Iron-catalyzed oxidative arylmethylation of activated alkenes using a peroxide as the methyl source

Article abstract of DOI:10.1055/s-0033-1340665

A novel, simple route for the synthesis of oxindoles is presented via iron-catalyzed oxidative arylmethylation of activated alkenes with peroxides. This work is realized by the use of a peroxide as the methyl source and 1,4-diazabicyclo[2.2.2]octane as the ligand and represents a new access to oxindoles through an alkene oxidative difunctionalization process. Georg Thieme Verlag Stuttgart. New York.

Full text of DOI:10.1055/s-0033-1340665

Accounts and
Rapid Communications in
Synthetic Organic Chemistry
SYNLETT
SUPPORTING INFORMATION
Supporting Information
for DOI: 10.1055/s-0033-1340665
© Georg Thieme Verlag KG Stuttgart · New York 2014
Thieme

Iron-catalyzed oxidative
arylmethylation of activated alkenes
using Dꢀperoxide as the methyl source
Jian-Hong Fan, Ming-Bo Zhou, Yu Liu, Wen-Ting Wei, Xuan-Hui Ouyang,
Ren-Jie Song,* and Jin-Heng Li*
State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry
and Chemical Engineering, Hunan University, Changsha 410082, China
E-mail: jhli@hnu.edu.cn and srj0731@hnu.edu.cn
Supporting Information
List of Contents
(A) Typical experimental procedure
(B) Analytical data
(C) References
S2
S2-S10
S10
(D) Spectra
S11-S26
S1

(A) Typical Experimental Procedure
(a) Synthesis of Substrates 1:
[S1]
Substrates 1 were prepared according to the known procedures.
.
(b) Typical Experimental Procedure for the Iron-catalyzed Oxidative
Arylmethylation of Activated Alkenes Using Peroxides as the Methyl Resource:
To a Schlenk tube were added alkens 1 (0.3 mmol), Fe(OAc)2 (5 mol%), DABCO
(10 mol%), (peroxybis(propane-2,2-diyl))dibenzene (DCP, 2 equiv), and DMSO (2
o
mL). Then the tube was charged with argon, and was stirred at 120 C (oil bath
temperature) for the indicated time until complete consumption of starting material as
monitored by TLC and GC-MS analysis. After the reaction was finished, the reaction
mixture was cooled to room temperature, diluted in ethyl acetate, and washed with
brine. The aqueous phase was re-extracted with ethyl acetate. The combined organic
extracts were dried over Na2SO4 and concentrated in vacuum, and the resulting
residue was purified by silica gel column chromatography (hexane/ethyl acetate =
20:1) to afford the desired products 3.
(B) Analytical data
O
N
3-Ethyl-1,3-dimethylindolin-2-one (3aa): [S2]
1
Yellow oil; H NMR (400 MHz, CDCl3) G: 7.26 (t, J = 6.4 Hz, 1H), 7.17 (d, J = 7.2
Hz, 1H), 7.07 (t, J = 7.2 Hz, 1H), 6.84 (d, J = 8.0 Hz, 1H), 3.22 (s, 3H), 1.97-1.89 (m,
S2

13
1H), 1.82-1.73 (m, 1H), 1.35 (s, 3H), 0.59 (t, J = 7.6 Hz, 3H); C NMR (100 MHz,
CDCl3) G: 180.8, 143.5, 133.9, 127.6, 122.5, 122.4, 107.8, 48.9, 31.4, 26.0, 23.3, 8.8;
IR (KBr, cm-1): 1722, 1461; LRMS (EI, 70 eV) m/z (%): 189 (M+, 21), 161 (100), 190
(6); HRMS m/z (ESI) calcd for C12H16NO ([M+H]+) 190.1154, found 190.1161.
O
N
1,3-Dimethyl-3-propylindolin-2-one (3ae):
1
Yellow oil; H NMR (400 MHz, CDCl3) G: 7.26 (t, J = 8.0 Hz, 1H), 7.17 (d, J = 7.2
Hz, 1H), 7.06 (t, J = 7.6 Hz, 1H), 6.84 (d, J = 8.0 Hz, 1H), 3.21 (s, 3H), 1.91-1.84 (m,
1H), 1.74-1.67 (m, 1H), 1.35 (s, 3H), 1.07-0.95 (m, 1H), 0.90-0.83 (m, 1H), 0.77 (t, J
= 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) G: 180.9, 143.3, 134.3, 127.6, 122.5,
122.4, 107.8, 48.5, 40.8, 26.1, 23.7, 17.8, 14.1; IR (KBr, cm-1): 1719, 1466; LRMS
(EI, 70 eV) m/z (%): 203 (M+, 20), 161 (100), 204 (3); HRMS m/z (ESI) calcd for
C13H18NO ([M+H]+) 204.1310, found 204.1315.
O
N
Bn
1-Benzyl-3-ethyl-3-methylindolin-2-one (3ba): [S3]
1
Yellow oil; H NMR (400 MHz, CDCl3) G: 7.32-7.22 (m, 5H), 7.18-7.11 (m, 2H),
7.02 (t, J = 7.6 Hz, 1H), 6.72 (d, J = 7.6 Hz, 1H), 4.99 (t, J = 15.6 Hz, 1H), 4.85 (t, J
= 15.6 Hz, 1H), 2.05-1.96 (m, 1H), 1.87-1.78 (m, 1H), 1.41 (s, 3H), 0.64 (t, J = 7.6 Hz,
3H); 13C NMR (100 MHz, CDCl3) G: 180.8, 142.5, 136.1, 133.8, 128.7, 127.5, 127.4,
127.2, 122.5, 122.4, 108.9. 48.9, 43.6, 31.4, 23.7, 9.0; IR (KBr, cm-1): 1743, 1442;
S3

LRMS (EI, 70 eV) m/z (%): 265 (M+, 45), 91 (100), 266 (9); HRMS m/z (ESI) calcd
for C18H20NO ([M+H]+) 266.1539, found 266.1551.
O
N
3-Ethyl-1,3,5-trimethylindolin-2-one (3da):[S4]
1
Yellow oil; H NMR (400 MHz, CDCl3) G: 7.06 (d, J = 8.0 Hz, 1H), 6.98 (s, 1H),
6.73 (d, J = 7.6 Hz, 1H), 3.19 (s, 3H), 2.35 (s, 3H), 1.96-1.87 (m, 1H), 1.79-1.70 (m,
13
1H), 1.34 (s, 3H), 0.58 (t, J = 7.6 Hz, 3H); C NMR (100 MHz, CDCl3) G: 180.7,
141.1, 134.0, 131.9, 127.8, 123.4, 107.5, 49.0, 31.5, 26.1, 23.4, 21.2, 8.9; IR (KBr,
cm-1): 1738, 1442; LRMS (EI, 70 eV) m/z (%): 203 (M+, 36), 174 (100), 204 (5);
HRMS m/z (ESI) calcd for C13H18NO ([M+H]+) 204.1383, found 204.1381.
O
N
3-Ethyl-1,3,7-trimethylindolin-2-one (3ea):
1
Yellow oil; H NMR (400 MHz, CDCl3) G: 7.00-6.93 (m, 3H), 3.50 (s, 3H), 2.59 (s,
3H), 1.95-1.88 (m, 1H), 1.77-1.68 (m, 1H), 1.32 (s, 3H), 0.57 (t, J = 7.6 Hz, 3H); 13C
NMR (100 MHz, CDCl3) G: 181.5, 141.2, 134.6, 131.3, 122.3, 120.4, 119.4, 48.2,
31.8, 29.4, 23.8, 19.1, 8.9; IR (KBr, cm-1): 1722, 1461; LRMS (EI, 70 eV) m/z (%):
203 (M+, 32), 174 (100), 204 (5); HRMS m/z (ESI) calcd for C13H18NO ([M+H]+)
204.1383, found 204.1383.
S4

3-Ethyl-1,3,6-trimethylindolin-2-one (3fa) and 3-Ethyl-1,3,4-trimethylindolin-2-
one (3fa’) (1.7:1):
1
Yellow oil; H NMR (400 MHz, CDCl3) G: 7.17 (t, J = 7.6 Hz, 1H), 7.04 (d, J = 7.2
Hz, 0.67H), 6.88 (d, J = 7.2 Hz, 0.67H), 6.83 (d, J = 7.6 Hz, 1H), 6.70 (s, 0.67H),
6.68 (s, 1H), 3.21 (s, 3H), 3.20 (s, 2H), 2.39 (s, 2H), 2.36 (s, 3H), 2.04-1.86 (m, 2.7H),
1.77-1.1.70 (m, 0.7H), 1.43 (s, 3H), 1.33 (s, 2H), 0.59 (t, J = 7.6 Hz, 2H), 0.49 (t, J =
7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) G: 181.1, 180.7, 143.5, 137.7, 134.2, 131.0,
130.3, 127.5, 125.0, 122.9, 122.3, 108.8, 105.6, 50.2, 48.7, 31.4, 29.4, 26.2, 23.4, 22.1,
21.8, 18.1, 14.1, 9.2, 8.9; IR (KBr, cm-1): 1738, 1442; LRMS (EI, 70 eV) m/z (%):
203 (M+, 36), 174 (100), 204 (5); HRMS m/z (ESI) calcd for C13H18NO ([M+H]+)
204.1383, found 204.1381.
n-Bu
O
N
5-Butyl-3-ethyl-1,3-dimethylindolin-2-one (3ga):
1
Yellow oil; H NMR (400 MHz, CDCl3) G: 7.06 (d, J = 8.0 Hz, 1H), 6.98 (s, 1H),
6.75 (d, J = 7.6 Hz, 1H), 3.20 (s, 3H), 2.60 (t, J = 7.6 Hz, 3H), 1.96-1.87 (m, 1H),
1.80-1.71 (m, 1H), 1.63-1.55 (m, 2H), 1.41-1.31 (m, 2H), 1.34 (s, 3H), 0.93 (t, J = 7.6
Hz, 3H), 0.59 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3) G: 180.8, 141.3, 137.2,
133.9, 127.2, 122.7, 107.5, 49.0, 35.5, 34.1, 31.5, 26.1, 23.4, 22.4, 14.0, 8.9; IR (KBr,
S5

cm-1): 1746, 1456; LRMS (EI, 70 eV) m/z (%): 245 (M+, 33), 202 (100), 246 (5);
HRMS m/z (ESI) calcd for C16H24NO ([M+H]+) 246.1852, found 246.1842.
3-Ethyl-5-methoxy-1,3-dimethylindolin-2-one (3ha): [S5]
1
Yellow oil; H NMR (400 MHz, CDCl3) G: 6.80-6.77 (m, 2H), 6.74 (t, J = 6.0 Hz,
1H), 3.81 (s, 3H), 3.19 (s, 3H), 1.97-1.89 (m, 1H), 1.79-1.67 (m, 1H), 1.34 (s, 3H),
13
0.59 (t, J = 7.2 Hz, 3H); C NMR (100 MHz, CDCl3) G: 180.4, 156.0, 137.1, 135.4,
111.5, 110.3, 108.0, 55.8, 49.4, 31.5, 26.2, 23.4, 8.9; IR (KBr, cm-1): 1741, 1472;
LRMS (EI, 70 eV) m/z (%): 219 (M+, 58), 190 (100), 210 (10); HRMS m/z (ESI)
calcd for C13H18NO2 ([M+H]+) 220.1332, found 220.1333.
5-Chloro-3-ethyl-1,3-dimethylindolin-2-one (3ia): [S4]
Yellow oil; 1H NMR (400 MHz, CDCl3) G: 7.24 (d, J = 8.4 Hz, 1H), 7.14 (d, J = 2.0
Hz, 1H), 6.76 (d, J = 8.0 Hz, 1H), 3.20 (s, 3H), 1.98-1.80 (m, 1H), 1.78-1.71 (m, 1H),
13
1.35 (s, 3H), 0.59 (t, J = 7.6 Hz, 3H); C NMR (100 MHz, CDCl3) G: 180.2, 142.1,
135.7, 127.9, 127.6, 123.1, 108.8, 49.3, 31.4, 26.2, 23.3, 8.8; IR (KBr, cm-1): 1728,
1459; LRMS (EI, 70 eV) m/z (%): 223 (M+, 48), 194 (100), 224 (7); HRMS m/z (ESI)
calcd for C12H15ClNO ([M+H]+) 224.0837, found 224.0843.
S6

3-Ethyl-5-fluoro-1,3-dimethylindolin-2-one (3ja): [S4]
1
Yellow oil; H NMR (400 MHz, CDCl3) G: 6.99-6.90 (m, 2H), 6.76 (d, J = 8.4 Hz,
1H), 3.21 (s, 3H), 1.99-1.88 (m, 1H), 1.79-1.70 (m, 1H), 1.35 (s, 3H), 0.59 (t, J = 7.6
13
Hz, 3H); C NMR (100 MHz, CDCl3) G: 180.4, 159.4 (d, J = 238.7 Hz, 1C), 139.4,
135.7 (d, J = 7.6 Hz, 1C), 113.7 (d, J = 23.3 Hz, 1C), 110.7 (d, J = 24.3 Hz, 1C),
108.2 (d, J = 8.1 Hz, 1C), 49.5, 31.4, 26.2, 23.3, 8.8; IR (KBr, cm-1): 1728, 1465;
LRMS (EI, 70 eV) m/z (%): 207 (M+, 42), 178 (100), 208 (6); HRMS m/z (ESI) calcd
for C12H15FNO ([M+H]+) 208.1132, found 208.1140.
F3C
O
N
3-Ethyl-1,3-dimethyl-5-(trifluoromethyl)indolin-2-one (3ka):
1
Yellow oil; H NMR (400 MHz, CDCl3) G: 7.56 (d, J = 8.4 Hz, 1H), 7.40 (s, 1H),
6.92 (d, J = 8.0 Hz, 1H), 3.25 (s, 3H), 2.01-1.92 (m, 1H), 1.85-1.76 (m, 1H), 1.38 (s,
13
3H), 0.60 (t, J = 7.6 Hz, 3H); C NMR (100 MHz, CDCl3) G: 180.6, 146.5, 134.5,
125.5 (m, 1C), 124.1 (m, 1C), 119.5 (m, 1C), 107.6, 49.0, 31.4, 26.3, 23.2, 8.8; IR
(KBr, cm-1): 1733, 1472; LRMS (EI, 70 eV) m/z (%): 257 (M+, 73), 228 (100), 258
(11); HRMS m/z (ESI) calcd for C13H15F3NO ([M+H]+) 258.1100, found 258.1100.
S7

O
N
Cl
7-Chloro-3-ethyl-1,3-dimethylindolin-2-one (3la):
1
Yellow oil; H NMR (400 MHz, CDCl3) G: 7.18 (d, J = 8.0 Hz, 1H), 7.04-6.95 (m,
2H), 3.58 (s, 3H), 1.99-1.90 (m, 1H), 1.78-1.69 (m, 1H), 1.34 (s, 3H), 0.58 (t, J = 7.2
13
Hz, 3H); C NMR (100 MHz, CDCl3) G: 179.9, 138.3, 135.8, 128.9, 122.2, 120.0,
114.3, 47.8, 30.8, 28.4, 22.7, 7.8; IR (KBr, cm-1): 1728, 1459; LRMS (EI, 70 eV) m/z
(%): 223 (M+, 48), 194 (100), 224 (7); HRMS m/z (ESI) calcd for C12H15ClNO
([M+H]+) 224.0837, found 224.0828.
Ph
O
N
3-Ethyl-1-methyl-3-phenylindolin-2-one (3ma): [S6]
o
1
Yellow solid; mp 77.9-78.6 C (uncorrected); H NMR (400 MHz, CDCl3) G: 7.38-
7.20 (m, 7H), 7.12 (t, J = 7.6 Hz, 1H), 6.90 (d, J = 7.6 Hz, 1H), 3.22 (s, 3H), 2.47-
2.39 (m, 1H), 2.28-2.19 (m, 1H), 0.68 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3) G: 178.6, 144.1, 140.3, 132.1, 128.5, 128.1, 127.2, 127.0, 124.8, 122.6, 108.2,
57.3, 30.9, 26.3, 9.1; IR (KBr, cm-1): 1740, 1473; LRMS (EI, 70 eV) m/z (%): 251
(M+, 75), 222 (100), 252 (14); HRMS m/z (ESI) calcd for C17H18NO ([M+H]+)
252.1383, found 252.1390.
S8

3-Ethyl-3-(hydroxymethyl)-1-methylindolin-2-one (3na):
1
Yellow oil; H NMR (400 MHz, CDCl3) G: 7.32 (t, J = 7.6 Hz, 1H), 7.21 (t, J = 7.2
Hz, 1H), 7.11 (t, J = 7.2 Hz, 1H), 6.88 (t, J = 7.6 Hz, 1H), 3.89 (t, J = 10.8 Hz, 1H),
3.75 (t, J = 10.8 Hz, 1H), 3.28 (s, 3H), 2.11-2.02 (m, 1H), 1.88-1.79 (m, 1H), 1.26 (s,
13
1H), 0.62 (t, J = 7.2 Hz, 3H); C NMR (100 MHz, CDCl3) G: 179.4, 144.4, 129.8,
128.2, 122.9, 122.7, 108.2, 66.9, 55.3, 42.7, 26.1, 8.3; IR (KBr, cm-1): 3620, 1728,
1461; LRMS (EI, 70 eV) m/z (%): 205 (M+, 28), 160 (100), 206 (4); HRMS m/z (ESI)
calcd for C12H16NO2 ([M+H]+) 206.1176, found 206.1161.
(3-Ethyl-1-methyl-2-oxoindolin-3-yl)methyl acetate (3oa):
1
Yellow oil; H NMR (400 MHz, CDCl3) G: 7.33-7.28 (m, 1H), 7.20 (d, J = 7.2 Hz,
1H), 7.08 (t, J = 7.6 Hz, 1H), 6.87 (t, J = 7.6 Hz, 1H), 4.53 (d, J = 10.8 Hz, 1H), 4.19
13
(t, J = 10.8 Hz, 1H), 3.24 (s, 3H), 1.96-1.82 (m, 5H), 0.60 (t, J = 7.6 Hz, 3H); C
NMR (100 MHz, CDCl3) G: 177.5, 170.4, 144.2, 129.3, 128.3, 123.2, 122.5, 107.9,
67.2, 53.1, 26.7, 26.1, 20.5, 8.0; IR (KBr, cm-1): 1743, 1712, 1433; LRMS (EI, 70 eV)
m/z (%): 247 (M+, 33), 175 (100), 248 (5); HRMS m/z (ESI) calcd for C14H18NO3
([M+H]+) 248.1281, found 248.1296.
Ph
O
N
dr = 8.3:1
1-Methyl-3-(1-phenylethyl)indolin-2-one (3pa): [S4]
S9

1
Yellow oil; H NMR (400 MHz, CDCl3) G: 7.35-7.25 (m, 4H), 7.12 (d, J = 7.2 Hz,
2H), 7.05 (d, J = 8.0 Hz, 1H), 6.98 (t, J = 7.6 Hz, 1H), 6.84 (d, J = 7.6 Hz, 1H), 3.87
13
(d, J = 8.8 Hz, 1H), 3.41 (s, 3H), 2.97-2.89 (m, 1H), 1.15 (t, J = 7.2 Hz, 3H); C
NMR (100 MHz, CDCl3) G: 172.3, 141.1, 139.9, 128.9, 128.8, 128.5, 128.3, 127.8,
127.1, 123.0, 114.6, 48.9, 42.1, 29.9, 15.5; IR (KBr, cm-1): 1731, 1445; LRMS (EI, 70
eV) m/z (%): 251 (100), 252 (22); HRMS m/z (ESI) calcd for C17H18NO ([M+H]+)
252.1383, found 252.1393.
(C) References
[S1] (a) Mu; X.; Wu; T.; Wang, H.-Y.; Guo, Y.-L.; Liu, G.-S. J. Am. Chem. Soc. 2012,
134, 878. (b) Pinto, A.; Jia, Y.; Neuville, L.; Zhu, J. Chem. Eur. J. 2007, 13, 961. (c)
Jones, K.; Thompson, M.; Wright, C. J. Chem. Soc., Chem. Commun. 1986, 715.
[S2] Wu, T.; Zhang, H.; Liu, G.-S. Tetrahedron. 2012, 68, 5229.
[S3] Alluri, S.; Feng, H.; Livings, M.; Samp, L.; Biswas, D.; Lam, T. W.; Lobkovsky,
E.; Ganguly, A. K. Tetrahedron Lett. 2011, 52, 3945.
[S4] Xie, J.; Xu, P.; Li, H.-M.; Xue, Q.-C.; Jin, H.-M,; Cheng, Y.-X.; Zhu, C.-J. Chem.
Commun. 2013, 49, 5672.
[S5] Chen, B.; Ji, Q.-E. Yaoxue bao 1990, 25, 247.
[S6] Beyer, A.; Buendia, J.; Bolm, C. Org. Lett. 2012, 14, 3948.
S10

(D) Spectra
3-Ethyl-1,3-dimethylindolin-2-one (3aa)
S11

1,3-Dimethyl-3-propylindolin-2-one (3ae)
S12

1-Benzyl-3-ethyl-3-methylindolin-2-one (3ba)
S13

3-Ethyl-1,3,5-trimethylindolin-2-one (3da)
S14

3-Ethyl-1,3,7-trimethylindolin-2-one (3ea)
S15

3-Ethyl-1,3,6-trimethylindolin-2-one (3fa) and 3-Ethyl-1,3,4-trimethylindolin-2-
one (3fa’)
S16

5-Butyl-3-ethyl-1,3-dimethylindolin-2-one (3ga)
S17

3-Ethyl-5-methoxy-1,3-dimethylindolin-2-one (3ha)
S18

5-Chloro-3-ethyl-1,3-dimethylindolin-2-one (3ia)
S19

3-Ethyl-5-fluoro-1,3-dimethylindolin-2-one (3ja)
S20

3-Ethyl-1, 3-dimethyl-5-(trifluoromethyl)indolin-2-one (3ka)
S21

7-Chloro-3-ethyl-1,3-dimethylindolin-2-one (3la)
S22

3-Ethyl-1-methyl-3-phenylindolin-2-one (3ma)
S23

3-Ethyl-3-(hydroxymethyl)-1-methylindolin-2-one (3na)
S24

(3-Ethyl-1-methyl-2-oxoindolin-3-yl)methyl acetate (3oa)
S25

1-Methyl-3-(1-phenylethyl)indolin-2-one (3pa)
S26