Oxirane synthesis from diazocarbonyl compounds via NHC-Ag+ catalysis

Article abstract of DOI:10.1016/j.tetlet.2014.03.105

A new method was developed to synthesize oxirane products from the reaction of diazocarbonyl substrates with aryl aldehydes by using Ag(I) N-heterocyclic carbene complex as the catalyst. A combination of N-heterocyclic carbene silver complex (IPrAgCl) with another silver salt (AgOTf) generated the catalytic active IPr-Ag⁺ intermediate, which then catalyzed the epoxidation reaction.

Full text of DOI:10.1016/j.tetlet.2014.03.105

Tetrahedron Letters 55 (2014) 2969–2972
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Oxirane synthesis from diazocarbonyl compounds via NHC-Ag+
catalysis
⇑
Zhen Wang, Jian Wen, Qing-Wei Bi, Xiao-Qi Xu, Zhu-Qing Shen, Xiao-Xiao Li, Zili Chen
Department of Chemistry, Renmin University of China, Beijing 100872, China
a r t i c l e i n f o
a b s t r a c t
Article history:
A new method was developed to synthesize oxirane products from the reaction of diazocarbonyl sub-
strates with aryl aldehydes by using Ag(I) N-heterocyclic carbene complex as the catalyst. A combination
of N-heterocyclic carbene silver complex (IPrAgCl) with another silver salt (AgOTf) generated the catalytic
active IPr-Ag+ intermediate, which then catalyzed the epoxidation reaction.
Received 14 February 2014
Revised 18 March 2014
Accepted 23 March 2014
Available online 28 March 2014
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
N-Heterocyclic carbene silver complex
Carbene transfer reaction
Silver carbenoid
Oxirane synthesis
Introduction
Herein we will report a new method of oxirane synthesis from
the reaction of diazocarbonyl compounds with aldehydes via
The catalytic role of silver(I) complexes in homogeneous organ-
ic reactions was commonly used either as co-catalyst or as Lewis
acid,1 and thus, it has long been considered to be of low catalytic
efficiency.2,3 One famous and early exception to this notion is
Arndt–Eistert reaction, which involved a silver carbenoid interme-
diate in the late step. Nevertheless, this in situ generated silver
carbenoid exhibited an atypical intramolecular reactivity (Wolff
rearrangement) as compared with dirhodium catalysis.4
NHC-silver catalysis. In the previous research, Ag(I) N-heterocyclic
carbene complexes (NHC-AgX) were usually employed as the NHC
transfer agents, and has seldom been utilized in catalysis.9 This is
the first example, to our knowledge, of employing NHC-Ag+ as
catalysts in metal mediated carbene transfer reactions (Scheme 1).
The reaction of methyl phenyldiazoacetate 1a with electron-
rich anisaldehyde 2a was chosen as the model system for our ini-
tial investigation. As shown in Table 1, a mixture of 1a (0.1 mmol)
and 1 mol equiv of 2a in CH2Cl2 was treated with 5 mol % equiv of
AgOTf in the condition of 50 mg 4 Å molecular sieves. 24 h later,
only trace amounts of oxirane 3a could be detected, together with
The first example of intermolecular silver carbenoid chemistry
was documented by Dias group in 2003, in which, silver scorpio-
nate catalyst was utilized to catalyze a-diazo esters C–Cl insertion
reaction.5 In 2007, Davies group reported that silver salt (AgSbF6)
catalyzed cyclopropanation by using donor/acceptor substituted
diazo compounds.6 In this reaction, silver carbenoid intermediate
exhibited a high reactivity and high chemoselectivity, even for
the sterically hindered alkenes, which are unreactive under rho-
dium(II) acetate-catalyzed conditions. Despite these achievements,
however, extending this highly reactive silver carbenoid to other
types of carbene transfer reactions has never been explored.
Oxirane units are important precursors to a broad range of valu-
able small molecules and polymers,7 transition metal(Rh or Cu)
mediated [2+1] cycloaddition of a carbene with an aldehyde has
been reported to be an important synthetic route for the prepara-
tion of the oxirane structure.8
Previous work
NHC-AgCl
N2
NHC-M
M = other metal
Ref. 1
AgSbF6
Ref. 6
+
COOMe
Ph
Ph
COOMe
Rh, Cu
Ref. 8
O
N2
O
Ph
COOMe
Ph
+
Ph
COOMe
Ph
NHC-Ag+ as catalysts
This Work
⇑
Corresponding author. Tel./fax: +86 10 62516660.
E-mail address: zilichen@ruc.edu.cn (Z. Chen).
Scheme 1. Metal mediated [2+1] carbene cycloaddition.
http://dx.doi.org/10.1016/j.tetlet.2014.03.105
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

2970
Z. Wang et al. / Tetrahedron Letters 55 (2014) 2969–2972
Table 1
Table 2
Silver mediated epoxidation of phenyldiazoacetate 1a with anisaldehyde 2aa
NHC-Ag+ mediated epoxidation reaction of 1a with various aldehydes.a,
b,
c
N2
CHO
5 mol% IPrAgCl
/AgOTf
O
N2
O
O
+
Silver catalyst
& Additive
solvent, rt
COOMe
+
R
COOMe
MeOOC
DCM, rt
R
MeOOC
3a-m
1a
2a-m
OMe
2a
OMe
1a
3a
O
O
O
Ag catalyst (mol %)
Additive
(mol %)
Solvent/
time
(h)
Yieldb
(%)
O
MeOOC
OBn
MeOOC
3a,
MeOOC
N
OMe
H
3b,
3c,
88% yield
O
88% yield
O
54% yield
O
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20c
21
AgOTf (5)
No
No
No
No
DCM/24
DCM/8
DCM/8
DCM/24
DCM/8
DCM/8
DCM/8
DCM/8
DCM/8
DCM/8
DCM/8
DCM
DCM/8
CHCl3/8
DCE/8
Toluene
Et2O/8
DCM/24
DCM/24
DCM/8
DCM
<5
52
57
<5
69
41
42
39
12
26
54
NR
20
58
52
NR
40
42
30
88
NR
AgOTf (5)/Ph3P (5)
AgOTf(5)/Cy3P (5)
AgOTf (5)/(C6F5)3P (5)
IPrAgCl (5)
SIPrAgCl (5)
ICyAgCl (5)
IPrAgCl (5)
IPrAgCl (5)
IPrAgCl (5)
IPrAgCl (5)
IPrAgCl (5)
IPrAgCl (5)
IPrAgCl (5)
IPrAgCl (5)
IPrAgCl (5)
IPrAgCl (5)
IPrAgCl (5)
IPrAgCl (5)
IPrAgCl (5)
MeOOC
MeOOC
AgOTf (5)
AgOTf (5)
AgOTf (5)
AgBF4 (5)
AgSbF6 (5)
AgPF6 (5)
AgNTf2 (5)
Ag2CO3 (5)
AgClO4 (5)
AgOTf (5)
AgOTf (5)
AgOTf (5)
AgOTf (5)
AgOTf (2.5)
AgOTf (10)
AgOTf (5)
—
MeOOC
Br
Cl
3d,
3e,
3f,
62% yield
O
52% yield
O
58% yield
O
MeOOC
MeOOC
MeOOC
F
3g,
3h,
3i,
56% yield
91% yield
O
81% yield
O
O
MeOOC
3j,
Ph
MeOOC
MeOOC
Ph
3k,
3m,
95% yield
51% yield
72% yield
a
Unless noted, all reactions were carried out on 0.1 mmol scale in 2 mL CH2Cl2 at
rt with the addition of 50 mg 4 Å molecular sieves.
IPrAgCl (5)
b
Isolated yields.
a
c
In Table 1 scheme, 3a’s structure only shows relative configuration. Unless
Product 3a–m’s structure only show their relative configuration
noted, all reactions were carried out on 0.1 mmol scale in 2 mL solvent at rt with the
addition of 50 mg 4 Å molecular sieves.
The reaction yields were determined by 1H NMR spectral data.
b
c
2 mol equiv of 1a was used. NR = No Reaction.
the formation of a mixture of carbene dimerization and decompo-
sition products (Table 1, entry 1). When 4 Å molecular sieves were
removed, no desired product was obtained. We envisioned that
suitable ligand binding would enhance silver carbenoid stability
and therefore enhance their reactivity. To our delight, when 5 mo-
l % equiv of Ph3P was added, 3a’s yield could be improved to 52%
(Table 1, entry 2). Electron rich phosphine ligand Cy3P performed
better than Ph3P (Table 1, entry 3), while a combination of silver
salt with electron deficient (C6F5)3P showed poor reactivity. We
carbene source (Table 2). It has been reported that epoxidation
reaction started from the nucleophilic attack of an aldehyde onto
metal carbenoid. Therefore, the aldehyde substrate’s oxygen nucle-
ophilicity would affect the reaction yield. As shown in Table 1, sev-
eral para-, ortho-, and meta-substituted benzaldehydes were
scrutinized. Both electron-donating and electron-withdrawing
benzaldehydes worked very well in this silver carbene [2+1] cyclo-
addition reaction. Electron rich p-alkoxy benzaldehydes afforded
3a and 3b in high reaction yields (Table 2, 3a–b), while p-acetoa-
minobenzaldehyde gave only a moderate yield (Table 2, 3c). The
electron-poor p-halo substituted benzaldehydes provided the de-
sired oxiranes in relatively low yields (Table 2, 3e–g). The m- and
o-substituted benzaldehyde and 2-naphthaldehyde were then
considered that
r donating NHC ligand (N-heterocyclic carbene)
would further improve silver carbenoid reactivity. As shown in
Table 1, treating the reaction mixture with 5 mol % equiv of
IPrAgCl/AgOTf could provide the desired product 3a in 69% yield
(Table 1, entry 5). Other NHC ligands, such as: SIPrAgCl and ICyAgCl,
were also tested, which gave much less yields (Table 1, entry 6–7).
Then, different silver co-catalysts (Table 1, entry 8–13) and sol-
vents (Table 1, entry 14–17) were screened. It was found that
AgBF4, AgSbF6, AgPF6, and AgNTf2 gave the desired product in mod-
erate yields. AgClO4 afforded 3a in a relatively low yield, while Ag2-
CO3 gave no reaction. Further exploration on various solvents was
also fruitless. Thus, catalyst IPrAgCl/AgOTf in CH2Cl2 was proved to
be the best combination (Table 1, entry 5). Improving or lowering
the co-catalyst AgOTf’s equivalence reduced 3a’s reaction yield
(Table 1, entry 18–19). When 1a’s amount was improved to
2 equiv, 3a could be obtained in 88% yield (Table 1, entry 20). In
the control experiment, the sole silver catalyst IPrAgCl without sil-
ver co-catalyst gave no desired product (Table 1, entry 21).10
With the optimal reaction conditions in hand, the substrate
scope was explored and a series of oxirane derivatives were syn-
tested, which gave 3h, 3i, and 3j in moderate to good yields.
a,
b-Unsaturated aldehydes were also evaluated. Both vinyl and
alkynyl substrates worked very smoothly in this reaction (Table 2,
3k–m).
Various diazocarbonyl substrates were then explored (Table 3).
Both phenyl and vinyl diazocarbonyl substrates reacted smoothly
with 2a, which provided a series of desired oxirane products
(Table 3, 4b–g). Alkyl diazocarbonyl substrate was also tested,
but it did not give the desired oxirane product.
In order to elucidate the exact active reaction mediator, we
examined the effect of the ligand loading. As compared with the
effect of the sole silver salt (5 mol % of AgOTf, Table 1, entry 1)
and the combination of AgOTf/Cy3P (5 mol %, Table 1, entry 3),
improving Cy3P’s equivalence to 7 mol % lowered down 3a’s yield
(Scheme 2). Furthermore, only trace amounts of 3a could be de-
tected in the condition of 5 mol % AgOTf and 10 mol % of Cy3P. This
result, combined with the control experiment (Table 1, entry 21),
indicated that IPrAg+ might be the real active reaction mediator.
thesized. At first, various aromatic and
a, b-unsaturated aldehydes
were tested by using methyl phenyldiazoacetate 1a as the reacting

Z. Wang et al. / Tetrahedron Letters 55 (2014) 2969–2972
2971
Table 3
In summary, a new method was developed to synthesize oxi-
rane products from the reaction of diazocarbonyl substrates with
NHC-Ag+ mediated epoxidation reaction of 2a with various diazocarbonyl
a, b,
c
compounds.
aryl aldehydes by using Ag(I) N-heterocyclic carbene complex as
CHO
O
12
R1
the catalyst.
A combination of a N-heterocyclic carbene silver
N2
5 mol% IPrAgCl
/AgOTf
R2OOC
complex (IPrAgCl) with another silver salt (AgOTf) would generate
the catalytic active IPr-Ag+ intermediate, which then catalyzed
the epoxidation reaction. As compared with previous reports,
N-heterocyclic carbene ligand stabilized the silver catalyst and
enhanced its catalytic activity.
+
R1
COOR2
DCM, rt
OMe
OMe
1b-g
2a
4b-g
O
O
O
tBuOOC
nBuOOC
Acknowledgments
EtOOC
OMe
OMe
OMe
Financial support by the Fundamental Research Funds for the
Central Universities, and the Research Funds of Renmin University
of China (11XNI003) are gratefully acknowledged.
4b, 80% yield
4c, 95% yield
4d, 51% yield
O
OMe
O
O
O
O
Supplementary data
MeOOC
EtOOC
EtOOC
Supplementary data (a brief experimental details, and spectral
data for all new products and NOESY spectra for compound 4f)
associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.tetlet.2014.03.105.
OMe
OMe
OMe
4e,
4f,
4g,
53% yield
33% yield
86% yield
a
Unless noted, all reactions were carried out on 0.1 mmol scale in 2 mL CH2Cl2 at
rt with the addition of 50 mg 4 Å molecular sieves.
b
Isolated yields.
c
Product 4b–f’s structure only show relative configuration.
References and notes
1. Garrison, J. C.; Youngs, W. J. Chem. Rev. 2005, 105, 3978–4008.
2. (a) Álvarez-Corral, M.; Muñoz-Dorado, M.; Rodríguez-García, I. Chem. Rev.
2008, 108, 3174–3198; (b) Weibel, J.-M.; Blanc, A.; Pale, P. Chem. Rev. 2008, 108,
3149–3173; (c) Naodovie, M.; Yamamoto, H. Chem. Rev. 2008, 108, 3132–3148.
3. (a) Liu, J.; Fang, Z.; Zhang, Q.; Liu, Q.; Bi, X. Angew. Chem., Int. Ed. 2013, 52,
6953–6957; (b) Gao, M.; He, C.; Chen, H.; Bai, R.; Cheng, B.; Lei, A. Angew. Chem.,
Int. Ed. 2013, 52, 6958–6961; (c) Díaz-Requejo, M. M.; Pérez, P. J. J. Organomet.
Chem. 2005, 690, 5441–5450.
4. (a) Doyle, M. P.; McKervey, M. A.; Ye, T. Modern Catalytic Methods for Organic
Synthesis with Diazo Compounds; Wiley-Interscience: New York, 1998; (b) Gill,
G. B. In Comprehensive Organic Synthesis; Trost, B. M., Flemming, I., Eds.; John
Wiley: New York, 1991; Vol. 3, p 887; (c) Ye, T.; McKervey, A. Chem. Rev. 1994,
94, 1091; (d) Bachmann, W. E.; Struve, W. S. Org. React. 1946, 1, 38.
CHO
N2
O
Silver catalyst
4A MS
DCM, rt
+
COOMe
MeOOC
OMe
2a
OMe
1a
3a
5 mol% AgOTf/7 mol% Cy3P
5 mol% AgOTf/10 mol% Cy3P
31%Yield
Trace
5. (a) Dias, H. V. R.; Browning, R. G.; Polach, S. A.; Diyabalanage, H. V. K.; Lovely, C.
J. J. Am. Chem. Soc. 2003, 125, 9270; (b) Dias, H. V. R.; Browning, R. G.; Richey, S.
A.; Lovely, C. J. Organometallics 2004, 23, 1200; (c) Lovely, C. J.; Browning, R. G.;
Badarinarayana, V.; Dias, H. V. R. Tetrahedron Lett. 2005, 46, 2453; (d) Urbano,
J.; Belderrain, T. R.; Nicasio, M. C.; Trofimenko, S.; Diaz-Requejo, M. M.; Perez, P.
J. Organometallics 2005, 24, 1528; For a recent example describing ineffective
cyclopropanation by ethyl diazoacetate catalyzed by silver triflate, see: (e) Lee,
H. M.; Bianchini, C.; Jia, G.; Barbaro, P. Organometallics 1999, 18, 1961; For an
example of an intramolecular C–H insertion of donor/acceptor substituted
carbenoids catalyzed by silver salts, see: f Burgess, K.; Lim, H.-J.; Porte, A. M.;
Sulikowski, G. A. Angew. Chem., Int. Ed. 1996, 35, 220.
Scheme 2. Effect of Cy3P loading on the reaction yield.
It was proposed that a carbonyl ylide was generated as the
reaction intermediate, which then underwent an intramolecular
cyclization to provide the oxirane unit. Trapping this carbonyl
ylide intermediate with electron-poor aldehyde would provide
1,3-dioxolane products.11 As shown in Scheme 3, the reaction of
methyl phenyldiazoacetate 1a with anisaldehyde 2a and p-nitro-
benzaldehyde 5 gave 1,3-dioxolane 6 and 60 in 65% yield (6/
60 = 1.4/1), together with 27% yield of 3a.
6. Thompson, J. L.; Davies, H. M. L. J. Am. Chem. Soc. 2007, 129, 6090–6091.
7. (a) Zhang, J.; Chen, Z.; Wu, H.; Zhang, J. Chem. Commun. 2012, 1817–1819; (b)
Concellón, J. M.; Bardales, E.; Llavona, R. J. Org. Chem. 2003, 68, 1585–1588; (c)
Taylor, S. K. Tetrahedron 2000, 56, 1149–1163; (d) Hinterding, K.; Jacobsen, E. N.
O
MeOOC
CHO
N2
OMe
3a, 27% yield
COOMe
OMe
5 mol% IPrAgCl
OMe
/AgOTf
+
OMe
2a
DCM, rt
1a
+
CHO
O
O
O
O
MeOOC
MeOOC
NO2
5
NO2
NO2
6
6'
6/6' = 1.4/1, 65% total yield
3a, 6
6'
and structure only show relative configuration.
Product
Scheme 3. Trapping the carbonyl ylide with p-nitro benzaldehyde to give 1,3-dioxolane.

2972
Z. Wang et al. / Tetrahedron Letters 55 (2014) 2969–2972
J. Org. Chem. 1999, 64, 2164–2165; (e) Schmidt, J. A. R.; Lobkovsky, E. B.; Coates,
G. W. J. Am. Chem. Soc. 2005, 127, 11426–11435.
8. (a) de March, P.; Huisgen, R. J. Am. Chem. Soc. 1982, 104, 4952; (b) Doyle, M. P.;
Hu, W. H.; Timmons, D. J. Org. Lett. 2001, 3, 933–935; (c) Davies, H. M. L.;
DeMeese, J. Tetrahedron Lett. 2001, 42, 6803–6805.
12. General procedure for NHC ligated silver catalyzed carbene transfer reaction: To a
solution of IPrAgCl/AgOTf (5 mol %) in dry CH2Cl2 (2 mL), was added 100 mg
activated 4 Å MS, and was then added diazo ester compound 1a (0.2 mmol)
and anisaldehyde 2a (0.1 mmol). The reaction was stirred at rt until complete
consumption of the starting material with TLC monitoring. Then, the reaction
mixture was concentrated in vacuum, and the residue was purified by flash
chromatography over silica gel column using hexane/EtOAc (60:1) as the
eluent to afford 3a in 88% yield as a colorless oil. The spectral data of methyl 3-
(4-methoxyphenyl)-2-phenyloxirane-2-carboxylate 3a: 1H NMR (400 MHz,
CDCl3): d 7.65–7.62 (m, 2H), 7.41–7.37 (m, 3H), 7.32 (d, J = 8.7 Hz, 2H), 6.89
(d, J = 8.7 Hz, 2H), 4.10 (s, 1H), 3.82 (s, 3H), 3.58 (s, 3H); 13C NMR (100 MHz,
CDCl3): d 163.3, 159.9, 134.8, 128.7, 128.6, 127.3, 126.2, 125.8, 113.9, 67.1,
65.8, 55.3, 52.2; IR (neat) 2916, 2839, 1734, 1627, 1610, 1508, 1437, 1265,
9. (a) Sentman, A. C.; Csihony, S.; Nyce, G. W.; Waymouth, R. M.; Hedrick, J. L.
Polym. Prepr. 2004, 45, 299; (b) Ramírez, J.; Corberán, R.; Sanaú, M.; Peris, E.;
Fernandez, E. Chem. Commun. 2005, 3056; (c) Sentman, A. C.; Csihony, S.;
Waymouth, R. M.; Hedrick, J. L. J. Org. Chem. 2005, 70, 2391.
10. 3a’s relative stereochemistry was confirmed by comparing its 1H NMR spectral
data with the previous reports and was also deduced from the NOESY spectral
data for compound 4f.
11. Lu, C.; Chen, Z.; Liu, H.; Hu, W. H.; Mi, A. Org. Lett. 2004, 6, 3071.
1165, 739, 698 cmꢀ1
.