Selective iodine-catalyzed intermolecular oxidative amination of C(sp 3)-H bonds with ortho-carbonyl-substituted anilines to give quinazolines

Article abstract of DOI:10.1002/anie.201203880

Access to quinazolines: The selective amination of C(sp³)-H bonds adjacent to nitrogen or oxygen atoms of N-alkylamides, ethers, or alcohols with ortho-carbonyl-substituted anilines constitutes the first step in a tandem annulation that leads to quinazolines in good to excellent yields (see scheme; NIS=N-Iodosuccinimide, TBHP=tert-butyl hydroperoxide). The selectivity of the amination of primary and secondary C-H bonds is also noteworthy (left: >3:1, right: >99:1). Copyright

Full text of DOI:10.1002/anie.201203880

Angewandte
Chemie
DOI: 10.1002/anie.201203880
À
C H Amination
Selective Iodine-Catalyzed Intermolecular Oxidative Amination of
3
À
C(sp ) H Bonds with ortho-Carbonyl-Substituted Anilines to Give
Quinazolines**
Yizhe Yan, Yonghui Zhang, Chengtao Feng, Zhenggen Zha, and Zhiyong Wang*
3
À
Transition-metal-catalyzed intermolecular or intramolecular
and environmentally friendly catalyst for oxidative C(sp ) H
amination with anilines is highly desirable.
3
À
direct oxidative aminations of C(sp ) H bonds, including
3
À
activated and unactivated C(sp ) H bonds, have emerged as
Recently, Ishihara[6] and Wan[7] have developed Bu4NI-
catalyzed oxidative functionalization of C(a) H bonds for C
O bond formations. Meanwhile, our group has focused on the
development of metal-free C(sp ) H functionalization for C
À
À
À
important methods for C N bond formations, because they
are straightforward and have economic advantages over
present procedures by employing prefunctionalized sub-
strates (Scheme 1a).[1–3] However, these aminations are
restricted because of the toxicity of catalysts and their use
of expensive transition metals as catalysts. Furthermore, only
amides (acetamides or sulfonamides) were employed as
coupling partners in most cases. Recently, Chang[4] and
Muniz[5] have developed interesting metal-free aminations
3
À
À
[8]
À
C or C N bond formation. We hoped to realize iodine-
3
À
catalyzed intermolecular oxidative aminations of C(sp ) H
bonds with anilines. To the best of our knowledge, such
a protocol has not been reported to date.
Herein, we report an iodine-catalyzed intermolecular
oxidative amination of a C(sp ) H bond adjacent to the
nitrogen or oxygen atom of N-alkylamides, ethers, or alcohols
with ortho-carbonyl-substituted anilines. A domino process
that includes C N or C O bond cleavage, attack of ammonia,
condensation, and oxidation subsequently leads to quinazo-
lines in good to excellent yields (Scheme 1c). The additional
nitrogen and carbon atom of the quinazolines originate from
ammonia and the methyl group adjacent to the nitrogen or
oxygen atom of the solvents, respectively. To the best of our
knowledge, this is the first example of using a combination of
inorganic nitrogen sources and organic solvents for the
formation of hetercycles.
3
À
À
of benzylic and allylic C H bonds, respectively, with sulfona-
mides in the presence of stoichiometric amounts of hyper-
valent iodine(III) reagents. Although a transition metal was
not required, large amounts of iodobenzene were generated
as by-product, and the substrate scope was limited to
sulfonamides (Scheme 1b). Therefore, a new, more efficient,
À
À
We began our study with the reaction of one equivalent of
2-aminobenzophenone (1a), two equivalents of NH4HCO3,
four equivalents of tert-butyl hydroperoxide (TBHP, 70% in
water) as the oxidant, and 20 mol% of N-iodosuccinimide
(NIS) as the catalyst. When the reaction mixture was heated
in N,N-dimethylacetamide (DMA, 2a) in air at 1208C for four
hours, 4-phenylquinazoline (3a) was obtained in more than
99% yield, determined by GC–MS analysis (Table 1, entry 1).
In the absence of NH4HCO3, desired product 3a was not
detected, thus indicating that NH4HCO3 is the source of the
additional nitrogen atom of the product (Table 1, entry 2).
Various ammonia-based reagents could be used as N sources
without influencing the reaction yields (Table 1, entries 3–6).
To examine the source of the additional carbon atom, various
solvents (2b–2 f) were tested in the reaction. Use of solvents
2b, 2d, and 2 f gave desired product 3a, whereas solvents 2c
and 2e gave 2-methyl-4-phenylquinazoline (3a’) with low
yields, rather than product 3a (Table 1, entries 7–11). These
results implied that the additional carbon atom of 3a
presumedly originated from the N,N-dimethyl moiety of
DMA. In addition, various iodine reagents were used as the
catalyst; while PhI gave 3a in a similar yield, other iodine-
containing catalysts gave 3a in lower yields (Table 1,
entries 12–15). Among the various oxidants that were exam-
ined, such as di-tert-butylperoxide (DTBP), 2,3-dichloro-5,6-
3
À
Scheme 1. Strategies for oxidative C(sp ) H amination.
[*] Dr. Y.-Z. Yan, Y.-H. Zhang, Dr. C.-T. Feng, Prof. Z.-G. Zha,
Prof. Dr. Z.-Y. Wang
Hefei National Laboratory for Physical Sciences at Microscale,
CAS Key Laboratory of Soft Matter Chemistry, and Department of
Chemistry, University of Science and Technology of China
Hefei, 230026 (P. R. China)
E-mail: zwang3@ustc.edu.cn
[**] We are grateful to the Natural Science Foundation of China
(20932002, 207721118, and 20972144) and the Ministry of Science
& Technology of China (2010CB912103), and the support from the
Chinese Academy of Sciences.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201203880.
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Table 1: Optimization of reaction conditions.[a]
Entry
XI
Oxidant
N source
Solvent
Yield [%][b]
1
2
3
4
5
6
7
8
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
NIS
I2
Bu4NI
KI
PhI
NIS
NIS
NIS
NIS
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
TBHP
DTBP
Oxone
DDQ
O2
NH4HCO3
none
NH4OAc
NH4Cl
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2 f
2a
2a
2a
2a
2a
2a
2a
2a
>99
n.d.
>99
99
NH4F
99
NH3(aq)
NH3(aq)
NH3(aq)
NH3(aq)
NH3(aq)
NH3(aq)
NH3(aq)
NH3(aq)
NH3(aq)
NH3(aq)
NH3(aq)
NH3(aq)
NH3(aq)
NH3(aq)
>99 (99)
50
n.d.[c]
99
9
10
11[e]
12
13
14
15
16
17
18
19
n.d.[d]
40
95
89
76
99
Scheme 2. Substrate scope of ortho-carbonyl-substituted anilines.
Reaction conditions: 1 (0.2 mmol), ammonia (25% in H2O,
0.4 mmol), NIS (0.04 mmol), TBHP (70% aq, 0.8 mmol), DMA
(1 mL), 1208C, 4 h; yields of isolated products are given; n.d. =not
detected.
83
n.d.
n.d.
10
[a] Reaction conditions: 1a (0.2 mmol), N source (0.4 mmol), XI
(0.04 mmol), oxidant (0.8 mmol), solvent (1 mL), 1208C, 4 h. [b] Deter-
mined by GC–MS analysis using an internal standard, yields of isolated
products given in parentheses; n.d.=not detected. [c] 5% of 3a’ was
obtained. [d] 38% of 3a’ was obtained. [e] 24 h. Entry in bold marks
optimized reaction conditions.
À
À
À
the C F, C Cl, and C Br bonds of the substrates remained
intact during all reactions, thus providing an additional handle
for further functionalization of the products (Scheme 2, 3b–
3 f and 3o–3q).
À
The amination selectivity of primary versus secondary C
dicyano-1,4-benzoquinone (DDQ), oxone, and oxygen,
TBHP gave 3a in the highest yield (Table 1, entries 16–19).
We next investigated the substrate scope of the oxidative
H bonds was also investigated. When a 1:1 mixture of 2a and
2e was employed in the reaction, only 3a was obtained in
90% yield, and 2-methyl-4-phenylquinazoline (3a’) was not
detected (Scheme 3a). When N-benzyl-N-methylacetamide
(2g) was employed in the reaction, only 3a was obtained in
62% yield, and 2,4-diphenylquinazoline (3s) was not detected
(Scheme 3b). To the best of our knowledge, this is the first
À
C N coupling reaction under the optimized reaction con-
ditions (Scheme 2). Firstly, when R1 is an aromatic substitu-
ent, the reaction of substrates 1a–1h can be carried out
smoothly to give the corresponding products 3a–3h with
excellent yields, regardless of electron-withdrawing or elec-
tron-donating groups on the phenyl ring of R1. However,
substrate 1i (R1 = mesityl) didnꢀt give the desired product 3i,
perhaps as a result of steric hindrance. Product 3j (R1 = 2-
naphthyl) could be obtained in 98% yield of isolated produt.
In contrast, substrates with aliphatic substituents usually
afforded the desired products in lower yields, except that with
a tert-butyl substituent (3k). For example, 3m was obtained in
only 30% yield, while its oxidative product 3m’ was
generated with a yield of 50%. Moreover, desired product
3n could not be obtained, whereas its oxidative product 3n’
report of excellent selectivity of the amination of primary and
secondary C H bonds in oxidative C(sp ) H aminations.
Currently, the cause of the high selectivity of primary C H
3
À
À
À
bond amination is not clear to us.
To gain an insight into the reaction mechanism, we carried
out several control experiments. Expectedly, in the absence of
ammonia, direct C N coupling products 4 and 5 were formed
À
because domino annulation was inhibited (Scheme 3c). When
product 4 was subjected to the standard reaction conditions,
3a (85%) and 5 (9%) were obtained. Treatment of 5 with
ammonia also generated 3a through direct condensation,
albeit in a low yield (8%). These results indicate that 4 and 5
may be reaction intermediates, and that different yields may
be a result of different reaction pathways. When the reactions
of 1a with formic acid or formamide were subsequently
carried out under standard conditions, trace amounts of 3a
were obtained (see the Supporting Information). Therefore,
was generated with a yield of 45%. This result indicated that
1
À
benzylic C H bond oxidation of the R group in these
quinazolines could occur under standard conditions. In
addition, when Cl, Br, and NO2 substituents were introduced
at the 5 position of 2-aminobenzophenone, the desired
products 3p–3r were obtained in excellent yields. Notably,
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Scheme 5. Mechanism for domino synthesis of quinazolines by oxida-
3
À
tive C(sp ) H amination. r.d.s.=rate-determining step, SET=single-
electron transfer.
3
À
Scheme 3. Selectivity between primary and secondary C(sp ) H bonds
and control experiments for mechanism.
oxidation with I+.[11] The nucleophilic addition of 1a to B
provides amide intermediate C.[12] In the presence of
À
formamide and formic acid can be excluded as intermediates.
Moreover, when stoichiometric amounts of hypervalent
iodine reagents (such as PhI(OAc)2 or ortho-iodoxybenzoic
acid) were employed instead of our catalytic system, no
desired product was obtained. This result indicates that the
reaction pathway is not followed in catalysis involving in situ
generated hypervalent iodine. Finally, radical trapping experi-
ments were also carried out (see the Supporting Information).
We observed that the reaction was inhibited in the presence of
2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) or 2,6-di-tert-
butyl-4-methylphenol (BHT). This observation implied that
the reaction presumably underwent a radical pathway.
tBuOOH, a sequential C N bond cleavage in C gives unstable
intermediate 4, which is converted to D through an attack by
ammonia (path a). Finally, 3a is formed by oxidative cycliza-
tion. However, in the presence of NH3, D could also be
formed directly from C (path b). Furthermore, a minor
pathway may occur according to control experiments. Inter-
mediate 4 could generate 5 through elimination of tBuOH.
Then, 3a could be formed through direct condensation of 5
and ammonia (path c). Overall, the I2–I+ redox process[13]
À
plays a key role in the C N bond formation by promoting the
À
reductive cleavage of the O O bond in the peroxide and
oxidation of the N-bound carbon radical to an imine ion.
3
À
On the other hand, a large intermolecular kinetic isotope
effect (KIE, kH/kD = 3.3) was observed with N,N-dimethyl-
Recently, functionalizations of C(sp ) H bonds adjacent
À
to oxygen atoms have been developed for oxidative C C and
[14]
À
À
formamide (DMF) and [D7]DMF, thus indicating that the C
C X bond formations. In these reactions, an oxonium ion
H bond cleavage was the rate-determining step (Scheme 4a).
Moreover, a 13C-labeling experiment unambiguously estab-
lished that the additional carbon atom of quinazolines was
derived from the N-methyl group of N-methylamide, rather
than the acyl group (Scheme 4b).[9]
intermediate was generated. According to our proposed
mechanism, C(sp ) H amination of ethers should also be
3
À
possible through nucleophilic addition of 1a to oxonium ions,
which are generated in situ by our catalyst system. After
optimization,[15] reaction of 1a with methyl tert-butyl ether
(6a) instead of DMA afforded the desired product 3a in 95%
yield in the presence of 20 mol% iodine under very mild
conditions (Table 2, entry 1). However, when anisole (6b)
was employed, a trace amount of 3a was obtained, probably
On the basis of results described above and in previous
reports,[10] a plausible mechanism is proposed (Scheme 5).
Initially, DMA is presumably involved a hydrogen abstraction
À
from the C H bond adjacent to the nitrogen atom to give
À
a carbon radical A, and generation of an imine ion B by
because the following C O cleavage proceeded with diffi-
culty (Table 2, entry 2). When diethyl ether (6c) was
employed, the corresponding product 3a’ was also obtained
in 80% yield (Table 2, entry 3). In addition, ethers that bear
3
À
various C(sp ) H bonds adjacent to the oxygen atom were
examined (Table 2, entries 4–6). For example, 1,2-dimethoxy-
ethane (6d), which have two types of C(sp ) H bonds (a and
b) adjacent to the oxygen atom, afforded 3a and 3t in 70%
3
À
and 18% yields, respectively. Similarly, 2-methoxyethanol
3
À
(6e), which bears three types of C(sp ) H bonds adjacent to
its oxygen atoms, afforded 3a, 3t, and 3u in 62%, 17%, and
9% yields, respectively. It is noted that reactions with primary
À
C H bonds gave products in higher yields than with
Scheme 4. KIE and l3C-labeling experiments.
Angew. Chem. Int. Ed. 2012, 51, 1 – 6
secondary C H bond (see also Scheme 3). Alcohols, such as
À
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Table 2: The scope of various ethers or alcohols.[a]
À
Keywords: amination · C H functionalization · iodine ·
oxidative coupling · quinazolines
.
À
[1] For recent reviews on C H amination, see: a) A. Armstrong,
J. C. Collins, Angew. Chem. 2010, 122, 2332; Angew. Chem. Int.
Ed. 2010, 49, 2282; b) P. Thansandote, M. Lautens, Chem. Eur. J.
2009, 15, 5874; c) F. Collet, R. H. Dodd, P. Dauban, Chem.
Commun. 2009, 5061; d) H. M. L. Davies, J. R. Manning, Nature
2008, 451, 417; e) A. R. Dick, M. S. Sanford, Tetrahedron 2006,
62, 2439; f) H. M. L. Davies, M. S. Long, Angew. Chem. 2005,
117, 3584; Angew. Chem. Int. Ed. 2005, 44, 3518; g) P. Mꢁller, C.
Fruit, Chem. Rev. 2003, 103, 2905; h) F. Collet, C. Lescot, P.
Dauban, Chem. Soc. Rev. 2011, 40, 1926; i) D. N. Zalatan, J.
Du Bois, Top. Curr. Chem. 2010, 292, 347.
Entry
1
Ether (Alcohol)
Products
Yields [%][b]
95
6a
3a
2
3
6b
6c
3a
3a’
trace
80
4
6d
3a/3t
70/18
[2] For selected examples of oxidative amination of activated
3
À
À
C(sp ) H bonds, including allylic and benzylic C H bonds, and
À
5
6
6e
6 f
3a/3t/3u
62/17/9
–
92 (85[c])
75
C H bonds that have heteroatoms or electron-withdrawing
substituents on the carbon atom, see: a) M. M. Dꢂaz-Requejo,
T. R. Belderrain, M. C. Nicasio, S. Trofimenko, P. J. Perez, J. Am.
Chem. Soc. 2003, 125, 12078; b) M. R. Fructos, S. Trofimenko,
M. M. Diaz-Requejo, P. J. Perez, J. Am. Chem. Soc. 2006, 128,
11784; c) R. Bhuyan, K. M. Nicholas, Org. Lett. 2007, 9, 3957;
d) G. Pelletier, D. A. Powell, Org. Lett. 2006, 8, 6031; e) J. L.
Liang, S. X. Yuan, J. S. Huang, W. Y. Yu, C. M. Che, Angew.
Chem. 2002, 114, 3615; Angew. Chem. Int. Ed. 2002, 41, 3465;
f) J. L. Liang, S. X. Yuan, J. S. Huang, C. M. Che, J. Org. Chem.
2004, 69, 3610; g) C. G. Espino, K. W. Fiori, M. Kim, J. Du Bois,
J. Am. Chem. Soc. 2004, 126, 15378; h) K. W. Fiori, J. Du Bois, J.
Am. Chem. Soc. 2007, 129, 562; i) Y. Zhang, H. Fu, Y. Jiang, Y.
Zhao, Org. Lett. 2007, 9, 3813; j) Z. Wang, Y. Zhang, H. Fu, Y.
Jiang, Y. Zhao, Org. Lett. 2008, 10, 1863; k) E. Milczek, N.
Boudet, S. Blakey, Angew. Chem. 2008, 120, 6931; Angew. Chem.
Int. Ed. 2008, 47, 6825; l) K. J. Fraunhoffer, M. C. White, J. Am.
Chem. Soc. 2007, 129, 7274; m) S. A. Reed, M. C. White, J. Am.
Chem. Soc. 2008, 130, 3316; n) G. S. Liu, G. Y. Yin, L. Wu,
Angew. Chem. 2008, 120, 4811; Angew. Chem. Int. Ed. 2008, 47,
4733.
–
7
8
MeOH
EtOH
6g
6h
3a
3a’
9
6i
3a/3u
49/32
[a] Reaction conditions: 1a (0.2 mmol), ammonia (25% aq, 0.4 mmol),
iodine (0.04 mmol), oxidant (0.8 mmol), ethers or alcohols (1 mL),
508C, 12 h. [b] Yields of isolated products. [c] 10 mmol scale.
methanol, ethanol, and glycol, were also investigated as
substrates (Table 2, entries 7–9). Methanol and ethanol gave
the corresponding products 3a and 3a’ in good yields, while
glycol gave the corresponding product 3u in a low yield of
32%, because 3a was unexpectedly obtained in 49% yield.
Finally, the reaction conditions summarized in entry 7
(Table 2) turned out to be scalable, and product 3a was
obtained in a good yield under mild conditions. Compared to
typical methods for the synthesis of quinazolines,[16] requiring
a high temperature (1508C) and an excess of Brønsted acid,
our protocol represents a facile, efficient, and mild method
with a broad substrate scope (giving products, such as 3a’, 3t,
and 3u) using ethers or alcohols and ammonia as “clean”
reagents. These factors indicated that this method could be
widely applied in organic synthesis.
[3] For selected examples of oxidative amination of unactivated
3
À
C(sp ) H bonds, see: a) H. Y. Thu, W. Y. Yu, C. M. Che, J. Am.
Chem. Soc. 2006, 128, 9048; b) J. Neumann, S. Rakshit, T. Droge,
F. Glorius, Angew. Chem. 2009, 121, 7024; Angew. Chem. Int. Ed.
2009, 48, 6892; c) J. Pan, M. Su, S. L. Buchwald, Angew. Chem.
2011, 123, 8806; Angew. Chem. Int. Ed. 2011, 50, 8647; d) G. He,
Y. Zhao, S. Zhang, C. Lu, G. Chen, J. Am. Chem. Soc. 2012, 134,
3; e) E. T. Nadres, O. Daugulis, J. Am. Chem. Soc. 2012, 134, 7.
[4] H. J. Kim, J. Kim, S. H. Cho, S. Chang, J. Am. Chem. Soc. 2011,
133, 16382.
In summary, we have developed an iodine-catalyzed
3
À
oxidative amination of C(sp ) H bonds adjacent to nitrogen
or oxygen atoms for the synthesis of quinazolines from ortho-
carbonyl-substituted anilines, ammonia, and solvents, such as
N-alkylamides, ethers, and alcohols. Compared with previous
reports, this novel protocol is distinguished by 1) the lack of
expensive transition metals, 2) operational simplicity, 3) the
fact that an inert atmosphere or dry solvents are not required,
4) a wide tolerance of various functional groups, and 5) the
production of alcohol and water as the only waste. More
importantly, the selectivity of the reactions of primary and
[5] J. A. Souto, D. Zian, K. Muniz, J. Am. Chem. Soc. 2012, 134,
7242.
[6] a) M. Uyanik, H. Okamoto, T. Yasui, K. Ishihara, Science 2010,
328, 1376; b) M. Uyanik, D. Suzuki, T. Yasui, K. Ishihara, Angew.
Chem. 2011, 123, 5443; Angew. Chem. Int. Ed. 2011, 50, 5331;
c) M. Uyanik, K. Ishihara, ChemCatChem 2012, 4, 177.
[7] L. Chen, E. B. Shi, Z. J. Liu, S. L. Chen, W. Wei, H. Li, K. Xu,
X. B. Wan, Chem. Eur. J. 2011, 17, 4085.
[8] a) J. T. Zhang, D. P. Zhu, C. M. Yu, C. F. Wan, Z. Y. Wang, Org.
Lett. 2010, 12, 2841; b) Y. Z. Yan, K. Xu, Y. Fang, Z. Y. Wang, J.
Org. Chem. 2011, 76, 6849.
À
secondary C H bonds was the first observed in oxidative
À
[9] See the Supporting Information for details of KIE and l3C-
labeling experiments.
3
C(sp ) H aminations. The development of iodine-catalyzed
À
oxidative C H aminations for the synthesis of other heter-
[10] For reviews on the cross-dehydrogenative coupling (CDC)
reaction, see: a) C.-J. Li, Acc. Chem. Res. 2009, 42, 335;
b) C. S. Yeung, V. M. Dong, Chem. Rev. 2011, 111, 1215.
[11] For imine ion intermediates, see: a) Z. P. Li, C.-J. Li, J. Am.
Chem. Soc. 2004, 126, 11810; b) Z. P. Li, C.-J. Li, J. Am. Chem.
Soc. 2005, 127, 3672.
cycles is ongoing in our laboratory.
Received: May 20, 2012
Revised: June 13, 2012
Published online: && &&, &&&&
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3
À
[12] The nucleophilic addition of ammonia to B may also occur and
generate formamide through further oxidation. The final
product 3a was formed through the direct condensation of
formamide with 1a. However, when the reaction of formamide
and 1a was carried out under our standard conditions, a trace
amount of 3a was obtained. Therefore, an attack of ammonia to
B and generation of formamide can be excluded.
[14] For selected examples of functionalization of C(sp ) H bond
adjacent to an oxygen atom, see: a) Y. Zhang, C.-J. Li, J. Am.
Chem. Soc. 2006, 128, 4242; b) Y. Zhang, C.-J. Li, Angew. Chem.
2006, 118, 1983; Angew. Chem. Int. Ed. 2006, 45, 1949; c) S. G.
Pan, J. H. Liu, H. R. Li, Z. Y. Wang, X. W. Guo, Z. P. Li, Org.
Lett. 2010, 12, 1932, and reference [7].
[15] See the Supporting Information for details of the optimization.
[16] a) A. Witt, J. Bergman, Curr. Org. Chem. 2003, 7, 659; b) B. C.
Uff, B. L. Joshi, J. Chem. Soc. Perkin Trans. 1 1986, 2295.
[13] For I2 – I+ redox process, see: Y. Z. Yan, Z. Y. Wang, Chem.
Commun. 2011, 47, 9513. In this paper, amino acids were used as
carbon and nitrogen sources of quinazolines rather than
solvents; for IÀ – I2 redox process, see reference [7].
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Communications
À
C H Amination
Y.-Z. Yan, Y.-H. Zhang, C.-T. Feng,
Z.-G. Zha, Z.-Y. Wang*
&&&& — &&&&
Selective Iodine-Catalyzed Intermolecular
3
À
Oxidative Amination of C(sp ) H Bonds
with ortho-Carbonyl-Substituted Anilines
Access to quinazolines: The selective
leads to quinazolines in good to excellent
yields (see scheme; NIS=N-Iodosucci-
nimide, TBHP=tert-butyl hydroperox-
ide). The selectivity of the amination of
3
À
to Give Quinazolines
amination of C(sp ) H bonds adjacent to
nitrogen or oxygen atoms of N-alkyla-
mides, ethers, or alcohols with ortho-
carbonyl-substituted anilines constitutes
the first step in a tandem annulation that
À
primary and secondary C H bonds is also
noteworthy (left: >3:1, right: >99:1).
6
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Angew. Chem. Int. Ed. 2012, 51, 1 – 6
These are not the final page numbers!