Rh(III)-catalyzed aromatic C-H bond carbenoid functionalization of triazenes by α-diazomalonate

Article abstract of DOI:10.1016/j.tet.2015.06.024

A Rh(III)-catalyzed aromatic C-H bond carbenoid functionalization of triazenes by α-diazomalonates has been developed, with features of mild reaction condition and high efficiency. Furthermore, the functionalized triazenes could be subject to divergent synthesis.

Full text of DOI:10.1016/j.tet.2015.06.024

Tetrahedron xxx (2015) 1e6
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Rh(III)-catalyzed aromatic CeH bond carbenoid functionalization
of triazenes by
a-diazomalonate
*
Dahai Wang, Sunliang Cui
Institute of Materia Medica and College of Pharmaceutical Sciences, Zhejiang University, 866 Yuhangtang Road, Hangzhou 310058, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
A Rh(III)-catalyzed aromatic CeH bond carbenoid functionalization of triazenes by a-diazomalonates has
Received 24 April 2015
Received in revised form 2 June 2015
Accepted 5 June 2015
Available online xxx
been developed, with features of mild reaction condition and high efficiency. Furthermore, the func-
tionalized triazenes could be subject to divergent synthesis.
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
CeH activation
Rh(III) catalysis
Triazene
Carbenoid
Divergent synthesis
1. Introduction
CeH functionalization for biologically interesting small molecule
synthesis,7 herein we report a Rh(III)-catalyzed aromatic CeH bond
Recently, Rh(III)-catalyzed functionalization of aryl CeH bond
has enjoyed tremendous advance owing to their wide applications
to the rapid assembly of various complex molecular structures,
particular in the fields of medicinal chemistry.1 The direct CeH
functionalization has advantages over classical cross coupling re-
actions, avoiding the preactivation of coupling partners thus leads
to a more atom-economical process.2 In particular, diazo com-
pounds have acted as alkylation precursors in Rh(III)-catalyzed
CeH functionalization. For example, Yu reported a seminal work
of Rh(III)-catalyzed carbenoid functionalization of oximes and N-
Methylbenzylamines with diazomalonates.3 Diazo compounds
have also been investigated as coupling-cyclization components
under Rh(III) catalysis.4 Therefore, the development of Rh(III)-
catalyzed CeH functionalization using diazo compounds as cou-
pling partners remains interesting.
carbenoid functionalization of triazenes by a-diazomalonate.
Moreover, the functionalized triazenes could be subject to various
transformations to access divergent compounds (Scheme 1).
Triazenes are versatile building blocks in organic synthesis,
which could be transformed to diverse compounds under acidic
condition and transition-metal-catalysis.5 Recently, Huang and co-
workers explored the Rh(III)-catalyzed CeH activation of arenes
using triazene as substrates,6 which provides a versatile and re-
movable directing group in CeH functionalization and useful syn-
thetic utility. In continuation of our interest in Rh(III)-catalyzed
Scheme 1. Rh(III)-catalyzed carbenoid functionalization of triazenes.
2. Results and discussions
We commenced our study by investigating the coupling of
pyrrolidine-derived triazene 1a and
a-diazomalonate 2 using
[Cp*RhCl2]2 as catalyst. When the reaction was conducted in
* Corresponding author. Tel./fax: þ86 571 8898 1456; e-mail address: slcui@zju.
edu.cn (S. Cui).
methanol at 70 ꢀC without additives, the Rh(III) catalyzed CeH
http://dx.doi.org/10.1016/j.tet.2015.06.024
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.
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2
D. Wang, S. Cui / Tetrahedron xxx (2015) 1e6
functionalized was completely shut down (Table 1, entry 1), grati-
fyingly, catalytic addition of CsOAc led to the formation of mono-
alkylation triazene 3a in 21% yield and di-alkylation triazene
product 4a in 10% yield (Table 1, entry 2). This encouraged us to
screen other additives and found AgOAc was superior to afford 3a in
48% yield and 4a in 23% yield (Table 1, entries 3e4). The next survey
of silver salts showed that Ag2CO3 and AgSbF6 were inferior to af-
ford trace products (Table 1, entries 5e6). Further screening of
solvents were revealed that the use of EtOH would result in lower
yield (Table 1, entry 7), while other solvents was inferior to gen-
erate trace products (Table 1, entries 8e11). Moreover, decreasing
the temperature to 30 ꢀC would result in trace product formation
(Table 1, entry 12).
divergent intramolecular cyclization to afford indazole compounds
7 and 8.9
A proposed mechanism is depicted in Scheme 3. The initial
rhodium diacetate was generated from [Cp*RhCl2]2 and AgOAc, and
a carboxylate-assisted CeH activation of triazenes occurred to form
intermediate A with release of AcOH. Then A takes diazo insertion
with a-diazomalonate 2 to generate B, which sequentially takes
migratory insertion to provide C, with extrusion of N2. The final
protonation of C furnishes the carbenoid functionalized product 3,
with regeneration of Rh(III) catalysis. And another carbenoid
functionalization of 3 would lead to dialkylation product 4.
3. Conclusions
Table 1
In conclusion, we have developed a Rh(III)-catalyzed aromatic
Optimization of reaction conditionsa
CeH bond carbenoid functionalization of triazenes by
a-diazo-
malonate under mild reaction condition. Furthermore, the func-
tionalized triazenes could take divergent transformations to access
a variety of small molecules.
4. Experimental section
4.1. General
Entry
Additive
Solvent
T [ꢀC]
Yield [%]b
All commercially available reagents were used without purifi-
cation unless otherwise noted. Column chromatography was per-
formed using silica gel (100e200 mesh). Visualization of the
compounds was accomplished with UV light (254 nm) and iodine.
1H NMR and 13C NMR spectra were recorded in CDCl3 operating at
400 MHz and 100 MHz, respectively. Proton chemical shifts are
reported relative to the residual proton signals of the deuterated
solvent CDCl3 (7.26 ppm) or TMS. Carbon chemical shifts were in-
ternally referenced to the deuterated solvent signals in CDCl3
(77.16 ppm). Chemical shifts are reported in d (parts per million)
values. Coupling constants J are reported in Hertz. Proton coupling
patterns were described as singlet (s), doublet (d), triplet (t),
quartet (q), and multiple (m). High-resolution mass spectra were
recorded on Waters GCT Premier Time of Flight Mass Spectrometer
(EI).
3a
4a
1
2
3
4
5
6
7
8
none
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
EtOH
t-Amyl alcohol
CH3CN
DCE
70
70
70
70
70
70
70
70
70
70
70
30
0
21
16
48
Trace
Trace
25
Trace
Trace
Trace
Trace
Trace
0
10
7
23
Trace
Trace
11
Trace
Trace
Trace
Trace
Trace
CsOAc
Cu(OAc)2
AgOAc
Ag2CO3
AgSbF6
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
AgOAc
9
10
11
12
DMF
MeOH
a
Reaction conditions: 1a (0.2 mmol), 2 (0.2 mmol), [Cp*RhCl2]2 (1 mol %), addi-
tives (30 mol %), solvent (2 mL).
b
Yields of isolated products.
With the optimized reaction condition in hand, we next the
scope of this Rh(III)-catalyzed carbenoid functionalization using
various triazenes. As depicted in Table 2, various para-substituted
triazenes with valuable functional groups like methyl, chloro, ace-
tyl, ethoxylcarbonyl, could react smoothly with 2 in this process to
furnish the mono-alkylation products (3be3e) and di-alkylation
products (4be4e) in moderate yields. The ortho-substituted tri-
azenes were also applicable to exclusively furnish the mono-
alkylation product in moderate to excellent yields (3fe3i), with
functionalized group such as bromo, ethoxylcarbonyl, cyano, tri-
fluoromethoxy, thus offering ample opportunity for further de-
rivatization. Additionally, polysubstituted triazenes were also
tolerated to afford the mono-alkylation products in moderate to
excellent yields (3je3m). Interestingly, when 3,5-dimethoxy
substituted triazene 1n was used, the reaction only delivered the
mono-alkylation product 3n in 53% yield, and the reaction of 2-
naphthenyl substituted triazene exclusively generate the 3-
alkylation product 3o in 42% yield. Moreover, the structure of 3g
was unambibuously confirmed by X-ray analysis (Fig. 1).8As men-
tioned before, triazenes were versatile building block and could be
subject to divergent transformations. The unique features were
then studied using 3a as modeling substrate. As shown in
Scheme 2, when 3a was treated with styrene in the presence of
Pd(OAc)2, the Heck reaction occurred to form E-stilbene derivative
5 in 73% yield, in which triazene served as leaving group. 3a could
also be transformed into an iodobenzene derivative 6 in the pres-
ence of NaI under acidic condition. Interestingly, 3a would undergo
General procedure for the synthesis of compounds 3ae3o and
4ae4e. A mixture of Triazenes (0.2 mmol) and dimethyl diazo-
malonate (0.2 mmol) was dissolved in MeOH (2 mL), and
[Cp*RhCl2]2 (1.2 mg, 1 mol %) and AgOAc (10 mg, 30% mmol) was
added. Then the reaction was proceeded in a sealed tube at a tem-
perature of 70 ꢀC for 10 h. The resulting reaction mixture was
loaded on a silica gel column and flashed with 15e20 % ethyl ace-
tate in petroleum ether to afford the desired products 3 and 4 as
solid.
4.2. Compound (3a)
(E)-Dimethyl-2-(2-(pyrrolidin-1-yldiazenyl)phenyl)malonate
3a. White solid (29.3 mg, 48%); Mp 87e93 ꢀC; 1H NMR (CDCl3,
400 MHz),
7.29e7.25 (m, 1H), 7.15e7.11 (m, 1H), 5.55 (s, 1H), 3.92 (s, 2H), 3.74
(s, 6H), 3.59 (s, 2H), 2.01 (s, 4H); 13C NMR (CDCl3, 100 MHz),
d
: 7.48 (dd, J1¼8.4 Hz, J2¼1.2 Hz, 1H), 7.32e7.30 (m, 1H),
d
:
169.6, 148.4, 129.0, 128.8, 127.5, 125.2, 116.2, 52.7, 52.6, 51.0, 46.7,
24.0, 23.7; IR (KBr) v: 2952, 2930, 2879,1745,1728,1416,1259,1224,
1028, 768 cmꢁ1; HRMS (EI) (m/z): calcd for C15H19N3O4 (Mþ):
305.1376; Found: 305.1377.
4.3. Compound (3b)
(E)-Dimethyl-(5-methyl-2-(pyrrolidin-1-yldiazenyl)phenyl)
malonate 3b. Pale yellow solid (21.7 mg, 34%); Mp 97e99 ꢀC; 1H
NMR (CDCl3, 400 MHz),
d: 7.39 (d, J¼8.4 Hz, 1H), 7.11e7.07 (m, 2H),
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D. Wang, S. Cui / Tetrahedron xxx (2015) 1e6
3
Table 2
Rh(III)-catalyzed CeH carbenoid functionalizationa
Starting Material
Product / Yield [%]b
Entry
1
2
3
4
5
6
7
8
9
10
11
a
Reaction Conditions: 1 (0.2 mmol), 2 (0.2 mmol), [Cp*RhCl2]2 (1 mol %),
AgOAc (30 mol %), MeOH (2 mL), 70 oC, 8 h. b Isolated yields.
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D. Wang, S. Cui / Tetrahedron xxx (2015) 1e6
4.5. Compound (3d)
(E)-Dimethyl-2-(5-acetyl-2-(pyrrolidin-1-yldiazenyl)phenyl)
malonate 3d. Pale yellow solid (26.4 mg, 38%); Mp 126e129 ꢀC; 1H
NMR (CDCl3, 400 MHz),
d
: 7.92 (d, J¼2.0 Hz, 1H), 7.87 (dd, J1¼8.4 Hz,
J2¼2.0 Hz, 1H), 7.55 (d, J¼8.8 Hz, 1H), 5.49 (s, 1H), 3.95 (t, J¼6.4 Hz,
2H), 3.74 (s, 6H), 3.61 (t, J¼6.4 Hz, 2H), 2.56 (s, 3H), 2.07e2.00 (m,
4H); 13C NMR (CDCl3, 100 MHz),
d: 197.2, 169.1, 152.2, 133.5, 130.1,
129.1, 127.4, 115.9, 52.7, 51.4, 47.2, 26.5, 24.0, 23.5; IR (KBr) v: 2954,
2882, 1738, 1674, 1596, 1343, 1205, 1026, 834 cmꢁ1; HRMS (EI) (m/
z): calcd for C17H21N3O5 (Mþ): 347.1481; Found: 347.1480.
Fig. 1. ORTEP representation of the X-ray crystal structure of compound 3g.
4.6. Compound (3e)
(E)-Dimethyl-2-(5-(ethoxycarbonyl)-2-(pyrrolidin-1-
yldiazenyl)-phenyl)malonate 3e. Pale yellow solid (39.2 mg, 52%);
Mp 75e78 ꢀC; 1H NMR (CDCl3, 400 MHz),
d: 7.97e7.92 (m, 2H), 7.53
(d, J¼8.8 Hz, 1H), 5.46 (s, 1H), 4.33 (q, J¼6.8 Hz, 2H), 3.93 (t,
J¼6.4 Hz, 2H), 3.73 (s, 6H), 3.59 (t, J¼6.0 Hz, 2H), 2.05e1.98 (m, 4H),
1.36 (t, J¼7.2 Hz, 3H); 13C NMR (CDCl3, 100 MHz),
d: 169.2, 166.4,
152.0, 130.9, 130.3, 127.4, 126.6, 115.8, 60.8, 53.0, 52.7, 51.3, 47.1,
24.0, 23.5, 14.4; IR (KBr) v: 2955, 2884, 1742, 1711, 1605, 1432, 1208,
1027, 779 cmꢁ1; HRMS (EI) (m/z): calcd for C18H23N3O6 (Mþ):
377.1587; Found: 377.1587.
Scheme 2. Divergent transformation of 3a. Reaction conditions: (a) Pd(OAc)2 (10 mol
%), styrene (2 equiv), TFA (2 equiv), MeOH, 60 ꢀC; (b) NaI (3 equiv), TFA (10 equiv),
acetone, 0 ꢀC; (c) TFA (1 equiv), CH3CN, 65 ꢀC; (d) BF3∙Et2O (2.8 equiv), CH3CN, 0 ꢀC.
4.7. Compound (3f)
(E)-Dimethyl-2-(3-bromo-2-(pyrrolidin-1-yldiazenyl)phenyl)
malonate 3f. White solid (76.0 mg, 99%); Mp 72e78 ꢀC; 1H NMR
(CDCl3, 400 MHz),
d
: 7.57 (dd, J1¼8.0 Hz, J2¼1.2 Hz, 1H), 7.29 (dd,
J1¼7.6 Hz, J2¼1.2 Hz, 1H), 7.01 (t, J¼7.6 Hz, 1H), 4.94 (s, 1H), 3.89 (s,
2H), 3.72 (s, 6H), 3.68 (s, 2H), 2.04 (s, 4H); 13C NMR (CDCl3,
100 MHz), d: 169.0,148.2,133.3,129.6,128.7,127.3,125.9,117.6, 53.9,
52.8, 51.1, 46.6, 24.1, 23.6; IR (KBr) v: 2950, 2873, 1752, 1733, 1432,
1407, 1314, 1147, 1028, 758 cmꢁ1; HRMS (EI) (m/z): calcd for
C
15H18BrN3O4 (Mþ): 383.0481; Found: 383.0477.
4.8. Compound (3g)
(E)-Dimethyl-2-(3-(methoxycarbonyl)-2-(pyrrolidin-1-
yldiazeny-l)-phenyl)malonate 3g. Pale yellow solid (41.4 mg, 57%);
Mp 101e104 ꢀC; 1H NMR (CDCl3, 400 MHz),
d: 7.45e7.43 (m, 2H),
7.15 (t, J¼8.0 Hz, 1H), 5.48 (s, 1H), 3.83e3.82 (m, 2H), 3.76 (s, 3H),
3.71 (s, 6H), 3.63 (s, 2H), 2.03e2.00 (m, 4H); 13C NMR (CDCl3,
100 MHz), d: 170.3, 169.1, 147.6, 131.4, 129.3,128.0, 124.5,124.2, 52.7,
52.5, 51.8, 51.1, 46.8, 23.9, 23.6; IR (KBr) v: 2954, 2879, 1755, 1732,
1409, 1309, 1201, 1157, 771, 626 cmꢁ1; HRMS (EI) (m/z): calcd for
C
Scheme 3. Proposed mechanism.
17H21N3O6 (Mþ): 363.1430; Found: 363.1428.
5.53 (s, 1H), 3.86 (s, 2H), 3.74 (s, 6H), 3.60 (s, 2H), 2.32 (s, 3H), 2.00
4.9. Compound (3h)
(s, 4H); 13C NMR (CDCl3, 100 MHz),
d: 169.7, 146.1, 134.9, 129.6,
129.4, 127.3, 116.0, 52.7, 52.6, 50.8, 46.6, 23.9, 21.2; IR (KBr) v: 2953,
2872,1760, 1735,1405,1315,1148,1032, 827 cmꢁ1; HRMS (EI) (m/z):
calcd for C16H21N3O4 (Mþ): 319.1532; Found: 319.1532.
(E)-Dimethyl-2-(3-cyano-2-(pyrrolidin-1-yldiazenyl)phenyl)
malonate 3h. Yellow gel (27.1 mg, 41%); 1H NMR (CDCl3, 400 MHz),
d
: 7.57 (dd, J1¼8.0 Hz, J2¼1.2 Hz, 1H), 7.29 (dd, J1¼7.6 Hz, J2¼1.2 Hz,
1H), 7.01 (t, J¼7.6 Hz, 1H), 4.94 (s, 1H), 3.89 (s, 2H), 3.72 (s, 6H), 3.68
(s, 2H), 2.04 (s, 4H); 13C NMR (CDCl3, 100 MHz),
: 168.8, 151.1, 134.7,
4.4. Compound (3c)
d
133.6, 128.3, 124.5, 119.2, 102.7, 52.9, 52.7, 51.3, 47.1, 24.0, 23.5; IR
(KBr) v: 2954, 2919, 2879, 2221, 1736, 1405, 1310, 1153, 1031,
760 cmꢁ1; HRMS (EI) (m/z): calcd for C16H18N4O4 (Mþ): 330.1328;
Found: 330.1325.
(E)-Dimethyl-2-(5-chloro-2-(pyrrolidin-1-yldiazenyl)phenyl)
malonate 3c. Pale yellow solid (28.5 mg, 42%); Mp 83e88 ꢀC; 1H
NMR (CDCl3, 400 MHz),
1H), 7.22 (dd, J1¼8.4 Hz, J2¼2.4 Hz,1H), 5.51 (s,1H), 3.91 (s, 2H), 3.74
(s, 6H), 3.57 (s, 2H), 2.02 (s, 4H); 13C NMR (CDCl3,100 MHz),
: 169.1,
d
: 7.43 (d, J¼8.8 Hz, 1H), 7.32 (d, J¼2.4 Hz,
d
4.10. Compound (3i)
147.1, 130.3, 129.03, 128.95, 128.8, 117.4, 52.9, 52.4, 51.2, 46.9, 24.1,
23.6; IR (KBr) v: 2954, 2877, 1749, 1435, 1316, 1211, 1026, 905,
834 cmꢁ1; HRMS (EI) (m/z): calcd for C15H18ClN3O4 (Mþ): 339.0986;
Found: 339.0984.
(E)-Dimethyl-2-(2-(pyrrolidin-1-yldiazenyl)-3-(tri-
fluoromethox-y)phenyl)malonate 3i. Pale yellow solid (53.7 mg,
69%); Mp 90e92 ꢀC; 1H NMR (CDCl3, 400 MHz),
d: 7.29e7.27 (m,
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D. Wang, S. Cui / Tetrahedron xxx (2015) 1e6
5
1H), 7.25e7.23 (m, 1H), 7.12 (t, J¼8.0 Hz, 1H), 5.18 (s, 1H), 3.90 (s,
HRMS (EI) (m/z): calcd for C17H23N3O6 (Mþ): 365.1587; Found:
365.1590.
2H), 3.74 (s, 6H), 3.62 (s, 2H), 2.03 (s, 4H); 13C NMR (CDCl3,
100 MHz),
d
: 169.0, 142.8, 140.8 (q, J¼2.0 Hz), 128.9, 127.8, 124.8,
122.5, 120.8 (q, J¼255.0 Hz), 53.4, 52.8, 51.2, 46.3, 24.0, 23.6; IR
(KBr) v: 2972, 2881, 1754, 1738, 1410, 1310, 1145, 754 cmꢁ1; HRMS
(EI) (m/z): calcd for C16H18F3N3O5 (Mþ): 389.1199; Found: 389.1199.
4.16. Compound (3o)
(E)-Dimethyl-2-(3-(pyrrolidin-1-yldiazenyl)naphthalen-2-yl)
malonate 3o. Red solid (29.8 mg, 42%); Mp 92e96 ꢀC; 1H NMR
4.11. Compound (3j)
(CDCl3, 400 MHz),
(d, J¼8.8 Hz, 1H), 7.48e7.45 (m, 3H), 5.23 (s, 1H), 3.88 (s, 4H), 3.75
(s, 6H), 2.09 (s, 4H); 13C NMR (CDCl3,100 MHz),
: 169.7,134.1,128.3,
127.8, 126.7, 126.3, 125.9, 125.1, 124.6, 120.6, 54.0, 52.8, 51.1, 46.6,
24.0, 23.8; IR (KBr) v: 2952, 2872, 1759, 1733, 1359, 1263, 1152,
754 cmꢁ1; HRMS (EI) (m/z): calcd for C19H21N3O4 (Mþ): 355.1532;
Found: 355.1532.
d: 8.25e8.23 (m, 1H), 7.81e7.79 (m, 1H), 7.66
(E)-Dimethyl-2-(4-chloro-3-fluoro-2-(pyrrolidin-1-yldiazenyl)-
phenyl)malonate 3j. Pale brown solid (30.0 mg, 42%); Mp 63e68 ꢀC;
d
1H NMR (CDCl3, 400 MHz),
d
: 7.14e7.10 (m, 1H), 7.05 (dd, J1¼8.4 Hz,
J2¼1.6 Hz,1H), 5.21 (s,1H), 3.93 (t, J¼6.4 Hz, 2H), 3.73 (s, 6H), 3.61 (t,
J¼6.0 Hz, 2H), 2.09e2.01 (m, 4H); 13C NMR (CDCl3, 100 MHz),
d:
168.8, 150.2 (d, J¼252.0 Hz), 138.9 (d, J¼8.0 Hz), 127.8 (d, J¼2.0 Hz),
125.5, 124.5 (d, J¼4.0 Hz), 122.1 (d, J¼18.0 Hz), 52.91, 52.87, 51.4,
46.5, 24.1, 23.6; IR (KBr) v: 2955, 2877, 1747, 1434, 1410, 1024, 792,
4.17. Compound (4a)
728 cmꢁ1
;
HRMS (EI) (m/z): calcd for C15H17ClFN3O4 (Mþ):
(E)-Tetramethyl-2,20-(2-(pyrrolidin-1-yldiazenyl)-1,3-
357.0892; Found: 357.0888.
phenylene-)dimalonate 4a. Pale red solid (20.0 mg, 23%); Mp
131e133 ꢀC; 1H NMR (CDCl3, 400 MHz),
d
: 7.29 (s, 1H), 7.27 (s, 1H),
7.15 (t, J¼7.6 Hz, 1H), 5.09 (s, 2H), 3.82 (s, 2H), 3.72 (s, 12H), 3.58 (s,
2H), 2.02e2.01 (m, 4H); 13C NMR (CDCl3, 100 MHz),
: 169.4, 147.6,
4.12. Compound (3k)
d
(E)-Dimethyl-2-(5-chloro-3-methyl-2-(pyrrolidin-1-
129.4, 125.9, 124.9, 54.2, 52.7, 50.8, 46.5, 24.0, 23.6; IR (KBr) v: 2984,
2958,1756,1735,1406,1309,1150,1027, 769 cmꢁ1; HRMS (EI) (m/z):
calcd for C20H25N3O8 (Mþ): 435.1623; Found: 435.1626.
yldiazenyl)-phenyl)malonate 3k. Yellow solid (66.5 mg, 94%); Mp
98e102 ꢀC; 1H NMR (CDCl3, 400 MHz),
d
: 7.14 (d, J¼2.0 Hz, 1H), 7.12
(s, 1H), 5.02 (s, 1H), 3.83 (s, 2H), 3.72 (s, 6H), 3.59 (s, 2H), 2.24 (s,
3H), 2.02 (s, 4H); 13C NMR (CDCl3, 100 MHz),
: 169.0, 146.9, 132.5,
d
4.18. Compound (4b)
130.8, 129.4, 127.3, 126.7, 53.6, 52.8, 51.0, 46.3, 23.9, 23.8, 19.4; IR
(KBr) v: 2951, 2873, 1743, 1301, 1267, 1038, 769, 615 cmꢁ1; HRMS
(EI) (m/z): calcd for C16H20ClN3O4 (Mþ): 353.1142; Found: 353.1144.
(E)-Tetramethyl-2,20-(5-methyl-2-(pyrrolidin-1-yldiazenyl)-1,3-
phenylene)dimalonate 4b. Yellow solid (12.6 mg, 14%); Mp
146e149 ꢀC; 1H NMR (CDCl3, 400 MHz),
d
: 7.07 (s, 2H), 5.05 (s, 2H),
3.80 (s, 2H), 3.73 (s, 12H), 3.57 (s, 2H), 2.33 (s, 3H), 2.01 (s, 4H); 13
NMR (CDCl3, 100 MHz), : 169.6, 145.3, 134.6, 130.1, 125.7, 54.2, 52.7,
4.13. Compound (3l)
C
d
(E)-Dimethyl-2-(5-iodo-3-methyl-2-(pyrrolidin-1-yldiazenyl)
ph-enyl)malonate 3l. Yellow solid (58.7 mg, 66%); Mp 116e120 ꢀC;
50.8, 46.5, 24.1, 23.7; IR (KBr) v: 2955, 1762, 1733, 1437, 1416, 1311,
1149, 1030, 779 cmꢁ1; HRMS (EI) (m/z): calcd for C21H27N3O8 (Mþ):
449.1798; Found: 449.1801.
1H NMR (CDCl3, 400 MHz),
d
: 7.48 (d, J¼1.2 Hz, 1H), 7.44 (d,
J¼1.6 Hz, 1H), 4.98 (s, 1H), 3.83 (s, 2H), 3.72 (s, 6H), 3.59 (s, 2H), 2.21
(s, 3H), 2.02 (s, 4H); 13C NMR (CDCl3, 100 MHz),
: 169.0, 148.0,
139.7, 135.5, 133.0, 127.9, 88.6, 53.4, 52.8, 51.0, 46.3, 23.9, 23.7, 19.2;
d
4.19. Compound (4c)
IR (KBr) v: 2950, 2873, 1740, 1725, 1299, 1264, 1037, 862, 770 cmꢁ1
;
(E)-Tetramethyl-2,20-(5-chloro-2-(pyrrolidin-1-yldiazenyl)-1,3-
phenylene)dimalonate 4c. Yellow solid (13.2 mg, 14%); Mp
HRMS (EI) (m/z): calcd for C16H20IN3O4 (Mþ): 445.0499; Found:
445.0500.
121e125 ꢀC; 1H NMR (CDCl3, 400 MHz),
d
: 7.28 (s, 2H), 5.06 (s, 2H),
3.83e3.81 (m, 2H), 3.74 (s, 12H), 3.57e3.56 (m, 2H), 2.05e2.00 (m,
4H); 13C NMR (CDCl3, 100 MHz),
: 168.9, 146.4, 130.1, 129.5, 127.4,
4.14. Compound (3m)
d
54.0, 53.0, 51.0, 46.7, 24.1, 23.6; IR (KBr) v: 2918, 2881, 1755, 1732,
(E)-Dimethyl-2-(6-fluoro-3-(methoxycarbonyl)-2-(pyrrolidin-
1-yldiazenyl)phenyl)malonate 3m. White solid (46.5 mg, 61%); Mp
1347, 1157, 1029, 803, 787 cmꢁ1; HRMS (EI) (m/z): calcd for
C
20H24ClN3O8 (Mþ): 469.1252; Found: 469.1248.
128e131 ꢀC; 1H NMR (CDCl3, 400 MHz),
d
: 7.46 (dd, J1¼8.4 Hz,
J2¼6.0 Hz, 1H), 6.88 (t, J¼8.8 Hz, 1H), 5.36 (s, 1H), 3.83 (t, J¼6.4 Hz,
4.20. Compound (4d)
2H), 3.75 (s, 3H), 3.71 (s, 6H), 3.61 (t, J¼6.8 Hz, 2H), 2.06e1.97 (m,
4H); 13C NMR (CDCl3, 100 MHz),
d:
169.5, 168.2, 162.4 (d,
(E)-Tetramethyl-2,20-(5-acetyl-2-(pyrrolidin-1-yldiazenyl)-1,3-
phenylene)dimalonate 4d. Pale yellow solid (12.4 mg, 13%); Mp
J¼250.0 Hz), 150.1 (d, J¼7.0 Hz), 130.7 (d, J¼11.0 Hz), 120.4 (d,
J¼3.0 Hz), 116.6 (d, J¼16.0 Hz), 111.5 (d, J¼23.0 Hz), 52.8, 51.9, 51.3,
48.4, 47.0, 24.0, 23.6; IR (KBr) v: 2981, 2878, 1751, 1604, 1590, 1309,
1116, 786 cmꢁ1; HRMS (EI) (m/z): calcd for C17H20FN3O6 (Mþ):
381.1336; Found: 381.1339.
135e139 ꢀC; 1H NMR (CDCl3, 400 MHz),
d
: 7.89 (s, 2H), 5.10 (s, 2H),
3.86 (t, J¼6.4 Hz, 2H), 3.74 (s, 12H), 3.61 (t, J¼6.4 Hz, 2H), 2.57 (s,
3H), 2.08e2.01 (m, 4H); 13C NMR (CDCl3, 100 MHz),
: 196.7, 169.0,
151.3, 133.2, 130.0, 126.3, 54.4, 52.9, 51.2, 47.0, 26.6, 24.0, 23.5; IR
d
(KBr) v: 2990, 2955, 1731, 1682, 1402, 1162, 1033, 797, 784 cmꢁ1
;
4.15. Compound (3n)
HRMS (EI) (m/z): calcd for C22H27N3O9 (Mþ): 477.1747; Found:
477.1747.
(E)-Dimethyl-2-(2,4-dimethoxy-6-(pyrrolidin-1-yldiazenyl)ph-
enyl)malonate 3n.Yellow solid (38.7 mg, 53%); Mp 115e116 ꢀC; 1H
4.21. Compound (4e)
NMR (CDCl3, 400 MHz),
1H), 5.44 (s, 1H), 3.90 (s, 2H), 3.81 (s, 3H), 3.79 (s, 3H), 3.68 (s, 6H),
3.53 (s, 2H), 1.99 (s, 4H); 13C NMR (CDCl3, 100 MHz),
: 169.9, 160.6,
158.7, 150.2, 110.7, 96.4, 92.5, 56.0, 55.4, 52.3, 51.0, 47.9, 47.0, 24.0,
23.6; IR (KBr) v: 2952, 2855,1741, 1720, 1363, 1143, 709, 604 cmꢁ1
d
: 6.72 (d, J¼2.4 Hz, 1H), 6.30 (d, J¼2.4 Hz,
(E)-Tetramethyl-2,20-(5-(ethoxycarbonyl)-2-(pyrrolidin-1-
d
yldia-zenyl)-1,3-phenylene)dimalonate 4e. Brown solid (22.3 mg,
22%); Mp 113e118 ꢀC; 1H NMR (CDCl3, 400 MHz),
d: 7.93 (s, 2H),
;
5.07 (s, 2H), 4.34 (q, J¼7.2 Hz, 2H), 3.84 (t, J¼6.8 Hz, 2H), 3.73 (s,
Please cite this article in press as: Wang, D.; Cui, S., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.06.024

6
D. Wang, S. Cui / Tetrahedron xxx (2015) 1e6
12H), 3.59 (t, J¼6.4 Hz, 2H), 2.07e1.99 (m, 4H),1.36 (t, J¼7.2 Hz, 3H);
13C NMR (CDCl3, 100 MHz),
: 169.1, 165.9, 151.1, 131.0, 126.6, 126.2,
Typical procedure for the synthesis of compounds 8. A mixture
of 3a (62 mg, 0.203 mmol, 1 equiv) was dissolved in CH3CN (1 mL)
d
61.1, 54.6, 52.8, 51.1, 46.9, 24.1, 23.5,14.5; IR (KBr) v: 2957,1741,1708,
and BF3eEt2O (70.3 mL, 0.568 mmol, 2.8 equiv) was added. Then the
1403, 1275, 1217, 1024, 787, 770 cmꢁ1; HRMS (EI) (m/z): calcd for
reaction was proceeded in a sealed tube at 0 ꢀC for 2 h. The resulting
reaction mixture was loaded on a silica gel column and flashed with
15e20 % ethyl acetate in petroleum ether to afford the desired
products 8 as solid.
C
23H29N3O10 (Mþ): 507.1853; Found: 507.1853.
Typical procedure for the synthesis of compounds 5. A mixture
of 3a (20 mg, 0.0656 mmol, 1 equiv), palladium acetate (1.5 mg,
0.00656 mmol, 10 mol %) and styrene (15 L, 0.1312 mmol, 2 equiv)
was dissolved in MeOH (1 mL), TFA (10 L, 0.1312 mmol, 2 equiv)
m
m
4.25. Compound (8)
was added. Then the reaction was proceeded in a sealed tube at
a temperature of 60 ꢀC for 1 h. The resulting reaction mixture was
loaded on a silica gel column and flashed with 15e20 % ethyl ace-
tate in petroleum ether to afford the desired products 5 as solid.
Dimethyl 1H-indazole-1,3-dicarboxylate 8. White solid
(29.3 mg, 70%); Mp 167e170 ꢀC; 1H NMR (CDCl3, 400 MHz),
d
: 8.29
(t, J¼8.8 Hz, 2H), 7.64e7.60 (m, 1H), 7.48e7.44 (m, 1H), 4.16 (s, 3H),
4.06 (s, 3H); 13C NMR (CDCl3, 100 MHz),
: 162.2, 150.9, 141.2, 141.0,
d
4.22. Compound (5)
130.0, 125.6, 124.5, 122.5, 114.6, 55.1, 52.8; IR (KBr) v: 2920, 2851,
1766, 1732, 1607, 1261, 1131, 809, 771 cmꢁ1; HRMS (EI) (m/z): calcd
for C11H10N2O4 (Mþ): 234.0641; Found: 234.0640.
(E)-Dimethyl-2-(2-styrylphenyl)malonate 5. Pale yellow solid
(14.8 mg, 73%); Mp 58e68 ꢀC; 1H NMR (CDCl3, 400 MHz),
d:
7.61e7.58 (m, 1H), 7.52 (s, 1H), 7.50 (s, 1H), 7.44e7.42 (m, 1H),
7.39e7.36 (m, 3H) 7.34e7.30 (m, 2H), 7.29e7.26 (m, 1H), 6.95 (t,
Acknowledgements
J¼16 Hz, 1H), 5.07 (s, 1H), 3.75 (s, 6H); 13C NMR (CDCl3, 100 MHz),
d:
168.9, 137.6, 137.2, 133.1, 130.7, 129.7, 128.9, 128.7, 128.2, 128.0, 127.1,
126.8, 125.6, 54.6, 53.1; IR (KBr) v: 3003, 2951, 1750, 1732, 1496,
1434, 1207, 1148, 965, 763, 745 cmꢁ1; HRMS (EI) (m/z): calcd for
The authors are grateful for financial supports from National
Natural Science Foundation of China (21202143, 21402163).
C
19H18O4 (Mþ): 310.1205; Found: 310.1203.
Supplementary data
Typical procedure for the synthesis of compounds 6. A mixture
of sodium iodide (78.3 mg, 0.522 mmol, 3 equiv) was dissolved in
acetone (1 mL), TFA (129.6 L, 1.74 mmol, 10 equiv) and 3a (53 mg,
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2015.06.024.
m
0.174 mmol, 1 equiv) was added. Then the reaction was proceeded
in a sealed tube at a temperature of 0 ꢀC for 8 h. The resulting re-
action mixture was loaded on a silica gel column and flashed with
15e20 % ethyl acetate in petroleum ether to afford the desired
products 6 as solid.
References and notes
1. For reviews, see: (a) Satoh, T.; Ueura, K.; Miura, M. Pure Appl. Chem. 2008, 80,
1127; (b) Satoh, T.; Miura, M. Synthesis 2010, 3395; (c) Zhu, C.; Wang, R.; Falck, J.
R. Chem.dAsian J. 2012, 7, 1502; (d) Song, G.; Wang, F.; Li, X. Chem. Soc. Rev. 2012,
41, 3651; (e) Patureau, F. W.; Wencel-Delord, J.; Glorius, F. Aldrichimica Acta 2012,
45, 31.
4.23. Compound (6)
2. For reviews, see: (a) Giri, R.; Shi, B.-F.; Engle, K. M.; Maugel, N.; Yu, J.-Q. Chem.
Soc. Rev. 2009, 38, 3242; (b) Lyons, T. W.; Sanford, M. S. Chem. Rev. 2010, 110,
1147; (c) McMurray, L.; O’Hara, F.; Gaunt, M. J. Chem. Soc. Rev. 2011, 40, 1885; (d)
Wencel-Delord, J.; Droge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011, 40, 4740; (e)
Engle, K. M.; Mei, T.-S.; Wasa, M.; Yu, J.-Q. Acc. Chem. Res. 2012, 45, 788; (f)
Dimethyl-2-(2-iodophenyl)malonate 6. Pale yellow solid
(38.9 mg, 67%); Mp 57e61 ꢀC; 1H NMR (CDCl3, 400 MHz),
d: 7.87
€
(dd, J1¼8.0 Hz, J2¼1.2 Hz, 1H), 7.47 (dd, J1¼7.6 Hz, J2¼1.6 Hz, 1H),
7.39e7.35 (m, 1H), 7.04e7.00 (m, 1H), 5.18 (s, 1H), 3.78 (s, 6H); 13C
Wencel-Delord, J.; Glorius, F. Nat. Chem. 2013, 5, 369.
NMR (CDCl3, 100 MHz), d: 168.3, 139.8, 136.2, 130.0, 129.8, 128.8,
3. Chan, W.-W.; Lo, S.-F.; Zhou, Z.; Yu, W.-Y. J. Am. Chem. Soc. 2012, 134, 13565.
4. (a) Hyster, T. K.; Ruhl, K. E.; Rovis, T. J. Am. Chem. Soc. 2013, 135, 5364; (b) Shi, Z.;
Koester, D. C.; Boultadakis-Arapinis, M.; Glorius, F. J. Am. Chem. Soc. 2013, 135,
12204; (c) Yu, S.; Liu, S.; Lan, Y.; Wan, B.; Li, X. J. Am. Chem. Soc. 2015, 137, 1623;
(d) Lam, H.-W.; Man, K.-Y.; Chan, W.-W.; Zhou, Z.; Yu, W.-Y. Org. Biomol. Chem.
2014, 12, 4112; (e) Hu, F.; Xia, Y.; Ye, F.; Liu, Z.; Ma, C.; Zhang, Y.; Wang, J. Angew.
Chem., Int. Ed. 2013, 53, 1364; (f) Xia, Y.; Liu, Z.; Feng, S.; Zhang, Y.; Wang, J. J. Org.
Chem. 2015, 80, 223; (g) Hu, F.; Xia, Y.; Ma, C.; Zhang, Y.; Wang, J. Chem. Commun.
2015, 7986.
5. (a) Zhou, J.; Yang, W.; Wang, B.; Ren, H. Angew. Chem., Int. Ed. 2012, 51, 12293; (b)
Zhou, J.; He, J.; Wang, B.; Yang, W.; Ren, H. J. Am. Chem. Soc. 2011, 133, 6868; (c)
Yang, W.; Yang, Z.; Xu, L.; Zhang, L.; Xu, X.; Miao, M.; Ren, H. Angew. Chem., Int.
Ed. 2013, 52, 14135; (d) Shang, X.; Xu, L.; Yang, W.; Zhou, J.; Miao, M.; Ren, H. Eur.
J. Org. Chem. 2013, 5475.
101.7, 62.0, 53.2; IR (KBr) v: 2955, 2929, 1754, 1738, 1434, 1263, 1151,
1019, 747 cmꢁ1; HRMS (EI) (m/z): calcd for C11H11IO4 (Mþ):
333.9702; Found: 333.9710.
Typical procedure for the synthesis of compounds 7. A mixture
of 3a (20 mg, 0.0656 mmol, 1 equiv) was dissolved in CH3CN (1 mL)
and TFA (4.9 mL, 0.0656 mmol, 1 equiv) was added. Then the re-
action was proceeded in a sealed tube at a temperature of 65 ꢀC for
8 h. The resulting reaction mixture was loaded on a silica gel col-
umn and flashed with 15e20 % ethyl acetate in petroleum ether to
afford the desired products 7 as solid.
6. (a) Wang, C.; Chen, H.; Wang, Z.; Chen, J.; Huang, Y. Angew. Chem., Int. Ed. 2012,
51, 7242; (b) Wang, C.; Sun, H.; Fang, Y.; Huang, Y. Angew. Chem., Int. Ed. 2013, 52,
5795.
4.24. Compound (7)
7. (a) Cui, S.; Zhang, Y.; Wu, Q. Chem. Sci. 2013, 4, 3421; (b) Cui, S.; Zhang, Y.; Wang,
D.; Wu, Q. Chem. Sci. 2013, 4, 3912; (c) Zhang, Y.; Wu, Q.; Cui, S. Chem. Sci. 2014, 5,
297; (d) Zhang, Y.; Zheng, J.; Cui, S. J. Org. Chem. 2014, 79, 6490; (e) Zheng, J.;
Zhang, Y.; Cui, S. Org. Lett. 2014, 16, 3560; (f) Zhang, Y.; Shen, M.; Cui, S.; Hou, T.
Bioorg. Chem. Med. Lett. 2014, 24, 5470.
8. CCDC 1016343 contains the supplementary crystallographic data for this paper.
These data can be obtained free of charge from The Cambridge Crystallographic
Data Center via www.ccdc.cam.ac.uk/data_request/cif
Dimethyl-3H-indazole-3,3-dicarboxylate 7. Brown solid
(12.4 mg, 81%); Mp 78e92 ꢀC; 1H NMR (CDCl3, 400 MHz),
d:
8.16e8.14 (m, 1H), 7.85e7.83 (m, 1H), 7.65e7.57 (m, 2H), 3.83 (s,
6H); 13C NMR (CDCl3, 100 MHz),
d: 163.2, 158.5, 134.2, 131.4, 130.9,
124.7, 122.2, 54.2; IR (KBr) v: 2957, 2917, 2849, 1735, 1461, 1437,
1215, 1056, 752 cmꢁ1; HRMS (EI) (m/z): calcd for C11H10N2O4 (Mþ):
234.0641; Found: 234.0644.
9. For rearrangement of 7 to 8, see: Liu, Z.; Shi, F.; Martinez, P. D. G.; Raminelli, C.;
Larock, R. C. J. Org. Chem. 2008, 73, 219.
Please cite this article in press as: Wang, D.; Cui, S., Tetrahedron (2015), http://dx.doi.org/10.1016/j.tet.2015.06.024