Divergent Iron-Catalyzed Coupling of O-Acyloximes with Silyl Enol Ethers

Article abstract of DOI:10.1002/chem.201605636

An iron-catalyzed coupling reaction of O-acyloximes and O-benzoyl amidoximes with silyl enol ethers is reported. The protocol provides access to functionalized pyrroles, 1,6-ketonitriles, pyrrolines and imidazolines via carbon-centered radicals generated from an initially formed iminyl radical. The intramolecular cyclization and ring-opening processes of the iminyl radical take place preferentially over reactions that proceed through a 1,3-hydrogen transfer, providing insights into iron-catalyzed reactions with oxime derivatives. The cheap and environmentally friendly iron catalyst, the broad substrate scope and the functional group compatibility make this protocol useful for synthesis of valuable nitrogen-containing products.

Full text of DOI:10.1002/chem.201605636

A Journal of
Accepted Article
Title: Divergent Iron-Catalyzed Couplings of O-Acyloximes with Silyl
Enol Ethers
Authors: Hai-Bin Yang and Nicklas Selander
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To be cited as: Chem. Eur. J. 10.1002/chem.201605636
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Supported by

10.1002/chem.201605636
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COMMUNICATION
Divergent Iron-Catalyzed Couplings of O-Acyloximes with Silyl
Enol Ethers
Hai-Bin Yang and Nicklas Selander*[a]
Abstract: An iron-catalyzed coupling reaction of O-acyloxime/O-
benzoyl amidoximes with silyl enol ethers is reported. The protocol
provides access to functionalized pyrroles, 1,6-ketonitriles, pyrrolines
and imidazolines via carbon-centered radicals generated from an
initially formed iminyl radical. The intramolecular cyclization and ring-
opening processes of the iminyl radical take place preferentially over
formed via a metal-coordinated enamine intermediate (D). In the
third pathway, c, the release of ring-strain in a cyclobutanone-
derived O-acyloxime generates cyano-substituted radical C.7j,10
NOR
R1
a
1,3-hydrogen transfer, providing insights into iron-catalyzed
R2
reactions with oxime derivatives. The cheap and environmentally
friendly iron catalyst, the broad substrate scope and functional group
compatibility make this protocol useful for synthesis of valuable
nitrogen-containing products.
M
path b:
hydrogen
transfer
path a:
5-exo-dig/trig
cyclization
N
NH
H
N
R1
R1
M: Cu
M: Cu, Pd
R2
R2
R1
radical B
electrophilic iminyl radical
radical A
Transitional metal-catalyzed cross-coupling reactions are
pivotal for the construction of new C−C and C−X bonds. This
research area has for long been dominated by precious metals,
e.g. palladium.1 Compared with precious metals, iron is
advantageous in catalysis in terms of low cost and low toxicity.
Furthermore, the broad spectrum of oxidation states (-2 to +5) of
iron provides a rich reactivity platform which is useful for the
development of new transformations.2 In contrast to Pd-catalysis,
where the electrophilic cross-coupling partners are typically
activated via a two-electron oxidative addition, Fe-catalysis often
involves radical species and single electron transfer (SET)
mechanisms.3
As a part of our interest in the applications of N−O bond-
containing substrates we envisaged that oxime esters would
serve as viable electrophilic partners for iron-catalysis by
reduction of the N−O bond. Iminyl radicals are useful
intermediates4 that can be generated from oxime esters by
heat,5 transition metals6 or photo irradiation.7 As the heat-
induced activation of oxime esters usually requires harsh
conditions5a,5c-e or toxic reagents (e.g. Bu3SnH/AIBN)5h-i and
photo irradiation typically requires more complex oxime ester
derivatives (e.g. O−Ar or O2C−Ar groups),7a-c transition metal
catalysis is an attractive alternative.
R2 = allyl or propargyl
M
path c:
ring-opening
M: Ir, Pd
HN
R1
R2
from:
NOAc
D
N
radical C
Scheme 1. Divergent reaction modes of iminyl radicals
Unlike heat- or photo-induced generation of iminyl radicals,
transition metals can interact with the reactive radicals A-C
above to improve the reaction selectivity.11 Thus, it is highly
desirable to develop
a united transition metal-catalyzed
methodology to understand the competitive relationship between
the three different reaction modes, hitherto unexplored by a
single catalytic protocol.
Herein, we report on the iron-catalyzed coupling of O-
acyloximes/O-benzoylamidoximes with silyl enol ethers12 via the
three radical intermediates A-C above. Silyl enol ethers are
useful reaction partners as they react rapidly13 with the
electrophilic carbon-centered radicals. Thus, the competing self-
condensation6d and hydrolysis14 of α-iminyl radicals can be
avoided. Furthermore, the coupling with α-iminyl radicals
provides access to pyrroles via an intramolecular condensation
of the 1,4-ketoimine product. Although the synthesis of
biologically relevant pyrrole derivatives has extensively been
explored,15 the synthesis of unprotected electron-rich pyrroles,
amenable for N-functionalization,16 remains challenging.
Iminyl radicals8 are reactive electrophilic species that can be
transformed into carbon-centered radicals via three different
pathways (Scheme 1 path a-c). In path a, the iminyl radical is
added to a tethered alkene5e-h,7a-b or alkyne5a in a 5-exo-trig or 5-
exo-dig cyclization to form radical A.9 In path b, the electrophilic
iminyl radical can abstract
a
hydrogen atom via an
intramolecular 1,3-hydrogen transfer process to form the
stabilized radical B.6b,d The radical intermediate B may also be
We began our studies with O-acyloxime 1a and silyl enol
ether 2a. With 20 mol% of CuCl in 1,4-dioxane at 100 oC, pyrrole
3a was formed in 25% yield by 1H NMR. Further screening of
metal salts and reaction conditions (see the Supporting
Information), pointed towards FeCl2 as a better catalyst for this
transformation (57% yield).17 Improved yields were obtained in
MeCN; pyrrole 3a was obtained in 83% yield using 5 mol %
FeCl2 at 80 oC (Table 1). It should be pointed out that oxime
esters have previously been used as (N1+C2) synthons in
[a]
Dr. H.-B. Yang, Dr. N. Selander
Department of Organic Chemistry, Stockholm University
Arrhenius Laboratory, SE-106 91 Stockholm (Sweden)
E-mail: nicklas.selander@su.se
Supporting information for this article is given via a link at the end of
the document.
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10.1002/chem.201605636
Chemistry - A European Journal
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cyclizations with electron-deficient unsaturated substrates
through metal-coordinated enamine intermediates, however not
with electron-rich alkenes.18 In comparison, our method allows
for the synthesis of a variety of pyrrole derivatives.
A cyclic O-acyloxime provided the fused pyrrole 3e in 74% yield
and the thiophene-substituted oxime derivative gave the
corresponding pyrrole 3f in 55% yield. The highly conjugated
pyrrole 3g was obtained in 70% yield for the diphenyl-substituted
O-acyloxime. When non-conjugated O-acyloximes were applied,
lower yields were observed; pyrroles 3h-i were however isolated
in respectable yields. For compound 3h, two carbon-centered
radicals can be formed. As expected, the more stable secondary
radical determined the regiochemical outcome.19 The method is
also applicable for the hitherto unexplored ester-substituted
oxime derivative to yield pyrrole 3j in 31%. With respect to the
nucleophilic component, substituted acetophenone-derived silyl
enol ethers led to the formation of pyrroles 3k-o in 60-93% yield.
Electron-poor silyl enol ethers performed better than the
electron-rich counterparts. Furthermore, di-substituted silyl enol
ethers (R4 ≠H) were applied in the reaction to yield the tetra-
substituted pyrroles 3p-r. For the methyl substituted pyrrole 3p,
a yield of 65% was obtained, whereas the diphenyl-substituted
silyl enol ether resulted in a low yield, 14% of 3q, likely due to
the extended conjugation. Products 3r and 3s, formed from the
corresponding cyclic and alkenyl-derived silyl enol ethers were
unfortunately not stable upon concentration; the yields, 65% and
20% respectively were determined by 1H NMR. The naphthyl-
and furyl-substituted pyrroles 3t-u were obtained in good yields.
Notably, the method also provides access to the ester- and keto-
functionalized pyrroles 3v-w by employing the less explored
electron-poor silyl enol ethers (Table 2).
Table 1: Representative screening data
H
N
NOAc
OTMS
Ph
Ph
+ H2O
cond. a-c
Ph
1a
Ph
2a
3a
(0.1 mmol)
a) CuCl (20 mol%), 1,4-dioxane (1 mL), 100 oC / 24 h
b) FeCl2 (20 mol%), 1,4-dioxane (1 mL), 100 oC / 24 h 57%
(0.3 mmol)
25%
c) FeCl2 (5 mol%), MeCN (1 mL), 80 oC / 24 h
83% (82% isol.)
With these reaction conditions in hand, we continued to
investigate the substrate scope with respect to various oxime
acetates and silyl enol ethers. Propiophenone-derived O-
acyloximes provided pyrroles 3a-3d in high yields (70-82%),
regardless of the electronic character of the aryl group (Table 2).
Table 2: Substrate scope for pyrroles[a,b]
H
NOAc
R2
OTMS
R4
N
FeCl2 (5 mol%)
R3
R1
+
R1
R3
MeCN, 80 oC, 24 h
R4
R2
+ H2O
1
2
3
oxime acetates:
H
N
R
H
H
N
N
Ph
Ph
Ph
Br
Next, we investigated the effect of ring-strain by employing
cyclobutanone-derived O-acyloximes. In contrast to the pyrrole
formation (Table 2) where the iminyl radical is converted into a
carbon-centered radical through a hydrogen transfer process,
the cyclobutanone oxime derivatives underwent a selective ring-
opening. The resulting radical then coupled with the silyl enol
ether to yield the useful 1,6-ketonitrile building blocks 4 (Table
3).20 With the non-substituted cyclobutanone-derived O-
acyloxime, 1,6-ketonitrile 4a was obtained in 68% yield, without
traceable amounts of the cyclobutane-fused pyrrole.10 Moderate
yields, around 50%, were obtained for ketonitriles 4b-d from 3-
mono and 3,3-disubstituted cyclobutanone O-acyloximes
respectively. The opening of a 2,3-disubstituted cyclobutanone-
derived oxime acetate proceeded efficiently with a selective
cleavage to provide ketonitrile 4e in 72% yield (~4:1 isomeric
mixture). Interestingly, ketonitrile 4f was obtained in 31% yield,
indicating that the ring-opening process is preferred over a 5-
exo-trig cyclization with the allyl moiety. Furthermore, we were
able to use the previously unexplored benzene-fused
cyclobutanone derivative. The ring-opening yielded the more
stable benzylic radical for the selective formation of ketonitrile 4g
in 65% yield.19 Various para-substituted phenyl silyl enol ethers
gave the corresponding 1,6-ketonitriles 4h-k in moderate to
good yields. Lower yields (35-39%) were obtained with the
naphthyl-substituted silyl enol ether and a non-terminal coupling
partner (4l-m). The lower yields of the 1,6-ketonitriles (c.f. Table
2) is a consequence of the more reactive non-stabilized radical19
formed in the ring-opening process, making competitive
hydrogen abstraction processes inevitable.
3a, R = H, 82%
3b, R = Br, 77%
3d, 73%
3e, 74%
3c
, R = OMe, 70%
S
H
N
H
N
H
N
Ph
Ph
Ph
Ph
Ph
Ph
3g, 70%
3f, 55%
3h, 32%
H
H
N
N
Ph
Ph
Ph
CO2Et
3i, 30%
3j, 31%
silyl enol ethers:
H
R
H
H
N
N
N
Ph
Ph
Ph
Ph
Br
R
3k
, R = Cl, 77%
3l
,
R = CO2Me, 80%
3o, 66%
3p, R = Me, 65%
3q, R = Ph, 14%
3m, R = NO2, 93%
3n, R = OMe, 60%
H
N
H
N
H
N
Ph
Ph
Ph
Ph
[c]
[c]
3r
3s
, 20%
3t
, 65%
, 71%
O
O
H
N
H
N
H
N
Ph
EtO2C
Ph
Ph
Ph
3u, 70%
3v, 69%
3w, 22%
[a] Reaction conditions: 1 (0.20 mmol), 2 (0.60 mmol) and FeCl2 (5 mol%)
were stirred in MeCN (2.0 mL) under Ar for 24 h at 80 °C. [b] Isolated yields.
[c] Yields were determined by 1H NMR using CH2I2 as an internal standard.
For some oxime derivatives, an E/Z mixture was used, see the SI.
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10.1002/chem.201605636
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further expanded to thiohydroximic acid21 and amidoxime22
derivatives. Although thiazoline derivative 5c was obtained in
only 10% yield (due to hydrolysis), imidazoline 5d could be
obtained in 83% yield using the O-benzoylamidoxime derivative.
A methyl group on the alkene moiety lowered the efficiency,
providing 5e in 30% yield along with a comparable amount of a
aminooxygenated byproduct.23 The furyl-substituted imidazoline
5f was obtained in 43% yield. Furthermore, upon variation of the
silyl enol ether, imidazolines 5g-j were obtained in acceptable
yields, demonstrating that iron catalysis is useful for the
generation of amidinyl radicals and biologically relevant
imidazoline motifs.24
Table 3: Substrate scope for 1,6-ketonitriles[a,b]
O
NOAc
OTMS
R3
R1
R4
FeCl2 (5 mol%)
+
R5
R1
R5
R4
MeCN, 80 oC, 24 h
R3
R2
R2
NC
1
2
4
cyclobutanone O-acyloximes:
O
O
O
Ph
Ph
Ph
NC
Ph
R
NC
NC
Ph
4a, 68%
4b, R = H, 50%
4c
4d
, R = Me, 51%
, 50% (1:1 ratio)
CN
CN
CN
Upon subjecting oxime acetate 1x to the standard conditions,
we observed a mixture of products. Pyrrole 6a was obtained in
20% NMR-yield along with 10% of 3x, demonstrating the
competitive pathways of the 5-exo-dig cyclization and the 1,3-
hydrogen transfer of the iminyl radical for an intermolecular
coupling reaction (Scheme 2).
Ph
Ph
Ph
O
O
O
4e, 72% (3.7:1 ratio)
silyl enol ethers:
O
4f, 31%
4g, 65%
O
O
R
Ph
Ph
NOAc
OTMS
FeCl2 (5 mol%)
HN
HN
Ph
NC
NC
NC
+
+
2
2
2
Ph
4h, R = Cl, 73%
4i, R = CO2Me, 44%
4j, R = NO2, 46%
Ph
MeCN
80 oC, 24 h
4l, 35%
4m, 39%
Ph
6a
1x
2a
3x
, 10%
, 20%
4k
, R = OMe, 76%
[a] Reaction conditions: 1 (0.20 mmol), 2 (0.60 mmol) and FeCl2 (5 mol%)
were stirred in MeCN (2.0 mL) under Ar for 24 h at 80 °C. [b] Isolated yields.
For some oxime derivatives, an E/Z mixture was used, see the SI.
Scheme 2. Competitive 5-exo-dig cyclization vs. hydrogen transfer/coupling
We then investigated the possibility of an intramolecular C-N
bond-formation taking place in favor of a 1,3-hydrogen transfer
The addition of TEMPO to the presented reactions (Tables
2-4) did not result in any traces of products 3-5. Instead, we
were able to isolate TEMPO coupling products (See the
path for the iminyl radical. For
a γ,δ-unsaturated oxime
derivative, pyrroline 5a was formed in 81% yield, without traces
of the corresponding allyl-substituted pyrrole (Table 4).
Supporting Information). Thus, we propose
a mechanism
involving iminyl radicals (c.f., Scheme 1). In this process, the
applied iron catalyst first cleaves the N−O bond, and turns over
by forming the keto group after reaction with the silyl enol ether.
Table 4: Substrate scope for pyrrolines and thio-/aza-derivatives[a,b]
NOR1
R3
O
OTMS
N
R2
Our method was applied for the synthesis of the biologically
important pyrrolizine skeleton.7a,25 In a two-step reaction, oxime
acetate 1r was converted into pyrrolizine derivatives 7a-b in
57% and 48% yield (major diastereomers), respectively through
an iron-catalyzed coupling/reduction sequence.26 The sterically
hindered reagent NaBH(O2CiPr)3 led to an improved
diastereoselectivity (~2.5:1) for the formation of 7 (Scheme 3).27
FeCl2 (5 mol%)
+
R2
Z
R4
R4
MeCN, 80 oC, 24 h
Z
R3
1
2
5
5a-5b, Z = (-CH2-)0-1, R1 = Ac; 5c, Z = S, R1 = Ac; 5d-5j, Z = NBz, R1 = Bz[c]
olefinic O-acyloxime derivatives:
N
Ph
O
O
N
N
Ph
Ph
Ph
O
O
Ph
Ph
Ph
Ph
S
Ph
5a, 81%
5b, 0%
5c, 10%
Ph
R
1) FeCl2 (5 mol%)
MeCN, 80 oC, 24 h
NOAc
OTMS
R
O
O
O
Me
N
N
N
N
H
+
Ph
i
Ph
2) NaBH(O2CPr)2
Ph
iPr-COOH
N
N
N
1r
2a, R = Ph
2f, R = 4-MeOPh
CH2Cl2, rt - 50 o
C
[d]
[e]
Bz
Bz
Ph
Bz
Bz
5d
, 83%
5e
, 30%
5f
, 43%
major-7a, R = Ph, 57%
major-7b, R = 4-MeOPh, 48%
silyl enol ethers:
O
N
O
N
Ph
5h, R = Cl, 62%
N
5i
5j
, R = CO2Me, 59%
, R = OMe, 40%
Scheme 3. Synthesis of the pyrrolizine skeleton
R
N
Bz
5g, R = 1-naphth., 35%[d]
R
[a] Reaction conditions: 1 (0.20 mmol), 2 (0.60 mmol) and FeCl2 (5 mol%)
were stirred in MeCN (2.0 mL) under Ar for 24 h at 80 °C. [b] Isolated yields.
[c] The O-acetylamidoxime derivatives were synthetically inaccessible.
[d] Yields were determined by 1H NMR using 1,3,5-trimethoxybenzene as an
internal standard. [e] Performed on a 0.10 mmol scale. For some oxime
derivatives, an E/Z mixture was used, see the SI.
In summary, the iron-catalyzed reaction of silyl enol ethers
and oxime esters was demonstrated in three different reaction
modes of iminyl radicals for the synthesis of pyrroles, 1,6-
ketonitriles and imidazolines. Our studies show that the
intramolecular cyclization and ring-opening take place in favor of
reactions proceeding via a 1,3 hydrogen transfer. These results
are important for the further development of iron-catalyzed
coupling reactions via radical intermediates.
However, for the β,γ-unsaturated oxime acetate, a complex
mixture was obtained as the formation of 5b would require the
disfavored 5-endo-cyclization. The scope of the method was
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Campos, B. García, M. A. Rodríguez, Org. Lett. 2006, 8, 3521; j) J.
Boivin, E. Fouquet, S. Z. Zard, Tetrahedron Lett. 1991, 32, 4299.
Y.-J. Chi, H.-T. Yu, Comp. Theor. Chem. 2013, 1005, 75.
Acknowledgements
[8]
[9]
Financial support from the Swedish Research Council, VR (621-
2012-2981), the Carl Trygger foundation and the Wenner-Gren
Foundations is gratefully acknowledged.
a) Y. Guindon, B. Guérin, S. R. Landry, Org. Lett. 2001, 3, 2293; b) M.-
H. Le Tadic-Biadatti, A.-C. Callier-Dublanchet, J. H. Horner, B. Quiclet-
Sire, S. Z. Zard, M. Newcomb, J. Org. Chem. 1997, 62, 559.
[10] T. Nishimura, T. Yoshinaka, Y. Nishiguchi, Y. Maeda, S. Uemura, Org.
Lett. 2005, 7, 2425.
Keywords: acyloximes•iron•pyrroles•radicals•silyl enol ethers
[11] a) U. Jahn, Radicals in Synthesis III, Springer: Berlin, Heidelberg, 2012;
b) R. Poli, Eur. J. Inorg. Chem. 2011, 1513; c) M. T. Lemaire, Pure Appl.
Chem. 2004, 76, 277.
[1]
[2]
For selected recent reviews on Pd-catalyzed coupling reactions, see; a)
F.-S. Han, Chem. Soc. Rev. 2013, 42, 5270; b) C. E. I. Knappke, A.
Jacobi von Wangelin, Chem. Soc. Rev. 2011, 40, 4948.
[12] For selected recent articles on the addition of radicals to siliyl enol
ethers, see; a) T. Amaya, Y. Maegawa, T. Masuda, Y. Osafune, T.
Hirao, J. Am. Chem. Soc. 2015, 137, 10072; b) N. Matsuda, K. Hirano,
T. Satoh, M. Miura, Angew. Chem. 2012, 124, 11997; Angew. Chem.
Int. Ed. 2012, 51, 11827; c) H.-Y. Jang, J.-B. Hong, D. W. C. MacMillan,
J. Am. Chem. Soc. 2007, 129, 7004.
a) I. Bauer, H.-J. Knölker, Chem. Rev. 2015, 115, 3170; b) A. A. O.
Sarhan, C. Bolm, Chem. Soc. Rev. 2009, 38, 2730; c) B. Plietker, Iron-
catalysis in Organic Synthesis. Wiley-VCH: Weinheim, 2008; d) D.
Bézier, J.-B. Sortais, C. Darcel, Adv. Synth. Catal. 2013, 355, 19; e) W.
M. Czaplik, M. Mayer, J. Cvengroš, A. Jacobi von Wangelin,
ChemSusChem 2009, 2, 396; f) G. Cera, L. Ackermann, Top Curr
Chem 2016, 374, 57; g) T. C Atack, R. M. Lecker, S. P. Cook, J. Am.
Chem. Soc. 2014, 136, 9521; h) A. Guérinot, J. Cossy, Top Curr Chem
2016, 374, 49.
[13] a) N. Arai, K. Narasaka, Chem. Lett. 1995, 24, 987; b) Y. Kohno, K.
Narasaka, Bull. Chem. Soc. Jpn. 1995, 68, 322; c) P. Renaud,
Tetrahedron Lett. 1990, 31, 4601.
[14] M. Bingham, C. Moutrille, S. Z. Zard, Heterocycles 2014, 88, 953.
[15] a) G. M. Torres, J. S. Quesnel, D. Bijou, B. A. Arndtsen, J. Am. Chem.
Soc. 2016, 138, 7315; b) G.-Q. Chen, X.-N. Zhang, Y. Wei, X.-Y. Tang,
M. Shi, Angew. Chem. 2014, 126, 8632; Angew. Chem. Int. Ed. 2014,
53, 8492; c) J. Xuan, X.-D. Xia, T.-T. Zeng, Z.-J. Feng, J.-R. Chen, L.-Q.
Lu, W.-J. Xiao, Angew. Chem. 2014, 126, 5759; Angew. Chem. Int. Ed.
2014, 53, 5653; d) S. Rakshit, F. W. Patureau, F. Glorius, J. Am. Chem.
Soc. 2010, 132, 9585.
[3]
a) C. W. Cheung, F. E. Zhurkin, X. Hu, J. Am. Chem. Soc. 2015, 137,
4932; b) S. L. Daifuku, J. L. Kneebone, B. E. R. Snyder, M. L. Neidig, J.
Am. Chem. Soc. 2015, 137, 11432; c) T. Hatakeyama, T. Hashimoto, Y.
Kondo, Y. Fujiwara, H. Seike, H. Takaya, Y. Tamada, T. Ono, M.
Nakamura, J. Am. Chem. Soc. 2010, 132, 10674; d) R. Martin, A.
Fürstner, Angew. Chem. 2004, 116, 4045; Angew. Chem. Int. Ed. 2004,
43, 3955.
[16] a) H. McNab, L. Hill, S. Imam, W. O’Neill, Synthesis 2009, 2535; b) O.
Flögel, J. Dash, I. Brüdgam, H. Hartl, H.-U. Reißig, Chem. Eur. J. 2004,
10, 4283.
[4]
[5]
For selected recent reviews, see; a) J. C. Walton, Acc. Chem. Res.
2014, 47, 1406; b) M. Minozzi, D. Nanni, P. Spagnolo, Chem. Eur. J.
2009, 15, 7830; c) M. Kitamura, K. Narasaka, Bull. Chem. Soc. Jpn.
2008, 81, 539; d) S. Z. Zard, Chem. Soc. Rev. 2008, 37, 1603; e) H.
Huang, J. Cai, G.-J. Deng, Org. Biomol. Chem. 2016, 14, 1519.
a) Y. Cai, A. Jalan, A. R. Kubosumi, S. L. Castle, Org. Lett. 2015, 17,
488; b) S. J. Markey, W. Lewis, C. J. Moody, Org. Lett. 2013, 15, 6306;
c) F. Portela-Cubillo, J. S. Scott, J. C. Walton, J. Org. Chem. 2009, 74,
4934; d) F. Portela-Cubillo, J. S. Scott, J. C. Walton, Chem. Commun.
2008, 2935; e) F. Portela-Cubillo, J. S. Scott, J. C. Walton, J. Org.
Chem. 2008, 73, 5558; f) M. Yoshida, M. Kitamura, K. Narasaka, Bull.
Chem. Soc. Jpn. 2003, 76, 2003; g) F. Gagosz, S. Z. Zard, Synlett
1999, 1978; h) J. Boivin, A.-C. Callier-Dublanchet, B. Quiclet-Sire, A.-M.
Schiano, S. Z. Zard, Tetrahedron 1995, 51, 6517; i) A.-C. Callier-
Dublanchet, B. Quiclet-Sire, S. Z. Zard, Tetrahedron Lett. 1995, 36,
8791.
[17] M.-N. Zhao, Z.-H. Ren, L. Yu, Y.-Y. Wang, Z.-H. Guan, Org. Lett. 2016,
18, 1194.
[18] a) X. Tang, Z. Zhu, C. Qi, W. Wu, H. Jiang, Org. Lett. 2016, 18, 180; b)
H. Huang, J. Cai, L. Tang, Z. Wang, F. Li, G.-J. Deng, J. Org. Chem.
2016, 81, 1499; c) M. Zheng, P. Chen, W. Wu, H. Jiang, Chem.
Commun. 2016, 52, 84; d) H. Jiang, J. Yang, X. Tang, J. Li, W. Wu, J.
Org. Chem. 2015, 80, 8763; e) X. Tang, L. Huang, J. Yang, Y. Xu, W.
Wu, H. Jiang, Chem. Commun. 2014, 50, 14793; f) Q. Wu, Y. Zhang, S.
Cui, Org. Lett. 2014, 16, 1350; g) Y. Wei, N. Yoshikai, J. Am. Chem.
Soc. 2013, 135, 3756; h) Z.-H. Ren, Z.-Y. Zhang, B.-Q. Yang, Y.-Y.
Wang, Z.-H. Guan, Org. Lett. 2011, 13, 5394. For a relevant example of
pyrrole synthesis, see: i) X. Tang, L. Huang, C. Qi, W. Wu, H. Jiang
Chem. Commun. 2013, 49, 9597.
[19] a) J. Z. Hioe, H. Zipse, Radical Stability−Thermochemical Aspects. In
Encyclopedia of Radicals in Chemistry, Biology and Materials;, Wiley:,
Chichester, 2012; b) A. S. Menon, D. J. Henry, T. Bally, L. Radom, Org.
Biomol. Chem. 2011, 9, 3636; c) M. L. Coote, C. Y. Lin, A. L. J.
Beckwith, A. A. Zavitsas, Phys. Chem. Chem. Phys. 2010, 12, 9597.
[20] a) J. Streuff, M. Feurer, P. Bichovski, G. Frey, U. Gellrich, Angew.
Chem. 2012, 124, 8789; Angew. Chem. Int. Ed. 2012, 51, 8661; b) F. F.
Fleming, L. A. Funk, R. Altundas, V. Sharief, J. Org. Chem. 2002, 67,
9414.
[6]
a) N. J. Race, A. Faulkner, M. H. Shaw, J. F. Bower, Chem. Sci. 2016,
7, 1508; b) J. Ke, Y. Tang, H. Yi, Y. Li, Y. Cheng, C. Liu, A. Lei, Angew.
Chem. 2015, 127, 6704; Angew. Chem. Int. Ed. 2015, 54, 6604; c) A.
Faulkner, N. J. Race, J. S. Scott, J. F. Bower, Chem. Sci. 2014, 5,
2416; d) L. Ran, Z.-H. Ren, Y.-Y. Wang, Z.-H. Guan, Green Chem.
2014, 16, 112; e) W. Du, M.-N. Zhao, Z.-H. Ren, Y.-Y. Wang, Z.-H.
Guan, Chem. Commun. 2014, 50, 7437; f) M.-N. Zhao, H. Liang, Z.-H.
Ren, Z.-H. Guan, Synthesis 2012, 44, 1501; g) Y. Koganemaru, M.
Kitamura, K. Narasaka, Chem. Lett. 2002, 784; h) T. Nishimura, S.
Uemura, J. Am. Chem. Soc. 2000, 122, 12049.
[21] B. C. Lemercier, J. G. Pierce, Org. Lett. 2014, 16, 2074.
[22] D. Gennet, S. Z. Zard, H. Zhang, Chem. Commun. 2003, 1870.
[23] S. Sanjaya, S. Chiba, Org. Lett. 2012, 14, 5342.
[7]
a) S.-H. Cai, J.-H. Xie, S. Song, L. Ye, C. Feng, T.-P. Loh, ACS Catal.
2016, 6, 5571; b) J. Davies, S. G. Booth, S. Essafi, R. A. W. Dryfe, D.
Leonori, Angew. Chem. 2015, 127, 14223; Angew. Chem. Int. Ed. 2015,
54, 14017; c) H. Jiang, X. An, K. Tong, T. Zheng, Y. Zhang, S. Yu,
Angew. Chem. 2015, 127, 4127; Angew. Chem. Int. Ed. 2015, 54,
4055; d) R. T. McBurney, J. C. Walton, J. Am. Chem. Soc. 2013, 135,
7349; e) R. T. McBurney, A. M. Z. Slawin, L. A. Smart, Y. Yu, J. C.
Walton, Chem. Commun. 2011, 47, 7974; f) R. Alonso, P. J. Campos,
M. A. Rodríguez, D. Sampedro, J. Org. Chem. 2008, 73, 2234; g) F.
Portela-Cubillo, J. Lymer, E. M. Scanlan, J. S. Scott, J. C. Walton,
Tetrahedron 2008, 64, 11908; h) F. Portela-Cubillo, E. M. Scanlan, J. S.
Scott, J. C. Walton, Chem. Commun. 2008, 4189; i) R. Alonso, P. J.
[24] M. E. Giusepponi, C. Cifani, M. V. Micioni Di Bonaventura, L. Mattioli, A.
Hudson, E. Diamanti, F. Del Bello, M. Giannella, V. Mammoli, C. D.
Paoletti, A. Piergentili, M. Pigini, W. Quaglia, ACS Med. Chem. Lett.
2016. 7, 956.
[25] a) J. Robertson, K. Stevens, Nat. Prod. Rep. 2014, 31, 1721; b) K. M. G.
O’Connell, M. Díaz-Gavilán, W. R. J. D. Galloway, D. R. Spring,
Beilstein J. Org. Chem. 2012, 8, 850.
[26] A. Faulkner, J. S. Scott, J. F. Bower, J. Am. Chem. Soc. 2015, 137,
7224.
[27] S. Nawaz Khan, S.-Y. Bae, H.-S. Kim, Tetrahedron Lett. 2005, 46, 7675.
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10.1002/chem.201605636
Chemistry - A European Journal
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 2:
COMMUNICATION
Hai-Bin Yang, Nicklas Selander*
OTMS
R'
O
O
H
OAc
R'
R
FeII
N
NC
N
N
Page No. – Page No.
via three pathways:
hydrogen transfer
ring-opening
Divergent Iron-Catalyzed Couplings
of O-Acyloximes with Silyl Enol
Ethers
N
R
R
R'
Z
5-exo-dig cyclization
An iron-catalyzed coupling reaction of O-acyloxime/O-benzoyl amidoximes with silyl
enol ethers is reported. The protocol provides access to functionalized pyrroles,
1,6-ketonitriles, pyrrolines and imidazolines via carbon-centered radicals generated
from an initially formed iminyl radical. The intramolecular cyclization and ring-
opening processes of the iminyl radical take place preferentially over a 1,3-
hydrogen transfer, providing insights into iron-catalyzed reactions with oxime
derivatives. The cheap and environmentally friendly iron catalyst, the broad
substrate scope and functional group compatibility make this protocol useful for
synthesis of valuable nitrogen-containing products.
This article is protected by copyright. All rights reserved.