Iron-catalyzed aerobic oxidative functionalization of sp3 C-H bonds: A versatile strategy for the construction of N-heterocycles

Article abstract of DOI:10.1039/c4cy01618a

Iron-catalyzed aerobic oxidative functionalization of sp³ C-H bonds has been developed for the construction of N-heterocycles from easily available carboxylic acid derivatives and o-substituted anilines. This transformation represents a widely applicable protocol to N-heterocycles using biofriendly iron as a catalyst in combination with molecular oxygen or air as the sole oxidant. This journal is

Full text of DOI:10.1039/c4cy01618a

View Article Online
View Journal
Catalysis
Science &
Technology
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: S.-F. Yin, X.
Chen, T. Chen, Y. Zhou and F. Ji, Catal. Sci. Technol., 2015, DOI: 10.1039/C4CY01618A.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. We will replace this Accepted Manuscript with the edited
and formatted Advance Article as soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/catalysis

Catalysis Science & Technology
Page 1 of 5Journal Name
Dynamic Article Links ►
View Article Online
DOI: 10.1039/C4CY01618A
Cite this: DOI: 10.1039/c0xx00000x
www.rsc.org/xxxxxx
ARTICLE TYPE
Iron-Catalyzed Aerobic Oxidative Functionalization of sp3C-H Bonds: a Versatile
Strategy for the Construction of N-Heterocycles
Xiuling Chen,§ Tieqiao Chen,§ Fangyan Ji, Yongbo Zhou,* and Shuang-Feng Yin*
Received (in XXX, XXX) Xth XXXXXXXXX 200X, Accepted Xth XXXXXXXXX 200X
5
DOI: 10.1039/b000000x
An iron-catalyzed aerobic oxidative functionalization of sp3C-
H bonds has been developed for the construction of N-
heterocycles from easily available carboxylic acid derivatives
and o-substituted anilines. This transformation represents a
heterocyclic compounds which are ubiquitous core units of
various biologically active drugs and natural products.15,16
10 widely applicable protocol to N-heterocycles using biofriendly
iron as catalyst in combination with molecular oxygen or air
as the sole oxidant.
The application of iron salts as catalysts in organic synthesis
has attracted much attention due to their abundance, low price,
15 less toxic and biofriendly properties.1 For example, iron salts
have been utilized extensively to promote the traditional
cross-coupling,2 Friedel–Crafts benzylation,3 carbonylation4
and other processes.5-8 Iron-catalyzed oxidations for C-H
bonds have also been extensively developed6-8 with Gif
20 chemistry6 and Fenton chemistry being the most famous.7
However, these oxidations have commonly depended on
hazardous peroxides. Nowadays, the improvement emphasizes
on the development of synthetic models, using a “green”
oxidant such as readily available and nontoxic O2 or air.9
25 Therefore, the iron-catalyzed aerobic oxidation of C-H bonds
is highly desired. In 2012, Maes et al realized iron-catalyzed
aerobic oxidation of benzylic C-H bonds in diarylmethanes for
the preparation of diarylketones.10 Subsequently, Kappe et al
developed gas-liquid continuous-flow technology to improve
30 Maes’ iron-catalyzed aerobic oxidation system.11 Despite
these advances, further Iron-catalyzed aerobic oxidative
functionalization of sp3C-H bonds is rare.12 Currently, the
decarboxylation reactions are also emerging as the powerful
methodology for the construction of carbon-carbon bonds and
35 carbon-heteroatom bonds in organic synthesis due to the
readily available substrates, simple operation and clean
byproduct (only CO2 as the byproduct).13,14 Herein, we
communicate an efficient strategy of iron-catalyzed aerobic
oxidative functionalization of sp3C-H bonds to construct N-
40 heterocycles from easily accessible carboxylic acid
derivatives and o-substituted anilines (eq 1). In the present
catalytic system, we achieved aerobic oxidation of sp3C-H
bonds, decarboxylation and oxidative cyclization in one pot.
Compared to conventional methods, this procedure is
45 distinguished by using biofriendly iron catalyst in
combination of clean dioxygen oxidant. This new method
provides a general and environmentally friendly access to N-
50
o-Aminobenzamide 1a and phenylacetic acid 2a were
chosen as the model substrates for optimization of the present
iron-catalyzed aerobic oxidative functionalization of sp3C-H
55 bonds to construct N-heterocycles and the results are compiled
in Table 1. Preliminary screening shows that various iron
catalysts can catalyze the reaction alone without any ligands,
bases or additives, and FeCl3 shows the highest catalytic
efficiency among the examined iron catalysts (Table 1, entries
60 1-7). In the presence of 10 mol% FeCl3, this tandem reaction
takes place smoothly at 100 oC in DMF to produce the
corresponding 2-phenyl quinazolin-4(3H)-one compound 3a
in 92% yield (Table 1, entry 7). Worth noting is that iron
catalyst is essential for the current catalytic system. In the
65 absence of iron complex, this reaction cannot work and no
product is detectable at all (Table 1, entry 8). Other metal
complexes such as PdCl2, NiCl2.6H2O and CuCl2 (Note: Cu
salts are used as good catalyst for the oxidative
decarboxylation of the sp3C-H bonds9e-9g) cannot mediate the
70 present reaction (Table 1, entries 9-11). The solvents also play
an important role, and only DMF serves as the good solvent
(Table 1, entries 12-15). Under the similar reaction conditions,
replacement of dioxygen with other oxidants such as TBHP,
DTBP, mCPBA and K2S2O8 results in no yield of the desired
75 product (Table 1, entries 16-17). This transformation also
depends on the reaction temperature. For example, catalyzed
o
by 10 mol% FeCl3, the reaction doesn’t occur at 80 C (Table
1, entry 18), while the yield dramatically increases to 92% at
100 oC (Table 1, entry 7). However, further increase of
80 reaction temperature to 120 oC leads to no evident
improvement on product yield (Table 1, entry 19).
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 | 1

Catalysis Science & Technology
Page 2 of 5
View Article Online
DOI: 10.1039/C4CY01618A
Table 1. Optimization of the reaction conditionsa
Table 2. Synthesis of 2-substituted quinazolin-4(3H
)-onesa
Entry
Catalyst
Solvent
Yieldb (%)
5
aReaction conditions: 1a (0.2 mmol), 2a (0.22 mmol), catalyst (0.02
mmol), sovent (1 mL), O2 (1 atm) in a Schlenk tube (10 mL) at 100 oC, 12
b
h, recharging dioxygen after 6 h. GC yields based on 1a using dodecane
as an internal standard. c0.5 mmol m-CPBA (m-chloroperbenzoic acid) or
K2S2O8 was employed as oxidant under N2 (1 atm) atmosphere. d0.5 mmol
10 TBHP (tert-butylhydroperoxide) or DTBP (di-tert-butyl peroxide) was
f
used as oxidant under N2 (1 atm) atmosphere. e80 oC. 120 oC.
This iron-catalyzed aerobic oxidative functionalization of
sp3C-H bonds can be successfully applied to other substrates,
showing that this reaction is a general method for the
15 preparation of N-heterocyclic compounds, i.e. quinazolin-
4(3H)-ones (Table 2), quinazolines (Table 3), benzimidazoles
and benzothiazoles (Table 4). As shown in Table 2, o-
aminobenzamide 1a reacts readily with different kinds of
arylacetic acids bearing both electron-donating groups and
20 electron-withdrawing groups on the aromatic cycles to give
the corresponding quinazolin-4(3H)-ones. Various valuable
functional groups such as OMe 2b, OH 2c, NH2 2d, NO2 2e,
Br 2f and Cl 2g all survive in the present catalytic system and
the expected products are produced in high yields. Especially,
25 the iodine substituted phenylacetic acid also reacts readily
with o-aminobenzamide 1a under similar reaction conditions,
generating the desired product 3h in 68% yield. Catalyzed by
10 mol% FeCl3, both 1-naphthylacetic acid and 2-
naphthylacetic acid undergo aerobic oxidation tandem
30 reaction with 1a and the corresponding products 3i and 3j are
afforded in 82% and 85% yields, respectively. Furthermore,
different kinds of heterocycles can be introduced into
35
a
Reaction conditions: 1a-1d (0.2 mmol), 2a-2o (0.22 mmol), FeCl3
(0.02 mmol, 10 mol%), DMF (1 mL), O2 (1 atm) in a Schlenk tube (10
o
mL) at 100 C, 12 h, recharging dioxygen after 6 h. Chlorobenzene as
b
o
solvent, 3 equivs propionic acid, 140 C, 12 h, recharging dioxygen after
40 6 h.
quinazolin-4(3H)-one molecule using the current aerobic
oxidative functionalization of sp3C-H bonds. Under
dioxygen atmosphere, the reaction of 2-thiopheneacetic acid
and 1a takes place smoothly in the presence of 10 mol%
o
45 FeCl3 at 100 C in DMF, furnishing the expected product 3k
in 80% yield. 3-Pyridylacetic acid 2l is also an efficient
2
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 3 of 5
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C4CY01618A
substrate and can be converted to 3l in 80% yield. 2-(1H-
indol-3-yl)quinazolin-4(3 )-one 3m bearing indolyl has
been synthesized from the reaction of 2-(1H-indol-3yl)acetic
acid and 1a. In addition to
-aminobenzamides also serve as good substrates and react
with arylacetic acids to afford the corresponding quinazolin-
4(3 )-one derivatives 3n 3p. Using ethyl 2-phenylacetate
2n instead of 2-phenylacetic acid, the tandem reaction
compounds like benzimidazoles and benzothiazoles (Table 4).
Benzothiazole 5a is obtained from similar reaction of o-
aminothiophenol 1f with 2b. Other substituted phenylacetic
H
o
-aminobenzamide 1a, substituted 40 acid also serves as good substrates, affording the
5
o
corresponding benzothiazoles 5b-5d in high yields. Besides,
bioactive benzimidazoles 5e and 5f have been prepared from
the reaction of o-phenylenediamine 1g with phenylacetic acid
and 2-(thiophen-2-yl)aceticacid under similar reaction
H
-
proceeds smoothly, giving the desired product 3a in 69% 45 conditions and the yields are 80% and 81%, respectively.
10 yield. In addition, 2-methylquinazolin-4(3 )-one 3q is
H
Table 4. Fe-catalyzed aerobic oxidative amidation of sp3C-H bonds
obtained in 60% yield from propionic acid 2o and
o-
for the synthesis benzimidazoles and benzothiazolesa
aminobenzamide.
Table 3. Synthesis of 2-substituted quinazolinesa
N
N
N
N
N
N
4a, 90%
4b, 80%
4c, 79%
O
OH
2a, PhCH2COOH
2b, p-OMe-PhCH2COOH
2c, p-OH-PhCH2COOH
N
N
N
N
N
N
Br
NO2
NH2
4f, 83%
4d, 75%
4e, 90%
2e, p-NO2-PhCH2COOH
2f, p-Br-PhCH2COOH
2d, p-NH2-PhCH2COOH
N
N
N
S
N
N
N
50
4g. 83%
4h,78%
4i, 81%
Cl
aReaction conditions: 1f-1g (0.2 mmol), 2a-2i (0.22 mmol), FeCl3 (0.02
mmol, 10 mol%), DMF (1 mL), O2 (1 atm) in a Schlenk tube (10 mL) at
100 oC, 12 h, recharging dioxygen after 6 h.
2g,m-Cl-PhCH2COOH
2i, 1- C10H7CH2COOH 2k, 2-thiopheneacetic acid
15
aReaction conditions: 1e (0.2 mmol), 2a-2k (0.22 mmol), FeCl3 (0.02
mmol, 10 mol%), DMF (1 mL), air (1 atm) in a Schlenk tube (25 mL) at
100 oC, 18 h, recharging air after 6 h.
To clarify the reaction mechanism, several control
55 experiments were performed. In the nitrogen atmosphere,
phenylacetic acid 2a is recovered completely and no
decarboxylative products are detectable under similar
condition (eq 2). Thus it is reasonable that the aerobic
oxidation of sp3C-H bonds takes place prior to
60 decarboxylation.17 In addition, α-hydroxyphenylacetic acid 2p
reacts with o-aminobenzamide 1a smoothly under the optimal
condition to give the corresponding product 3a in 88% yield
(eq 3). When 2-oxo-2-phenylacetic acid 2q is used as
substrate without the aid of anhydrous FeCl3, the reaction with
65 1a takes place to give 3a in 81% yield (eq 4). While in the
absence of 1a, benzaldehyde is generated in 99% yield from
the iron-catalyzed aerobic oxidation of phenylacetic acid, and
the resulting benzaldehyde can further react with 1a to furnish
3a in 97% yield (eq 5). Therefore, it is speculated that α-
70 hydroxyphenylacetic acid, 2-oxo-2-phenylacetic acid and
benzaldehyde probably serve as the efficient intermediates in
the current iron-catalyzed aerobic oxidation-decarboxylation-
cyclization system. When phenylacetic acid 2a was replaced
To our delight, quinazoline derivatives 4 have been efficiently
20 synthesized using the current aerobic oxidative functionalization
of sp3C-H bonds (Table 3). It is noted that the reaction of 2-
aminobenzylamine with arylacetic acid can occur smoothly under
air atmosphere catalyzed by 10 mol% FeCl3 at 100 oC in DMF to
give the expected product 4a in 90% yield. As shown in Table 3,
25 similar to the substrate scope for the synthesis of quinazolin-
4(3H)-one derivatives, arylacetic acids holding both electron-
donating groups and electron-withdrawing groups on the
aromatic cycles work well and react readily with 2-
aminobenzylamine to give the corresponding quinazolines in high
30 yields. Noteworthy, valuable functional groups such as OMe, OH,
NH2, NO2, Br and Cl all are compatible under the present
reaction conditions. The heterocycle exemplified by 4i having
thiophenyl has also been introduced into quinazoline framework
by this strategy.
35
Under the optimal reaction conditions, the protocol can be
applied to preparation of the bioactive five-membered
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3

Catalysis Science & Technology
Page 4 of 5
View Article Online
DOI: 10.1039/C4CY01618A
by 1,2-propanediol 2r, the 2-methylquinazolin-4(3H)-one 3q
was obtained in 75% yield (eq 6). Moreover, when the radical
trapper BHT (2,6-di-tert-butyl-4-methylphenol) is loaded, the
reaction of 1a with 2a does not occur and no product 3a or
generating aldehyde, which is captured by o-substituted
anilines to produce N-heterocyclic compounds under oxygen
atmosphere.16
In summary, we have developed an efficient strategy of
sp3C-H
5
benzaldehyde can be detected, indicating that this iron- 25 iron-catalyzed
catalyzed bonds aerobic oxidation and functionalization
sp3C-H
bonds
aerobic
oxidative
The
to
construct
N-heterocycles.
decarboxylation of arylacetic acids proceeds via a radical
transformation occurs via a tandem sequence involving iron-
catalyzed sp3C-H bonds aerobic oxidation, decarboxylation
and subsequent oxidation cyclization. This method also
30 provides an environmentally friendly protocol to N-
heterocyclic compounds from easily accessible carboxylic
acid derivatives and o-substituted anilines with wide substrate
scope.
process (eq 7).
1a (0.2 mmol)
COOH
FeCl3 (10 mol%)
COOH
(2)
(3)
DMF, N2, 100 oC, 12 h
100% recover
2a, 0.22 mmol
O
OH
O
NH2
COOH
NH
+
FeCl3 (10 mol%)
Acknowledgements
DMF, O2, 100 oC,12 h
NH2
1a, 0.2 mmol
O
N
Ph
2p, 0.22 mmol
3a, 88%
35 This work was supported by the NSFC (U1162109, 21273066,
21172062, 21273067), Program for Changjiang Scholars and
Innovative Research Team in University (IRT1238), and the
Fundamental Research Funds for the Central Universities
(Hunan University).
O
O
NH2
+
NH2
NH
COOH
DMF, O2
100 oC, 5 h
(4)
(5)
N
Ph
1a, 0.2 mmol
2q, 0.22 mmol
3a, 81%
O
40 Notes and references
1a
100 o
COOH
H
FeCl3 (10 mol%)
§These authors contributed equally to this work.
* State Key Laboratory of Chemo/Biosensing and Chemometrics, College
of Chemistry and Chemical Engineering, Hunan University, Changsha,
410081, P. R. China. Fax: (+) 86-731-88821171.; E-mail:
45 zhouyb@hnu.edu.cn; sf_yin@hnu.edu.cn
C
3a
DMF, O2, 100 oC, 12 h
DMF, O2, 12 h
>99%
97%
2a, 0.2 mmol
O
O
HO
OH
H
FeCl3 (10 mol%)
NH
NH2
† Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See DOI:
10.1039/b000000x/
(6)
(7)
PhCl, O2, 100 oC,12 h
+
N
NH2
1a, 0.2 mmol
2r, 0.22 mmol
3q, 75%
1
For some reviews: a) C. Bolm, J. Legros, J. Le Paih and L. Zani,
Chem. Rev. 2004, 104, 6217-6254; b) C. Sun, B. Li and Z. Shi,
Chem. Rev. 2011, 111, 1293-1314; c) F. Jia and Z. Li, Org. Chem.
Front. 2014, 1, 194-214; d) J. E. M. N. Klein and B. Plietker, Org.
Biomol. Chem. 2013, 11, 1271-1279; e) K. C Majumdar, N. De, T.
O
O
50
NH2
COOH
BHT (4 eqiv)
FeCl3 (10 mol%)
DMF, O2, 100 oC, 12 h
NH
+
NH2
N
Ph
Ghosh
and
B.
Roy,
Tetrahedron.
2014,
doi:
3a, 0%
1a, 0.2 mmol
2a, 0.22 mmol
55
10.1016/j.tet.2014.04.025.
2
3
a) R. Chinchilla and C. Nájera, Chem. Rev. 2007, 107, 874-922; b)
B. D. Sherry and A. Fürstner, Acc. Chem. Res. 2008, 41, 1500-1511;
c) W. Liu, H. Cao and A. Lei, Angew. Chem. Int. Ed. 2010, 49,
2004-2008; d) J. P. Knowles and A.Whiting, Org. Biomol. Chem.
2007, 5, 31-44 and references therein.
10
On the basis of results described above and in
literatures,9,10,16,18 a plausible reaction process for the present
iron-catalyzed aerobic oxidative functionalization of sp3C-H
bonds is proposed as shown in Scheme 1. In the Fe/O2 system,
the C-H bonds are first oxidized to form α-hydroxycarboxylic
60
a) M. Bandini, M. Tragni and A. Umani-Ronchi, Adv. Synth. Catal.
2009, 351, 2521-2524; b) I. Iovel, K. Mertins, J. Kischel, A. Zapf
and M. Beller, 3981-3985; Angew. Chem. Int. Ed. 2005, 44, 3913-
3917.
15 acid via a radical path, followed by dehydrogenation to give
2-oxo-2-carboxylic acid.9,10,18 Subsequently, the resulting 2-
65
70
75
4
5
K. M. Driller, H. Klein, R. Jackstell and M. Beller, Angew. Chem.
Int. Ed. 2009, 48, 6041-6044.
a) W. Han and A. R. Ofial, Chem.Commun. 2009, 5024-5026; b) S.
Prateeptongkum, I. Jovel, R. Jackstell, N. Vogl, C. Weckbecker and
M. Beller, Chem. Commun. 2009, 1990-1992; c) K. Kohno, K.
Nakagawa, T. Yahagi, J. C. Choi, H. Yasuda and T. Sakakura, J. Am.
Chem. Soc. 2009, 131, 2784-2785; d) J. Kischel, I. Jovel, K. Mertins,
A. Zapf and M. Beller, Org. Lett. 2006, 8, 19-22; e) P. Spannring, I.
Prat, M. Costas, M. Lutz, P. C. A. Bruijnincx, B. M. Weckhuysend
and R. J. M. Klein Gebbink, Catal. Sci. Technol. 2014, 4, 708–716;
f) Y. Song, X. Tang, X. Hou and Y. Bai, Chin. J. Org. Chem. 2013,
33, 76-89 and references therein.
6
7
8
M. J. Perkins, Chem. Soc. Rev. 1996, 25, 229-236.
S. Goldstein, and D. Meyerstein, Acc. Chem. Res. 1999, 32, 547-550.
a) W. Nam, Acc. Chem. Res. 2007, 40, 522-531; b) S. Shaik, H.
Hirao and D. Kumar, Acc. Chem. Res. 2007, 40, 532-542; c) Z. Li, L.
Cao and C. Li, Angew. Chem. Int. Ed. 2007, 46, 6505-6507; d) Y.
Scheme 1. Plausible reaction process for the construction of N-
heterocycles from arylacetic acid and o-substituted anilines
80
20 oxo-2-carboxylicacetic acid undergoes decarboxylation
4
| Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 5 of 5
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C4CY01618A
Zhang and C. Li, Eur. J. Org. Chem. 2007, 4654-4657; e) C. Song,
G. Cai, T. R. Farrell, Z. Jiang, H. Li, L. Gan and Z. Shi, Chem.
Commun. 2009, 6002-6004; f) H. Li, Z. He, X. Guo, W. Li, X. Zhao
and Z. Li, Org. Lett. 2009, 11, 4176-4179; g) Z. Wang, Y. Zhang, H.
Fu, Y. Jiang and Y. Zhao, Org. Lett. 2008, 10, 1863-1866; h) F.
Szabó, B. Pethő, Z. Gonda and Z. Novák, RSC Adv. 2013, 3, 4903-
4908; i) T. Wang, W. Zhou, H. Yin, J. Ma and N. Jiao, Angew.
Chem. Int. Ed. 2012, 51, 10823-10826; j) S. Grupe and A. Jacobi
vonWangelin, ChemCatChem, 2013, 5, 706-710; k) S. Iwata, T.
Hata and H. Urabe, Adv. Synth. Catal. 2012, 354, 3480-3484; l) M.
Nakanishi and C. Bolm, Adv. Synth. Catal. 2007, 349, 861-864.
a) Z. Shi, C. Zhang, C. Tang and N. Jiao, Chem. Soc. Rev. 2012, 41,
3381-3430; b) W. Wu and H. Jiang, Acc. Chem. Res. 2012, 45,
1736-1748; c) S. E. Allen, R. R. Walvoord, R. Padilla-Salinas and
M. C. Kozlowski, Chem. Rev. 2013, 113, 6234-6458; d) H. Guo, A.
Al-Hunaiti, M. Kemell, S. Rautiainen, M. Leskelä and T. Repo,
ChemCatChem, 2011, 3, 1872-1875; e) Q. Song, Q. Feng, and K.
Yang, Org. Lett. 2014, 16, 624-627; f) Q. Feng and Q. Song, J. Org.
Chem. 2014, 79, 1867-1871; g) Q. Feng and Q. Song, Adv. Synth.
Catal. 2014, 356, 1697-1702.
because 100% 2n was recovered from the reaction system under N2
atmosphere (eq 9).
5
70
10
9
18 M. Kamitani, M. Ito, M. Itazaki and H. Nakazawa, Chem. Commun.
2014, 7941-7944.
15
20
10 J. D. Houwer, K. A. Tehrani and B. U. W. Maes, Angew.Chem. Int.
Ed. 2012, 51, 2745 -2748.
11 B. Pieber and C. O. Kappe, Green Chem. 2013, 15, 320-324.
12 A. Gonzalez-de-Castro, C. M. Robertson, and J. Xiao, J. Am. Chem.
Soc. 2014, 136, 8350−8360.
25
13 a) L. J. Goossen and K. Goossen, in Topics in Organometallic
Chemistry Vol. 44 (Ed.: L. J. Goossen), Springer, Heidelberg, 2013,
pp. 121–141; b) N. Rodr guez and L. J. Goossen, Chem. Soc. Rev.
2011, 40, 5030-5048; b) S. M. Bonesi and M. Fagnoni, Chem. Eur.
J. 2010, 16, 13572-13589.
30
14 a) H. Bi, W. Chen, Y. Liang and C. Li, Org. Lett. 2009, 11, 3246-
3249; b) H. Yang, H. Yan, P. Sun, Y. Zhu, L. Lu, D. Liu, G. Rong
and J. Mao, Green Chem. 2013, 15, 976-981; c) K. Yang, C. Zhang,
P. Wang, Y. Zhang and H. Ge, Chem. Eur. J. 2014, 20, 7241-7244.
35 15 a) R. W. DeSimone, K. S. Currie, S. A. Mitchell, J. W. Darrow and
D. A. Pippin, Comb. Chem. High Throughput Screen. 2004, 7, 473-
493; b) P. D. Leeson and B. Springthorpe, Nat. Rev. Drug Discov.
2007, 6, 881-890; c) X. Wu, L. He, H. Neumann and M. Beller,
Chem. Eur. J. 2013, 19, 12635-12638.
40 16 There are several methods to prepare N-heterocyclic compounds,
in which the coupling of 2-substituted aniline with aldehydes was
the popular choice. Although aldehydes can serve as the efficient
starting material for the preparation of N-heterocyclic compounds,
the aldehydes are chemically unstable for preparation and suffer
45
50
55
60
65
from difficult storage. Thus, efficient alternative methods are still
desired. For selected examples using aldehyde as starting material
see: a) G. Wang, C. Miao, H. Kang and Bull. Chem. Soc. Jpn. 2006,
79, 1426-1430; b) C. Balakumar, P. Lamba, D. P.Kishore, B. L.
Narayana, K. V. Rao, K. Rajwinder, A. R. Rao, B. Shireesha and B.
Narsaiah, Eur. J. Med. Chem. 2010, 45, 4904-4913; c) C.
Balakumar, P. Lamba, D. P. Kishore, B. L. Narayana, K. V. Rao, K.
Rajwinder, A. R. Rao, B. Shireesha and B. Narsaiah, Eur. J. Med.
Chem. 2010, 45, 4904-4913; For selected examples of Ullmann-type
N-arylation, see: d) D. S. Yang, Y. Y. Wang, H. J. Yang, T. Liu and
H. Fu, Adv. Synth. Catal. 2012, 354, 477-482; for selected examples
using alcohol as starting material, see: e) M. Heidary, M. Khoobi, S.
Ghasemi, Z. Habibi and M. Ali Faramarzi, Adv. Synth. Catal. 2014,
1789-1794; for CO insertion and intramolecular cyclization, see: f)
B. Ma, Y. Wang, J. L. Peng and Q. Zhu, J. Org. Chem. 2011, 76,
6362-6366; for selected examples using amines as starting material,
see: g) T. B. Nguyen, L. Ermolenko and A. Al-Mourabit, Green
Chem. 2013, 15, 2713-2717.
17 When ethyl 2-phenylacetate 2n (efficient substrate for the current
catalytic system, see Table 2) was loaded in the absence of 1a under
similar condition, ethyl 2-oxo-2-phenylacetate was produced in 31%
yield after 12 hours (eq 8). It should be noted that the hydrolysis of
ethyl 2-phenylacetate does not occur during the reaction process,
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 5