Palladium and copper cocatalyzed tandem N-H/C-H bond functionalization: Synthesis of CF3-containing indolo- and pyrrolo[2,1-a ]isoquinolines

Article abstract of DOI:10.1021/jo3000404

A palladium- and copper-catalyzed tandem N-H/C-H bond functionalization reaction of ortho-(2-chlorovinyl)bromobenzenes with indoles and pyrroles has been developed. A variety of CF₃-containing indolo- and pyrrolo[2,1-a]isoquinolines were prepared in moderate to good yields via the cyclization of 1-bromo-2-(2-chloro-3,3,3-trifluoroprop-1-enyl)benzenes with indoles and pyrroles.

Full text of DOI:10.1021/jo3000404

Article
pubs.acs.org/joc
Palladium and Copper Cocatalyzed Tandem N−H/C−H Bond
Functionalization: Synthesis of CF3-Containing Indolo- and
Pyrrolo[2,1-a]isoquinolines
Lei-Lei Sun, Zhi-Yong Liao, Ri-Yuan Tang, Chen-Liang Deng, and Xing-Guo Zhang*
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035, China
S
* Supporting Information
ABSTRACT: A palladium- and copper-catalyzed tandem N−
H/C−H bond functionalization reaction of ortho-(2-
chlorovinyl)bromobenzenes with indoles and pyrroles has
been developed. A variety of CF3-containing indolo- and
pyrrolo[2,1-a]isoquinolines were prepared in moderate to
good yields via the cyclization of 1-bromo-2-(2-chloro-3,3,3-trifluoroprop-1-enyl)benzenes with indoles and pyrroles.
Scheme 1
INTRODUCTION
■
Indolo- and pyrrolo[2,1-a]isoquinolines are important class of
nitrogen-containing fused polycyclic compounds, which occur
widely in pharmaceutical molecules,1 functional materials,2 and
natural products.3 Thus, a number of synthetic strategies have
been developed for the construction of these entities,4 most of
them requiring complicated multistep procedures involving
substantial byproducts.5 Recently, transition-metal-catalyzed
C−H bond functionalization has received considerable
attention owing to its atom economy, which could transform
the unreactive C−H bond into diverse functional groups.6 The
tandem reactions combining a C−H bond functionalization
with a C-heteroatom bond forming reaction have emerged as a
powerful tool for the synthesis of multiring heterocyclic
compounds because of their efficiency and selectivity.7 For
example, Larock and co-workers reported the synthesis of
indolo- and pyrrolo [2,1-a]isoquinolines by copper catalyzed
tandem C−N bond forming reaction and C−H bond arylation
of ortho-haloarylalkyne.8 Xi and co-workers also developed the
copper catalyzed consecutive N-alkenylation and C-alkenyla-
tion of azoles for the synthesis of N-bridgehead azolopyridines.9
It is well-known that the introduction of a trifluoromethyl
group into organic compounds has a significant effect on
biological activity and often manifests changes in chemical and
physical properties.10 As part of a continuing interest in the
synthesis of trifluoromethyl-containing heterocyclic com-
pounds,11 we wish to prepare CF3-containing isoquinoline
derivatives from our previous CF3-containing building blocks
via tandem cyclization. Herein, we report an efficient protocol
for the synthesis of trifluoromethyl-containing indolo- and
pyrrolo[2,1-a]isoquinolines from the palladium and copper
cocatalyzed tandem N−H/C−H bond functionalization
reaction of 1-bromo-2-(2-chloro-3,3,3-trifluoroprop-1-enyl)-
benzenes12 with indoles and pyrroles (Scheme 1).
RESULTS AND DISCUSSION
■
We began our study by examining the reaction between 2-
chloro-1-(2-bromophenyl)-3,3,3-trifluoropropylene 1a and 1H-
indole 2a to screen the optimal reaction conditions, and the
results are summarized in Table 1. Initially, substrate 1a was
treated with 1H-indole 2a, Pd(OAc)2, and Cs2CO3 in DMSO
at 140 °C for 5 h, but only trace amounts of the target product
3a was observed (entry 1). It was found that PPh3 could
promote the reaction and the yield increased to 21% in the
presence of 20 mol % PPh3 (entry 2). Larock and Xi’s results
revealed that copper catalysts could mediate the amination and
alkenylation of indole or imidazole.8,9 Therefore, various
copper salts such as CuI, CuBr, CuCl, Cu(OTf)2, and
Cu(OAc)2 were examined (entries 3−7). We found that the
desired product 3a could be isolated in 72% yield by adding 20
mol % of CuI as cocatalyst (entry 3). The other copper
catalysts were less effective than CuI. It is noteworthy that CuI
could not promote the reaction in the absence of Pd(OAc)2
(entry 8). Subsequently, some phosphine ligands were screened
to optimize the reaction conditions, but other ligands were
found less effective than PPh3 (entries 9−12). During the
examination of the effect of base (entries 13−15), we found
that the reaction yields decreased dramatically in the presence
of mild bases such as K2CO3 and K3PO4. Lower yield was also
observed when Cs2CO3 was replaced by t-BuONa. Finally, the
effects of solvents and reaction temperature were evaluated
(entries 16−19). The results showed that the reaction
proceeded optimally in DMSO at 140 °C.
Received: January 11, 2012
Published: February 21, 2012
© 2012 American Chemical Society
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a
Table 1. Screening Conditions
entry
catalyst
Pd(OAc)2
ligand
base
solvent
yield (%)
1
−
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
t-BuONa
K2CO3
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMSO
DMF
<5
21
72
34
31
42
49
0
2
Pd(OAc)2
L1
L1
L1
L1
L1
L1
L1
L2
L3
L4
L5
L1
L1
L1
L1
L1
L1
L1
3
Pd(OAc)2/CuI
Pd(OAc)2/CuBr
Pd(OAc)2/CuCl
Pd(OAc)2/Cu(OTf)2
Pd(OAc)2/Cu(OAc)2
CuI
4
5
6
7
8
9
Pd(OAc)2/CuI
Pd(OAc)2/CuI
Pd(OAc)2/CuI
Pd(OAc)2/CuI
Pd(OAc)2/CuI
Pd(OAc)2/CuI
Pd(OAc)2/CuI
Pd(OAc)2/CuI
Pd(OAc)2/CuI
Pd(OAc)2/CuI
Pd(OAc)2/CuI
37
43
39
47
65
14
12
60
25
<5
53
10
11
12
13
14
15
16
17
18
K3PO4
Cs2CO3
Cs2CO3
Cs2CO3
Cs2CO3
NMP
toluene
DMSO
b
19
a
Reaction conditions: 1a (0.2 mmol), 2a (0.22 mmol), Pd(OAc)2 (10 mol %), [Cu] (20 mol %), ligand (20 mol %) and base (3 equiv) in solvent (2
b
mL) at 140 °C under N2 atmosphere for 5 h. At 120 °C.
With the optimal reaction conditions in hand, the substrate
scope of both indoles and ortho-(2-chlorovinyl)bromobenzenes
for this tandem reactions was examined (Table 2). We initially
investigated the reaction of a variety of indoles 2b−2j with 1-
bromo-2-(2-chloro-3,3,3-trifluoroprop-1-enyl)benzenes 1a (en-
tries 1−9). The results demonstrated that a wide range of
indoles bearing both electron-withdrawing and electron-
donating groups were suitable substrates for the cyclization
and gave the corresponding products in moderate to excellent
yields. For example, electron-rich indoles (2b−2e) bearing
methyl, ethyl or methoxyl substituents provided the desired
products in good yields (entries 1−4). The configuration of the
product was confirmed by X-ray single-crystal diffraction
analysis of compound 3e. The 5-aminoindole 2f could be
converted to indolo[2,1-a]isoquinoline 3f in 51% yield and the
unprotected amino group did not participate in amination
(entry 5). Indoles containing halogen atom (Br, F) or electron-
withdrawing substituents (cyano, nitro) also underwent the
cyclization smoothly to afford the corresponding product in
moderate yields (entries 6−9). Subsequently, various ortho-(2-
chlorovinyl)bromobenzenes 1b−1f bearing different functional
groups on the aryl moiety were examined (entries 10−14). The
results showed that several substituents (such as methyl,
methoxy, chloro, fluoro, and trifluoromethyl groups) were
tolerated well under the standard conditions. Substrate 1c with
a 4-methoxy group, for instance, was treated with indole 2a,
Pd(OAc)2, CuI, PPh3, and Cs2CO3 to afford desired product 3l
in 86% yield (entry 11). Interestingly, substrate 1f bearing an
electron-withdrawing trifluoromethyl group also underwent the
tandem reactions smoothly with indole 2a to give product 3o in
73% yield (entry 14).
The tandem N−H/C−H bond functionalization reaction
was successfully extended to pyrroles and various pyrrolo[2,1-
a]isoquinolines were prepared. As listed in Table 3, the reaction
of substrate 1a with 1H-pyrrole 4a under the standard
conditions generated the desired pyrrolo[2,1-a]isoquinoline
5a in 70% yield (entry 1). 2,4-Dimethyl-1H-pyrrole 4b could
also react with substrate 1a successfully to afford product 5b in
61% yield (entry 2). Subsequently, the reactions of a variety of
ortho-(2-chlorovinyl)bromobenzenes 1b−1f with 1H-pyrrole
4a were investigated (entries 3−7). Several functional groups
(such as Me, MeO, Cl, F, and CF3 groups) on the aromatic ring
of bromobenzenes were suitable for the tandem reactions
(entries 3−7). Methyl-substituted substrate 1b, for instance,
underwent the reaction with pyrrole 4a smoothly to provide
product 5c in 62% yield (entry 3). Other substituents such as
methoxyl, Cl, and F groups furnished the desired products in
good yields (entries 4−6). Notably, substrate 1f, bearing an
electron-withdrawing CF3 group, could also be converted to
pyrrolo[2,1-a]isoquinoline 5g in 50% yield (entry 7).
To elucidate the mechanism, some control experiments were
carried out (Scheme 2). Treatment of (2-chloro-3,3,3-
trifluoroprop-1-en-1-yl)benzene 1g with 1H-indole 2a under
the standard conditions afforded the N-alkenylated product 6
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Table 2. Pd(OAc)2/CuI Catalyzed Tandem Reaction of
ortho-(2-Chlorovinyl)bromobenzenes with Indoles
Table 3. Pd(OAc)2/CuI Catalyzed Tandem Reaction of
a
a
ortho-(2-Chlorovinyl)bromobenzenes with Pyrroles
a
Reaction conditions: 1 (0.2 mmol), 4 (0.22 mmol), Pd(OAc)2 (10
mol %), CuI (20 mol %), PPh3 (20 mol %) and Cs2CO3 (3 equiv) in
DMSO (2 mL) at 140 °C under N2 atmosphere for 5 h.
Scheme 2. Control Experiments
On the basis of the present results and the reported
mechanism,8,9,13 a possible mechanism was proposed as
outlined in Scheme 3. After copper-catalyzed amination of
substrate 1a, the obtained compound 7 undergoes an oxidative
addition process with Pd(0) to afford intermediate A. The
intramolecular coordination of Pd(II) with indole moiety might
provide palladium complex B, and the following elimination of
HBr in the presence of Cs2CO3 provides intermediate C.
Finally, reductive elimination of C affords product 3a and
regenerated Pd(0) species.
a
Reaction conditions: 1 (0.2 mmol), 2 (0.22 mmol), Pd(OAc)2 (10
mol %), CuI (20 mol %), PPh3 (20 mol %) and Cs2CO3 (3 equiv) in
DMSO (2 mL) at 140 °C under N2 atmosphere for 5 h.
in 51% yield (Scheme 2, eq 1). The result indicated that the
N−H bond was activated preferentially under the standard
conditions. Subsequently, a control reaction of substrate 1a and
1H-indole 2a was carried out in the absence of Pd(OAc)2 (eq
2). However, only the N-alkenylated product 7 could be
isolated in 41% yield and cyclization product 3a could not be
observed. This result suggested that the copper-catalyzed
amination of vinyl chlorides with indole could proceed
successfully. As expected, compound 7 could be converted
into the desired product 3a in 90% yield under the standard
conditions (eq 3).
CONCLUSION
■
In summary, we have developed an efficient route for the
synthesis of trifluoromethyl substituted indolo- and pyrrolo-
[2,1-a]isoquinolines. In the presence of Pd(OAc)2, CuI, PPh3,
and Cs2CO3, a variety of 1-bromo-2-(2-chloro-3,3,3-trifluor-
oprop-1-enyl)benzenes undergo tandem N−H/C−H bond
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122.3, 121.9, 121.7 (q, JC−F = 270.1 Hz), 118.4, 113.7 (q, JC−F = 8.0
Hz), 111.9 (q, JC−F = 7.3 Hz), 107.5, 11.8; 19F NMR (470 MHz,
CDCl3) δ: −62.8 (s, 3F); IR (neat, cm−1): 3089, 2903, 1714, 1652,
1599, 1481, 1418, 1314, 1198, 1124, 735; LRMS (EI, 70 eV) m/z (%):
299 (M+, 100), 278 (7), 228 (12), 150 (8), 130 (23); HRMS (ESI)
calcd for C18H13F3N+ ([M + H]+) 300.0995; found, 300.0991.
8-Ethyl-6-(trifluoromethyl)indolo[2,1-a]isoquinoline (3d). Yellow
oil (41.9 mg, 67% yield); 1H NMR (500 MHz, CDCl3) δ 8.06 (d, J =
7.5 Hz, 1H), 7.61 (d, J = 8.0 Hz, 2H), 7.55−7.52 (m, 1H), 7.46−7.43
(m, 1H), 7.34−7.31 (m, 1H), 7.29 (s, 1H), 7.22−7.20 (m, 2H), 3.08
(q, J = 7.5 Hz, 2H), 1.21 (t, J = 7.5 Hz, 3H); 13C NMR (125 MHz,
CDCl3) δ 137.7, 134.4, 132.3, 130.8, 129.5, 129.3 (q, JC−F = 34.8 Hz),
128.0, 127.7, 127.6, 126.5, 123.3, 123.3, 122.4 (q, JC−F = 273.3 Hz),
122.1, 117.7, 115.5 (q, JC−F = 4.9 Hz), 97.5, 25.2, 14.9; 19F NMR (470
MHz, CDCl3) δ: −56.3 (s, 3F); IR (neat, cm−1): 2926, 1714, 1625,
1458, 1418, 1313, 1124, 741; LRMS (EI, 70 eV) m/z (%): 313 (M+,
100), 298 (21), 244 (70), 229 (21), 114 (13); HRMS (ESI) calcd for
C19H15F3N+ ([M + H]+) 314.1151; found, 314.1146.
Scheme 3. Possible Mechanism
functionalization reactions with various indoles and pyrroles to
afford the corresponding isoquinolines in moderate to good
yields. The present process could facilitate the synthetic
applications of trifluoromethyl-containing building blocks, and
also provides a new optional route for the construction of the
isoquinoline ring.
10-Methoxy-6-(trifluoromethyl)indolo[2,1-a]isoquinoline (3e).
1
Yellow solid (46.1 mg, 73% yield), mp 117.0−118.2 °C; H NMR
(500 MHz, CDCl3) δ 8.15 (d, J = 8.0 Hz, 1H), 7.99−7.96 (m, 1H),
7.63−7.56 (m, 2H), 7.48−7.45 (m, 1H), 7.34 (s, 1H), 7.25 (s, 1H),
7.22 (s, 1H), 7.02−6.99 (m, 1H), 3.92 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 155.7, 136.6, 130.6, 129.6, 127.9, 127.7, 127.0, 126.2, 125.7,
124.9 (q, JC−F = 34.3 Hz), 123.3, 121.6 (q, JC−F = 270.0 Hz), 114.9 (q,
JC−F = 7.8 Hz), 112.5, 111.5 (q, JC−F = 7.0 Hz), 101.2, 96.2, 55.6; 19F
NMR (470 MHz, CDCl3) δ: −63.6 (s, 3F); IR (neat, cm−1): 2931,
1615, 1462, 1420, 1328, 1129, 741; LRMS (EI, 70 eV) m/z (%): 315
(M+, 100), 286 (9), 272 (79), 203 (7), 157 (8); HRMS (ESI) calcd for
C18H13F3NO+ ([M + H]+) 316.0944; found, 316.0944.
EXPERIMENTAL SECTION
■
Typical Experimental Procedure for the Palladium and
Copper Cocatalyzed Tandem Reaction. A mixture of 1-bromo-2-
(2-chloro-3,3,3-trifluoroprop-1-enyl)benzenes 1 (0.2 mmol), indole 2
or pyrrole 4 (0.22 mmol), Pd(OAc)2 (4.5 mg, 10 mol %), CuI (7.6
mg, 20 mol %), PPh3 (10.5 mg, 20 mol %), Cs2CO3 (195.5 mg, 3
equiv), in DMSO (2 mL), was evacuated and backfilled with nitrogen
(3 cycles) and then stirred at 140 °C for 5 h or until complete
consumption of starting material was indicated by TLC or GC−MS
analysis. After the reaction was completed, the mixture was filtered
through glass filter and washed with ethyl acetate. The mixture was
washed with brine and extracted with ethyl acetate. The organic layers
were dried with anhydrous Na2SO4 and evaporated under vacuum, and
the residue was purified by flash column chromatography (hexane/
ethyl acetate) to give products 3, and 5−7.
6-(Trifluoromethyl)indolo[2,1-a]isoquinolin-10-amine (3f). Yel-
1
low solid (30.5 mg, 51% yield), mp 153.3−154.1 °C; H NMR (300
MHz, CDCl3) δ 8.12 (d, J = 8.5 Hz, 1H), 7.90−7.86 (m, 1H), 7.61−
7.52 (m, 2H), 7.47−7.41 (m, 1H), 7.22−7.20 (m, 2H), 7.04 (s, 1H),
6.81−6.77 (m, 1H), 3.73 (s, 2H); 13C NMR (125 MHz, CDCl3) δ
141.8, 136.5, 130.9, 129.4, 127.8, 127.6, 127.0, 125.8, 125.8, 124.9 (q,
JC−F = 34.3 Hz), 123.2, 121.6 (q, JC−F = 270.0 Hz), 114.7 (q, JC−F = 7.6
Hz), 112.9, 111.0 (q, JC−F = 7.0 Hz), 103.9, 95.4; 19F NMR (470 MHz,
CDCl3) δ: −63.7 (s, 3F); IR (neat, cm−1): 3421, 3246, 2357, 1621,
1599, 1459, 1419, 1115, 834; LRMS (EI, 70 eV) m/z (%): 300 (M+,
100), 280 (10), 231 (8), 150 (18), 115 (6); HRMS (ESI) calcd for
6-(Trifluoromethyl)indolo[2,1-a]isoquinoline (3a). Yellow solid
(41.1 mg, 72% yield), mp 90.0−91.0 °C; 1H NMR (500 MHz,
CDCl3) δ 8.17 (d, J = 8.0 Hz, 1H), 8.11−8.09 (m, 1H), 7.85−7.83 (m,
1H), 7.64−7.55 (m, 2H), 7.49−7.46 (m, 1H), 7.42 (s, 1H), 7.40−7.35
(m, 2H), 7.27 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 136.0, 131.1,
129.7, 129.5, 127.9, 127.9, 127.3, 125.7, 125.2 (q, JC−F = 34.5 Hz),
+
C17H12F3N2 ([M + H]+) 301.0947; found, 301.0947.
10-Bromo-6-(trifluoromethyl)indolo[2,1-a]isoquinoline (3g). Yel-
1
low solid (42.4 mg, 58% yield), mp 148.5−150.2 °C; H NMR (500
MHz, CDCl3) δ 8.12 (d, J = 8.0 Hz, 1H), 7.93−7.91 (m, 2H), 7.63−
7.58 (m, 2H), 7.51−7.48 (m, 1H), 7.42−7.40 (m, 1H), 7.29−7.28 (m,
2H); 13C NMR (125 MHz, CDCl3) δ 137.0, 131.1, 129.9, 129.7,
128.3, 128.0, 126.9, 125.8, 124.8, 124.8 (q, JC−F = 34.6 Hz), 123.5,
122.9, 121.5 (q, JC−F = 270.1 Hz), 116.1, 115.3 (q, JC−F = 7.8 Hz),
112.7 (q, JC−F = 6.9 Hz), 95.8; 19F NMR (470 MHz, CDCl3) δ: −63.3
(s, 3F); IR (neat, cm−1): 3082, 1649, 1593, 1455, 1405, 1224, 749;
LRMS (EI, 70 eV) m/z (%): 365 (M+, 96), 363 (M+, 100), 284 (46),
264 (27), 142 (17), 93 (11); HRMS (ESI) calcd for C17H10BrF3N+
([M + H]+) 363.9943; found, 363.9941.
123.3, 122.5, 122.1, 121.6 (q, JC−F = 270.0 Hz), 120.7, 113.9 (q, JC−F
=
7.6 Hz), 112.1 (q, JC−F = 7.1 Hz), 96.5; 19F NMR (470 MHz, CDCl3)
δ: −63.2 (s, 3F); IR (neat, cm−1): 3026, 1601, 1556, 1454, 1416, 1121,
737; LRMS (EI, 70 eV) m/z (%): 285 (M+, 100), 265 (14), 216 (11),
142 (14); HRMS (ESI) calcd for C17H11F3N+ ([M + H]+) 286.0838;
found, 286.0836.
10-Methyl-6-(trifluoromethyl)indolo[2,1-a]isoquinoline (3b). Yel-
1
low solid (36.3 mg, 61% yield), mp 131.4−132.1 °C; H NMR (500
MHz, CDCl3) δ 8.14 (d, J = 8.0 Hz, 1H), 7.97−7.95 (m, 1H), 7.61−
7.55 (m, 3H), 7.47−7.43 (m, 1H), 7.32 (s, 1H), 7.23 (s, 1H), 7.20−
7.17 (m, 1H), 2.52 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 136.0,
10-Fluoro-6-(trifluoromethyl)indolo[2,1-a]isoquinoline (3h). Yel-
1
low solid (36.5 mg, 60% yield), mp 132.1−132.8 °C; H NMR (500
MHz, CDCl3) δ 8.14 (d, J = 8.0 Hz, 1H), 8.02−8.00 (m, 1H), 7.63−
7.57 (m, 2H), 7.50−7.47 (m, 1H), 7.43−7.40 (m, 1H), 7.34 (s, 1H),
7.27 (s, 1H), 7.11−7.07 (m, 1H); 13C NMR (125 MHz, CDCl3) δ
159.0 (d, JC−F = 238.3 Hz), 137.4, 130.4 (d, JC−F = 10.4 Hz), 129.8,
128.2, 128.0, 127.7, 126.8, 125.7, 124.9 (q, JC−F = 34.4 Hz), 123.4,
132.0, 129.8, 129.6, 129.4, 127.9, 127.7, 127.3, 125.7, 125.1 (q, JC−F
=
34.4 Hz), 123.9, 123.3, 121.6 (q, JC−F = 270.0 Hz), 120.1, 113.6 (q,
JC−F = 7.5 Hz), 111.7 (q, JC−F = 7.0 Hz), 96.0, 21.3; 19F NMR (470
MHz, CDCl3) δ: −63.4 (s, 3F); IR (neat, cm−1): 2914, 1627, 1540,
1463, 1417, 1116, 752; LRMS (EI, 70 eV) m/z (%): 299 (M+, 100),
278 (6), 228 (8), 149 (12), 129 (6); HRMS (ESI) calcd for
C18H13F3N+ ([M + H]+) 300.0995; found, 300.0989.
12-Methyl-6-(trifluoromethyl)indolo[2,1-a]isoquinoline (3c). Yel-
low solid (46.0 mg, 77% yield), mp 111.0−112.2 °C; H NMR (500
MHz, CDCl3) δ 8.34 (d, J = 8.5 Hz, 1H), 8.08−8.07 (m, 1H), 7.84−
7.82 (m, 1H), 7.58−7.55 (m, 2H), 7.43−7.37 (m, 3H), 7.16 (s, 1H),
2.81 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 130.9, 130.3, 129.6,
129.3, 128.9, 127.8, 126.8, 126.7, 125.2 (q, JC−F = 34.1 Hz), 124.4,
121.5 (q, JC−F = 270.0 Hz), 115.2 (q, JC−F = 8.1 Hz), 112.2 (q, JC−F
=
7.1 Hz), 110.6 (d, JC−F = 25.8 Hz), 104.9 (d, JC−F = 23.0 Hz), 96.4 (d,
JC−F = 4.5 Hz); 19F NMR (470 MHz, CDCl3) δ: −63.4 (s, 3F), −120.7
(s, 1F); IR (neat, cm−1): 3037, 1607, 1562, 1463, 1416, 1314, 1129,
753; LRMS (EI, 70 eV) m/z (%): 303 (M+, 100), 283 (16), 234 (15),
151 (13), 117 (5); HRMS (ESI) calcd for C17H10F4N+ ([M + H]+)
304.0744; found, 304.0738.
1
6-(Trifluoromethyl)indolo[2,1-a]isoquinoline-10-carbonitrile (3i).
1
Yellow solid (32.8 mg, 53% yield), mp 207.1−208.8 °C; H NMR
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Article
(500 MHz, CDCl3) δ 8.18 (d, J = 8.0 Hz, 1H), 8.16 (s, 1H), 8.12 (d, J
= 9.0 Hz, 1H), 7.69−7.65 (m, 2H), 7.58−7.54 (m, 2H), 7.44 (s, 1H),
7.38 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 137.9, 132.2, 130.4,
129.3, 129.1, 128.3, 126.6, 126.0, 125.7, 124.6 (q, JC−F = 34.8 Hz),
124.1, 123.7, 121.3 (q, JC−F = 269.9 Hz), 119.8, 114.8 (q, JC−F = 8.0
Hz), 114.0 (q, JC−F = 6.9 Hz), 105.8, 96.7; 19F NMR (470 MHz,
CDCl3) δ: −63.0 (s, 3F); IR (neat, cm−1): 2223, 1644, 1540, 1463,
1413, 1317, 1119, 745; LRMS (EI, 70 eV) m/z (%): 310 (M+, 100),
290 (6), 241 (8), 207 (8), 155 (7); HRMS (ESI) calcd for
3,6-Bis(trifluoromethyl)indolo[2,1-a]isoquinoline (3o). Yellow
solid (51.5 mg, 73% yield), mp 100.4−102.0 °C; 1H NMR (500
MHz, CDCl3) δ 8.20 (d, J = 8.5 Hz, 1H), 8.09−8.08 (m, 1H), 7.86−
7.83 (m, 2H), 7.75 (d, J = 8.5 Hz, 1H), 7.47 (s, 1H), 7.42−7.40 (m,
2H), 7.25 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 134.6, 131.3,
129.7, 129.6 (q, JC−F = 32.6 Hz), 129.3, 126.5 (q, JC−F = 34.8 Hz),
125.9 (q, JC−F = 3.4 Hz), 125.6, 125.0 (q, JC−F = 4.0 Hz), 123.8, 123.8
(q, JC−F = 270.5 Hz), 123.1, 122.9, 121.3 (q, JC−F = 270.4 Hz), 121.1,
114.0 (q, JC−F = 7.6 Hz), 111.2 (q, JC−F = 7.1 Hz), 98.5; 19F NMR
(470 MHz, CDCl3) δ: −62.5 (s, 3F), −63.5 (s, 3F); IR (neat, cm−1):
3028, 1615, 1556, 1458, 1402, 1313, 1118, 737; LRMS (EI, 70 eV) m/
z (%): 353 (M+, 100), 333 (10), 284 (11), 277 (13), 151(6); HRMS
(ESI) calcd for C18H10F6N+ ([M + H]+) 354.0712; found, 354.0703.
5-(Trifluoromethyl)pyrrolo[2,1-a]isoquinoline (5a). Yellow oil
+
C18H10F3N2 ([M + H]+) 311.0791; found, 311.0792.
10-Nitro-6-(trifluoromethyl)indolo[2,1-a]isoquinoline (3j). Yellow
solid (37.5 mg, 57% yield), mp 184.6−186.0 °C; 1H NMR (500 MHz,
CDCl3) δ 8.75 (s, 1H), 8.23−8.13 (m, 3H), 7.71−7.67 (m, 2H),
7.61−7.57 (m, 2H), 7.42 (s, 1H); 13C NMR (125 MHz, CDCl3) δ
1
(32.9 mg, 70% yield); H NMR (300 MHz, CDCl3) δ 8.04 (d, J =
143.2, 138.8, 133.2, 130.5, 129.1, 128.3, 126.8, 126.6, 124.6 (q, JC−F
=
8.1 Hz, 1H), 7.63−7.50 (m, 3H), 7.40−7.35 (m, 1H), 7.24 (s, 1H),
7.07−7.05 (m, 1H), 6.83−6.81 (m, 1H); 13C NMR (125 MHz,
CDCl3) δ 130.7, 129.7, 128.2, 127.4, 126.0, 124.2, 123.9, 122.0, 121.3
34.8 Hz), 123.8, 121.3 (q, JC−F = 270.3 Hz), 117.1, 116.6, 114.4 (q,
JC−F = 6.9 Hz), 114.2 (q, JC−F = 8.1 Hz), 107.2, 96.7; 19F NMR (470
MHz, CDCl3) δ: −63.0 (s, 3F); IR (neat, cm−1): 1613, 1556, 1517,
1462, 1341, 1114, 737; LRMS (EI, 70 eV) m/z (%): 330 (M+, 100),
300 (42), 284 (77), 264 (31), 150 (9); HRMS (ESI) calcd for
(q, JC−F = 270.1 Hz), 114.6 (q, JC−F = 2.9 Hz), 112.9, 112.3 (q, JC−F
=
5.1 Hz), 101.1; 19F NMR (470 MHz, CDCl3) δ: −68.8 (s, 3F); IR
(neat, cm−1): 3058, 1646, 1500, 1447, 1423, 1116, 749; LRMS (EI, 70
eV) m/z (%): 235 (M+, 100), 216 (5), 166 (16), 139 (8), 117 (8);
HRMS (ESI) calcd for C13H9F3N+ ([M + H]+) 236.0682; found,
236.0688.
+
C17H10F3N2O2 ([M + H]+) 331.0689; found, 331.0694.
2-Methyl-6-(trifluoromethyl)indolo[2,1-a]isoquinoline (3k). Yel-
1
low solid (32.9 mg, 55% yield), mp 113.4−114.2 °C; H NMR (500
MHz, CDCl3) δ 8.09 (d, J = 7.5 Hz, 1H), 7.95 (s, 1H), 7.84−7.82 (m,
1H), 7.49 (d, J = 8.0 Hz, 1H), 7.39−7.34 (m, 3H), 7.27 (d, J = 8.0 Hz,
1H), 7.23 (s, 1H), 2.52 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
140.1, 136.0, 131.1, 129.5, 129.3, 127.8, 127.2, 124.3 (q, JC−F = 34.5
Hz), 123.4, 123.3, 122.4, 121.9, 121.7 (q, JC−F = 272.4 Hz), 120.6,
113.9 (q, JC−F = 7.6 Hz), 112.1 (q, JC−F = 7.1 Hz), 96.2, 21.9; 19F
NMR (470 MHz, CDCl3) δ: −62.9 (s, 3F); IR (neat, cm−1): 3044,
2920, 1615, 1534, 1454, 1415, 1330, 1136, 735; LRMS (EI, 70 eV) m/
z (%): 299 (M+, 100), 279 (10), 230 (14), 149 (12), 114 (7); HRMS
(ESI) calcd for C18H13F3N+ ([M + H]+) 300.0995; found, 300.0993.
3-Methoxy-6-(trifluoromethyl)indolo[2,1-a]isoquinoline (3l). Yel-
1,3-Dimethyl-5-(trifluoromethyl)pyrrolo[2,1-a]isoquinoline (5b).
1
Yellow solid (32.1 mg, 61% yield), mp 122.1−123.5 °C; H NMR
(300 MHz, CDCl3) δ 8.27 (d, J = 8.4 Hz, 1H), 7.64 (d, J = 6.9 Hz,
1H), 7.52−7.46 (m, 1H), 7.32−7.28 (m, 2H), 6.41 (s, 1H), 2.91 (s,
3H), 2.39 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 136.7, 129.6,
128.9, 126.4, 123.5 (q, JC−F = 269.8 Hz), 123.3, 122.7 (q, JC−F = 3.6
Hz), 120.6, 120.2 (q, JC−F = 32.5 Hz), 119.4, 117.9 (q, JC−F = 7.4 Hz),
115.8, 112.2, 18.6, 13.0; 19F NMR (470 MHz, CDCl3) δ: −60.3 (s,
3F); IR (neat, cm−1): 3024, 2936, 1643, 1517, 1457, 1327, 1116, 740;
LRMS (EI, 70 eV) m/z (%): 263 (M+, 100), 248 (25), 178 (7), 122
(10); HRMS (ESI) calcd for C15H13F3N+ ([M + H]+) 264.0995;
found, 264.0998.
1
low solid (54.1 mg, 86% yield), mp 107.1−108.5 °C; H NMR (500
MHz, CDCl3) δ 8.07 (d, J = 9.0 Hz, 2H), 7.80 (d, J = 7.5 Hz, 1H),
7.38−7.31 (m, 2H), 7.26 (s, 1H), 7.21 (s, 1H), 7.19−7.17 (m, 1H),
7.04 (s, 1H), 3.89 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 159.4,
136.2, 130.8, 129.8, 127.2, 125.6 (q, JC−F = 34.4 Hz), 125.0, 122.5,
9-Methyl-5-(trifluoromethyl)pyrrolo[2,1-a]isoquinoline (5c). Yel-
low oil (30.8 mg, 62% yield); 1H NMR (500 MHz, CDCl3) δ 7.82 (s,
1H), 7.50−7.48 (m, 2H), 7.20−7.18 (m, 2H), 7.02 (d, J = 3.0 Hz,
1H), 6.79 (t, J = 3.0 Hz, 1H), 2.50 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 140.0, 130.7, 128.1, 127.5, 127.4, 123.2 (q, JC−F = 34.6 Hz),
122.0, 121.9, 121.5 (q, JC−F = 270.0 Hz), 114.5 (q, JC−F = 2.9 Hz),
112.7, 112.4 (q, JC−F = 5.1 Hz), 100.8, 21.9; 19F NMR (470 MHz,
CDCl3) δ: −68.7 (s, 3F); IR (neat, cm−1): 2974, 1620, 1504, 1408,
1326, 1121, 744; LRMS (EI, 70 eV) m/z (%): 249 (M+, 100), 180
(15), 152 (9), 124 (8); HRMS (ESI) calcd for C14H11F3N+ ([M +
H]+) 250.0838; found, 250.0844.
8-Methoxy-5-(trifluoromethyl)pyrrolo[2,1-a]isoquinoline (5d).
Yellow solid (38.6 mg, 73% yield), mp 53.5−54.8 °C; 1H NMR
(500 MHz, CDCl3) δ 7.96 (d, J = 8.5 Hz, 1H), 7.45 (s, 1H), 7.20−
7.17 (m, 2H), 7.06 (s, 1H), 6.93−6.92 (m, 1H), 6.80−6.79 (m, 1H),
3.89 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 157.9, 131.0, 125.6,
124.5 (q, JC−F = 34.6 Hz), 123.7, 121.5, 121.4 (q, JC−F = 270.4 Hz),
119.1, 113.7 (q, JC−F = 2.9 Hz), 112.9, 111.9 (q, JC−F = 5.1 Hz),109.6,
99.4, 55.5; 19F NMR (470 MHz, CDCl3) δ: −68.9 (s, 3F); IR (neat,
cm−1): 2931, 1615, 1559, 1473, 1309, 1175, 733; LRMS (EI, 70 eV)
m/z (%): 265 (M+, 100), 250 (76), 222 (47), 153 (10), 132 (8);
HRMS (ESI) calcd for C14H11F3NO+ ([M + H]+) 266.0787; found,
266.0795.
121.6 (q, JC−F = 270.3 Hz), 121.5, 120.9, 120.4, 118.6, 113.8 (q, JC−F
=
7.6 Hz), 111.8 (q, JC−F = 7.1 Hz), 109.7, 94.8, 55.5; 19F NMR (470
MHz, CDCl3) δ: −63.2 (s, 3F); IR (neat, cm−1): 2830, 1644, 1607,
1456, 1407, 1253, 1122, 736; LRMS (EI, 70 eV) m/z (%): 315 (M+,
100), 300 (25), 272 (56), 203 (13), 158 (11); HRMS (ESI) calcd for
C18H13F3NO+ ([M + H]+) 316.0944; found, 316.0946.
3-Chloro-6-(trifluoromethyl)indolo[2,1-a]isoquinoline (3m). Yel-
1
low solid (36.0 mg, 56% yield), mp 130.0−131.5 °C; H NMR (500
MHz, CDCl3) δ 8.08−8.05 (m, 2H), 7.83−7.81 (m, 1H), 7.58 (s, 1H),
7.52−7.50 (m, 1H), 7.39−7.37 (m, 3H), 7.15 (s, 1H); 13C NMR (125
MHz, CDCl3) δ 135.1, 133.5, 131.1, 130.0, 129.5, 127.1, 126.3 (q, JC−F
= 34.6 Hz), 123.6 (q, JC−F = 270.4 Hz), 122.8, 120.8, 113.9 (q, JC−F
=
7.6 Hz), 110.8 (q, JC−F = 7.1 Hz), 97.0; 19F NMR (470 MHz, CDCl3)
δ: −63.4 (s, 3F); IR (neat, cm−1): 3076, 1568, 1483, 1450, 1403, 1295,
1118, 730; LRMS (EI, 70 eV) m/z (%): 321 (M+, 34), 319 (M+, 100),
299 (12), 263 (5), 214 (12), 159 (14) ; HRMS (ESI) calcd for
C17H10ClF3N+ ([M + H]+) 320.0449; found, 320.0448.
2-Fluoro-6-(trifluoromethyl)indolo[2,1-a]isoquinoline (3n). Yel-
1
low solid (33.3 mg, 55% yield), mp 123.8−125.1 °C; H NMR (500
MHz, CDCl3) δ 8.09−8.08 (m, 1H), 7.85−7.83 (m, 1H), 7.80−7.78
(m, 1H), 7.62−7.59 (m, 1H), 7.41−7.37 (m, 3H), 7.24 (s, 1H), 7.20−
7.16 (m, 1H); 13C NMR (125 MHz, CDCl3) δ 163.3 (d, JC−F = 248.5
Hz), 135.0, 131.2, 130.2 (d, JC−F = 9.1 Hz), 129.3, 129.2 (d, JC−F = 9.5
8-Chloro-5-(trifluoromethyl)pyrrolo[2,1-a]isoquinoline (5e). Yel-
low solid (33.0 mg, 61% yield), mp 61.3−62.7 °C; H NMR (500
1
MHz, CDCl3) δ 7.93 (d, J = 8.5 Hz, 1H), 7.58 (s, 1H), 7.50−7.47 (m,
2H), 7.13 (s, 1H), 7.03−7.02 (m, 1H), 6.82 (t, J = 3.5 Hz, 1H); 13C
NMR (125 MHz, CDCl3) δ 131.5, 131.1, 130.0, 127.4, 125.7, 125.4,
125.1 (q, JC−F = 34.9 Hz), 123.5, 121.1 (q, JC−F = 270.5 Hz), 114.9 (q,
JC−F = 2.9 Hz), 113.3, 111.1 (q, JC−F = 5.3 Hz), 101.5; 19F NMR (470
MHz, CDCl3) δ: −69.0 (s, 3F); IR (neat, cm−1): 3024, 1656, 1550,
1453, 1407, 1124, 741; LRMS (EI, 70 eV) m/z (%): 271 (M+, 34),
269 (M+, 100), 234 (11), 200 (9), 117 (6); HRMS (ESI) calcd for
C13H8ClF3N+ ([M + H]+) 270.0292; found, 270.0300.
Hz), 124.6 (q, JC−F = 34.8 Hz), 122.7, 122.6, 122.2, 121.6 (q, JC−F
=
270.3 Hz), 120.9, 116.2 (d, JC−F = 23.3 Hz), 114.0 (q, JC−F = 7.6 Hz),
111.4 (q, JC−F = 6.6 Hz), 109.2 (d, JC−F = 23.4 Hz), 97.4; 19F NMR
(470 MHz, CDCl3) δ: −63.1 (s, 3F), −108.7 (s, 1F); IR (neat, cm−1):
3020, 1607, 1565, 1495, 1416, 1325, 1118, 734; LRMS (EI, 70 eV) m/
z (%): 303 (M+, 100), 283 (12), 234 (20), 152 (14), 127 (7); HRMS
(ESI) calcd for C17H10F4N+ ([M + H]+) 304.0744; found, 304.0740.
2854
dx.doi.org/10.1021/jo3000404 | J. Org. Chem. 2012, 77, 2850−2856

The Journal of Organic Chemistry
Article
9-Fluoro-5-(trifluoromethyl)pyrrolo[2,1-a]isoquinoline (5f). Yel-
low solid (34.8 mg, 68% yield), mp 56.3−57.0 °C; H NMR (500
Science Foundation of China (No. Y4100307) for financial
support.
1
MHz, CDCl3) δ 7.67−7.60 (m, 2H), 7.51 (s, 1H), 7.22 (s, 1H), 7.12−
7.08 (m, 1H), 7.04−7.03 (m, 1H), 6.83−6.82 (m, 1H); 13C NMR
(125 MHz, CDCl3) δ 163.4 (d, JC−F = 248.0 Hz), 130.6 (d, JC−F = 9.4
Hz), 130.0 (d, JC−F = 4.1 Hz), 129.1 (d, JC−F = 10.0 Hz), 123.5 (q, JC−F
= 34.9 Hz), 121.3 (q, JC−F = 270.1 Hz), 120.7, 115.2 (q, JC−F = 2.9
Hz), 114.6 (d, JC−F = 23.6 Hz), 113.1, 111.7 (q, JC−F = 4.8 Hz), 107.6
(d, JC−F = 23.3 Hz), 102.1; 19F NMR (470 MHz, CDCl3) δ: −68.8 (s,
3F), −109.0 (s, 1F); IR (neat, cm−1): 3032, 1623, 1505, 1411, 1328,
1112, 740; LRMS (EI, 70 eV) m/z (%): 253 (M+, 100), 184 (24), 157
(8), 127 (15); HRMS (ESI) calcd for C13H8F4N+ ([M + H]+)
254.0588; found, 254.0582.
REFERENCES
■
(1) (a) Anderson, W. K.; Heider, A. R.; Raju, N.; Yucht, J. A. J. Med.
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(3) (a) Ewing, J.; Hughes, G. K.; Ritchie, E.; Taylor, W. C. Nature
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2007, 63, 2263. (c) de Koning, C. B.; Michael, J. P.; Pathak, R.; van
Otterlo, W. A. L. Tetrahedron Lett. 2004, 45, 1117. (d) Mamane, V.;
5,8-Bis(trifluoromethyl)pyrrolo[2,1-a]isoquinoline (5g). Yellow
1
solid (30.3 mg, 50% yield), mp 67.2−68.0 °C; H NMR (500 MHz,
CDCl3) δ 8.10 (d, J = 8.5 Hz, 1H), 7.89 (s, 1H), 7.75−7.73 (m, 1H),
7.56 (s, 1H), 7.26−7.25 (m, 1H), 7.16−7.15 (m, 1H), 6.88−6.87 (m,
1H); 13C NMR (125 MHz, CDCl3) δ 129.8, 129.6, 127.8 (q, JC−F
=
32.6 Hz), 125.8 (q, JC−F = 3.5 Hz), 125.5 (q, JC−F = 4.2 Hz), 125.1 (q,
JC−F = 34.9 Hz), 123.8, 122.6, 121.8 (q, JC−F = 270.3 Hz), 121.0 (q,
JC−F = 270.5 Hz), 115.8 (q, JC−F = 2.8 Hz), 113.7, 111.7 (q, JC−F = 5.0
Hz), 103.1; 19F NMR (470 MHz, CDCl3) δ: −62.3 (s, 3F), −69.1 (s,
3F); IR (neat, cm−1): 2974, 1624, 1473, 1410, 1349, 1074, 743; LRMS
(EI, 70 eV) m/z (%): 303 (M+, 100), 284 (10), 234 (16), 151 (7);
HRMS (ESI) calcd for C14H8F6N+ ([M + H]+) 304.0556; found,
304.0553.
̈
Hannen, P.; Furstner, A. Chem.Eur. J. 2004, 10, 4556.
̈
(e) Waldmann, H.; Eberhardt, L.; Wittsteinab, K.; Kumar, K. Chem.
Commun. 2010, 46, 4622. (f) Menes-Arzate, M.; Martınez, R.; Cruz-
Almanza, R.; Muchowski, J. M.; Osornio, Y. M.; Miranda, L. D. J. Org.
(Z)-1-(3,3,3-Trifluoro-1-phenylprop-1-en-2-yl)-1H-indole (6). Col-
1
orless oil (29.3 mg, 51% yield); H NMR (500 MHz, CDCl3) δ 7.64
Chem. 2004, 69, 4001. (g) Reboredo, F. J.; Treus, M.; Estev
Castedo, L.; Estevez, R. J. Synlett 2003, 1603. (h) Ackermann, L.;
Wang, L.; Lygin, A. V. Chem. Sci. 2012, 3, 177.
́
ez, J. C.;
(d, J = 8.0 Hz, 1H), 7.43−7.40 (m, 1H), 7.34−7.31 (m, 2H), 7.26−
7.25 (m, 1H), 7.18−7.16 (m, 2H), 7.13−7.10 (m, 1H), 7.05−7.02 (m,
1H), 6.79 (d, J = 8.5 Hz, 1H), 6.71−6.70 (m, 1H), 6.18−6.13 (m,
1H); 13C NMR (125 MHz, CDCl3) δ 146.6 (q, JC−F = 5.5 Hz), 136.7,
135.3, 131.0, 129.6 (q, JC−F = 1.9 Hz), 129.2, 129.0, 127.2, 122.5, 122.3
(q, JC−F = 268.1 Hz), 121.0, 120.8, 111.8, 111.5 (q, JC−F = 34.9 Hz),
104.4; 19F NMR (470 MHz, CDCl3) δ: −57.8 (s, 3F); IR (neat,
cm−1): 3030, 1651, 1573, 1457, 1398, 1268, 1119, 757; LRMS (EI, 70
eV) m/z (%): 287 (M+, 100), 218 (31), 151 (53), 117 (61), 89(14);
HRMS (ESI) calcd for C17H13F3N+ ([M + H]+) 288.0995; found,
288.0996.
́
(5) (a) Ambros, R.; Schneider, M. R.; von Angerer, S. J. Med. Chem.
1990, 33, 153. (b) Elwan, N. M.; Abdelhadi, H. A.; Abdallah, T. A.;
Hassaneen, H. M. Tetrahedron 1996, 52, 3451. (c) Zhao, B.-X.; Yu, Y.;
Eguchi, S. Tetrahedron 1996, 52, 12049. (d) Katritzky, A. R.; Qiu, G.;
Yang, B.; He, H.-Y. J. Org. Chem. 1999, 64, 7618. (e) Orito, K.;
Uchiito, S.; Satoh, Y.; Tatsuzawa, T.; Harada, R.; Takuda, M. Org. Lett.
2000, 2, 307. (f) Barun, O.; Chakrabarti, S.; Ila, H.; Junjappa, H. J. Org.
Chem. 2001, 66, 4457. (g) Orito, K.; Harada, R.; Uchiito, S.; Tokuda,
(Z)-1-(1-(2-Bromophenyl)-3,3,3-trifluoroprop-1-en-2-yl)-1H-in-
dole (7). Yellow oil (29.9 mg, 41% yield); 1H NMR (500 MHz,
CDCl3) δ 7.73 (s, 1H), 7.58−7.56 (m, 1H), 7.55−7.53 (m, 1H),
7.12−7.11 (m, 1H), 7.10−7.05 (m, 3H), 7.02−6.98 (m, 1H), 6.81−
6.78 (m, 1H), 6.68−6.67 (m, 1H), 6.38−6.36 (m, 1H); 13C NMR
(125 MHz, CDCl3) δ 135.9, 132.9, 132.0 (q, JC−F = 4.1 Hz), 131.4,
131.1, 128.9, 128.7, 127.4, 127.1, 126.4 (q, JC−F = 34.0 Hz), 124.9,
123.0, 121.7 (q, JC−F = 273.8 Hz), 120.9, 120.8, 110.6, 105.4; 19F NMR
(470 MHz, CDCl3) δ: −68.3 (s, 3F); IR (neat, cm−1): 3058, 1653,
1517, 1457, 1435, 1266, 1122, 741; LRMS (EI, 70 eV) m/z (%): 365
(M+, 18), 367 (M+, 18), 286 (100), 217 (29), 151 (53), 133 (9),
108(8); HRMS (ESI) calcd for C17H12BrF3N+ ([M + H]+) 366.0100;
found, 366.0097.
M. Org. Lett. 2000, 2, 1799. (h) Vincze, Z.; Beatrix Bíro,
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A.; Csekei,
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■
S
* Supporting Information
1
Copies of H and 13C NMR of compounds 3a−3o, 5a−5g, 6,
and 7, and X-ray data of 3e. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: zxg@wzu.edu.cn.
■
Notes
The authors declare no competing financial interest.
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Angew. Chem., Int. Ed. 2009, 48, 1138.
ACKNOWLEDGMENTS
We thank the National Natural Science Foundation of China
(No. 21002070 and 21102104) and Zhejiang Provincial Natural
■
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