commun. 2013, 49, 1521. (g) Race, N. J.; Bower,
J. F. Org. Lett. 2013, 15, 4616. (h) Hong, W. P.; Iosub, A.
V.; Stahl, S. S. J. Am. Chem. Soc. 2013, 135, 13664.
(11) For recent examples of N–O bond cleavage of oxime esters
or ethers in catalytic reactions using metals other than
palladium, see: (a) Too, P. C.; Wang, Y. F.; Chiba, S. Org.
Lett. 2010, 12, 5688. (b) Yoshida, Y.; Kurahashi, T.;
Matsubara, S. Chem. Lett. 2011, 40, 1140. (c) Too, P. C.;
Chua, S. H.; Wong, S. H.; Chiba, S. J. Org. Chem. 2011, 76,
6159. (d) Ren, Z.-H.; Zhang, Z.-Y.; Yang, B.-Q.; Wang, Y.-
Y.; Guan, Z.-H. Org. Lett. 2011, 13, 5394. (e) Qi, X.; Jiang,
Y.; Park, C.-M. Chem. Commun. 2011, 47, 7848.
(f) Nakamura, I.; Iwata, T.; Zhang, D.; Terada, M. Org. Lett.
2012, 14, 206. (g) Jiang, Y.; Chan, W. C.; Park, C.-M. J. Am.
Chem. Soc. 2012, 134, 4104. (h) Yoshida, Y.; Kurahashi, T.;
Matsubara, S. Chem. Lett. 2012, 41, 1498. (i) Wei, Y.;
Yoshikai, N. J. Am. Chem. Soc. 2013, 135, 3756. (j) Shi, Z.;
Koester, D. C.; Boultadakis-Arapinis, M.; Glorius, F. J. Am.
Chem. Soc. 2013, 135, 12204. (k) Nakamura, I.; Onuma, T.;
Zhang, D.; Terada, M. Tetrahedron Lett. 2014, 55, 1178.
(l) Tang, X.; Huang, L.; Xu, Y.; Yang, J.; Wu, W.; Jiang, H.
Angew. Chem. Int. Ed. 2014, 53, 4205. (m) Nakamura, I.;
Ishida, Y.; Terada, M. Org. Lett. 2014, 16, 2562.
Imidazole 4a
White solid (43.8 mg, 0.20 mmol, 99% yield; mp 160.1–
160.5 °C). 1H NMR (400 MHz, CDCl3): δ = 7.22–7.45 (m, 7
H), 7.75 (d, J = 7.4 Hz, 2 H), 7.87 (d, J = 7.3 Hz, 2 H). 13
C
NMR (100 MHz, acetone-d6): δ = 114.3, 125.4, 125.9, 127.2,
129.0, 129.3, 129.5, 131.8, 135.6, 142.6, 147.4. HRMS–
FAB: m/z calcd for C15H13N2 [M + H]+: 221.1079; found:
221.1069.
Imidazole 4c
White solid (46.0 mg, 0.19 mmol, 97% yield; mp 65.0–66.1
°C). 1H NMR (400 MHz, CDCl3): δ = 7.08 (dd, JHH = 8.8 Hz,
(12) Xie, H.; Lin, F.; Yang, L.; Chen, X.; Ye, X.; Tian, X.; Lei,
Q.; Fang, W. J. Organomet. Chem. 2013, 745-746, 417.
(13) For the mechanism of aza-Wittig reactions, see: Cossío, F.
P.; Alonso, C.; Lecea, B.; Ayerbe, M.; Rubiales, G.;
Palacios, F. J. Org. Chem. 2006, 71, 2839.
(14) For examples on the intramolecular aza-Wittig-type
reactions giving N-heterocyclic compounds: (a) Hickey, D.
M. B.; MacKenzie, A. R.; Moody, C. J.; Rees, C. W. J.
Chem. Soc., Perkin Trans. 1 1987, 921. (b) Kennedy, M.;
Moody, C. J.; Rees, C. W.; Vaquero, J. J. J. Chem. Soc.,
Perkin Trans. 1 1987, 1395. (c) Takeuchi, H.; Yanagida, S.-
J
HF = 8.8 Hz, 2 H), 7.27 (t, J = 7.3 Hz, 1 H), 7.37 (s, 1 H),
7.39 (t, J = 7.3 Hz, 2 H), 7.74 (d, J = 7.3 Hz, 2 H), 7.82 (dd,
JHH = 8.3 Hz, JHF = 4.9 Hz, 2 H). 13C NMR (100 MHz,
CDCl3): δ = 115.7 (d, JCF = 21.7 Hz), 117.7, 125.0, 126.4 (d,
JCF = 3.1 Hz), 127.2, 127.3, 127.5 (d, JCF = 8.0 Hz), 128.8,
132.4, 146.7, 163.0 (d, JCF = 248 Hz). HRMS–FAB: m/z
calcd for C15H12FN2 [M + H]+: 239.0985; found: 239.0990.
Imidazole 4i
White solid (30.1 mg, 0.13 mmol, 67% yield; mp 168.5–
171.0 °C). 1H NMR (400 MHz, CDCl3): δ = 7.08 (dd, J = 5.1,
© Georg Thieme Verlag Stuttgart · New York
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1920
T. Shimbayashi et al.
LETTER
i.; Ozaki, T.; Hagiwara, S.; Eguchi, S. J. Org. Chem. 1989,
54, 431. (d) Chen, J.; Forsyth, C. J. Org. Lett. 2003, 5, 1281.
(e) Marsden, S. P.; McGonagle, A. E.; Mckeever-Abbas, B.
Org. Lett. 2008, 10, 2589.
N
N
Ph
O
N
Pd2(dba)3 (100 mol% Pd)
dioxane, 100 °C, 24 h
Ph
Ph
O
N
H
O
(15) Only 15% of imidazole 4a was obtained in the reaction of the
stoichiometric amount of Pd2(dba)3 with oxadiazolone 3a
(Scheme 8). This result indicates that the reaction pathway
bypassing the iminophosphorane intermediate (path b) also
exists but is only a minor pathway.
4a 15%
Ph
3a
Scheme 8
Synlett 2014, 25, 1916–1920
© Georg Thieme Verlag Stuttgart · New York

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