SnCl4 mediated synthesis of γ-amino ketones derivatives via the ring-opening reaction of 4,5-dihydropyrroles

Article abstract of DOI:10.1016/j.tet.2013.08.027

This paper presents an alternative route to γ-amino ketones via a SnCl₄·5H₂O mediated ring-opening reaction of the 4,5-dihydropyrroles with the advantages of readily available reactants, good to excellent yields and applicability to a wide range of substrates.

Full text of DOI:10.1016/j.tet.2013.08.027

Tetrahedron 69 (2013) 9063e9067
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
SnCl4 mediated synthesis of
g-amino ketones derivatives via the
ring-opening reaction of 4,5-dihydropyrroles
,
a
b
a
a
a
Zhiguo Zhang a , Dan Wang , Bing Wang , Qingfeng Liu , Tongxin Liu , Wei Zhang ,
*
Beibei Yuan a, Zhijia Zhao a, Dandan Han a, Guisheng Zhang a
,
*
a Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, School of Chemistry and Chemical Engineering,
Henan Normal University, Xinxiang, Henan 453007, PR China
b School of Chemistry and Chemical Engineering, Mudanjiang Normal University, Mudanjiang, Heilongjiang 157012, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 16 May 2013
Received in revised form 23 July 2013
Accepted 15 August 2013
Available online 20 August 2013
This paper presents an alternative route to g-amino ketones via a SnCl4$5H2O mediated ring-opening
reaction of the 4,5-dihydropyrroles with the advantages of readily available reactants, good to excel-
lent yields and applicability to a wide range of substrates.
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
4,5-Dihydropyrrole
SnCl4$5H2O
Lewis acid
g-Amino ketones
Pyrrole ring-opening
1. Introduction
acids to
methods for the preparation of
g
-amino ketones.5b,13 However, the existing synthetic
-amino ketones more or less suffer
g
The compounds with a side chain of
g
-amino ketones are
from strong Brønsted acid, unsatisfactory yields, tedious reaction
procedure, significant expensive reactants, and/or need of inert
atmosphere, a remarkably limited substrate range and so on. So far
as we know, only one case of Lewis acid mediated was that Shi et al.
identified with diverse biological activities as anti-inflammatory
phospholipase-A2 inhibitors,1
-lactam inhibitors of human leu-
kocyte elastase-1,2 hypotensive agents,3 central nervous system
b
agents,4 etc. Moreover,
g
-amino ketones themselves are also useful
reported the synthesis of g-amino ketones in the presence of
intermediates in organic synthesis.5 Among their applications, the
preparation of highly functionalized tryptamines is a well-known
Zr(OTf)4 in 2004, but it encountered uncontrollable yield of the
desired products.11 Herein, we present a facile approach for the
example.5a,6 In reviewing previous reports,
g
-amino ketones can
preparation of g-amino ketones in good to excellent yields medi-
be prepared in several methods as follows (Scheme 1): (a) Hydro-
lysis of 4,5-dihydropyrrole derivatives in the presence of Brønsted
acid, however, an obvious drawback of this method is that it can not
ated by SnCl4$5H2O via ring-opening reaction of substituted
4,5-dihydropyrroles 1, which were prepared in high yield by the
reaction of amines and doubly activated cyclopropanes in EtOH at
reflux (Scheme 1).14
provide structural diverse
g-amino ketones due to the substrate
limitations.5a,6,7 (b) Treating N-substituted 2-pyrrolidinones with
RMgX.5c,8 (c) Hydration reaction of the functional groups (such as
alkene or alkyne) of which can be converted into a carbonyl group.9
(d) Nucleophilic substitution of halide by amines.10 (e) Ring-
opening reaction of cyclopropyl aryl ketones with sulfonamides.11
Besides, there are also some other synthetic methods, such as the
ring-opening reaction of aziridines,12 the conversion of carboxylic
2. Results and discussion
Combined with our recent research on the synthesis of
nitrogen-containing heterocyclic compounds from readily available
acetoacetamides precursors,15 we made a lot of efforts to realize
the intramolecular cyclization form 1 to 3 catalyzed by Lewis acids.
We first focused on the reactivity of 1i but the results were dis-
appointing. The experiments showed that pyrrolo[3,2-c]quinolin-
4-one 3i could not be obtained in the presence of FeCl3, TiCl4, AlCl3,
and BF3$Et2O (Scheme 2).15c However, after many attempts, it was
* Corresponding authors. Fax: þ86 373 3325250; e-mail addresses: zhangzg@
htu.edu.cn (Z. Zhang), zgs6668@yahoo.com (G. Zhang).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.08.027

9064
Z. Zhang et al. / Tetrahedron 69 (2013) 9063e9067
Scheme 1. Synthetic approaches of g-amino ketones 2.
demonstrated that other solvents, such as DMSO, MeNO2, and di-
oxane were proved to be fundamentally ineffective (entry 6) or low
efficiency (entries 7, 8). It was observed that FeCl3, TiCl4, AlCl3, and
BF3$Et2O were proved to be ineffective or less effective for the
transformation (entries 11e14).
Under the optimal conditions (Table 1, entry 1), a range of
substrates 1 was carried out to extend the scope of the ring-
opening reaction, and some of the results were summarized in
Table 2. It has been found that the reactions of 1aer proceeded
Scheme 2. The reaction of 4,5-dihydropyrroles 1i in the presence of Lewis acid.
found that the ring-opening product 5-((4-chlorophenyl)amino)
pentan-2-one 2i could be isolated in the yield of 85% by treating 1i
(0.5 mmol) with SnCl4$5H2O (0.6 mmol) in xylene (2.0 mL) at reflux
after 18 h (Table 1, entry 1). Further exploration disclosed that
lowering the reaction temperature had significant influence on the
conversion (entry 1 vs 2 and 3). Similarly, treatment of 1i with
1.0 equiv of SnCl4$5H2O for 20 h could only afford 2i in 63% yield
along with the recovered 1i (30%) (entry 4). The screening also
smoothly to afford the corresponding substituted g-amino ketones
2 in the presence of SnCl4$5H2O at reflux (Table 2). Obviously, the
substituents on the 4,5-dihydro-1H-pyrrole ring had significant
effects on the yields and reaction times of the ring-opening re-
action. For compounds 1aec with an electron donating group
(EDG) (OMe) on the benzene ring of the N-phenyl moiety, the
isolated yield of 2b (92%) with a methoxy group at meta-position
was slightly higher than that of the products with a methoxy group
at ortho- (2a: 85%) and para- (2c: 65%) positions (entries 1e3).
Quite similar with the phenyl non-substituted product 2d (entry 4),
it required a dramatically longer reaction times to provide the
product 2g in approximately equal yield to 2e, 2f, and 2h when the
substrates 1eeh with an electron withdrawing group (EWG) (Cl,
CO2Et) on the N-phenyl moiety were used for the conversion (en-
Table 1
Survey of the reaction conditionsa
tries 5e8). For
change of the electronic effects of the aryl group on N-phenyl
moiety could affect the yields of the reaction. The -amino ketone
a-methyl substituted reactants 1iel, the small
Entry
Catalyst (equiv)
Solvent
T/ꢀC
Time/h
Yield/%b
g
1
2
3
4
5
6
7
8
SnCl4$5H2O (1.2)
SnCl4$5H2O (1.2)
SnCl4$5H2O (1.2)
SnCl4$5H2O (1.0)
SnCl4$5H2O (1.2)
SnCl4$5H2O (1.2)
SnCl4$5H2O (1.2)
SnCl4$5H2O (1.2)
SnCl4 (1.2)
Xylene
Xylene
Xylene
Xylene
Xylene
DMSO
MeNO2
Dioxane
Xylene
Xylene
Xylene
Xylene
Xylene
Xylene
Reflux
120
90
Reflux
Reflux
145
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
18
24
48
20
13
5.5
5.5
18
8
85
63c
0d
2i with an EWG on the benzene ring was obtained in the yields of
85% and 86%, respectively (entries 9 and 10), which were little
higher than the yields of 2j and 2k in entries 11, 12, and 13 (60%,
63%, and 67%, respectively) with an EDG on the benzene ring. To our
delight, all of the 3-ester substituted pyrroles 1neq could also
smoothly slide into the corresponding products 2 in high yields
(82e96%) regardless of the electronic nature of the diversity
substituent (entries 14e17). However, N-benzyl substituted 4,5-
dihydro-1H-pyrrole derivatives 1r provided an unidentified com-
plex mixture instead of the desired 2m (entry 18). It is worth noting
that all the synthesized compounds 2 are unstable, and should be
stored under an inert atmosphere in the dark.
Unfortunately, any intermediate, as direct evidence for the
mechanism of the ring-opening reactions, was not isolated in the
control experiments of quenching the reaction in 13 h (Table 1,
entry 5) or performing the reaction at slightly lower temperature
(Table 1, entries 2 and 3). But by analysis of the structure of the
product 2, we can see that it should experience the hydrolysis and
decarboxylation steps during the conversion from 1 to 2. So we
deduced that it should not afford the desired product 2 under an-
hydrous conditions. The controlled experiments were carried out
under anhydrous conditions. 1i was subjected into anhydrous SnCl4
63e
77f
0g
52g
69h
Tracei
80%
0%
9
10
11
12
13
14
SnCl4 (1.2)þH2O (6.0)
8
FeCl3 (1.2)
18
18
18
18
TiCl4 (1.2)
BF3$Et2O (1.2)
AlCl3 (1.2)
0%j
70%k
57%l
a
All reactions were carried out with 1i (0.5 mmol) in solvent (2.0 mL).
Isolated yield.
20% 1i was recovered.
80% 1i was recovered.
30% 1i was recovered.
13% 1i was recovered.
Along with a complex mixture without any recognizable product.
17% 1i was recovered.
b
c
d
e
f
g
h
i
Reaction was carried out in N2 atmosphere, 23% 1i was recovered along with
unidentified complex mixture.
j
75% 1i was recovered.
10% 1i was recovered.
20% 1i was recovered.
k
l

Z. Zhang et al. / Tetrahedron 69 (2013) 9063e9067
9065
Table 2
Table 2 (continued )
Reaction extensiona,b
Entry
Substrates 1
Products 2
9
1i
Entry
Substrates 1
Products 2
2i: 18 h, 85%
10
1
1j
2i: 24 h, 86%
2j: 22 h, 60%
2a: 13 h, 85%
1a
1b
11
12
1k
1l
2
3
4
2b: 12 h, 92%
2j: 22 h, 63%
2k: 6.5 h, 67%
2i: 4.0 h, 96%
2g: 4.0 h, 95%
2j: 4.0 h, 89%
13
14
2c: 12 h, 65%
1c
1m
1n
2d: 13 h, 94%
1d
15
16
5
2e: 4.0 h, 85%
1o
1p
1e
6
2f: 5.0 h, 90%
2g: 19 h, 92%
1f
17
2l: 4.0 h, 82%
7
1q
1r
1g
18
2m: 4.0 d, trace
8
a
All reactions were carried out with 1 (0.5 mmol), SnCl4$5H2O (0.6 mmol) in
xylene (2.0 mL) at reflux.
b
2h: 4.0 h, 87%
1h
Isolated yield.

9066
Z. Zhang et al. / Tetrahedron 69 (2013) 9063e9067
at 130 ꢀC for 8.0 h in N2, then the reaction was quenched. After
work-up, the residue was investigated by means of LC-MS. We
found 23% 1i and only a trace amount of 2i in the reaction mixture
along with some unrecognizable products (Table 1, entry 9). Ad-
ditionally, it could provide 2i in the yield of 80% when
6.0 equiv water was added to the reaction mixture in the presence
of anhydrous SnCl4 after 8.0 h (Table 1, entry 10). All of these
controlled experiments indicated the importance of water on the
transformation. We deduced the plausible mechanism according to
the conditions screening and above controlled experiments to-
gether with some previous literature results. In a simplified, gen-
erally accepted mechanistic model as shown in Scheme 3, highly
spectrometer Bruker microTOF (ESI-oa-TOF). Melting points were
measured on a YuHua X-5 apparatus.
4.2. General procedure for the ring-opening reaction (Table 2)
A mixture of 1 (0.5 mmol) and SnCl4$5H2O (210 mg, 0.6 mmol)
in xylene (2.0 mL) in a round-bottom flask (25 mL) equipped with
a spherical condenser (40 cm length) was well stirred for 18 h at
reflux. After cooling off, the mixture was added water (5.0 mL) and
NaOH (144 mg) at stirring. After 10 min, the mixture was extract
with CH2Cl2 (5.0 mLꢁ3) and the combined organic phases were
dried over anhydrous MgSO4, then removed under reduced pres-
Scheme 3. Proposed mechanism.
substituted 4,5-dihydro-1H-pyrroles 1 initially coordinated with
the SnCl4$5H2O to generate N-arylpyrrolinium analogue A. Sub-
sure, and the residue was purified through a short flash silica gel
column chromatography to give compound 2.
sequently, species A further converted into the chain
substituted -dicarbonyl intermediate D via the hydrolysis of the
imine5a,6,7,8b and dehydrochlorination process.15b,c Finally, the in-
a-mono-
b
4.2.1. 4-((2-Methoxyphenyl)amino)-1-phenylbutan-1-one
(2a). White solid. Mp: 78e80 ꢀC; 1H NMR (400 MHz, CDCl3)
termediates D produced the
g
-amino ketones 2 via the hydrolysis
d 7.98e7.96 (m, 2H), 7.57e7.55 (m, 1H), 7.48e7.44 (m, 2H),
and decarboxylation reaction.12a,15b,c
6.90e6.86 (m, 1H), 6.78e6.76 (m, 1H), 6.69e6.63 (m, 2H), 4.27 (br,
1H), 3.84 (s, 3H), 3.26e3.25 (m, 2H), 3.14 (t, J¼7.2 Hz, 2H), 2.15e2.08
(m, 2H). 13C NMR (100 MHz, CDCl3)
d 199.94, 146.95, 138.40, 137.13,
3. Conclusion
133.13, 128.71, 128.17, 121.49, 116.51, 109.99, 109.64, 55.55, 43.29,
36.22, 24.17. HRMS (ESI), m/z calcd for C17H19NO2 ([MþH]þ)
270.1489, found: 270.1489.
In summary, a facile and efficient method for the synthesis of
g-amino ketones 2 has been developed from readily available
multi-substituted-4,5-dihydropyrroles. The procedure involves
a continuous multiple bond cleavage process in the presence of
SnCl4$5H2O. This protocol is associated with readily available
starting materials, a wide range of substrates scope, excellent
yields, dense, and flexible substituted patterns, and important
synthetic potential of the products.
4.2.2. 4-((3-Methoxyphenyl)amino)-1-phenylbutan-1-one
(2b). White solid. Mp: 67e69 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.98
(s, 1H), 7.96 (s, 1H), 7.57 (t, J¼7.6 Hz, 1H), 7.46 (t, J¼8.0 Hz, 2H),
7.10e7.06 (m, 1H), 6.28e6.23 (m, 2H), 6.18 (t, J¼2.4 Hz, 1H), 3.80 (br,
1H), 3.77 (s, 3H), 3.22 (t, J¼6.8 Hz, 2H), 3.12 (t, J¼6.8 Hz, 2H),
2.12e2.05 (m, 2H). 13C NMR (100 MHz, CDCl3)
d 199.95, 160.96,
149.78, 136.95, 133.23, 130.10, 128.74, 128.14, 106.02, 102.56, 98.73,
55.20, 43.57, 36.16, 23.86. HRMS (ESI), m/z calcd for C17H19NO2
([MþH]þ) 270.1489, found: 270.1489.
4. Experimental
4.1. General
4.2.3. 4-((4-Methoxyphenyl)amino)-1-phenylbutan-1-one
All reagents were purchased from commercial sources and used
without further treatment, unless otherwise indicated. Xylene were
distilled from sodium/benzophenone ketyl and purged with nitro-
gen atmosphere prior to use. 1H NMR and 13C NMR spectra were
recorded on a Bruker Avance/400 (1H: 400 MHz, 13C: 100 MHz at
25 ꢀC) and TMS as internal standard. Data are represented as
follows: chemical shift, integration, multiplicity (br¼broad,
s¼singlet, d¼doublet, dd¼double doublet, t¼triplet, q¼quartet,
m¼multiplet), coupling constants in Hertz (Hz). All high-resolution
mass spectras (HRMS) were measured on a Bruker MicroTOF mass
(2c). Yellow solid. Mp: 77e79 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.96
(d, J¼7.6 Hz, 2H), 7.57 (t, J¼7.2 Hz, 1H), 7.46 (t, J¼7.6 Hz, 2H), 6.78 (d,
J¼8.8 Hz, 2H), 6.59 (d, J¼8.8 Hz, 2H), 3.74 (s, 3H), 3.47 (br, 1H), 3.18
(t, J¼6.8 Hz, 2H), 3.12 (t, J¼7.2 Hz, 2H), 2.12e2.03 (m, 2H). 13C NMR
(100 MHz, CDCl3)
d 200.05, 152.19, 142.65, 137.00, 133.23, 128.75,
128.17, 115.04, 114.20, 55.96, 44.56, 36.24, 24.10. HRMS (ESI), m/z
calcd for C17H19NO2 ([MþH]þ) 270.1489, found: 270.1489.
4.2.4. 1-Phenyl-4-(phenylamino)butan-1-one (2d).16 White solid.
Mp: 76e78 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.97 (d, J¼7.2 Hz, 2H),

Z. Zhang et al. / Tetrahedron 69 (2013) 9063e9067
9067
7.57 (t, J¼6.8 Hz, 1H), 7.47 (t, J¼7.2 Hz, 2H), 7.18 (t, J¼6.8 Hz, 2H),
6.70 (t, J¼6.8 Hz, 1H), 6.63 (d, J¼7.6 Hz, 2H), 3.75 (br, 1H), 3.24 (t,
J¼6.4 Hz, 2H), 3.12 (t, J¼6.8 Hz, 2H), 2.13e2.05 (m, 2H). 13C NMR
(s, 3H), 1.96e1.89 (m, 2H). 13C NMR (100 MHz, CDCl3)
146.87, 138.30, 121.43, 116.50, 109.83, 109.53, 55.53, 43.09, 41.27,
30.14, 23.63. HRMS (ESI), m/z calcd for C12H17NO2 ([MþH]þ)
208.1332, found: 208.1335.
d
208.62,
(100 MHz, CDCl3)
d 199.94, 148.43, 137.08, 133.19, 129.39, 128.74,
128.16, 117.45, 112.91, 43.65, 36.22, 24.04. HRMS (ESI), m/z calcd for
C
16H17NO ([MþH]þ) 240.1386, found: 240.1383.
4.2.12. 4-((4-Chlorophenyl)amino)-1-(4-methoxyphenyl)butan-1-
one (2l). White solid. Mp: 125e127 ꢀC; 1H NMR (400 MHz, CDCl3)
4.2.5. 4-((2-Chlorophenyl)amino)-1-phenylbutan-1-one (2e). White
solid. Mp: 63e65 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.95e7.92 (m, 2H), 7.12e7.08 (m, 2H), 6.94e6.91 (m, 2H),
d
7.98 (d, J¼7.6 Hz,
6.54e6.50 (m, 2H), 3.86 (s, 3H), 3.83 (br, 1H), 3.17 (t, J¼6.8 Hz, 2H),
2H), 7.57 (t, J¼7.2 Hz, 1H), 7.47 (t, J¼8.0 Hz, 2H), 7.25 (d, J¼8.0 Hz,
1H), 7.14 (t, J¼8.0 Hz, 1H), 6.70 (d, J¼8.0 Hz, 1H), 6.62 (t, J¼8.0 Hz,
1H), 4.40 (br,1H), 3.29 (dd, J¼12.4, 6.4 Hz, 2H), 3.14 (t, J¼6.8 Hz, 2H),
3.05 (t, J¼6.8 Hz, 2H), 2.08e2.02 (m, 2H). 13C NMR (100 MHz, CDCl3)
d
198.45, 163.63, 146.97, 130.40, 129.98, 129.13, 121.75, 113.86,
113.85, 55.59, 43.77, 35.74, 23.85. HRMS (ESI), m/z calcd for
2.17e2.10 (m, 2H). 13C NMR (100 MHz, CDCl3)
d
199.73, 144.09,
C
17H18ClNO2 ([MþH]þ) 304.1099, found: 304.1092.
136.95, 133.27, 129.23, 128.76, 128.16, 127.95, 119.20, 117.22, 111.27,
43.23, 35.98, 23.66. HRMS (ESI), m/z calcd for C16H16ClNO ([MþH]þ)
274.0993, found: 274.0993.
Acknowledgements
We thank the NSFC (21002051, 21172056, and 21272057),
PCSIRT (IRT1061), China Postdoctoral Science Foundation funded
project (2012M521397 and 2013M530339), Key Project of Henan
Educational Committee (13A150546), and the Foundation and
Frontier Technology Research Program of Henan Province
(112300410312) for financial supports of this research.
4.2.6. 4-((3-Chlorophenyl)amino)-1-phenylbutan-1-one (2f). White
solid. Mp: 102e104 ꢀC; 1H NMR (400 MHz, CDCl3)
d 7.97 (d,
J¼7.2 Hz, 2H), 7.58 (t, J¼7.2 Hz, 1H), 7.47 (t, J¼8.0 Hz, 2H), 7.06 (t,
J¼8.0 Hz, 1H), 6.64 (dd, J1¼8.0 Hz, J2¼1.6 Hz, 1H), 6.58 (t, J¼2.0 Hz,
1H), 6.47 (dd, J1¼8.0 Hz, J2¼1.6 Hz, 1H), 3.90 (br, 1H), 3.20e3.19 (m,
2H), 3.12 (t, J¼6.8 Hz, 2H), 2.12e2.05 (m, 2H). 13C NMR (100 MHz,
CDCl3) d 199.88, 149.47,136.84,135.11, 133.33,130.29, 128.77, 128.13,
Supplementary data
117.13, 112.31, 111.18, 43.43, 36.11, 23.59. HRMS (ESI), m/z calcd for
C
16H16ClNO ([MþH]þ) 274.0989, found: 274.0993.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.08.027.
4.2.7. 4-((4-Chlorophenyl)amino)-1-phenylbutan-1-one (2g). White
solid. Mp: 126e129 ꢀC; 1H NMR (400 MHz, CDCl3)
7.96 (d,
d
References and notes
J¼7.6 Hz, 2H), 7.57 (t, J¼7.2 Hz, 1H), 7.46 (t, J¼7.6 Hz, 2H), 7.12e7.08
(m, 2H), 6.56e6.51 (m, 2H), 3.83 (br, 1H), 3.18 (t, J¼6.8 Hz, 2H), 3.10
(t, J¼7.2 Hz, 2H), 2.10e2.03 (m, 2H). 13C NMR (100 MHz, CDCl3)
1. Wilkerson, W.; DeLucca, I.; Galbraith, W.; Kerr, J. Eur. J. Med. Chem. 1992, 27,
595e610.
2. Shah, S. K.; Dorn, C. P.; Finke, P. E.; Hale, J. J.; Hagmann, W. K.; Brause, K. A.;
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d
199.81, 146.81, 136.79, 133.21, 129.05, 128.67, 128.03, 121.76,
113.82, 43.64, 36.01, 23.61. HRMS (ESI), m/z calcd for C16H16ClNO
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solid. Mp: 83e85 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.95 (d, J¼6.8 Hz,
2H), 7.86 (d, J¼8.8 Hz, 2H), 7.58e7.55 (m, 1H), 7.46 (t, J¼7.6 Hz, 2H),
6.56 (d, J¼8.8 Hz, 2H), 4.39 (br,1H), 4.30 (dd, J¼7.2 Hz, 2H), 3.26 (dd,
J¼6.4 Hz, 2H), 3.12 (t, J¼6.8 Hz, 2H), 2.13e2.06 (m, 2H), 1.35 (t,
J¼7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3)
d 199.82, 167.00, 151.99,
136.76, 133.35, 131.60, 128.76, 128.09, 118.59, 111.44, 60.27, 43.06,
36.04, 23.45, 14.56. HRMS (ESI), m/z calcd for C19H21NO3 ([MþH]þ)
312.1597, found: 312.1594.
ꢀ
7. (a) Danion-Bougot, R.; Danion, D.; Carrie, R. Tetrahedron 1985, 41, 1953e1958;
(b) Gabriel, S. Chem. Ber. 1909, 42, 1238e1243.
8. (a) Raj, A. R. N.; Huq, C. A. M. A. J. Indian Chem. Soc. 2008, 86, 429e433; (b)
Dunsmore, C. J.; Carr, R.; Fleming, T.; Turner, N. J. J. Am. Chem. Soc. 2006, 128,
2224e2225; (c) Katritzky, A. R.; Jurczyk, S.; Rachwal, B.; Rachwal, S.; Shcher-
bakova, I.; Yannakopoulou, K. Synthesis 1992, 1992, 1295e1298; (d) Giovannini,
A.; Savoia, D.; Umani-Ronchi, A. J. Org. Chem. 1989, 54, 228e234.
9. (a) Liu, X.-Y.; Che, C.-M. Angew. Chem., Int. Ed. 2009, 48, 2367e2371; (b) He-
gedus, L. S.; McKearin, J. M. J. Am. Chem. Soc. 1982, 104, 2444e2451.
10. (a) Yi, L.; Sun, H.; Wu, Y.-W.; Triola, G.; Waldmann, H.; Goody, R. S. Angew.
Chem., Int. Ed. 2010, 49, 9417e9421; (b) Stewart, C. J.; Wieland, T. Liebigs Ann.
Chem. 1978, 1978, 57e65; (c) Gabriel, S.; Colman, J. Chem. Ber. 1908, 41,
513e521; (d) Martin, D. P.; Bibart, R. T.; Drueckhammer, D. G. J. Am. Chem. Soc.
1994, 116, 4660e4668.
11. Shi, M.; Yang, Y.-H.; Xu, B. Synlett 2004, 1622e1624.
12. (a) Stamm, H.; Gailius, V. Chem. Ber. 1981, 114, 3599e3608; (b) Enders, D.; Janeck,
C. F.; Runsink, J. Synlett 2000, 641e643.
13. Lu, Y.; Taylor, R. T. Tetrahedron Lett. 2003, 44, 9267e9269.
14. Celerier, J. P.; Haddad, M.; Jacoby, D.; Lhommet, G. Tetrahedron Lett. 1987, 28,
6597e6600.
4.2.9. 5-((4-Chlorophenyl)amino)pentan-2-one (2i). White solid.
Mp: 100e102 ꢀC; 1H NMR (400 MHz, CDCl3)
d
7.02 (d, J¼8.2 Hz, 2H),
6.43 (d, J¼8.2 Hz, 2H), 3.66 (br, 1H), 3.01 (t, J¼6.8 Hz, 2H), 2.48 (t,
J¼6.8 Hz, 2H), 2.08 (s, 3H), 1.84e1.77 (m, 2H). 13C NMR (100 MHz,
CDCl3)
d 208.62, 146.91, 129.15, 121.87, 113.83, 43.64, 41.21, 30.13,
23.27. HRMS (ESI), m/z calcd for C11H14ClNO ([MþH]þ) 212.0834,
found: 212.0837.
4.2.10. 5-(p-Tolylamino)pentan-2-one (2j). White solid. Mp:
72e74 ꢀC; 1H NMR (400 MHz, CDCl3)
d
6.99 (d, J¼8.0 Hz, 2H), 6.53
(d, J¼8.0 Hz, 2H), 3.53 (br, 1H), 3.11 (t, J¼6.8 Hz, 2H), 2.56 (t,
J¼6.8 Hz, 2H), 2.24 (s, 3H), 2.15 (s, 3H), 1.92e1.86 (m, 2H). 13C NMR
(100 MHz, CDCl3)
d 208.74, 146.07, 129.84, 126.62, 112.98, 77.48,
15. (a) Zhang, Q.; Zhang, Z.; Yan, Z.; Liu, Q.; Wang, T. Org. Lett. 2007, 9, 3651e3653;
(b) Zhang, Z.; Zhang, Q.; Sun, S.; Xiong, T.; Liu, Q. Angew. Chem., Int. Ed. 2007, 46,
1726e1729; (c) Zhang, Z.; Zhang, Q.; Yan, Z.; Liu, Q. J. Org. Chem. 2007, 72,
9808e9810; (d) Zhang, Z.; Zhang, Q.; Ni, Z.; Liu, Q. Chem. Commun. 2010,
1269e1271; (e) Zhang, Z.; Xue, C.; Liu, X.; Zhang, Q.; Liu, Q. Tetrahedron 2011, 67,
7081e7084; (f) Zhang, Z.; Fang, S.; Liu, Q.; Zhang, G. Adv. Synth. Catal. 2012, 354,
927e932; (g) Zhang, Z.; Fang, S.; Liu, Q.; Zhang, G. J. Org. Chem. 2012, 77,
7665e7670.
76.84, 43.82, 41.30, 30.13, 23.56, 20.47. HRMS (ESI), m/z calcd for
C
12H17NO ([MþH]þ) 192.1383, found: 192.1377.
4.2.11. 5-((2-Methoxyphenyl)amino)pentan-2-one (2k). Brown liq-
uid. 1H NMR (400 MHz, CDCl3)
d
6.87 (t, J¼7.6 Hz, 1H), 6.76
(d, J¼7.6 Hz, 1H), 6.66 (t, J¼7.6 Hz, 1H), 6.60 (d, J¼8.0 Hz, 1H), 4.19
(br,1H), 3.84 (s, 3H), 3.15 (t, J¼6.8 Hz, 2H), 2.58 (t, J¼7.2 Hz, 2H), 2.16
16. Naresh Raj, A. R.; Huq, C. A. M. A. J. Indian Chem. Soc. 2009, 86, 429e432.