Palladium-catalyzed carbonylative synthesis of N-(2-cyanoaryl)benzamides and sequential synthesis of quinazolinones

Article abstract of DOI:10.1016/j.tet.2013.11.055

A convenient procedure for the synthesis of N-(2-cyanoaryl)benzamides has been developed. Using aryl bromides and 2-aminobenzonitriles as the substrates, Mo(CO)₆ as the CO source, the desired amides were produced in good yields. Quinazolinones

Full text of DOI:10.1016/j.tet.2013.11.055

Tetrahedron 70 (2014) 23e29
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Palladium-catalyzed carbonylative synthesis of N-(2-cyanoaryl)
benzamides and sequential synthesis of quinazolinones
,
b
,
b
,
,
Xiao-Feng Wu a , Stefan Oschatz c, Muhammad Sharif b d, Matthias Beller b,
*
,c,
Peter Langer b
*
a Department of Chemistry, Zhejiang Sci-Tech University, Xiasha Campus, Hangzhou 310018, Zhejiang Province, People’s Republic of China
Leibniz-Institut fur Katalyse e.V. an der Universitat Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
b
€
€
c
€
€
Universitat Rostock, Institut fur Chemie, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
d Department of Chemistry, Comsats Institute of Information Technology, 22060 Abbottabad, Pakistan
a r t i c l e i n f o
a b s t r a c t
Article history:
A convenient procedure for the synthesis of N-(2-cyanoaryl)benzamides has been developed. Using aryl
bromides and 2-aminobenzonitriles as the substrates, Mo(CO)6 as the CO source, the desired amides
were produced in good yields. Quinazolinones were produced in good yields in a sequential manner as
well.
Received 1 November 2013
Received in revised form 13 November 2013
Accepted 18 November 2013
Available online 22 November 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Palladium catalyst
Carbonylation
Mo(CO)6
Amide
Quinazolinone
1. Introduction
Functionalized benzamides are an important class of com-
pounds with broad applications in pharmaceuticals and advanced
materials (Fig. 1).1 Since the pioneering work of Schoenberg and
Heck in 1974 on palladium-catalyzed aminocarbonylation of aryl
halides,2 impressive progresses have been realized in this area.3 As
expensive high-pressure equipment is needed to perform the re-
actions with this odorless, toxic, and flammable gas, synthetic
chemists are usually reluctant to use CO gas-based carbonylation
methodologies in laboratories.
Based on the interesting applications of carbonylation reactions
and the above-mentioned limitations, many research groups are
working on alternative CO sources exploration.4 Such as, Larhed
et al. did a great work on the carbonylative coupling chemistry with
Mo(CO)6 as CO precursor.5 Amongst others, they reported the
aminocarbonylation of aryl halides with Mo(CO)6 under microwave
irradiation.6 So far, Mo(CO)6 as CO source has also been applied for
many other carbonylative coupling reactions, such as Suzuki-,7
Stille-,8 and Sonogashira-coupling.9 Recently, Skrydstrup et al.
* Corresponding authors. E-mail addresses: xiao-feng.wu@catalysis.de (X.-F. Wu),
peter.langer@uni-rostock.de (P. Langer).
Fig. 1. Selected examples of biologically active benzamides.
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.11.055

24
X.-F. Wu et al. / Tetrahedron 70 (2014) 23e29
published a two-chamber carbonylation method via ex situ gen-
eration of CO from acid chloride derivatives.10 Among the amides,
benzanilides are an interesting analogue of compounds and many
procedures have been reported for their preparation.11 For exam-
ple, the condensation of aniline with benzoic acid, oxidation pro-
cedures, and coupling reactions.
Palladium-catalyzed aminocarbonylation was applied in their
preparation as well.12 Such as the procedure developed by Beller
et al. based on one-pot diazotization/aminocarbonylation of ani-
lines to give symmetric benzamides using CO gas (10 bar) at
50 ꢀC.12a More recently, Iranpoor et al. reported a Mo(CO)6/nor-
bornadiene-mediated aminocarbonylation of aryl iodides with
electron-rich amines in diglyme.13 However, to the best of our
knowledge, the use of steric hindered and low nucleophilic anilines
as nucleophiles are not reported.
Scheme 2. Quinazolinones from N-(2-cyanoaryl)-benzamides.
intermediates of these bromides may be responsible for the de-
creased yields.
2. Results
Subsequently, we carried out the one-pot transformation of
different N-(2-cyanoaryl)benzamides (Table 2). Four different types
of quinazolinones were produced in moderate to good yields by
this sequential procedure. The best yield was observed with our
model substrate and electron donating substituted examples (Table
2, entries b1 and b2). Substituents in ortho-position to the cyano
group did not give any quinazolinone product. This can be
explained by the steric hindrance and the suppressed attack of the
hydroperoxide anion. Good to excellent yields of quinazolinones
can be obtained if the yields are calculated based on the formation
of amides. Notably, compared with our previous developed
palladium-catalyzed carbonylative synthesis of quinazolinones,16
the current methodology successfully avoids the manipulation of
carbon monoxide gas.
In this work we wish to present here a convenient palladium-
catalyzed method to synthesize N-(2-cyanoaryl)benzamides from
steric hindered 2-aminobenzonitriles. A range of the desired
products has been isolated in good yields. Interestingly, Mo(CO)6
was applied as a CO source in this procedure. CataCXium AÒ was
proved to be the best ligand for this reaction. Additionally, the one-
pot synthesis of quinazolinones from N-(2-cyanoaryl)benzamides
was realized as well.
The general procedure for the synthesis of benzamides from aryl
bromides and 2-aminobenzonitrile derivative has been shown in
Scheme 1. The model reaction was performed with 2-
aminobenzonitrile and 1.2 equiv of bromobenzene in DMF with
0.5 equiv Mo(CO)6, under the assistant of Pd(OAc)2 (3 mol %) and
CataCXium A (6 mol %) at 130 ꢀC for 16 h. DBU (1.5 equiv) was used
as the base, which additionally acts as a promoter to assist the re-
lease of CO from Mo(CO)6. In the absence of palladium catalyst, no
desired amide could be observed. Temperatures below 130 ꢀC lead
to a drastically decrease of the conversion.
3. Conclusion
In conclusion, we developed a convenient way to synthesize N-
(2-cyanoaryl)benzamides from electron withdrawing substituted
and steric hindered amines through aminocarbonylation with dif-
ferent bromoarenes. The reactions were carried out using Mo(CO)6
as solid CO source. We showed that these reactions can be carried
out with many different weak nucleophilic amines as well as a va-
riety of bromoarenes in 21e92% yields. This methodology does not
require special equipment, such as microwave irradiation or auto-
claves. Furthermore, we elaborated an advantageous way to syn-
thesize N-phenyl-quinazolinones through aminocarbonylation of
2-aminobenzonitriles with bromoarenes and a subsequent oxi-
dant assisted rearrangement in a one-pot manner. Through the
presented method, biological interesting heterorganic compounds
can be easily prepared.
Scheme 1. Synthesis of N-(2-cyanoaryl)benzamides.
Furthermore, we investigated the urea hydroperoxide (UHP)
mediated-cyclization of the obtained N-(2-cyanoaryl)benzamides
to yield the corresponding quinazolinones. This structure holds
very important applications in the pharmaceutical chemistry.14 We
performed the reactions directly in the vessel without further pu-
rification of the amides. The proposed mechanism for this trans-
formation is shown in Scheme 2. The hydroperoxide anion attacks
the nitrile group, followed by a rearrangement to give the quina-
zolinones after intramolecular condensation.15
The substrate-scope for the aminocarbonylation to yield amides
is shown in Table 1. Various substituents and heteroaromatic 2-
aminonitriles were tested and gave the desired products in mod-
erate to good yields under standard conditions (Table 1, entries
a1e12). But low conversion was observed when we try to apply 4-
chloro-2-benzonitrile as substrate (Table 1, entry a2). Subsequently,
different aryl bromides were tested with 2-aminobenzonitrile
(Table 1, entries a13e25). In general, better results were obtained
with electron withdrawing substituents (Table 1, entries a13, a14,
a20), while heteroaromatic arenes gave lower yields (Table 1, en-
tries a11, a12, a16, a23). The low stability of the Pd-arene
4. Experimental section
4.1. General
DMF was 99.7% over molecular sieve purchased by Sigma
Aldrich. All Chemicals were commercial available and were used
without further purification. NMR-data was recorded by a Bruker
ARX 300 and Bruker ARX 400 spectrometers. 13C and 1H spectra
were referenced to deuterated solvent signals. Peaks were charac-
terized as singlet (s), doublet (d), doublet of doublet (dd), triplet (t),
triplet of triplets (tt), quartet (q) and multiplet (m). Gas-chroma-
tographiy-mass-analysis was measured by an Agilent HP-5890
with Agilent HP-5973 Mass Selective Detector (EI) and HP-5-
capillary column using helium as carrier gas. Column-chromatog-
raphiy was carried out using Merck 60 Silica-Gel (0.043e0.06 mm)
and distilled solvents were used.

X.-F. Wu et al. / Tetrahedron 70 (2014) 23e29
25
Table 1
Synthesis of N-(2-cyanoaryl)benzamides with Mo(CO)6 as CO-sourcea
Entry
ArNH2
ArBr
Product
Yieldb (%)
a1
79
0c
a2
a3
21
66
a4
a5
a6
a7
92
42
64
a8
71
54
44
a9
a10
a11
a12
a13
50
66
36
(continued on next page)

26
X.-F. Wu et al. / Tetrahedron 70 (2014) 23e29
Table 1 (continued )
Entry
ArNH2
ArBr
Product
Yieldb (%)
a14
68
a15
a16
a17
31
40
61
a18
a19
39
82
a20
a21
49
61
a22
43
a
Reaction conditions: 1 equiv amine, 1.2 equiv bromoarene, 0.5 equiv Mo(CO)6, 1.5 equiv DBU, 3 mol % Pd(OAc)2, 6 mol % CataCXium A, 4 mL DMF, 130 ꢀC, 16 h.
Isolated yields.
Traces of the desired product been detected in GC/MS.
b
c
General procedure for the synthesis of N-(2-cyanoaryl)benzamides
CHAr(6þ10þ11þ12)), 7.44 (ddd, 1H, 3J¼7.6 Hz, 3J¼7.6 Hz, 4J¼1.2 Hz,
from 2-aminobenzonitriles and bromoarenes with Mo(CO)6 as CO
source: 1 mmol 2-aminobenzonitrile (118 mg), 1.2 mmol bromo-
benzene, 6.7 mg Pd(OAc)2 (3 mol %), 21.5 mg CataCXium A
CHAr(4)) ppm; 13C NMR (75 MHz, DMSO-d6):
d¼165.7 (C]O(7)),
140.4 (Cquart(1)), 133.8 (CH(5)), 133.5 (Cquart(8)), 133.1 (CH(3)), 132.2
(CH(11)), 128.6 (CH(10þ12)), 127.8 (CH(9þ13)), 126.8 (CH(6)), 126.4
(CH(4)), 117.0 (Cquart(14)), 109.4 (Cquart(2)) ppm; MS (EI, 70 eV): m/z
(%)¼222 ([M]þ, 23), 105 (100), 77 (52), 51 (15).
(6 mol %), 1.5 mmol DBU (225 ml), 0.5 mmol Mo(CO)6 (132 mg), and
4 mL DMF were given in an argon flushed pressure tube, which was
subsequently sealed. The mixture was heated to 130 ꢀC under
stirring for 16 h. After cooling to room temperature, the crude
mixture was diluted in ethyl acetate and washed with water. The
aqueous phase was extracted twice with ethyl acetate. The organic
layers were combined, dried over Na2SO4, and the solvent was re-
moved under reduced pressure. Column chromatography (hexane/
ethyl acetate 8:2) gave 176 mg (79%) N-(2-cyanophenyl)benzamide
(a1) as a white solid. Mp 154e156 ꢀC; 1H NMR (300 MHz, DMSO-
General procedure for the synthesis of quinazolinones: To the
crude reaction mixture described above was given 1.8 equiv of urea
hydrogen peroxide. The mixture was heated to 100 ꢀC under stir-
ring for 7 h. After cooling, 20 mL water was added to precipitate the
crude quinazolinone. The solid was filtered off and washed with
hexane/ethyl acetate (8:2). The residue was dissolved in the mini-
mum amount of boiling ethyl acetate and recrystallized by the
addition of hexane. Filtering gave 170 mg (76%) N-phenyl-
quinazolinone (b1) as a white solid. Mp 241e243 ꢀC; 1H NMR
d6):
d
¼10.63 (s, 1H, NH), 8.04e7.97 (m, 2H, CHAr(9þ13)), 7.89
(dd, 1H, 3J¼7.8 Hz, 4J¼1.6 Hz, CHAr(3)), 7.76 (ddd, 1H,
(300 MHz, DMSO-d6):
d
¼12.55 (s, 1H, NH), 8.23e8.13 (m, 3H,
3J¼7.8 Hz, 3J¼7.8 Hz, 4J¼1.6 Hz, CHAr(5)), 7.70e7.53 (m, 4H,
CH(7þ10þ14), 7.85 (ddd, 3J¼8.5 Hz, 3J¼7.0 Hz, 3J¼1.6 Hz, CH(5)),

X.-F. Wu et al. / Tetrahedron 70 (2014) 23e29
27
(CH(4)), 112.2 (Cquart(14)), 98.38 (d, 2J¼17.2 Hz, (Cquart(2)) ppm; MS
(EI, 70 eV): m/z (%)¼240 (14), 108 (12), 105 (100), 77 (60), 51 (21).
Table 2
Synthesis of quinazolinones from N-(2-cyanoaryl)-benzamidesa
Entry
Amide
Product
Yieldb,c (%)
76/96
4.1.4. N-(2-Cyano-4-methylphenyl)benzonitrile (a6). Mp 204e206 ꢀC;
1H NMR (300 MHz, DMSO-d6):
d
¼10.52 (s, 1H, NH), 7.99 (dd, 2H,
3J¼8.3 Hz, 4J¼1.5 Hz, CHAr(10þ14)), 7.71e7.68 (m, 1H, CHAr(3)),
b1
7.67e7.52 (m, 4H, CHAr(5þ11þ12þ13)), 7.46 (d, 1H, 3J¼8.3 Hz,
CHAr(6)), 2.36 (s,1H) ppm; 13C NMR (75 MHz, DMSO-d6):
d¼165.7 (C]
O(7)), 137.9 (Cquart(1)), 136.2 (CH(4)), 134.4 (CH(5)), 133.6 (Cquart(8)),
133.0 (CH(3)), 132.1 (CH(11)), 128.6 (CH(10þ12)), 127.8 (CH(9þ13)),
126.9 (CH(6)), 117.1 (Cquart(14)), 109.3 (Cquart(2)), 20.1 (CH3) ppm; MS
(EI, 70 eV): m/z (%)¼236 ([Mþ], 26), 105 (100), 77 (67), 51 (20).
b2
b3
41/98
29/41
4.1.5. N-(2-Cyano-3-methylphenyl)benzonitrile (a7). Mp 152e154 ꢀC;
1H NMR (300 MHz, DMSO-d6):
d
¼10.56 (s, 1H, NH), 8.02e7.97 (m,
2H, CHAr(10þ14)), 7.68e7.51 (m, 4H, CHAr(5þ11þ12þ13)), 7.41 (d,1H,
3J¼8.0 Hz, CHAr(4)), 7.34 (d, 1H, 3J¼7.7 Hz, CHAr(6)), 2.52 (s, 3H,
CH3) ppm; 13C NMR (75 MHz, DMSO-d6):
d¼165.7 (C]O(7)), 142.3
(Cquart(3)), 140.7 (Cquart(1)), 133.7 (Cquart(8)), 133.1 (CH(3)), 132.1
(CH(11)), 128.6 (CH(10þ12)), 127.8 (CH(9þ13)), 127.3 (CH(6)), 124.2
(CH(4)), 115.9 (Cquart(2)), 110.1 (Cquart(14)), 20.2 (CH3) ppm; MS (EI,
70 eV): m/z (%)¼236 ([M]þ, 28), 105 (100), 77 (65), 51 (20).
b4
25/57
4.1. 6. N-(2- Cyano-4, 5-dimethoxyphenyl )benz onitrile
(a8). Mp 191e193 ꢀC; 1H NMR (300 MHz, DMSO-d6):
1H, NH), 8.03e7.97 (m, 2H, CHAr(9þ13)), 7.67e7.40 (m, 3H,
CHAr(10þ11þ12)), 7.40 (s, 1H, CHAr(3)), 7.16 (s, 1H, CHAr(6)), 3.84 (s,
3H, CH3), 3.83 (s, 3H, CH3) ppm; 13C NMR (75 MHz, DMSO-d6):
d
¼10.45 (s,
a
Reaction conditions: 1.8 equiv UHP to the crude solution of the amino-
carbonylation, 100 ꢀC, 7 h.
b
Isolated yields based on amines.
Yields calculated based on amides.
c
d
¼165.6 (C]O(7)), 152.6 (Cquart(5)), 146.8 (Cquart(4)), 135.2
(Cquart(1)), 133.7 (Cquart(8)), 132.0 (CH(11)), 130.3 (CH(10þ12)),
128.5 (CH(9þ13)), 127.7 (CH(3)), 114.2 (Cquart(14)), 110.6 (Cquart(2)),
100.6 (CH(6)), 56.11 (COMe), 56.0 (COMe) ppm; MS (EI, 70 eV): m/z
(%)¼283 (10), 282 ([M]þ, 45), 105 (100), 77 (49), 51 (10).
7.77e7.71 (m, 1H, CH(12)), 7.62e7.49 (m, 4H, CH(4þ6
þ11þ13)) ppm; 13C NMR (75 MHz, DMSO-d6):
¼162.3 (C]O(4)),
d
152.4 (Cquart(2)), 148.7 (Cquart(8a)), 134.6 (CH(7)), 132.8 (Cquart(9)),
131.4 (CH(12)), 128.6 (CH(10þ14)), 127.8 (CH(11þ13)), 127.4 (CH(6)),
126.6 (CH(7)), 125.8 (CH(5)), 121.0 (Cquart(4a)) ppm; MS (EI, 70 eV):
m/z (%)¼222 ([M]þ, 100), 119 (99), 104 (11), 92 (14), 90 (17), 77 (22),
76 (11), 51 (10).
4.1.7. 2-Cyanophenylbenzoate (a9). Mp 104e106 ꢀC; 1H NMR
(300 MHz, DMSO-d6):
d
¼8.23e8.15 (m, 2H, CHAr(9þ13)), 8.01 (ddd,
1H, 3J¼7.8 Hz, 4J¼1.7 Hz, 5J¼0.5 Hz, CHAr(3)), 7.92e7.75 (m, 2H,
CHAr(4þ5)), 7.72e7.59 (m, 3H, CHAr(10þ11þ12)), 7.55 (dd,
3J¼7.6 Hz, 3J¼7.6 Hz, 2J¼1.1 Hz, CHAr(6)) ppm; 13C NMR (75 MHz,
4.1.1. N-(4-Chloro-2-cyanophenyl)benzonitrile (a3). Mp 177e179 ꢀC;
1H NMR (300 MHz, DMSO-d6):
d
¼10.69 (s, 1H, NH), 8.08 (d, 1H,
DMSO-d6):
d
¼163.8 (C]O(7)), 152.1 (Cquart(1)), 135.2 (CH(5)), 134
4J¼2.5 Hz, CHAr(3)), 8.02e7.96 (m, 2H, CHAr(9þ13)), 7.83 (dd, 1H,
(CH(3)), 133.6 (CH(11)), 130.1 (Cquart(8)), 129.2 (CH(10þ12)), 127.8
(CH(9þ13)), 127.2 (CH(4)), 123.8 (CH(6)), 115.2 (Cquart(14)), 106.3
(Cquart(2)) ppm; MS (EI, 70 eV): m/z (%)¼240 (14), 108 (12), 105
(100), 77 (60), 51 (21).
3J¼8.7 Hz, 4J¼2.5 Hz, CHAr(5)), 7.69e7.53 (m, 4H,
CHAr(6þ10þ11þ12)) ppm; 13C NMR (75 MHz, DMSO-d6):
¼165.6
d
(C]O(7)), 139.5 (Cquart(1)), 133.9 (CH(5)), 133.3 (Cquart(8)), 132.5
(CH(3)), 132.3 (CH(11)), 130.1 (Cquart(4)), 128.6 (CH(10þ12)), 128.3
(CH(6)), 127.9 (CH(9þ13)), 115.7 (Cquart(14)), 110.7 (Cquart(2)) ppm;
MS (EI, 70 eV): m/z (%)¼256 ([M]þ, 13), 105 (100), 77 (55), 51 (19).
4.1.8. N-(3-Cyanothiophen-2-yl)benzamide (a10). Mp 172e174 ꢀC;
1H NMR (300 MHz, DMSO-d6):
d
¼11.89 (s, 1H), 8.01e7.93 (m, 2H),
7.70e7.63 (m, 1H), 7.62e7.53 (m, 2H), 7.30 (d, 3J¼5.8 Hz, 1H), 7.24
4.1.2. N-(3-Chloro-2-cyanophenyl)benzonitrile (a4). Mp 163e165 ꢀC;
(d, 3J¼5.8 Hz, 1H) ppm; 13C NMR (75 MHz, DMSO-d6):
¼165.4 (C]
d
1H NMR (300 MHz, DMSO-d6):
d
¼10.79 (s, 1H, NH), 8.03e7.96 (m,
O(6)), 152.7 (Cquart(2)), 134.9 (Cquart(7)); 132.6 (CH(10)), 128.5 (CH
(9þ11)), 128.4 (CH(8þ12)), 125.4 (CH(4)), 120.2 (CH(5)), 114.8
(Cquart(13)), 95.4 (Cquart(3)) ppm; MS (EI, 70 eV): m/z (%)¼229 ([M]þ,
14), 105 (100), 77 (63), 51 (24).
2H, CHAr(10þ14)), 7.77 (dd, 1H, 3J¼8.1 Hz, 3J¼8.1 Hz, CHAr(5)),
7.70e7.53 (m, 5H, CHAr(4þ6þ11þ12þ13)) ppm; 13C NMR (75 MHz,
DMSO):
d
¼165.7 (C]O(7)), 142.6 (Cquart(1)), 135.6 (Cquart(3)), 134.7
(CH(5)), 133.2 (Cquart(8)), 132.4 (CH(11)), 128.7 (CH(10þ12)), 127.9
(CH(9þ13)), 126.8 (CH(6)), 125.3 (CH(4)), 114.2 (Cquart(14)), 109.9
(Cquart(2)) ppm; MS (EI, 70 eV): m/z (%)¼256 ([M]þ, 16), 105 (100), 77
(50), 51 (16).
4.1. 9 . N-(3-Cyano-4, 5-dimethylfuran-2-yl)benzamide
(a11). Mp 190e192 ꢀC; 1H NMR (300 MHz, DMSO-d6):
d
¼11.44 (s,
1H, NH), 8.02e7.97 (m, 2H, CH(8þ12)), 7.70e7.62 (m, 1H, CH(10)),
7.56 (ddd,1H, 3J¼7.5 Hz, 3J¼7.0 Hz, 3J¼1.6 Hz, CH(9þ11)), 2.22 (s, 3H,
4.1.3. N-(2-Cyano-3-fluorophenyl)benzonitrile (a5). Mp 167e169 ꢀC;
CH3), 2.01 (s, 3H, CH3) ppm; 13C NMR (75 MHz, DMSO-d6):
d¼164.5
1H NMR (300 MHz, DMSO-d6):
d
¼10.81 (s, 1H, NH), 8.05e7.97 (m,
(C]O(6)), 149.3 (Cquart(5)), 143.0 (Cquart(2)), 132.7 (Cquart(7)), 132.2
(CH(10)), 128.7 (CH(9þ11)), 128.0 (CH(8þ12)), 115.2 (Cquart(4)), 113.3
(Cquart(13)), 88.1 (Cquart(3)), 10.8 (CH3), 8.4 (CH3) ppm; MS (EI,
70 eV): m/z (%)¼240 ([M]þ, 10), 105 (100), 77 (42), 51 (12).
2H, CHAr(9þ13)), 7.81 (ddd, 1H, 3J¼8.4 Hz, 3J¼8.4 Hz, 4J¼6.6 Hz,
CHAr(5)), 7.71e7.35 (m, 5H, CHAr(4þ6þ10þ11þ12)) ppm; 13C NMR
(75 MHz, DMSO-d6):
C
133.3 (Cquart(8)), 132.4 (CH(11)), 128.7 (CH(9þ13)), 128.0
d
¼165.7 (C]O(7)), 162.8 (d, 1J¼254.5 Hz,
quart(3)), 142.0 (d, 4J¼2.5 Hz, (Cquart(1)),135.5 (d, 3J¼10.2 Hz, CH(5)),
4.1.10. N-(2-Cyanophenyl)-4-trifluoromethylbenzamide
(CH(10þ12)), 122.3 (d, 4J¼3.1 Hz, CH(6)), 112.9 (d, 2J¼19.4 Hz,
(a12). Mp 189e191 ꢀC; 1H NMR (300 MHz, DMSO-d6):
d¼10.88 (s,

28
X.-F. Wu et al. / Tetrahedron 70 (2014) 23e29
1H, NH), 8.23e8.11 (m, 2H, CH(10þ12)), 8.03e7.94 (m, 2H,
CH(9þ13)), 7.91 (ddd,1H, 3J¼7.8, 4J¼1.6, 5J¼0.5 Hz, CH(3)), 7.77 (ddd,
1H, 3J¼8.1, 3J¼7.5, 4J¼1.6 Hz, CH(5)), 7.61 (ddd, 1H, 3J¼8.2, 4J¼1.2,
5J¼0.5 Hz, CH(6)), 7.47 (ddd, 3J¼7.6, 3J¼7.6 3J¼1.2 Hz, CH(4)) ppm;
d
¼164.4 (C]O(7)), 139.9 (Cquart(1)), 137.5 (CH(5)), 133.9 (Cquart(9)),
133.2 (CH(3)), 132.7 (CH(9þ13)), 128.6 (CH(10þ12)), 126.9 (CH(6)),
126.8 (CH(4)), 118.2 (Cquart(15)), 116.8 (Cquart(14), 114.4 (Cquart(12)),
109.4 (Cquart(2)) ppm; MS (EI, 70 eV): m/z (%)¼247 ([M]þ, 25), 130
(100), 102 (51), 75 (14).
13C NMR (75 MHz, DMSO-d6):
d¼164.6 (C]O(7)), 139.9 (Cquart(1)),
133.8 (CH(5)), 133.2 (CH(8)), 131.9 (q, 3J¼32.0 Hz, CH(10þ11)), 128.7
(CH(3)), 126.9 (CH(6)), 126.7 (CH(4)), 125.6 (q, 4J¼3.9 Hz, CH(9þ13)),
123.7 (q, 1J¼256.1 Hz, CF3), 116.8 (Cquart(14)), 109.4 (Cquart(2)) ppm;
MS (EI, 70 eV): m/z (%)¼290 ([Mþ], 23), 173 (100), 145 (58).
4 .1.16 . N - ( 2 - C ya n o p h e nyl ) t h i o p h e n e - 2 - c a r b o x a m i d e
(a18). Mp 134e136 ꢀC; 1H NMR (300 MHz, DMSO-d6):
d¼10.64 (s,
1H, NH), 8.02 (dd, 1H 3J¼3.8 Hz, 4J¼1.2 Hz, 1H, CH(9)), 7.92 (dd, 1H,
3J¼5.0 Hz, 4J¼1.1 Hz, CH(11)), 7.90e7.86 (m, 1H (CH(3)), 7.75 (ddd,
1H, 3J¼8.2 Hz, 3J¼7.5 Hz, 4J¼1.6 Hz, CH(5)), 7.57 (m, 1H, CH(6)), 7.44
(ddd, 1H, 3J¼7.6 Hz, 3J¼7.6 Hz, 4J¼1.2 Hz, (CH4)), 7.27 (dd, 1H,
3J¼5.0 Hz, 4J¼3.7 Hz CH(10)) ppm; 13C NMR (75 MHz, DMSO-d6):
4 . 1. 11. N - ( 2 - C y a n o p h e n y l ) - 4 - m e t h o x y b e n z a m i d e
(a13). Mp 170e172 ꢀC; 1H NMR (300 MHz, DMSO-d6):
d
¼10.45 (s,
1H, NH), 8.03e7.96 (m, 2H, CHAr(9þ13)), 7.86 (dd, 1H, 3J¼7.7,
4J¼1.5 Hz, CHAr(3)), 7.73 (ddd, 1H, 3J¼8.0, 3J¼7.5, 4J¼1.6 Hz,
CHAr(5)), 7.61e7.52 (m, 1H, CHAr(6)), 7.41 (ddd, 1H, 3J¼7.6, 3J¼7.6,
4J¼1.2 Hz, CHAr(4)), 7.10 (m, 1H, CHAr(10þ12)), 3.34 (s, 3H,
d
¼160.1 (C]O(7)), 139.8 (Cquart(1)), 138.5 (Cquart(8)), 133.8 (CH(5)),
133.2 (CH(3)), 132.5 (CH(9)), 129.9 (CH(11)), 128.2 (CH(10)), 126.9
(CH(6)), 126.5 (CH(4)), 116.9 (Cquart(12)), 109.3 (Cquart(2)) ppm; MS
(EI, 70 eV): m/z (%)¼228 ([Mþ], 23), 111 (100), 39 (20).
CH3) ppm; 13C NMR (75 MHz, DMSO-d6):
d
¼165.0 (C]O(7)), 162.3
(Cquart(11)), 140.6 (Cquart(1)), 133.7 (CH(5)), 133.1 (CH(3)), 129.8
(CH(9þ13)), 126.8 (CH(6)), 126.1 (CH(4)), 125.59 (Cquart(8)), 117.1
(Cquart(14)), 113.81 (CH(10þ12)), 109.3 (Cquart(2)), 55.51 (CH3) ppm;
MS (EI, 70 eV): m/z (%)¼252 ([M]þ,11),135 (100), 92 (16), 77 (17), 64
(10).
4.1.17. N-(2-Cyanophenyl)-1-naphthamide (a19). Mp 159e161 ꢀC;
1H NMR (300 MHz, DMSO-d6):
d
¼10.88 (s, 1H, NH), 8.40e8.32 (m,
1H, CH(16)), 8.12 (ddd, 1H, 3J¼8.4 Hz, 3J¼8.4 Hz, 4J¼1.0 Hz, CH(11)),
8.07e8.00 (m, 1H, CH(13)), 7.92 (dd, 1H, 3J¼7.7 Hz, 3J¼1.5 Hz,
CH(9)), 7.87 (dd, 1H, 3J¼7.2 Hz, 4J¼1.2 Hz, CH(3)), 7.83e7.74 (m, 1H,
CH(5)), 7.69e7.57 (m, 4H, CH(6þ9þ14þ15)), 7.47 (ddd, 1H,
3J¼7.6 Hz, 3J¼7.6 Hz, 3J¼1.2 Hz, CH(4)) ppm; 13C NMR (75 MHz,
4 . 1 . 1 2 . 4 - A c e t y l - N - ( 2 - c y a n o p h e n y l ) b e n z a m i d e
(a14). Mp 240e242 ꢀC; 1H NMR (300 MHz, DMSO-d6):
d
¼10.81 (s,
1H, NH), 8.32 (d, 2H, 3J¼8.5 Hz, (CH(10þ14)), 8.23e8.07 (m, 2H,
(CH(11þ13)), 7.91 (dd, 3J¼7.8 Hz, 4J¼1.6 Hz,1H, CH(3)), 7.82e7.73 (m,
1H, CH(5)), 7.56 (ddd, 1H, 3J¼8.1 Hz, 3J¼7.0 Hz, 4J¼1.3 Hz, CH(4)),
DMSO-d6):
d¼167.7 (C]O(7)), 140.1 (Cquart(1)), 134.0 (CH(5)), 133.4
(Cquart(8)), 133.3 (CH(3)), 133.3 (Cquart(12)), 130.8 (CH(11)), 129.8
(Cquart(17)), 128.4 (CH(13)), 127.2 (CH(14)), 126.8 (CH(6)), 126.6
(CH(9)), 126.6 (CH(4)), 126.0 (CH(10)), 125.3 (CH(15)), 125.1
(CH(13)),117.2 (Cquart(18)),109.3 (Cquart(2)) ppm; MS (EI, 70 eV): m/z
(%)¼272 ([M]þ, 19), 155 (100), 127 (77), 126 (16).
2.65 (s, 3H, CH3)) ppm; 13C NMR (75 MHz, DMSO):
d¼197.7 (C]
O(16)), 165.0 (C]O(7)), 140.1 (Cquart(2)), 137.3 (Cquart(15)), 133.9
(CH(5)), 133.2 (CH(3)), 128.5 (CH(10þ14)), 128.2 (CH(11þ13)), 126.9
(CH(6)), 126.6 (CH(4)), 116.9 (Cquart(15)), 109.4 (Cquart(2)), 27.06
(CH3) ppm; MS (EI, 70 eV): m/z (%)¼264 ([M]þ, 22), 147 (100), 104
(14), 91 (19), 76 (17).
4.1.18. N-(2-Cyanophenyl)picolinamide (a20). Mp 126e128 ꢀC; 1H
NMR (300 MHz, DMSO-d6):
d¼10.92 (s, 1H, NH), 8.78 (ddd, 1H,
3J¼4.8 Hz, 4J¼1.7 Hz, 5J¼0.9 Hz, (CH9)), 8.25e8.16 (m, 1H, CH(12)),
8.12 (dd, 1H, 3J¼7.6 Hz, 4J¼1.7 Hz, CH(11)), 8.07 (m, 1H, CH(10)), 7.89
(dd, 1H, 3J¼7.8 Hz, 4J¼1.6 Hz, CH(3)), 7.84e7.68 (m, 2H (CH(5þ6)),
7.39 (ddd, 1H, 3J¼7.6 Hz, 3J¼7.6 Hz, 3J¼1.1 Hz, CH(4)) ppm; 13C NMR
4 .1.13 . N - ( 2 - C y a n o p h e n y l ) - 4 - p e n t a n o y l b e n z a m i d e
(a15). Mp 148e150 ꢀC; 1H NMR (300 MHz, DMSO-d6):
d¼10.80 (s,
1H, NH), 8.13 (m, 4H, CH(9þ10þ12þ13)), 7.90 (dd, 1H, 3J¼7.7 Hz,
4J¼1.5 Hz, CH(3)), 7.85e7.70 (m, 1H, CH(5)), 7.60 (dd, 1H, 3J¼8.2 Hz,
3J¼1.1 Hz, CH(6)), 7.46 (ddd, 1H, 3J¼7.6 Hz, 3J¼7.6 Hz, 3J¼1.2 Hz,
CH(4)), 3.09 (t, 1H, 3J¼7.2 Hz, H2(16)), 1.73e1.54 (m, 2H, CH2(17)),
1.38 (m, 2H, CH2(18)), 0.92 (t, 3J¼7.3 Hz, 3H, CH3(19)) ppm; 13C NMR
(75 MHz, DMSO-d6):
d¼162.5 (C]O(7)), 148.7 (Cquart(8)), 148.7
(CH(9)), 140.0 (Cquart(1)), 138.4 (CH(11)), 134.1 (CH(5)), 133.0
(CH(3)), 127.6 (CH(6)), 125.5 (CH(4)), 123.8 (CH(10)), 122.6 (CH(12)),
116.6 (Cquart(13)),105.9 (Cquart(2)) ppm; MS (EI, 70 eV): m/z (%)¼223
([M]þ, 69), 106 (30), 90 (17), 79 (99), 78 (100), 76 (100), 63 (11), 52
(31), 51 (32), 50 (12).
(75 MHz, DMSO-d6):
d
¼199.9 (C]O(15)), 164.9 (C]O(7)), 140.0
(Cquart(1)), 139.2 (Cquart(11)), 137.06 (Cquart(8)), 133.8 (CH(5)), 133.1
(CH(3)), 128.1 (CH(9þ13)), 128.0 (CH(10þ12)), 126.9 (CH(6)), 126.6
(CH(4)), 116.8 (Cquart(14)), 109.4 (Cquart(2)), 38.0 (CH2(16)), 25.8
(CH2(17)), 21.7 (CH2(18)), 13.8 (CH3(19)) ppm; MS (EI, 70 eV): m/z
(%)¼306 ([M]þ, 28), 264 (11), 249 (14), 147 (18), 104 (29), 76 (19).
4.1.19. N-(2-Cyanophenyl)-1-methyl-1H-indole-5-carboxamide
(a21). Mp 165e167 ꢀC; 1H NMR (300 MHz, DMSO-d6):
d¼10.47 (s,
1H, NH), 8.31 (d, 1H, 4J¼1.6 Hz, CH(13)), 7.92e7.80 (m, 2H,
CH(3þ10)), 7.74 (ddd, 1H, 3J¼8.1 Hz, 3J¼7.5 Hz, 4J¼1.6 Hz, CH(5)),
7.60 (m, 2H (CH(6þ9), 7.47 (d, 1H, 4J¼3.1 Hz, CH(11)), 7.41 (ddd, 1H,
3J¼7.6 Hz, 3J¼7.6 Hz, 4J¼1.2 Hz, (CH(4)), 6.62 (dd, 1H, 3J¼3.1 Hz,
4J¼0.8 Hz, CH(12)), 3.86 (s, CH3) ppm; 13C NMR (75 MHz, DMSO-
4 . 1 . 1 4 . N - ( 2 - C y a n o p h e n y l ) - 4 - fl u o r o b e n z a m i d e
(a16). Mp 185e187 ꢀC; 1H NMR (300 MHz, DMSO-d6):
d¼10.66 (s,
1H), 8.12e8.04 (m, 2H), 7.88 (dd, J¼7.8, 1.5 Hz, 1H), 7.75 (ddd, J¼8.1,
7.5, 1.6 Hz, 1H), 7.58 (dd, J¼8.2, 1.1 Hz, 1H), 7.48e7.37 (m, 3H) ppm;
d6):
d
¼166.4 (C]O(7)), 141.0 (Cquart(1)), 138.2 (Cquart(10a)), 133.6
13C NMR (75 MHz, DMSO-d6):
d
¼164.6 (C]O(7)), 164.42 (d,
(CH(5)), 133.0 (CH(3)), 131.4 (Cquart(12a)), 129.3 (Cquart(8)), 127.3
(CH(11)), 126.6 (CH(6)), 125.8 (Cquart(8)), 121.1 (CH(10)), 121.0
(CH(13)), 117.1 (Cquart(14)), 109.5 (CH(9)), 109.0 (Cquart(2)), 101.7
(CH(12)), 32.67 (CH3) ppm; MS (EI, 70 eV): m/z (%)¼275 ([M]þ, 21),
159 (11), 158 (100), 130 (28), 103 (13), 77 (15).
1J¼249.8 Hz, CF(11)), 140.2 (Cquart(1)), 133.8 (CH(5)), 133.1 (CH(3)),
130.6 (d, 3J¼9.3 Hz, CH(9þ13)), 130.0 (d, 4J¼3.0 Hz, Cquart(8)), 126.9
(CH(6)), 126.5 (CH(4)), 117.0 (Cquart(14)), 115.6 (d, 2J¼21.9 Hz,
CH(10þ12)), 109.4 (Cquart(2)) ppm; MS (EI, 70 eV): m/z (%)¼240
([M]þ, 18), 123 (100), 95 (48), 75 (21).
4.1.20. N-(2-Cyanophenyl)benzo[b]thiophene-2-carboxamide
4 . 1 . 1 5 . N - ( 2 - C y a n o p h e n y l ) - 4 - c y a n o b e n z a m i d e
(a22). Mp 164e166 ꢀC; 1H NMR (300 MHz, DMSO-d6):
d¼10.69 (s,
(a17). Mp 228e230 ꢀC; 1H NMR (300 MHz, DMSO-d6):
d¼10.89 (s,
1H, NH), 8.65 (s, 1H, CH(13)), 8.48e8.43 (m, 1H, CH(9)), 8.13e8.09
(m, 1H, (CH(12)), 7.90 (ddd, 1H, 3J¼7.7 Hz, 4J¼1.6 Hz, 5J¼0.5 Hz,
(CH3)), 7.77 (ddd, 1H, 3J¼8.1 Hz, 3J¼7.5 Hz, 4J¼1.6 Hz, CH(5)), 7.61
(ddd, 1H, 3J¼8.1 Hz, 4J¼1.2 Hz, 5J¼0.5 Hz, CH(6)), 7.51e7.44 (m, 3H,
1H, NH), 8.15 (d, 2H, 3J¼8.3 Hz, CH(9þ13)), 8.07 (d, 2H, 3J¼8.2 Hz,
CH(10þ12)), 7.91 (dd, 1H, 3J¼7.6 Hz, 4J¼1.6 Hz, CH(3)), 7.77 (ddd, 1H,
3J¼7.7 Hz, 4J¼1.6 Hz, CH(5)), 7.60 (d, 1H, 3J¼8.1 Hz, CH(6)), 7.47 (ddd,
3J¼7.7 Hz, 4J¼1.3 Hz, CH(4)) ppm; 13C NMR (75 MHz, DMSO-d6):
(CH(4þ10þ11)) ppm; 13C NMR (75 MHz, DMSO-d6):
¼161.9 (C]
d

X.-F. Wu et al. / Tetrahedron 70 (2014) 23e29
29
O(7)), 148.2 (Cquart(8)), 140.0 (Cquart(1)), 139.5 (Cquart(9a)), 136.9
References and notes
(Cquart(12a)), 133.8 (CH(5)), 133.1 (CH(3)), 126.5 (CH(6)), 126.2
(CH(4)), 125.1 (CH(11)), 125.1 (CH(10)), 124.5 (CH(12)), 124.3 (CH9)),
122.9 (CH(13)), 117.0 (Cquart(14)), 109.1 (Cquart(2)) ppm; MS (EI,
70 eV): m/z (%)¼278 ([M]þ, 21),162 (11),161 (100),133 (20), 90 (10),
89 (38).
1. (a) Von Hoff, D. D.; LoRusso, P. M.; Rudin, C. M.; Reddy, J. C.; Yauch, R. L.; Tibes,
R.; Weiss, G. J.; Borad, M. J.; Hann, C. L.; Brahmer, J. R.; Mackey, H. M.; Lum, B. L.;
Darbonne, W. C.; Marsters, J. C.; de Sauvage, F. J.; Low, J. A. N. Engl. J. Med. 2009,
1164e1172; (b) Reddy, E. P.; Aggarwal, A. K. Genes Cancer 2012, 447e454; (c) Yi,
S.; Jeon, H.; Yoon, S. H.; Cho, J. Y.; Shin, S. G.; Jang, I. J.; Yu, K. S. J. Cardiovasc.
Pharmacol. 2012, 315e322; (d) See for examples:N-Aryl Amides: The Merck
Index, 11th ed.; Merck: Rahway, USA, 1989.
4 . 1 . 2 1 . 6 - M e t h y l - 2 - p h e n y l q u i n a z o l i n - 4 ( 3 H ) - o n e
2. Schoenberg, A.; Heck, R. F. J. Org. Chem. 1974, 39, 3327e3331.
(b5). Mp 262e264 ꢀC; 1H NMR (300 MHz, DMSO-d6):
d
¼12.47 (s, 1H,
€
3. For reviews on carbonylations, see: (a) Brennfuhrer, A.; Neumann, H.; Beller, M.
Angew. Chem., Int. Ed. 2009, 48, 4114e4133; (b) Wu, X.-F.; Neumann, H.; Beller,
M. Chem. Soc. Rev. 2011, 40, 4986e5009; (c) Wu, X.-F.; Neumann, H.; Beller, M.
Chem. Rev. 2013, 113, 1e35; (d) Wu, X.-F.; Neumann, H.; Beller, M. ChemSusChem
2013, 6, 229e241; (e) Liu, Q.; Zhang, H.; Lei, A. Angew. Chem., Int. Ed. 2011, 50,
10788e10799; (f) Barnard, C. F. J. Organometallics 2008, 27, 5402e5422.
4. Morimoto, T.; Kakiuchi, K. Angew. Chem. 2004, 116, 5698e5706 Angew. Chem.,
Int. Ed. 2004, 43, 5580e5588.
5. For an excellent review and recent examples on this using Mo(CO)6 as CO
source, see: (a) Odell, L. R.; Russo, F.; Larhed, M. Synlett 2012, 685e698; (b)
Mane, R. S.; Nordeman, P.; Odell, L. R.; Larhed, M. Tetrahedron Lett. 2013, 54,
6912e6915; (c) Motwani, H. V.; Larhed, M. Eur. J. Org. Chem. 2013, 4729e4733;
(d) Rao, K. P.; Basak, A. K.; Deb, P. K.; Sharma, S.; Reddy, L. K. Tetrahedron Lett.
2013, 54, 3694e3696; (e) Wu, X. F.; Sharif, M.; Shoaib, K.; Neumann, H.; Pews-
Davtyan, A.; Langer, P.; Beller, M. Chem.dEur. J. 2013, 19, 6230e6233; (f) Bo-
rhade, S. R.; Sandstroem, A.; Arvidsson, P. I. Org. Lett. 2013, 15, 1056e1059; (g)
Nordeman, P.; Odell, L. R.; Larhed, M. J. Org. Chem. 2012, 77, 11393e11398; (h)
Iranpoor, N.; Firouzabadi, H.; Motevalli, S.; Talebi, M. Tetrahedron 2013, 69,
418e426.
NH), 8.20e8.13 (m, 2H, CH(10þ14)), 7.95 (d, 4J¼1.9 Hz, 1H, (CH(5))),
7.66e7.64 (m, 2H, CH(7þ8)), 7.59e7.50 (m, 3H, CH(11þ12þ13)), 2.46
(s, 3H, CH3) ppm; 13C NMR (75 MHz, DMSO-d6):
d¼162.2 (C]O(4)),
151.5 (Cquart(2)), 146.8 (Cquart(8a)), 136.3 (Cquart(6)), 135.90 (Cquart(9)),
132.9 (CH(7)), 131.2 (CH(12)), 128.6 (CH(11þ13)), 127.6 (CH(10þ14)),
127.4 (CH(5)), 125.3 (CH(8)), 120.7 (CH(4a)), 20.9 (CH3) ppm; MS (EI,
70 eV): m/z (%)¼237 (18), 236 ([M]þ, 100), 133 (81), 105 (13), 104 (40),
89 (12), 78 (13), 77 (47), 76 (13), 51 (19).
4.1. 22. 6, 7-Dimethoxy-2-phenylquinazolin-4(3H)-one
(b7). Mp 290e292 ꢀC; 1H NMR (300 MHz, DMSO-d6):
d
¼12.42 (s,
1H, NH), 8.23e8.11 (m, 2H, CH(10þ14)), 7.59e7.50 (m, 3H,
CH(11þ12þ13)), 7.49 (s, 1H, CH(5)), 7.22 (s, 1H, CH(8)), 3.94 (s, 3H,
CH3), 3.90 (s, 3H, CH3) ppm; 13C NMR (75 MHz, DMSO-d6):
d
¼161.6
6. (a) Kaiser, N.-F. K.; Hallberg, A.; Larhed, M. J. Comb. Chem. 2002, 4, 109e111; (b)
Wannberg, J.; Larhed, M. J. Org. Chem. 2003, 68, 5750e5753; (c) Wu, X.;
Wannberg, J.; Larhed, M. Tetrahedron 2006, 62, 4665e4670; (d) Wu, X.; Larhed,
M. Org. Lett. 2005, 7, 3327e3329; (e) Wu, X.; Ekegren, J. K.; Larhed, M. Organ-
ometallics 2006, 25, 1434e1439.
(C]O(4)), 154.8 (Cquart(8a)), 150.8 (Cquart(9)), 148.6 (Cquart(7)), 144.8
(Cquart(6)), 132.8 (Cquart(9)), 131.0 (CH(12)), 128.6 (CH(11þ13)), 127.4
(CH(9þ14)), 114.0 (Cquart(4a)), 108.3 (CH(8)), 104.9 (CH(5)), 56.0
(CH3), 55.7 (CH3) ppm; MS (EI, 70 eV): m/z (%)¼283 (16), 282 ([M]þ,
100), 281 (20), 268 (12), 267 (47), 239 (24), 237 (16), 104 (19), 32
(11).
7. Jafarpour, F.; Rashidi-Ranjbar, P.; Kashani, A. O. Eur. J. Org. Chem. 2011,
2128e2132.
€
8. Savmarker, J.; Lindh, J.; Nilsson, P. Tetrahedron Lett. 2010, 51, 6886e6889.
9. Iizuka, M.; Kondo, Y. Eur. J. Org. Chem. 2007, 2007, 5180e5182.
10. For selected recent examples, see: (a) Bjerglund, K. M.; Lindhardt, A. T.;
Skrydstrup, T. J. Org. Chem. 2012, 77, 3793e3799; (b) Nielsen, D. U.; Lindhardt,
A. T.; Skrydstrup, T. Org. Lett. 2012, 10, 2536e2539; (c) Nielsen, D. U.; Neumann,
K. T.; Taaning, R. H.; Lindhardt, A. T.; Modvig, A.; Skrydstrup, T. J. Org. Chem.
2012, 77, 6155e6165; (d) Burhardt, M. N.; Taaning, R. H.; Skrydstrup, T. Org. Lett.
2013, 15, 948e951; (e) Gogsig, T.; Taaning, R. H.; Lindhardt, A. T.; Skrydstrup, T.
Angew. Chem., Int. Ed. 2012, 51, 798e801.
11. (a) Xu, H.; Wolf, C. Chem. Commun. 2009, 1715e1717; (b) Allen, C. L.; Atkinson,
B. N.; Williams, J. M. J. Angew. Chem., Int. Ed. 2012, 51, 1383e1386; (c) Liang, J.;
Lv, J.; Shang, Z. C. Tetrahedron 2011, 67, 8532e8535; (d) Chen, J.; Ling, G.; Lu, S.;
Wu, S.; Wu, X.; Yu, Z.; Zhao, X. Adv. Synth. Catal. 2004, 346, 1267e1270; (f) Wu,
X.-F.; Sharif, M.; Pews-Davtyan, A.; Langer, P.; Ayub, K.; Beller, M. Eur. J. Org.
Chem. 2013, 2783e2787; (g) Qin, C.; Zhou, W.; Chen, F.; Qu, Y.; Jiao, N. Angew.
Chem., Int. Ed. 2011, 50, 12595e12599.
4 .1. 2 3 . 2 - P h e n y l t h i e n o [ 2 , 3 - d ] p y r i m i d i n - 4 ( 3 H ) - o n e
(b9). Mp 233e235 ꢀC; 1H NMR (300 MHz, DMSO-d6):
d
¼13.44 (s,
1H, NH), 7.93 (m, 2H, CH(5þ6)), 7.65 (m, 5H, CH(
10þ11þ12þ13þ14)) ppm; 13C NMR (75 MHz, DMSO-d6):
¼167.4
d
(CH(6)), 162.5 (C]O(4)), 146.2 (Cquart(2)), 132.7 (Cquart(7)), 132.1
(CH(10)), 129.3 (CH(8þ12)), 127.0 (CH(9þ11)), 123.2, 116.5
(Cquart(6a)), 115.7 (Cquart(4a)) ppm; MS (EI, 70 eV): m/z (%)¼229
([M]þ, 32), 105 (100), 77 (82), 51 (24), 50 (11).
12. (a) Wu, X.-F.; Schranck, J.; Neumann, H.; Beller, M. Tetrahedron Lett. 2011, 52,
3702e3704; (b) Tambade, P. J.; Patil, Y. P.; Mayur, M. J.; Bhanage, B. M. Synthesis
2008, 2347e2352; (c) Salvadori, J.; Balducci, E.; Zaza, S.; Petricci, E.; Taddei, M. J.
Org. Chem. 2010, 75, 1841e1847; (d) Bhanage, B. M.; Mayur, M. V.; Sasaki, T. ACS
Catal. 2013, 3, 287e293; (e) Chen, A.; Dang, T. T.; Ghosh, S. C.; Ngiam, J. S. Y.;
Seayad, A. M.; Zhu, Y.; Ghosh, S. C. ACS Catal. 2013, 3, 1406e1410; (f) Ma, C.; Ma,
Y.; Andrus, M. B.; Song, C.; Chai, Q. Synthesis 2003, 2886e2889.
13. Iranpoor, N.; Firouzabadi, H.; Motevalli, S.; Talebi, M. Tetrahedron 2013, 69,
418e426.
Acknowledgements
The authors thank the state of Mecklenburg-Vorpommern and
the Bundesministerium fur Bildung und Forschung (BMBF) for fi-
nancial support. We also thank Drs. W. Baumann, C. Fischer, Ms. S.
Schareina and Ms. S. Buchholz (LIKAT) for analytical support.
€
14. (a) Ramadan, A.; El-Sooud, K. A.; El-Bahy, M. M. Res. Vet. Sci. 1997, 175e178; (b)
Anshul, C.; Batra, B. Int. Res. J. Pharm. 2013, 49e58.
15. Bandgar, B. P. Synth. Commun. 1997, 27, 2065e2068.
Supplementary data
16. (a) Wu, X. F.; He, L.; Neumann, H.; Beller, M. Chem.dEur. J. 2013, 19,
12635e12638; (b) Li, H.; He, L.; Neumann, H.; Beller, M.; Wu, X. F. Green Chem.
2013, doi:C3GC42089B.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.11.055.