Copper(I)-catalyzed cascade sulfonimidate to sulfonamide rearrangement: Synthesis of imidazo[1,2-a][1,4]diazepin-7(6 H)-one

Article abstract of DOI:10.1021/jo300855f

A novel strategy of copper(I)-catalyzed cascade intramolecular nucleophilic attack on N-sulfonylketenimine followed by rearrangement of sulfonimidates to sulfonamides resulting in a library of substituted 8,9-dihydro-5H-imidazo[1,2-a] [1,4]diazepin-7(6H)-ones has been developed.

Full text of DOI:10.1021/jo300855f

Note
pubs.acs.org/joc
Copper(I)-Catalyzed Cascade Sulfonimidate to Sulfonamide
Rearrangement: Synthesis of Imidazo[1,2-a][1,4]diazepin-7(6H)-one
Muthupandi Nagaraj,† Muthusamy Boominathan,† Devanathan Perumal,†
Shanmugam Muthusubramanian,*,† and Nattamai Bhuvanesh‡
†Department of Organic Chemistry, School of Chemistry, Madurai Kamaraj University, Madurai 625 021, India
‡X-ray Diffraction Laboratory, Department of Chemistry, Texas A&M University, College Station, Texas 77842, United States
S
* Supporting Information
ABSTRACT: A novel strategy of copper(I)-catalyzed cascade intramolecular nucleophilic attack on N-sulfonylketenimine
followed by rearrangement of sulfonimidates to sulfonamides resulting in a library of substituted 8,9-dihydro-5H-imidazo[1,2-a]-
[1,4]diazepin-7(6H)-ones has been developed.
etenimines1 find extensive usage as building blocks to syn-
Scheme 1. Allylic Imidate to Amide Rearrangement
K
thesize differently ring-sized nitrogen heterocycles by the
addition of nucleophiles2 and carbon-centered radicals3 to their
central carbon atom. Their structural arrangement facilitates
their involvement in pericyclic events such as cycloaddition
reactions, electrocyclic ring closures, and sigmatropic rearrange-
ments.4 Ketenimines have attracted much attention in recent
years because of their easy preparation and reasonable reactivity
resulting in a range of products.
In our continued interest in synthesizing heterocyclic com-
pounds from open chain compounds,16 it has been planned to
exploit the reactivity of ketenimine functionality to generate
new heterocyclic systems. In this attempt, a seven-membered
ring fused to another five-membered ring, an imidazodiazepi-
none nucleus, has been generated. An interesting cascade
process, an internal nucleophilic addition followed by a rearrange-
ment similar to imidate amide conversion, has been observed dur-
ing this reaction.
Alkynes 1 were obtained by the sodium borohydride reduc-
tion of the respective ketones.16e The structure of 1a was
confirmed by single crystal X-ray analysis17 (see the Supporting
Information for details). Ketenimines are known to react with
alcohols yielding imidates. Accordingly, we examined the two-
component reaction of tolylsulfonyl azide (2a) with alkyne
(1a) in the presence of copper iodide and triethylamine in
dichloromethane at room temperature (Scheme 2). Instead of
the anticipated N-(2,9-diphenyl-5,6-dihydroimidazo[2,1-c]-
[1,4]oxazepin-7(9H)-ylidene)-4-methylbenzene sulfonamide
3a (Scheme 2), 2,9-diphenyl-8-tosyl-8,9-dihydro-5H-imidazo-
[1,2-a][1,4]diazepin-7(6H)-one (4a) was obtained in high
Recently, the copper-catalyzed azide−alkyne cycloaddition
(CuAAC) has been shown to deliver ketenimines, which can be
used to construct various compounds with economic and ecolo-
gical values.5−8 The ketenimines generated by the above protocol
can be subjected to nucleophilic attack by amines, alcohols, or water
leading to amidines, imidates, and amides, respectively. It has been
shown that substrates containing both a triple bond and nucleo-
phile, when added with sulfonyl azide, yield cyclic compounds.9 The
electron-rich aromatic ring can also play the role of the nucleophile
in this class of reactions.10 Obviously, several ketenimine-based
multiple cascade reactions are constantly being explored.11
Sigmatropic rearrangements have been a mainstay of syn-
thetic organic chemistry to produce structurally complex targets
with excellent regio- and stereocontrol.12 The imidate−amide
interconversion (Scheme 1) played an important role in the
evolution of modern concepts of molecular structure and
tautomerization.13 Baeyer14 in 1882, as part of his classic
investigations of indigo, was the first to correctly formulate the
concept of tautomerization to describe the imidic acid-amide
isomerization of isatin. This type of conversion has been fre-
quently applied as a key step in total syntheses.15
Received: April 28, 2012
© XXXX American Chemical Society
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Note
Scheme 2. Copper(I)-Catalyzed Intramolecular Rearrangement of Sulfonimidate to Sulfonamide
yield, involving the rearrangement. Trace amount of sulfonyl
amide 5 has also been formed. The structure of 4 has been
unambiguously assigned by spectral and analytical data, and
that of 4b has been confirmed by single crystal X-ray analysis18
also (see the Supporting Information for details).
The reaction conditions were then optimized for the forma-
tion of 4a, and as shown in Table 1, the desired product could
the reaction was extended with various sulfonyl azides 2 and
differently substituted imidazole derivatives 1 under the opti-
mized reaction condition (Table 2). It could be seen that all the
aryl and alkylsulfonyl azides reacted well to give the respective 4
in excellent yields.
The reaction is believed to proceed initially through a
nucleophilic attack on the ketenimine central carbon resulting
in the intramolecular ring closure leading to the intermediate 3
(Scheme 3). The intermediate 3 should have undergone an
intramolecular [1,3]-sigmatropic shift providing N-sulfona-
mides 4, though a pericyclic [1,3]-sigmatropic rearrangement
is thermally unfavorable. To the best of our knowledge, this is
the first report of this type of rearrangement. The reported
imidate amide rearrangement involves a [3,3]-sigmatropic
rearrangement, and it has been found to occur in the presence
of palladium reagent.19 The rearrangement reported in this
work occurs in situ, probably driven by the thermodynamic
factors.
Encouraged by these results, to expand the scope of this
novel cyclization, the higher homologues of propargyl alcohols
6 were treated with tosyl azide 2a. However, the anticipated
cyclic N-sulfonyl lactam 7 has not been formed. Only the
sulfonyl amide 5 was obtained quantitatively in each case
(Scheme 4).
a
Table 1. Optimization of Reaction Conditions
reaction time
b
entry
catalyst
base
TEA
solvent
yield
(h)
1
2
3
4
5
6
7
8
9
CuI (20 mol %)
CuI (10 mol %)
CuI (5 mol %)
CuI (1 mol %)
DCM
DCM
DCM
DCM
DCM
DCM
DCM
90
0.5
0.5
1.0
2.0
5.0
5.0
4.0
1.0
1.0
1.5
4.0
6.0
6.0
TEA
TEA
TEA
90
87
82
CuI (0.1 mol %) TEA
62
CuI (10 mol %)
CuI (10 mol %)
CuI (10 mol %)
K2CO3
pyridine
trace
42
A copper-catalyzed cascade reaction involving intramolecular
nucleophilic addition to N-sulfonylketenimine furnishing cyclic
sulfonimidate, which subsequently undergoes rearrangement to
sulfonamide, has been described. A library of novel 8,9-dihydro-
5H-imidazo[1,2-a][1,4]diazepin-7(6H)-one derivatives has
been successfully synthesized.
2,6-lutidine DCM
85
CuBr (10 mol %) TEA
THF
78
10 CuCl (10 mol %) TEA
CHCl3
CH3CN
toluene
benzene
69
11 CuI (10 mol %)
12 CuI (10 mol %)
13 CuI (10 mol %)
TEA
TEA
TEA
48
42
44
a
Reaction conditions: p-Toluenesulfonyl azide 2a (1.2 mmol), 1a (1.0
EXPERIMENTAL SECTION
mmol), TEA (2.0 mmol), copper (I) salt, solvent (10 mL), rt, N2 atm.
Isolated yield.
■
b
General Information and Materials. All the reagents were
obtained commercially or synthesized according to literature
procedures. Nuclear magnetic resonance (1H and 13C NMR) spectra
were recorded on a 300 MHz spectrometer in CDCl3 using TMS
as internal standard. Chemical shifts are reported in parts per million
(δ), coupling constants (J values) are reported in Hertz (Hz). The
hydroxyl hydrogen was not seen in many cases. 13C NMR spectra were
routinely run with broadband decoupling. Infrared spectra were
recorded on a FT-IR instrument. Band positions are reported in
reciprocal centimeters (cm−1). Melting points were determined on a
melting point apparatus equipped with a thermometer and were
uncorrected. Column chromatography was carried out in silica gel
(60−120 mesh) using petroleum ether−ethyl acetate as eluent.
General Procedure for the Preparation of (1). 4-Aryl-2-aryloyl-
(1-(prop-2-ynyl)-imidazole derivatives were prepared by literature
procedure.16e,20 4-Aryl-2-aryloyl-(1-(prop-2-ynyl)-imidazole (1.7 mmol)
was dissolved in methanol (10.0 mL), and sodium borohydride (0.13 g,
3.4 mmol) was added slowly. After completion of the reaction, the
be obtained in 44−90% yield using CH3CN, THF, CHCl3,
toluene, and CH2Cl2 as solvents. Dichloromethane has been
found to be the solvent of choice. Other bases like pyridine
and potassium carbonate resulted in lower yield of 4a. It has
been found that the presence of copper catalyst in less than
10 mol % yields the product quantitatively but requires
more time for the reaction to get completed (Table 1,
entries 3, 4 and 5). Addition of the catalyst in higher mole
ratio has also not resulted in any improvement (Table 1,
entry 1).
The interesting observation related to 4 is that the benzylic
hydrogen appears relatively in the downfield region, around 7
1
ppm in the H NMR spectra, while the corresponding carbon
appears around 50 ppm in the 13C NMR spectra. The scope of
B
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Note
reaction mixture was poured into ice-cold water and filtered to yield 1
(80−95%).
Phenyl(4-phenyl-1-(prop-2-ynyl)-1H-imidazol-2-yl)methanol
(1a). Isolated yield 0.440 g (90%); colorless solid: mp 142−144 °C; IR
b
Table 2. Synthesis of Substituted Imidazo[1,2-a][1,4]diazepin-7(6H)-one
C
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Note
Table 2. continued
a
b
Isolated yield. All reactions were carried out on 1.0 mmol scale with 1/sulfonyl azide/TEA = 1:1.2:2.0, 10 mol % of CuI with 10.0 mL of
dichloromethane.
1
(KBr) 3279, 1285, 908, 684 cm−1; H NMR (300 MHz, CDCl3) δ
2.28 (t, J = 2.4 Hz, 1H), 4.29 (dd, J = 12.0 Hz, 2.4 Hz, 1H), 4.37 (dd,
J = 12.0 Hz, 2.4 Hz, 1H), 6.04 (s, 1H), 7.26−7.32 (m, 4H), 7.34
(s, 1H), 7.37−7.42 (m, 4H), 7.75 (dd, J = 7.8 Hz, 1.2 Hz, 2H); 13C
NMR (75 MHz, CDCl3) δ 35.5, 68.8, 73.9, 76.5, 116.1, 124.8, 125.9,
126.9, 127.5, 128.5, 128.6, 133.4, 139.3, 139.9, 148.8; MS (M + 1) 289.25.
D
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Note
Scheme 3. Proposed Mechanism
(4-Methoxyphenyl)(4-(4-methoxyphenyl)-1-(prop-2-ynyl)-1H-imi-
Scheme 4. Attempted Synthesis of N-Sulfonyl Lactam
dazol-2-yl)methanol (1e). Isolated yield 0.485 g (82%); colorless
1
solid: mp 92−94 °C; IR (KBr) 3399, 1292, 916, 689 cm−1; H NMR
(300 MHz, CDCl3) δ 2.29 (t, J = 2.7 Hz, 1H), 3.78 (s, 3H), 3.83 (s,
3H), 4.31 (d, J = 2.4 Hz, 2H), 5.97 (s, 1H), 6.85 (d, J = 8.7 Hz, 2H),
6.91 (d, J = 8.7 Hz, 2H), 7.15 (s, 1H), 7.27 (d, J = 8.7 Hz, 2H), 7.66
(d, J = 8.7 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 35.5, 55.1, 55.2,
68.8, 73.9, 76.8, 113.9, 114.0, 115.0, 126.0, 126.4, 127.6, 132.2, 139.4,
148.5, 158.7, 159.2. Anal. Calcd. for C21H20N2O3: C, 72.40; H, 5.79;
N, 8.04. Found: C, 72.23; H, 5.69; N, 7.96.
Anal. Calcd. for C19H16N2O: C, 79.14; H, 5.59; N, 9.72. Found: C,
78.98; H, 5.42; N, 9.59.
(4-Chlorophenyl)(4-(4-chlorophenyl)-1-(prop-2-ynyl)-1H-imida-
Naphthalen-2-yl(4-(naphthalen-2-yl)-1-(prop-2-ynyl)-1H-imida-
zol-2-yl)methanol (1b). Isolated yield 0.558 g (92%); colorless
zol-2-yl)methanol (1f). Isolated yield 0.561 g (85%); colorless solid:
1
solid: mp 144−146 °C; IR (KBr) 3289, 1275, 910, 685 cm−1; H
1
mp 88−90 °C; IR (KBr) 3388, 1289, 913, 687 cm−1; H NMR (300
NMR (300 MHz, CDCl3) δ 2.30 (t, J = 2.4 Hz, 1H), 4.28 (dd, J =
17.7, Hz, 2.4 Hz, 1H), 4.43 (dd, J = 17.7, Hz 2.4 Hz, 1H), 6.01 (s,
1H), 7.22 (s, 1H), 7.24 (d, J = 8.4 Hz, 2H), 7.29−7.35 (m, 4H), 7.62
(d, J = 8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 35.7, 68.0, 74.3,
76.4, 116.4, 125.9, 127.1, 128.5, 128.6, 131.5, 132.5, 133.4, 138.1,
138.3, 148.4; MS (M + 1) 357.17. Anal. Calcd. for C19H14Cl2N2O: C,
63.88; H, 3.95; N, 7.84. Found: C, 63.72; H, 3.87; N, 7.69.
MHz, CDCl3) δ 2.26 (t, J = 2.4 Hz, 1H), 4.30 (dd, J = 18.0 Hz, 2.4 Hz,
1H), 4.45 (dd, J = 18.0 Hz, 2.4 Hz, 1H), 6.26 (s, 1H), 7.43−7.49 (m,
7H), 7.82−7.86 (m, 6H), 7.93 (s, 1H), 8.32 (s, 1H); 13C NMR (75
MHz, CDCl3) δ 35.8, 69.4, 74.2, 76.9, 116.7, 122.7, 123.5, 124.2,*
124.6, 125.2, 125.8, 125.9, 127.4, 127.5,* 127.8, 127.9, 128.1, 131.1,
132.4, 132.7, 133.1, 133.6, 137.6, 139.6, 148.7. Anal. Calcd. for
C27H20N2O: C, 83.48; H, 5.19; N, 7.21. Found: C, 83.34; H, 5.08; N,
7.12. [* Two carbon signals have merged together].
(4-Bromophenyl)(4-(4-bromophenyl)-1-(prop-2-ynyl)-1H-imida-
zol-2-yl)methanol (1c). Isolated yield 0.720 g (95%); colorless solid:
Biphenyl-4-yl(4-(biphenyl-4-yl)-1-(prop-2-ynyl)-1H-imidazol-2-
yl)methanol (1g). Isolated yield 0.629 g (84%); colorless solid: mp
1
mp 160−162 °C; IR (KBr) 3292, 1291, 911, 696 cm−1; H NMR
1
182−184 °C; IR (KBr) 3379, 1272, 927, 701 cm−1; H NMR (300
(300 MHz, CDCl3) δ 2.33 (t, J = 2.4 Hz, 1H), 4.31 (dd, J = 17.7 Hz,
2.4 Hz, 1H), 4.45 (dd, J = 17.7 Hz, 2.4 Hz, 1H), 5.98 (s, 1H), 7.22−
7.27 (m, 4H), 7.45 (s, 1H), 7.49 (d, J = 7.2 Hz, 2H), 7.59 (d, J =
8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 35.8, 68.2, 74.5, 76.7,
116.6, 120.7, 121.7, 126.3, 127.5, 131.4, 131.8, 132.7, 138.5, 138.7,
148.5. Anal. Calcd. for C19H14Br2N2O: C, 51.15; H, 3.16; N, 6.28
Found: C, 50.98; H, 3.08; N, 6.19.
MHz, CDCl3) δ 2.23 (t, J = 2.4 Hz, 1H), 4.37 (dd, J = 17.7, 2.4 Hz,
1H), 4.48 (dd, J = 17.7, 2.4 Hz, 1H), 6.21 (s, 1H), 7.29 (s, 1H), 7.33−
7.43 (m, 6H), 7.47 (d, J = 8.1 Hz, 2H), 7.56−7.65 (m, 8H), 7.81 (d,
J = 8.1 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 35.9, 69.1, 74.3, 77.1,
116.4, 125.3, 126.7,* 126.9,* 127.0,* 127.2, 127.3, 128.7, 132.6, 139.0,
139.5, 139.6, 140.7, 140.8, 140.9, 148.8. Anal. Calcd. for C31H24N2O:
C, 84.52; H, 5.49; N, 6.36. Found: C, 84.36; H, 5.32; N, 6.20. [* Two
carbon signals have merged together].
(4-Fluorophenyl)(4-(4-fluorophenyl)-1-(prop-2-ynyl)-1H-imida-
zol-2-yl)methanol (1d). Isolated yield 0.490 g (89%); colorless solid:
mp 164−166 °C; IR (KBr) 3294, 1293, 919, 694 cm−1; 1H NMR (300
MHz, CDCl3) δ 2.27 (t, J = 2.4 Hz, 1H), 4.28 (dd, J = 17.7 Hz, 2.4 Hz,
1H), 4.38 (dd, J = 17.7 Hz, 2.4 Hz, 1H), 6.02 (s, 1H), 6.98 (t, J =
8.7 Hz, 2H), 7.07 (t, J = 8.7 Hz, 2H), 7.17 (s, 1H), 7.30−7.35
(m, 2H), 7.63−7.68 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 35.4,
68.3, 74.0, 76.4, 114.7, 115.5, 115.6, 126.0, 127.5, 129.8, 136.1, 138.5,
148.5, 160.0, 163.2. Anal. Calcd. for C19H14F2N2O: C, 70.36; H, 4.35;
N, 8.64. Found: C, 70.22; H, 4.26; N, 8.52.
(1-(Prop-2-ynyl)-4-p-tolyl-1H-imidazol-2-yl)(p-tolyl)methanol
(1h). Isolated yield 0.462 g (86%); colorless solid: mp 112−114 °C; IR
1
(KBr) 3311, 1284, 916, 693 cm−1; H NMR (300 MHz, CDCl3) δ
2.20 (t, J = 2.4 Hz, 1H), 2.30 (s, 3H), 2.35 (s, 3H), 4.24 (d, J = 2.4 Hz,
2H), 6.04 (s, 1H), 7.10 (d, J = 7.8 Hz, 2H), 7.14 (d, J = 7.8 Hz, 2H),
7.18 (s, 1H), 7.23 (d, J = 7.8 Hz, 2H), 7.59 (d, J = 7.8, 2H); 13C NMR
(75 MHz, CDCl3) δ 20.9, 21.0, 35.5, 68.7, 73.8, 76.5, 115.5, 124.6,
125.9, 128.9, 129.1, 130.6, 136.3, 136.9, 137.1, 139.3, 148.6. Anal.
E
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Note
Calcd. for C21H20N2O: C, 79.72; H, 6.37; N, 8.85. Found: C, 79.63; H,
6.28; N, 8.72.
(d, J = 7.2 Hz, 2H), 7.61 (d, J = 8.7 Hz, 2H), 7.82 (dd, J = 7.5 Hz,
1.2 Hz, 2H), 7.86 (d, J = 8.7 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ
35.6, 43.1, 58.1, 116.9, 125.1, 125.5, 127.3, 128.2, 128.7,* 129.3, 130.4,
132.1, 133.4, 137.5, 138.4, 141.3, 142.6, 170.5; MS (M + 1) 524.25. Anal.
Calcd. for C25H20BrN3O3S: C, 57.48; H, 3.86; N, 8.04; S, 6.14. Found: C,
57.33; H, 3.74; N, 7.95; S, 6.06. [* Two carbon signals have merged
together].
(1-(Prop-2-ynyl)-4-(thiophen-2-yl)-1H-imidazol-2-yl)(thiophen-2-
yl)methanol (1i). Isolated yield 0.408 g (80%); viscous liquid: IR
1
(KBr) 3398, 1273, 922, 697 cm−1; H NMR (300 MHz, CDCl3) δ
2.31 (t, J = 2.7 Hz, 1H), 4.49 (d, J = 2.7 Hz, 2H), 6.22 (s, 1H), 6.80 (d,
J = 3.6 Hz, 1H), 6.91 (t, J = 4.2 Hz, 1H), 7.01 (t, J = 3.6 Hz, 1H),
7.14−7.18 (m, 2H), 7.25−7.29 (m, 2H); 13C NMR (75 MHz, CDCl3)
δ 35.8, 66.1, 74.3, 74.6, 116.0, 121.9, 123.4, 124.6, 125.5, 127.0, 127.5,
134.7, 136.7, 144.0, 147.7. Anal. Calcd. for C15H12N2OS2: C, 59.97; H,
4.03; N, 9.33; S, 21.35. Found: C, 59.82; H, 3.95; N, 9.22; S, 21.19.
(5-Bromothiophen-2-yl)(4-(5-bromothiophen-2-yl)-1-(prop-2-
ynyl)-1H-imidazol-2-yl)methanol (1j). Isolated yield 0.638 g (82%);
8-(Benzylsulfonyl)-2,9-diphenyl-8,9-dihydro-5H-imidazo[1,2-a]-
[1,4]diazepin-7(6H)-one (4e). Isolated yield 0.407 g (89%); colorless
1
solid: mp 195−197 °C; IR (KBr) 1673, 1365, 1156 cm−1; H NMR
(300 MHz, CDCl3) δ 2.54 (dt, J = 13.8 Hz, 3.0 Hz, 1H), 2.92 (td, J =
13.8 Hz, 4.5 Hz, 1H), 3.86 (td, J = 13.8 Hz, 3.0 Hz, 1H), 4.04 (dt, J =
13.8 Hz, 4.5 Hz, 1H), 4.71 (d, J = 14.1 Hz, 1H), 5.04 (d, J = 14.1 Hz,
1H), 6.74 (s, 1H), 6.92−6.98 (m, 2H), 7.00−7.07 (m, 4H), 7.22 (s,
1H), 7.24−7.32 (m, 5H), 7.41 (t, J = 7.8 Hz, 2H), 7.70 (d, J = 7.8 Hz,
2H); 13C NMR (75 MHz, CDCl3) δ 34.9, 43.2, 57.7, 59.9, 116.4,
125.0, 125.6, 126.9, 127.1, 128.0, 128.5, 128.6, 129.1, 129.2, 129.7,
133.4, 138.5, 141.0, 141.1, 171.8; MS (M + 1) 458.42. Anal. Calcd. for
C26H23N3O3S: C, 68.25; H, 5.07; N, 9.18; S, 7.01. Found: C, 68.12; H,
4.98; N, 9.06; S, 6.92.
1
viscous liquid: IR (KBr) 3392, 1262, 928, 692 cm−1; H NMR (300
MHz, CDCl3) δ 2.37 (t, J = 2.4 Hz, 1H), 4.50 (dd, J = 17.7 Hz, 2.4 Hz,
1H), 4.62 (dd, J = 17.7 Hz, 2.4 Hz, 1H), 6.00 (s, 1H), 6.44 (d, J =
3.3 Hz, 1H), 6.82 (d, J = 3.6 Hz, 1H), 6.88−6.92 (m, 2H), 7.11 (d, J =
3.3 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 36.2, 65.8, 74.8, 76.5,
110.3, 112.8, 116.3, 122.7, 125.0, 129.7, 130.3, 134.1, 138.0, 145.3,
147.3. Anal. Calcd. for C15H10Br2N2OS2: C, 39.32; H, 2.20; N, 6.11; S,
14.00. Found: C, 39.07; H, 2.08; N, 6.01; S, 13.81.
2,9-Bis(4-chlorophenyl)-8-tosyl-8,9-dihydro-5H-imidazo[1,2-a]-
[1,4]diazepin-7(6H)-one (4f). Isolated yield 0.431 g (82%); colorless
General Procedure for Synthesis of Substituted Imidazo-
[1,2-a][1,4]diazepin-7(6H)-one (4). To a mixture of cuprous iodide
(0.02 g, 0.1 mmol), imidazole derivative 1 (1.0 mmol), and sulfonyl
azide 2 (1.2 mmol) in dried dichloromethane (10.0 mL), triethylamine
(0.20 g, 2.0 mmol) in dichloromethane (2.0 mL) was added under N2
atmosphere. The mixture was then stirred at room temperature for
10−30 min. Completion of the reaction was confirmed by TLC, and
then the solvent was evaporated under a vacuum. The residue was
subjected to silica gel column chromatography with petroleum ether/
ethyl acetate (80:20) to yield 4 (72−90%).
1
solid: mp 138−140 °C; IR (KBr) 1663, 1369, 1182 cm−1; H NMR
(300 MHz, CDCl3) δ 2.41 (s, 3H), 2.55 (bd, J = 14.7 Hz, 1H), 2.94
(td, J = 14.7 Hz, 4.8 Hz, 1H), 4.00−4.14 (m, 2H), 7.09 (d, J = 8.4 Hz,
2H), 7.17 (s, 1H), 7.26 (s, 1H), 7.29 (d, J = 7.2 Hz, 2H), 7.34 (d, J =
7.2 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.73 (d, J = 8.4 Hz, 2H), 7.87
(d, J = 8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 21.6, 35.6, 43.1, 57.3,
117.1, 126.3, 127.0, 128.8, 128.9, 129.5, 131.8,* 132.9, 134.3, 135.1, 137.1,
140.1, 142.5, 145.4, 170.1. Anal. Calcd. for C26H21Cl2N3O3S: C, 59.32; H,
4.02; N, 7.98; S, 6.09. Found: C, 59.21; H, 3.96; N, 7.85; S, 5.99. [* Two
carbon signals have merged together].
2,9-Diphenyl-8-tosyl-8,9-dihydro-5H-imidazo[1,2-a][1,4]-
diazepin-7(6H)-one (4a). Isolated yield 0.411 g (90%); colorless solid:
2,9-Bis(4-chlorophenyl)-8-(methylsulfonyl)-8,9-dihydro-5H-
imidazo[1,2-a][1,4]diazepin-7(6H)-one (4g). Isolated yield 0.396 g
(88%); colorless solid: mp 202−204 °C; IR (KBr) 1655, 1402, 1176
1
mp 178−180 °C; IR (KBr) 1666, 1408, 1192 cm−1; H NMR (300
MHz, CDCl3) δ 2.40 (s, 3H), 2.52 (dt, J = 14.4 Hz, 3.6 Hz, 1H), 3.00
(td, J = 14.4 Hz, 5.4 Hz, 1H), 3.98−4.13 (m, 2H), 7.15−7.18 (m, 3H),
7.26−7.35 (m, 5H), 7.40 (d, J = 7.8 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H),
7.83 (d, J = 8.1 Hz, 2H), 7.88 (d, J = 8.4 Hz, 2H); 13C NMR (75 MHz,
CDCl3) δ 21.6, 35.8, 43.2, 58.1, 116.8, 125.1, 125.7, 127.3, 128.1,
128.7, 128.9, 129.3, 129.4, 133.5, 135.7, 138.8, 141.3, 142.9, 145.1,
170.5; MS (M + 1) 458.33. Anal. Calcd. for C26H23N3O3S: C, 68.25;
H, 5.07; N, 9.18; S, 7.01. Found: C, 68.09; H, 5.01; N, 9.09; S, 6.94.
8-(Methylsulfonyl)-2,9-diphenyl-8,9-dihydro-5H-imidazo[1,2-a]-
[1,4]diazepin-7(6H)-one (4b). Isolated yield 0.335 g (88%); colorless
1
cm−1; H NMR (300 MHz, CDCl3) δ 2.70 (dt, J = 14.4 Hz, 3.0 Hz,
1H), 3.11 (td, J = 14.4 Hz, 5.4 Hz, 1H), 3.48 (s, 3H), 4.18−4.345 (m,
2H), 7.16 (d, J = 8.1 Hz, 2H), 7.24 (s, 1H), 7.26 (s, 1H), 7.32 (d, J =
7.2 Hz, 2H), 7.75 (d, J = 8.1 Hz, 2H), 7.81 (d, J = 8.1 Hz, 2H); 13C
NMR (75 MHz, CDCl3) δ 35.7, 42.7, 43.3, 57.4, 117.1, 126.3, 127.0,
128.9, 129.6, 131.8, 132.9, 135.1, 140.2, 142.6, 145.4, 170.1. Anal.
Calcd. for C20H17Cl2N3O3S: C, 53.34; H, 3.80; N, 9.33; S, 7.12.
Found: C, 53.22; H, 3.72; N, 9.22; S, 7.01
8-(Benzylsulfonyl)-2,9-bis(4-chlorophenyl)-8,9-dihydro-5H-
imidazo[1,2-a][1,4]diazepin-7(6H)-one (4h). Isolated yield 0.452 g
(86%); colorless solid: mp 175−177 °C; IR (KBr) 1653, 1387, 1199
1
solid: mp 196−198 °C; IR (KBr) 1656, 1388, 1162 cm−1; H NMR
(300 MHz, CDCl3) δ 2.69 (bd, J = 14.4 Hz, 1H), 3.07 (td, J = 14.4 Hz,
5.1 Hz, 1H), 3.47 (s, 3H), 4.21−4.29 (m, 2H), 7.16 (d, J = 7.2 Hz,
2H), 7.24−7.31 (m, 4H), 7.35−7.43 (m, 4H), 7.79 (d, J = 7.2 Hz,
2H); 13C NMR (75 MHz, CDCl3) δ 35.7, 42.6, 43.4, 57.3, 116.9,
125.1, 125.6, 127.3, 128.2, 128.7, 129.4, 133.3, 138.5, 141.4, 142.7,
172.1. Anal. Calcd. for C20H19N3O3S: C, 62.97; H, 5.02; N, 11.02; S,
8.41. Found: C, 62.88; H, 4.95; N, 10.98; S, 8.33.
1
cm−1; H NMR (300 MHz, CDCl3) δ 2.59 (dt, J = 13.8 Hz, 3.0 Hz,
1H), 2.85 (td, J = 13.8 Hz, 4.5 Hz, 1H), 3.90 (td, J = 13.8 Hz, 3.0 Hz,
1H), 4.04 (dt, J = 13.8 Hz, 4.5 Hz, 1H), 4.71 (d, J = 14.1 Hz, 1H), 5.04
(d, J = 14.1 Hz, 1H), 6.66 (s, 1H), 6.94 (d, J = 7.2 Hz, 2H), 6.98 (s,
1H), 7.04 (t, J = 7.2 Hz, 2H), 7.21- 7.27 (m, 3H), 7.43- 7.46 (m, 2H),
7.38 (d, J = 8.4 Hz, 2H), 7.64 (d, J = 8.4 Hz, 2H); 13C NMR (75 MHz,
CDCl3) δ 34.9, 43.3, 57.1, 61.9, 116.5, 126.2, 127.0, 128.5, 128.8,
129.1, 129.4, 129.7, 129.9, 131.8, 132.8, 134.2, 137.0, 140.1, 140.8,
171.5. Anal. Calcd. for C26H21Cl2N3O3S: C, 59.32; H, 4.02; N, 7.98; S,
6.09. Found: C, 59.23; H, 3.95; N, 7.84; S, 5.99.
2,9-Diphenyl-8-(phenylsulfonyl)-8,9-dihydro-5H-imidazo[1,2-a]-
[1,4]diazepin-7(6H)-one (4c). Isolated yield 0.399 g (90%); colorless
1
solid: mp 124−126 °C; IR (KBr) 1645, 1418, 1199 cm−1; H NMR
(300 MHz, CDCl3) δ 2.51 (dt, J = 14.1 Hz, 3.0 Hz, 1H), 2.97 (td, J =
14.1 Hz, 5.1 Hz, 1H), 4.00 (td, J = 14.1 Hz, 3.0 Hz, 1H), 4.05−4.13
(m, 1H), 7.13 (d, J = 7.2 Hz, 2H), 7.18 (s, 1H), 7.26−7.36 (m, 4H),
7.38−7.49 (m, 4H), 7.52−7.61 (m, 2H), 7.81 (d, J = 7.5 Hz, 2H), 7.99
(d, J = 7.2 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 35.6, 43.1, 57.9,
116.9, 125.0, 125.5, 126.3, 127.2, 128.1, 128.7, 128.8, 129.0, 129.3,
134.0, 138.4, 138.5, 141.1, 142.7, 170.6. Anal. Calcd. for C25H21N3O3S:
C, 67.70; H, 4.77; N, 9.47; S, 7.23. Found: C, 67.63; H, 4.58; N, 9.35;
S, 7.11.
2,9-Bis(4-bromophenyl)-8-tosyl-8,9-dihydro-5H-imidazo[1,2-a]-
[1,4]diazepin-7(6H)-one (4i). Isolated yield 0.504 g (82%); colorless
1
solid: mp 190−192 °C; IR (KBr) 1665, 1402, 1189 cm−1; H NMR
(300 MHz, CDCl3) δ 2.40 (s, 3H), 2.56 (dt, J = 14.7 Hz, 3.3 Hz, 1H),
2.91 (td, J = 14.7 Hz, 5.4 Hz, 1H), 3.99−4.13 (m, 2H), 7.00 (d, J =
7.8 Hz, 2H), 7.19 (s, 1H), 7.34 (s, 1H), 7.46 (d, J = 8.7 Hz, 2H), 7.50
(d, J = 7.8 Hz, 2H), 7.66 (d, J = 8.7 Hz, 2H), 7.79 (d, J = 8.4 Hz, 2H),
7.85 (d, J = 8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 21.6, 35.8,
43.2, 58.0, 104.4, 108.6, 115.9, 121.1, 122.4, 127.3, 128.3, 130.6, 131.4,
131.5, 133.4, 135.6, 137.3, 140.4, 143.7, 170.5. Anal. Calcd. for
C26H21Br2N3O3S: C, 50.75; H, 3.44; N, 6.83; S, 5.21. Found: C, 50.66;
H, 3.33; N, 6.78; S, 5.12.
8-(4-Bromophenylsulfonyl)-2,9-diphenyl-8,9-dihydro-5H-
imidazo[1,2-a][1,4]diazepin-7(6H)-one (4d). Isolated yield 0.449 g
(86%); colorless solid: mp 152−154 °C; IR (KBr) 1670, 1400,
1
1120 cm−1; H NMR (300 MHz, CDCl3) δ 2.54 (dt, J = 14.4 Hz,
3.6 Hz, 1H), 3.01 (td, J = 14.4 Hz, 5.4 Hz, 1H), 4.01−4.16 (m, 2H), 7.16
(dd, J = 7.5 Hz, 1.2 Hz, 2H), 7.19 (s, 1H), 7.25−7.38 (m, 5H), 7.42
2,9-Bis(4-fluorophenyl)-8-tosyl-8,9-dihydro-5H-imidazo[1,2-a]-
[1,4]diazepin-7(6H)-one (4j). Isolated yield 0.429 g (87%); colorless
F
dx.doi.org/10.1021/jo300855f | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
solid: mp 196−198 °C; IR (KBr) 1671, 1397, 1199 cm−1; H NMR
(300 MHz, CDCl3) δ 2.39 (s, 3H), 2.55 (dt, J = 14.7 Hz, 3.0 Hz, 1H),
2.92 (td, J = 14.7 Hz, 5.1 Hz, 1H), 3.98−4.16 (m, 2H), 7.03 (d, J =
8.1 Hz, 2H), 7.07 (s, 1H), 7.09−7.12 (m, 2H), 7.15 (s, 1H), 7.25 (t, J =
7.5 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 7.74−7.78 (m, 2H), 7.84 (d, J =
8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 21.3, 35.6, 43.1, 57.2,
115.5, 116.3, 116.7, 126.7, 127.4, 129.4, 129.5, 134.3, 135.1, 140.2, 142.5,
143.3, 145.4, 160.6, 163.9, 170.4. Anal. Calcd. for C26H21F2N3O3S: C,
63.28; H, 4.29; N, 8.51; S, 6.50. Found: C, 63.16; H, 4.20; N, 8.46; S,
6.42.
C28H27N3O3S: C, 69.25; H, 5.60; N, 8.65; S, 6.60. Found: C, 69.12; H,
5.48; N, 8.42; S, 6.49.
1
8-(Methylsulfonyl)-2,9-di(thiophen-2-yl)-8,9-dihydro-5H-
imidazo[1,2-a][1,4]diazepin-7(6H)-one (4p). Isolated yield 0.283 g
1
(72%); viscous liquid: IR (KBr) 1671, 1396, 1198 cm−1; H NMR
(300 MHz, CDCl3) δ 2.71 (dt, J = 14.4 Hz, 3.3 Hz, 1H), 3.09 (td, J =
14.4 Hz, 5.1 Hz, 1H), 3.49 (s, 3H), 4.23−4.36 (m, 2H), 7.09 (d, J =
3.6 Hz, 1H), 7.10−7.18 (m, 2H), 7.29 (d, J = 5.7 Hz, 1H), 7.37−7.50
(m, 2H), 7.55 (d, J = 3.6 Hz, 1H), 7.80 (d, J = 5.7 Hz, 1H) 13C NMR
(75 MHz, CDCl3) δ 35.7, 42.7, 43.4, 57.3, 100.5, 113.1, 117.3, 124.7,
125.9, 127.3, 127.6, 136.7, 137.5, 138.7, 138.8, 172.1. Anal. Calcd. for
C16H15N3O3S3: C, 48.84; H, 3.84; N, 10.68; S, 24.45. Found: C, 48.72;
H, 3.75; N, 10.52; S, 24.22.
2,9-Bis(5-bromothiophen-2-yl)-8-(methylsulfonyl)-8,9-dihydro-
5H-imidazo[1,2-a][1,4]diazepin-7(6H)-one (4q). Isolated yield 0.419 g
(76%); viscous liquidIR (KBr) 1665, 1385, 1192 cm−1; 1H NMR
(300 MHz, CDCl3) δ 2.72 (dt, J = 14.4 Hz, 3.3 Hz, 1H), 3.09 (td, J =
14.4 Hz, 5.4 Hz, 1H), 3.49 (s, 3H), 4.24−4.36 (m, 2H), 7.02 (d, J =
3.9 Hz, 1H), 7.10 (d, J = 3.6 Hz, 1H), 7.16 (d, J = 3.9 Hz, 1H), 7.19 (s,
1H), 7.30 (d, J = 3.6 Hz, 1H), 7.60 (s, 1H); 13C NMR (75 MHz,
CDCl3) δ 35.4, 42.5, 43.7, 57.7, 11.6, 120.2, 123.1, 125.6, 130.5, 130.8,
136.2, 136.4, 138.1, 140.3, 141.6, 172.2. Anal. Calcd. for C16H13Br2N3O3S3:
C, 34.86; H, 2.38; N, 7.62; S, 17.45. Found: C, 34.71; H, 2.22; N, 7.54; S,
17.31.
8-(Benzylsulfonyl)-2,9-bis(4-fluorophenyl)-8,9-dihydro-5H-
imidazo[1,2-a][1,4]diazepin-7(6H)-one (4k). Isolated yield 0.424 g
(86%); colorless solid: mp 156−158 °C; IR (KBr) 1666, 1408, 1192
1
cm−1; H NMR (300 MHz, CDCl3) δ 2.60 (dt, J = 13.8 Hz, 2.7 Hz,
1H), 2.91 (td, J = 13.8 Hz, 4.8 Hz, 1H), 3.90 (td, J = 13.8 Hz, 2.7 Hz,
1H), 4.07 (dt, J = 13.8 Hz, 4.8 Hz, 1H), 4.72 (d, J = 14.4 Hz, 1H), 5.04
(d, J = 14.4 Hz, 1H), 6.67 (s, 1H), 6.92 (s, 1H), 6.98 (d, J = 7.2 Hz,
2H), 7.03−7.13 (m, 4H), 7.23 (d, J = 8.1 Hz, 2H), 7.36−7.40 (m,
3H), 7.65 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 34.9, 43.2, 57.1,
59.9, 115.5, 116.0, 126.5, 127.5, 128.8, 129.1, 129.7, 130.7, 134.3,
140.3, 140.9, 143.3, 145.4, 160.6, 163.9, 171.7. Anal. Calcd. for
C26H21F2N3O3S: C, 63.28; H, 4.29; N, 8.51; S, 6.50. Found: C, 63.17;
H, 4.18; N, 8.44; S, 6.41.
2,9-Bis(4-methoxyphenyl)-8-tosyl-8,9-dihydro-5H-imidazo[1,2-
a][1,4]diazepin-7(6H)-one (4l). Isolated yield 0.465 g (90%); colorless
solid: mp 192−194 °C; IR (KBr) IR (KBr) 1666, 1408, 1192 cm−1; 1H
NMR (300 MHz, CDCl3) δ 2.32 (s, 3H), 2.44 (bd, J = 14.7 Hz, 1H),
2.99 (m, 1H), 3.75 (s, 3H), 3.81 (s, 3H), 3.98−4.11 (m, 2H), 6.83 (d,
J = 7.8 Hz, 2H), 6.92 (d, J = 7.5 Hz, 2H), 7.01 (d, J = 7.5 Hz, 2H),
7.08 (s, 1H), 7.23 (d, J = 7.8 Hz, 2H), 7.36 (s, 1H), 7.71 (d, J =
7.5 Hz, 2H), 7.84 (d, J = 7.5 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ
21.5, 35.7, 43.0, 55.3,* 57.5, 114.2, 114.6, 115.9, 126.3, 126.9, 128.8,
129.4, 129.5, 130.7, 135.6, 140.9, 142.9, 145.1, 159.1, 159.4, 170.7.
Anal. Calcd. for C28H27N3O5S: C, 64.97; H, 5.26; N, 8.12; S, 6.19.
Found: C, 64.82; H, 5.19; N, 8.03; S, 6.11. [* Two carbon signals have
merged together].
4-Methylbenzenesulfonamide (5). Isolated yield 0.138 g (81%);
colorless solid: mp 136−138 °C; 1H NMR (300 MHz, CDCl3) δ 2.47
(s, 3H), 5.82 (s, 2H), 7.32 (d, J = 7.8 Hz, 2H), 7.75 (d, J = 7.8 Hz,
2H); 13C NMR (75 MHz, CDCl3) δ 21.4, 125.9, 129.2, 139.7, 142.6.
ASSOCIATED CONTENT
■
S
* Supporting Information
1H and 13C NMR and mass spectra for synthesized compounds
and X-ray crystallographic data of 1a and 4b. This material is
available free of cost via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: muthumanian2001@yahoo.com.
2,9-Di(naphthalen-2-yl)-8-tosyl-8,9-dihydro-5H-imidazo[1,2-a]-
■
[1,4]diazepin-7(6H)-one (4m). Isolated yield 0.446 g (80%); colorless
1
solid: mp 182−184 °C; IR (KBr) 1669, 1405, 1193 cm−1; H NMR
(300 MHz, CDCl3) δ 2.23 (s, 3H), 2.24 (m, 1H), 2.96−2.98 (m, 1H),
3.61−3.64 (m, 2H), 7.22−7.25 (m, 3H), 7.29 (s, 1H), 7.35 (d, J =
8.1 Hz, 2H), 7.44−7.46 (m, 5H), 7.66 (s, 1H), 7.79−7.82 (m, 3H), 7.87−
7.92 (m, 4H), 8.39 (s, 1H); 13C NMR (75 MHz, CDCl3) δ 21.6, 35.8,
43.2, 58.2, 117.6, 123.1, 123.4, 123.6, 124.7, 125.6, 126.3, 126.7, 126.8,
127.4, 127.7, 128.1, 128.3, 128.9, 129.5, 130.2, 130.8, 132.7, 132.8,
133.2, 133.8, 135.5, 136.0, 141.1, 143.2, 145.2, 146.2, 170.5. Anal.
Calcd. for C34H27N3O3S: C, 73.23; H, 4.88; N, 7.54; S, 5.75. Found: C,
73.13; H, 4.76; N, 7.46; S, 5.66.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors thank DST, New Delhi for assistance under the
IRHPA program for the NMR facility. Financial support from
CSIR-JRF, New Delhi is gratefully acknowledged.
2,9-Di(biphenyl-4-yl)-8-(methylsulfonyl)-8,9-dihydro-5H-imidazo-
[1,2-a][1,4]diazepin-7(6H)-one (4n). Isolated yield 0.427 g (80%);
colorless solid: mp 196−198 °C; IR (KBr) 1662, 1402, 1199 cm−1; 1H
NMR (300 MHz, CDCl3) δ 2.69 (bd, J = 14.4 Hz, 1H), 3.07 (td, J =
14.4 Hz, 5.1 Hz, 1H), 3.49 (s, 3H), 4.23−4.35 (m, 2H), 7.26 (s, 1H),
7.30 (d, J = 8.1 Hz, 2H), 7.36 (dd, J = 7.5 Hz, 2.1 Hz, 2H), 7.41−7.47
(m, 6H), 7.54 (s, 1H), 7.57 (dd, J = 7.2 Hz, 1.2 Hz, 2H), 7.61 (d, J =
8.1 Hz, 2H), 7.65 (d, J = 8.1 Hz, 2H), 7.88 (d, J = 8.1 Hz, 2H); 13C
NMR (75 MHz, CDCl3) δ 35.8, 43.4, 46.3, 57.2, 117.1, 125.5, 126.1,
126.9, 127.0, 127.2, 127.3, 127.4, 127.7, 128.0, 128.7, 128.8, 128.9,
132.3, 137.4, 139.9, 140.1, 140.8, 141.3, 172.1. Anal. Calcd. for
C32H27N3O3S: C, 72.02; H, 5.10; N, 7.87; S, 6.01. Found: C, 71.80; H,
4.99; N, 7.72; S, 5.89.
2,9-Di-p-tolyl-8-tosyl-8,9-dihydro-5H-imidazo[1,2-a][1,4]-
diazepin-7(6H)-one (4o). Isolated yield 0.398 g (82%); viscous liquid:
IR (KBr) 1659, 1396, 1198 cm−1; 1H NMR (300 MHz, CDCl3) δ 2.31
(s, 3H), 2.38−2.44 (bs, 6H), 2.49 (bd, J = 14.7 Hz, 1H), 3.00 (td, J =
14.7 Hz, 5.1 Hz, 1H), 4.00−4.12 (m, 2H), 7.00 (d, J = 8.4 Hz, 2H),
7.12−7.26 (m, 7H), 7.42 (s, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.86 (d, J =
8.4 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ 20.9, 21.2, 21.6, 35.7,
43.1, 57.8, 116.4, 124.9, 126.4, 128.8, 129.3, 129.6, 129.9, 130.6, 135.5,
135.6, 136.9, 137.8, 141.1, 142.9, 145.1, 170.6. Anal. Calcd. for
REFERENCES
■
(1) For reviews on the chemistry of ketenimines, see: (a) Kim, S. H.;
Park, S. H.; Choi, J. H.; Chang, S. Chem.Asian J. 2011, 6, 2618.
(b) Lu, P.; Wang, Y. G. Synlett 2010, 165. (c) Hein, J. E.; Fokin, V. V.
Chem. Soc. Rev. 2010, 39, 1302. (d) Yoo, E. J.; Chang, S. Curr. Org.
Chem. 2009, 13, 1766.
(2) (a) Bae, I.; Han, H.; Chang, S. J. Am. Chem. Soc. 2005, 127, 2038.
(b) Cho, S. H.; Yoo, E. J.; Bae, I.; Chang, S. J. Am. Chem. Soc. 2005,
127, 16046. (c) Cassidy, M. P.; Raushel, J.; Fokin, V. V. Angew. Chem.,
Int. Ed. 2006, 45, 3154. (d) Cho, S. H.; Chang, S. Angew. Chem., Int.
Ed. 2007, 46, 1897.
(3) (a) Alajarın, M.; Vidal, A.; Ortın, M. M. Tetrahedron Lett. 2003,
44, 3027. (b) Alajarın, M.; Vidal, A.; Ortín, M. M. Org. Biomol. Chem.
2003, 1, 4282. (c) Alajarín, M.; Vidal, A.; Ortín, M. M.; Bautista, D.
Synlett 2004, 991.
(4) (a) Alajarın, M.; Ortín, M. M.; Andrada, P. S.; Vidal, A.; Bautista,
D. Org. Lett. 2005, 7, 5281. (b) Alajarın, M.; Ortın, M. M.; Andrada,
P. S.; Vidal, A. J. Org. Chem. 2006, 71, 8126 and references therein.
(5) (a) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem., Int. Ed. 2002, 41, 2596. (b) Tornoe, C. W.; Christensen,
C.; Meldal, M. J. Org. Chem. 2002, 67, 3057.
G
dx.doi.org/10.1021/jo300855f | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Note
(6) Four-component reactions via the CuAAC mechanism: (a) Song,
W. Z.; Lu, W.; Wang, J.; Lu, P.; Wang, Y. G. J. Org. Chem. 2010, 75,
3481. (b) Husmann, R.; Na, Y. S.; Bolm, C.; Chang, S. Chem.
Commun. 2010, 46, 5494.
(7) (a) Jin, H. W.; Xu, X. L.; Gao, J. R.; Zhong, J. H.; Wang, Y. G.
Adv. Synth. Catal. 2010, 352, 347. (b) Cui, S. L.; Wang, J.; Wang, Y. G.
Org. Lett. 2008, 10, 1267. (c) Kim, J.; Chang, S. Chem. Commun. 2008,
3052.
(8) (a) Shen, Y.; Cui, S. L.; Wang, J.; Chen, X. P.; Lu, P.; Wang, Y. G.
Adv. Synth. Catal. 2010, 352, 1139. (b) Shang, Y. J.; Ju, K.; He, X. W.;
Hu, J. S.; Yu, S. Y.; Zhang, M.; Liao, K. S.; Wang, L. F.; Zhang, P.
J. Org. Chem. 2010, 75, 5743.
(9) (a) Chang, S.; Lee, M.; Jung, D. Y.; Yoo, E. J.; Cho, S. H.; Han, S.
K. J. Am. Chem. Soc. 2006, 128, 12366. (b) Yoo, E. J.; Chang, S. Org.
Lett. 2008, 10, 1163.
(10) (a) Cho, S. H.; Chang, S. Angew. Chem., Int. Ed. 2008, 47, 2836.
(11) (a) Namitharan, K.; Pitchumani, K. Org. Lett. 2011, 13, 5728.
(b) Yavari, I.; Nematpour, M.; Yavari, S.; Sadegehizade, F. Tetrahedron
Lett. 2012, 53, 1889.
(12) (a) Wipf, P. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, p 827.
(b) Ziegler, F. E. Chem. Rev. 1988, 88, 1423. (c) Nubbemeyer, U.
Synthesis 2003, 7, 961. (d) Enders, D.; Knopp, M.; Schiffers, R.
Tetrahedron: Asymmetry 1996, 7, 1847.
(13) For the rearrangement of allylic acyl(aryl)imidates, see:
(a) Overman, L. E. J. Am. Chem. Soc. 1978, 98, 2901. (b) Overman,
L. E. Acc. Chem. Res. 1980, 13, 218. (c) Chen, B.; Mapp, A. K. J. Am.
Chem. Soc. 2004, 126, 5364.
(14) Baeyer, A.; Oekonomides, S. Chem. Ber. 1882, 15, 2093.
(15) For example, see: Danishefsky, S.; Lee, J. Y. J. Am. Chem. Soc.
1989, 111, 4829.
(16) (a) Saravanan, S.; Azath, I. A.; Muthusubramanian, S. J. Org.
Chem. 2008, 73, 2323. (b) Nagaraj, M.; Boominathan, M.;
Muthusubramanian, S.; Bhuvanesh, N. Org. Biomol. Chem. 2011, 9,
4642. (c) Boominathan, M.; Nagaraj, M.; Muthusubramanian, S.;
Krishnakumar, R. V. Tetrahedron 2011, 67, 6057. (d) Suresh, R.;
Muthusubramanian, S.; Senthilkumaran, R.; Manickam, G. J. Org.
Chem. 2012, 77, 1468. (e) Nagaraj, M.; Boominathan, M.;
Muthusubramanian, S.; Bhuvanesh, N. Synlett 2012, 23, 1353.
(17) CCDC number 876973.
(18) CCDC number 876972.
(19) Yoo, E. J.; Bae, I.; Cho, S. H.; Han, H.; Chang, S. Org. Lett.
2006, 8, 1347.
(20) (a) Khalili, B.; Tondro, T.; Hashemi, M. M. Tetrahedron 2009,
65, 6882. (b) Abbiati, G.; Casoni, A.; Canevari, V.; Nava, D.; Rossi, E.
Org. Lett. 2006, 8, 4839.
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