Synthesis of chromeno[2,3-b ]indol-11(6 H)-one via PhI(OAc)2-mediated intramolecular oxidative C(sp2)-N(H2) bond formation

Article abstract of DOI:10.1021/jo502276b

Various chromeno[2,3-b]indol-11(6H)-ones were conveniently constructed via phenyliodine(III) diacetate (PIDA)-mediated intramolecular oxidative annulation. This method, while realizing a direct oxidative C-N bond formation between an aromatic ring and a p

Full text of DOI:10.1021/jo502276b

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Note
Synthesis of Chromeno[2,3-b]indol-11(6H)-one via PhI(OAc)2-
Mediated Intramolecular Oxidative C(sp2)-N(H2) Bond Formation
Jiyun Sun, Daisy Zhang-Negrerie, Yunfei Du, and Kang Zhao
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 15 Dec 2014
Downloaded from http://pubs.acs.org on December 16, 2014
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Synthesis of Chromeno[2,3ꢀb]indolꢀ11(6H)ꢀone via
PhI(OAc)2ꢀMediated Intramolecular Oxidative
C(sp2)–N(H2) Bond Formation
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Jiyun Sun,† Daisy ZhangꢀNegrerie,† Yunfei Du*,†,‡ and Kang Zhao*,†
†School of Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, China
‡Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin 300072,
China
duyunfeier@tju.edu.cn; kangzhao@tju.edu.cn
Abstract: Various chromeno[2,3ꢀb]indolꢀ11(6H)ꢀones were conveniently constructed
via phenyliodine(III) diacetate (PIDA)ꢀmediated intramolecular oxidative annulation.
This method, while realizing a direct oxidative C–N bond formation between an
aromatic ring and a pendent freeꢀNH2 moiety, features a metalꢀfree protocol, mild
reaction conditions, simple workup, and the readily availability of the starting
substrates.
Constructing intramolecular aromatic C–N bonds is one of the most robust
approaches for the assembly of the Nꢀcontaining heterocycles. In addition to the most
common strategies such as via transition metalꢀcatalyzed oxidative C–halogen or C–B
bond activation,1 an alternative straightforward approach is the intramolecular
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aromatic amination of unfunctionalized C–H bond carried out through transition
metalꢀcatalyzed direct oxidative C–N bond formation. However, most of the reported
examples seem to suggest that a substituted nitrogen atom is indispensable for such
transformations.2
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To our knowledge, there are less than a handful of examples describing the direct
oxidative C–N bond formations between unactived arenes and a pendant free
NH2ꢀmoiety. Cacchi and coꢀworkers realized the synthesis of 4ꢀarylꢀ2ꢀquinolones
from 3,3ꢀdiarylacrylamides bearing a free NH2ꢀmoiety through CuIꢀmediated
oxidative C–N bond formation (Scheme 1a).3a Horaguchi reported an intramolecular
annulation of Nꢀalkylated 2ꢀaminobiphenyls leading to carbazoles in the presence of
CaO and under high temperature (Scheme 1b).3bꢀc Later on, Matsubara also realized
the same oxidative C–N(H2) bond formation but by using Pt/C at high temperature
(Scheme 1b).3d In 2013, Cheng and coꢀworkers reported a CuI/bpyꢀcatalyzed
synthesis of acridone derivatives through C–H functionalization and C–N bond
formation within 2ꢀaminobenzophenone, containing a nonsubstituted N atom (Scheme
1c).3e In our previous work, we also achieved the synthesis of carbazolones from
phenyliodine bis(trifluoroacetate) (PIFA)ꢀmediated direct oxidative annulation of the
free NH2ꢀmoiety on the sideꢀchain to the phenyl ring (Scheme 1d).4
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Scheme 1. Direct oxidative C–N bond formation between arenes and a free
NH2ꢀmoiety
Figure 1. Known synthetic routes to chromeno[2,3ꢀb]indolꢀ11(6H)ꢀones
In this note, we report a new application of the protocol that we developed in our
previous work, which gave rise to an alternative approach to forming a class of
biologically meaningful compounds, namely, chromeno[2,3ꢀb]indolꢀ11(6H)ꢀones.
Even though the chromeno[2,3ꢀb]indolꢀ11(6H)ꢀone skeleton has been identified as
a key intermediate in the synthesis of the chromeno[2,3ꢀb]indole derivatives, which
have shown potent antitumor activities,5 only a few synthetic approaches have been
reported until just about a decade ago. Löwe and coꢀworkers found that these
compounds
could
be
obtained
from
reduction
of
7ꢀ(2ꢀpiperidinꢀ1ꢀylethoxy)ꢀisoflavone derivatives with zinc dust in acetic acid
followed by oxidation with oxygen (Figure. 1, path a).6 Bergman et al reported the
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building of this skeleton through cyclization of 2ꢀphenoxyindoleꢀ3ꢀcarboxylates,
made available from the coupling of indoleꢀ3ꢀcarboxylate and phenols (Figure. 1, path
b).7ꢀ9 Our work reported here adds to the list of methods.
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2ꢀAminoꢀ3ꢀphenylꢀ4Hꢀchromenꢀ4ꢀone, readily prepared via condensation of benzyl
cyanide with methyl salicylate,10 was chosen as the model substrate to probe the
feasibility of the proposed conversion. By applying the conditions developed in our
previous work, substrate 1a was successfully converted to the desired
chromeno[2,3ꢀb]indolꢀ11(6H)ꢀone 2a, albeit in a mere 13% of yield (Table 1, entry 1).
Table 1. Optimization of reaction conditions for the synthesis of chromeno[2,3ꢀb]
indolꢀ11(6H)ꢀonea
At the switching of PIFA to the less potent PIDA, another commonly used
hypervalent iodine(III) oxidant, we were pleased to witness a nearꢀcomplete
conversion of 1a into 2a within 4 h with a 87% yield in 1,2ꢀdichloroethane as solvent
o
(Table 1, entries 2–6). When the reaction was allowed to take place at 60 C, it took
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shorter time to completion, but accompanied by a much lower yield of 68%, due to
the formation of more byproducts (Table 1, entry 7). On the other hand, lowering
reaction temperature to 0 oC rendered the reaction very sluggish and eventually it took
72 h for the reaction to go completion (Table 1, entry 8). Further study showed that
when 1a was diluted from 0.10 mol/L (supersaturated solution) to 0.01 mol/L, the
yield of the product 2a was insignificantly affected (Table 1, entry 9). Attempts to
further improve the yield by adding additives such as BF3·Et2O or Na2CO3 were
shown to be unsuccessful (Table 1, entries 10 and 11).
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To explore the scope and limitation of this newly developed method, various
substituted 2ꢀaminoꢀ3ꢀphenylꢀ4Hꢀchromenꢀ4ꢀones were examined under the
optimized reaction conditions. As shown in Table 2, a wide range of substituents on
either of the two phenyl rings could be well tolerated for the application of the method.
Concerning the substituent effect of R′ (Table 2, entries 2–9), the
electronꢀwithdrawing halogen groups at the paraꢀposition gave the expected product
in good to excellent yields (Table 2, entries 2, 4, and 6). The low yields of 38% and
45% (Table 2, entries 3 and 9) from the orthoꢀsubstituted R′, be it
electronꢀwithdrawing or electronꢀdonating, could be ascribed to the steric repulsion of
the orthoꢀsubstituent and the reduced number of available coupling carbon atoms.
Yields from substrates bearing an electronꢀdonating substituent, R′ = OMe, at either
para or meta position, were reasonably high (Table 2, entries 7 and 8), with the latter
giving two separable regioisomeric products (2h:2h′ in a ratio of 1:3) (Table 2, entry
8). It is worth noting that only one regioisomeric product 2e was isolated by filtration
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from the reaction of the metaꢀsubstituted substrate 1e, with R′ = Cl (Table 2, entry 5),
although crude 1H NMR analysis showed that the other regioisomeric product 2e′ was
also formed. Studies on the substituent effect of R on the reaction show very minor
impact on the yield. To our delight, all substrates with the various substituents on the
A ring are extremely well tolerated and the cyclized products were obtained in
consistently high yields, including that where the A ring was switched to naphthalene
(Table 2, entries 10–15). Yield values from doubly substituted substrates shadow the
observations of the substitution effect of R and R′, such that the extent of influence of
R is small (Table 2, entries 16–18). In these reactions except entries 5 and 8, no
column chromatography was needed during the workup, as the desired product could
be obtained by simple filtrations.
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Table 2. Synthesis of chromeno[2,3ꢀb]indolꢀ11(6H)ꢀones mediated by PIDAa
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Two mechanistic pathways were possible for this transformation. As shown in
Scheme 2, path a, the intermolecular reaction of enamine 1 and PIDA generated the
Nꢀiodo intermediate 3 after losing one molecule of acetic acid. Afterwards, the nitrene
intermediate 4, formed through cleavage of the N–I bond at the release of a molecule
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of PhI and acetic acid, was inserted into the aromatic ring through electrophilic
substitution reaction, and led to the final product 2. Alternatively, the Nꢀiodo
intermediate 3 might undergo a concerted cyclization process to give oxonium ion 6,
with the release of a molecule of PhI and acetic acid. Finally, rearomatizaiton of 6 by
loss of a proton would give the compound 2. In order to testify which pathway is
more preferable, we carried out a control experiment and found that the reaction was
inhibited by the presence of the radical inhibitor, i.e., TEMPO. This result might
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suggest that the reaction proceeds via a nonꢀionic mechanism.
a) Mechanistic pathway involving nitrene intermediate:
O
O
R'
R'
R'
OAc
R
R
I
Ph
- PhI
- AcOH
O
O
N
H
I
Ph
O
NH2
OAc
- AcOH
OAc
1
O
3
O
R'
R
R
H
N
N
H
O
O
N
H
O
5
4
2
b) Mechanistic pathway involving concerted cyclization:
O
O
R'
- PhI
- H
R'
R
R
2
- AcO
N
H
O
N
H
I
Ph
O
H
OAc
6
3
Scheme 2. Proposed Mechanism
Conclusion
In summary, we have developed a novel method for the synthesis of biologically
important chromeno[2,3ꢀb]indolꢀ11(6H)ꢀone derivatives from enamines, mediated by
the hypervalent iodine(III) reagents. Other than the metalꢀfree advantage, the reported
method also bears desirable features such as the readily availability of the substrates,
mild reaction conditions and remarkably simple workup procedure.
Experimental Section
1
I. General Information H and 13C NMR spectra were recorded on a 400 MHz or
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600 MHz (100 MHz or 150 MHz for 13C NMR) spectrometer at 25 °C. Chemical shift
values are given in ppm and referred as the internal standard to TMS
(tetramethylsilane). The peak patterns are indicated as follows: s, singlet; d, doublet; t,
triplet; q, quadruplet; m, multiplet; dd, doublet of doublets and br s, broad singlet. The
coupling constants (J) are reported in Hertz (Hz). High resolution mass spectrometry
(HRMS) was obtained on a QꢀTOF microspectrometer. Melting points were
determined with a micromelting point apparatus without corrections. Infrared spectra
were measured on a FT/IR instrument. Tetrahydrofuran (THF), 1,1ꢀdichloroethane
(DCE) and N,Nꢀdimethylformamide (DMF) were dried by CaH2 before use.
II. Preparation of 2ꢀAminoꢀ3ꢀphenylꢀ4Hꢀchromenꢀ4ꢀones 1. General
procedure:10 To a suspension of 60% sodium hydride (40 mmol, 4.0 equiv) in THF
(30 mL) was added methyl salicylate (11 mmol, 1.1 equiv) and benzyl cyanide (10
mmol, 1.0 equiv). The mixture was stirred at 60 °C until TLC indicated the total
consumption of the benzyl cyanide. After cooling, hydrochloric acid (2 N, 20 mL)
was added, and the formed precipitate was filtered and washed with EtOAc (3 × 30
mL), air dried.
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Following general procedure, 2ꢀaminoꢀ3ꢀphenylꢀ4Hꢀchromenꢀ4ꢀones 1 were
prepared in 7% ꢀ 90% yields. The spectral and physical data of known 1a, 1d, 1g, 1p,
1r
were
reported
in
the
published
literature.10
The
novel
2ꢀaminoꢀ3ꢀphenylꢀ4Hꢀchromenꢀ4ꢀones were characterized as follows:
2ꢀAminoꢀ3ꢀ(4ꢀfluorophenyl)ꢀ4Hꢀchromenꢀ4ꢀone (1b). Following the general
procedure for 4 h, 1b was isolated as a white solid. Yield: 1.38 g, 54%, mp 244–246
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1
ºC; H NMR (600 MHz, DMSOꢀd6) δ 7.96 (dd, J = 7.8, 1.2 Hz, 1H), 7.67 – 7.62 (m,
1H), 7.40 (d, J = 8.4 Hz, 1H), 7.38 (t, J = 7.8 Hz, 1H), 7.36 – 7.31 (m, 2H), 7.22 (t, J
= 9.0 Hz, 2H), 7.18 (s, 2H). 13C NMR (150 MHz, DMSOꢀd6) δ 172.5, 162.3, 161.1 (d,
J = 241.1 Hz), 152.5, 133.2 (d, J = 8.0 Hz), 132.2, 129.4 (d, J = 3.0 Hz), 125.1, 124.4,
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+
122.7, 116.3, 115.1 (d, J = 21.0 Hz), 97.9. HRMS (ESI) calcd for C15H11FNO2 [M +
H+] 256.0768, found 256.0770. IR (KBr, neat) 3279, 3009, 1642, 1603, 1536, 1510,
1451, 1282, 1220, 753 cmꢀ1.
2ꢀAminoꢀ3ꢀ(2ꢀfluorophenyl)ꢀ4Hꢀchromenꢀ4ꢀone (1c). Following the general
procedure for 2 h, 1c was isolated as a white solid. Yield: 1.82 g, 71%, mp 204–206
1
ºC; H NMR (600 MHz, DMSOꢀd6) δ 7.95 (d, J = 7.8 Hz, 1H), 7.66 (t, J = 7.2 Hz,
13
1H), 7.49 – 7.35 (m, 3H), 7.35 – 7.27 (m, 3H), 7.24 (t, J = 7.8 Hz, 2H). C NMR
(150 MHz, DMSOꢀd6) δ 172.3, 162.1, 160.7 (d, J = 243.3 Hz), 152. 7, 133.9 (d, J =
3.5 Hz), 132.3, 129.3 (d, J = 8.1 Hz), 125.1, 124.5, 124.3 (d, J = 3.0 Hz), 122.4, 120.6
(d, J = 16.5 Hz), 116.4, 115.6 (d, J = 22.1 Hz), 92.9. HRMS (ESI) calcd for
C15H11FNO2 [M + H+] 256.0768, found 256.0772. IR (KBr, neat) 3470, 3117, 1649,
+
1602, 1578, 1540, 1494, 1293, 752 cmꢀ1.
2ꢀAminoꢀ3ꢀ(3ꢀchlorophenyl)ꢀ4Hꢀchromenꢀ4ꢀone (1e). Following the general
procedure for 4 h, 1e was isolated as a light gray solid. Yield: 1.64 g, 60%, mp
1
238–240 ºC; H NMR (600 MHz, DMSOꢀd6) δ 7.97 (d, J = 7.8 Hz, 1H), 7.65 (t, J =
7.8 Hz, 1H), 7.44 (t, J = 7.8 Hz, 1H), 7.42 – 7.38 (m, 2H), 7.36 (s, 2H), 7.34 (s, 2H),
7.29 (d, J = 7.2 Hz, 1H). 13C NMR (150 MHz, DMSOꢀd6) δ 172.3, 162.2, 152.5,
135.5, 132.7, 132.3, 131.1, 130.0, 129.9, 126.6, 125.1, 124.4, 122.6, 116.4, 97.7.
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+
HRMS (ESI) calcd for C15H1135ClNO2 [M + H+] 272.0473, found 272.0476. IR (KBr,
5
6
7
8
neat) 3298, 3141, 1634, 1605, 1568, 1536, 1486, 1461, 1410, 750, 679 cmꢀ1.
2ꢀAminoꢀ3ꢀ(4ꢀbromophenyl)ꢀ4Hꢀchromenꢀ4ꢀone (1f). Following the general
procedure for 6 h, 1f was isolated as a light gray solid. Yield: 1.30 g, 41%, mp
9
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1
272–274 ºC; H NMR (600 MHz, DMSOꢀd6) δ 7.97 (d, J = 7.2 Hz, 1H), 7.64 (t, J =
7.2 Hz, 1H), 7.58 (d, J = 8.4 Hz, 2H), 7.44 – 7.35 (m, 2H), 7.29 (d, J = 8.4 Hz, 4H).
13C NMR (150 MHz, DMSOꢀd6) δ 172.3, 162.1, 152.5, 133.4, 132.6, 132.2, 131.2,
125.1, 124.4, 122.6, 119.8, 116.3, 97.7. HRMS (ESI) calcd for C15H1179BrNO2 [M +
+
H+] 315.9968, found 315.9966. IR (KBr, neat) 3284, 3108, 1641, 1603, 1533, 1492,
1460, 1448, 1004, 753 cmꢀ1.
2ꢀAminoꢀ3ꢀ(3ꢀmethoxyphenyl)ꢀ4Hꢀchromenꢀ4ꢀone (1h). Following the general
procedure for 4 h, 1h was isolated as a light yellow solid. Yield: 0.80 g, 30%, mp
1
180–182 ºC; H NMR (600 MHz, DMSOꢀd6) δ 7.97 (d, J = 7.8 Hz, 1H), 7.64 (t, J =
7.8 Hz, 1H), 7.38 (dd, J = 18.0, 8.1 Hz, 2H), 7.33 (t, J = 7.2 Hz, 1H), 7.18 (s, 2H),
13
6.93 – 6.83 (m, 3H), 3.77 (s, 3H). C NMR (150 MHz, DMSOꢀd6) δ 172.4, 162.1,
159.2, 152.5, 134.5, 132.1, 129.2, 125.2, 124.3, 123.4, 122.8, 116.5, 116.3, 112.4,
98.8, 54.8. HRMS (ESI) calcd for C16H14NO3 [M + H+] 268.0968, found 268.0968.
+
IR (KBr, neat) 3430, 3060, 1649, 1608, 1537, 1489, 1462, 1413, 1033, 754, 702 cmꢀ1.
2ꢀAminoꢀ3ꢀ(oꢀtolyl)ꢀ4Hꢀchromenꢀ4ꢀone (1i). Following the general procedure for
1
2 h, 1i was isolated as a white solid. Yield: 0.70 g, 28%, mp 192–194 ºC; H NMR
(400 MHz, CDCl3) δ 8.20 (d, J = 8.0 Hz, 1H), 7.55 (t, J = 7.2 Hz, 1H), 7.34 (t, J = 7.6
Hz, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.19 (d, J = 6.4 Hz, 1H), 7.17 – 7.08 (m, 3H), 5.11
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(s, 2H), 2.15 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 174.5, 161.7, 153.3, 139.0, 132.0,
131.8, 131.5, 130.5, 128.3, 126.4, 126.0, 124.5, 123.1, 116.5, 100.0, 19.4. HRMS
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8
9
(ESI) calcd for C16H14NO2 [M + H+] 252.1019, found 252.1015. IR (KBr, neat) 3465,
+
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3130, 1638, 1602, 1574, 1533, 1475, 1442, 764, 751 cmꢀ1.
2ꢀAminoꢀ7ꢀfluoroꢀ3ꢀphenylꢀ4Hꢀchromenꢀ4ꢀone (1j). Following the general
procedure for 4 h, 1j was isolated as a light yellow solid. Yield: 0.59 g, 23%, mp
1
232–234 ºC; H NMR (600 MHz, DMSOꢀd6) δ 8.02 (t, J = 6.9 Hz, 1H), 7.43 (t, J =
6.9 Hz, 2H), 7.37 – 7.29 (m, 4H), 7.25 (s, 3H). 13C NMR (150 MHz, DMSOꢀd6) δ
172.3, 164.3 (d, J = 247.4 Hz), 162.9, 153.8 (d, J = 13.4 Hz), 133.4, 131.6, 128.8,
128.1 (d, J = 10.4 Hz), 127.2, 120.3, 112.9 (d, J = 22.1 Hz), 104.0 (d, J = 25.7 Hz),
+
98.9. HRMS (ESI) calcd for C15H11FNO2 [M + H+] 256.0768, found 256.0772. IR
(KBr, neat) 3279, 3108, 1644, 1619, 1533, 1493, 1451, 1437, 1148, 844, 689 cmꢀ1.
2ꢀAminoꢀ5ꢀchloroꢀ3ꢀphenylꢀ4Hꢀchromenꢀ4ꢀone (1k). Following the general
procedure for 4 h, 1k was isolated as a light yellow solid. Yield: 0.46 g, 17%, mp
1
235–237 ºC; H NMR (600 MHz, DMSOꢀd6) δ 7.56 (t, J = 8.4 Hz, 1H), 7.41 (t, J =
7.2 Hz, 2H), 7.37 (d, J = 8.4 Hz, 2H), 7.30 (dd, J = 13.8, 7.2 Hz, 3H), 7.10 (s, 2H).
13C NMR (150 MHz, DMSOꢀd6) δ 171.6, 160.8, 154.3, 133.0, 131.8, 131.7, 131.2,
128.3, 127.5, 126.7, 119.2, 116.2, 99.6. HRMS (ESI) calcd for C15H1135ClNO2 [M +
+
H+] 272.0473, found 272.0471. IR (KBr, neat) 3311, 3142, 1640, 1593, 1534, 1498,
1457, 1434, 928 cmꢀ1.
2ꢀAminoꢀ7ꢀbromoꢀ3ꢀphenylꢀ4Hꢀchromenꢀ4ꢀone (1l). Following the general
procedure for 4 h, 1l was isolated as a white solid. Yield: 1.08 g, 34%, mp > 300 ºC;
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1H NMR (600 MHz, DMSOꢀd6) δ 8.01 (s, 1H), 7.79 (d, J = 9.0 Hz, 1H), 7.45 – 7.38
(m, 3H), 7.37 – 7.28 (m, 5H). 13C NMR (150 MHz, DMSOꢀd6) δ 170.9, 162.3, 151.4,
134.6, 132.8, 131.1, 128.3, 127.3, 126.8, 124.6, 119.0, 116.6, 98.9. HRMS (ESI)
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+
calcd for C15H1179BrNO2 [M + H+] 315.9968, found 315.9962. IR (KBr, neat) 3473,
3104, 1634, 1595, 1585, 1523, 1494, 1460, 1434, 1270, 810 cmꢀ1.
2ꢀAminoꢀ7ꢀ(benzyloxy)ꢀ3ꢀphenylꢀ4Hꢀchromenꢀ4ꢀone (1m). Following the
general procedure for 3 h, 1m was isolated as a light gray solid. Yield: 3.10 g, 90%,
mp 252–254 ºC; 1H NMR (600 MHz, DMSOꢀd6) δ 7.87 (d, J = 8.4 Hz, 1H), 7.49 (d, J
= 7.2 Hz, 2H), 7.45 – 7.38 (m, 4H), 7.36 (t, J = 7.2 Hz, 1H), 7.29 (dd, J = 14.7, 7.2 Hz,
3H), 7.07 – 6.97 (m, 3H), 6.93 (d, J = 1.2 Hz, 1H), 5.25 (s, 2H). 13C NMR (150 MHz,
DMSOꢀd6) δ 172.4, 162.0, 161.3, 153.8, 136.4, 133.3, 131.2, 128.5, 128.2, 128.0,
127.8, 126.5, 126.5, 116.4, 113.1, 100.8, 98.1, 69.8. HRMS (ESI) calcd for
C22H18NO3 [M + H+] 344.1281, found 344.1284. IR (KBr, neat) 3490, 3089, 1637,
+
1606, 1587, 1529, 1494, 1460, 1421, 1259, 1183, 1022, 774, 742, 701 cmꢀ1.
2ꢀAminoꢀ8ꢀmethylꢀ3ꢀphenylꢀ4Hꢀchromenꢀ4ꢀone (1n). Following the general
procedure for 4 h, 1n was isolated as a white solid. Yield: 1.24 g, 49%, mp 276ꢀ278
1
ºC; H NMR (600 MHz, DMSOꢀd6) δ 7.79 (d, J = 7.8 Hz, 1H), 7.49 (d, J = 7.2 Hz,
1H), 7.42 (t, J = 7.2 Hz, 2H), 7.31 (dd, J = 20.1, 7.6 Hz, 3H), 7.25 (t, J = 7.8 Hz, 1H),
7.13 (s, 2H), 2.43 (s, 3H). 13C NMR (150 MHz, DMSOꢀd6) δ 172.8, 161.9, 150.8,
133.3, 132.9, 131.1, 128.3, 126.6, 125.4, 123.7, 122.7, 122.6, 98.6, 14.7. HRMS (ESI)
calcd for C16H14NO2 [M + H+] 252.1019, found 252.1026. IR (KBr, neat) 3477, 3166,
+
1635, 1606, 1574, 1536, 1496, 1454, 1434, 764 cmꢀ1.
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2ꢀAminoꢀ3ꢀphenylꢀ4Hꢀbenzo[g]chromenꢀ4ꢀone (1o). Following the general
procedure for 3 h, 1o was isolated as a light gray solid. Yield: 1.64 g, 57%, mp
296–298 ºC; 1H NMR (600 MHz, DMSOꢀd6) δ 8.62 (s, 1H), 8.17 (d, J = 7.8 Hz, 1H),
8.06 (d, J = 7.8 Hz, 1H), 7.93 (s, 1H), 7.63 (t, J = 6.9 Hz, 1H), 7.54 (t, J = 7.2 Hz, 1H),
7.45 (t, J = 7.2 Hz, 2H), 7.41 – 7.28 (m, 5H). 13C NMR (150 MHz, DMSOꢀd6) δ
172.5, 162.7, 149.6, 134.5, 133.4, 131.3, 129.7, 129.1, 128.3, 127.9, 127.2, 126.6,
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125.6, 125.5, 122.4, 112.1, 98.1. HRMS (ESI) calcd for C19H14NO2 [M + H+]
+
288.1019, found 288.1019. IR (KBr, neat) 3477, 3109, 1629, 1608, 1586, 1551, 1536,
1468, 1447, 1429, 746 cmꢀ1.
2ꢀAminoꢀ3ꢀ(4ꢀchlorophenyl)ꢀ8ꢀmethylꢀ4Hꢀchromenꢀ4ꢀone (1q). Following the
general procedure for 5 h, 1q was isolated as a white solid. Yield: 1.58 g, 55%, mp
1
300ꢀ302 ºC; H NMR (600 MHz, DMSOꢀd6) δ 7.78 (d, J = 7.2 Hz, 1H), 7.49 (d, J =
7.2 Hz, 1H), 7.45 (d, J = 7.8 Hz, 2H), 7.33 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 7.8 Hz,
1H), 7.22 (d, J = 8.4 Hz, 2H), 2.43 (s, 3H). Unfortunately, the poor solubility of 1q
+
prevented 13C NMR characterization. HRMS (ESI) calcd for C16H1335ClNO2 [M + H+]
286.0629, found 286.0633. IR (KBr, neat) 3495, 3143, 1637, 1606, 1575, 1535, 1494,
1450, 1428, 758 cmꢀ1.
III. Preparation of Chromeno[2,3ꢀb]indolꢀ11(6H)ꢀones 2. General procedure: To
a suspension of 2ꢀaminoꢀ3ꢀphenylꢀ4Hꢀchromenꢀ4ꢀone 1 (1.0 mmol, 1.0 equiv) in
DCE (10 mL) was added PIDA (1.0 mmol, 1.0 equiv). The mixture was stirred at
room temperature until TLC indicated the total consumption of the
2ꢀaminoꢀ3ꢀphenylꢀ4Hꢀchromenꢀ4ꢀone. Then the formed precipitate was filtered,
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washed with MeOH (3
×
30 mL), and air dried.
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2h and 2h′ were separated by silica gel (200−300 mesh) column chromatography
using a mixture of DCM and MeOH (98/3, v/v) as eluent.
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The ratio of 2e and 2e′ was calculated by 1H NMR analysis.
The
spectral
and
physical
data
of
known
3ꢀbromochromeno[2,3ꢀb]indolꢀ11(6H)ꢀone 2l was reported in the published
literature.5
Chromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2a). Following the general procedure for 4 h,
1
2a was isolated as a white solid. Yield: 205 mg, 87%, mp > 300 ºC; H NMR (600
MHz, DMSOꢀd6) δ 12.88 (s, 1H), 8.26 (d, J = 7.8 Hz, 1H), 8.12 (d, J = 7.8 Hz, 1H),
7.81 (t, J = 7.5 Hz, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.55 (t, J = 7.2 Hz, 1H), 7.51 (d, J =
13
7.2 Hz, 1H), 7.34 (t, J = 7.5 Hz, 1H), 7.30 (t, J = 7.2 Hz, 1H). C NMR (150 MHz,
DMSOꢀd6) δ 171.5, 156.2, 153.6, 132.7, 132.4, 125.5, 124.8, 123.5, 123.5, 122.1,
121.8, 120.4, 117.6, 112.0, 98.8. HRMS (ESI) calcd for C15H10NO2 [M + H+]
+
236.0706, found 236.0708. IR (KBr, neat) 3026, 1622, 1604, 1590, 1551, 1522, 1200,
876, 829, 757, 736 cmꢀ1.
8ꢀFluorochromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2b). Following the general procedure
1
for 24 h, 2b was isolated as a light gray solid. Yield: 226 mg, 89%, mp > 300 ºC; H
NMR (600 MHz, DMSOꢀd6) δ 13.06 (s, 1H), 8.25 (d, J = 7.8 Hz, 1H), 8.08 (dd, J =
8.7, 5.7 Hz, 1H), 7.81 (t, J = 7.2 Hz, 1H), 7.75 (d, J = 8.4 Hz, 1H), 7.55 (t, J = 7.5 Hz,
1H), 7.33 (dd, J = 9.6, 1.8 Hz, 1H), 7.21 – 7.10 (m, 1H). 13C NMR (150 MHz,
DMSOꢀd6) δ 171.5, δ 159.5 (d, J = 236.0 Hz), 156.1, 153.5, 133.0, 132.3 (d, J = 12.6
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Hz), 125.5, 125.0, 123.4, 121.5 (d, J = 10.1 Hz), 118.4, 117.8, 109.8 (d, J = 23.4 Hz),
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+
98.9 (d, J = 26.6 Hz), 98.50. HRMS (ESI) calcd for C15H9FNO2 [M + H+] 254.0612,
8
9
found 254.0619. IR (KBr, neat) 2993, 2841, 1626, 1605, 1557, 1524, 1505, 1198,
1130, 755 cmꢀ1.
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10ꢀFluorochromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2c). Following the general
procedure for 120 h, 2c was isolated as a white solid. Yield: 97 mg, 38%, mp > 300 ºC;
1H NMR (600 MHz, DMSOꢀd6) δ 13.23 (s, 1H), 8.26 (d, J = 7.8 Hz, 1H), 7.81 (t, J =
7.5 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.33 (s, 2H), 7.10 –
7.03 (m, 1H). 13C NMR (150 MHz, DMSOꢀd6) δ 170.1, 155.7 (d, J = 248.7 Hz),
155.6, 153.2, 134.5 ((d, J = 11.0 Hz), 133.1, 125.9, 125.1, 124.8 (d, J = 7.4 Hz), 123.4,
117.5, 109.9 (d, J = 22.4 Hz), 108.1 (d, J = 3.5 Hz), 108.0 (d, J = 19.8 Hz), 97.5 (d, J
+
= 5.6 Hz). HRMS (ESI) calcd for C15H9FNO2 [M + H+] 254.0612, found 254.0615.
IR (KBr, neat) 3041, 1626, 1607, 1594, 1555, 1509, 1458, 787, 750 cmꢀ1.
8ꢀChlorochromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2d). Following the general procedure
1
for 24 h, 2d was isolated as a light gray solid. Yield: 249 mg, 92%, mp > 300 ºC; H
NMR (600 MHz, DMSOꢀd6) δ 13.12 (s, 1H), 8.25 (d, J = 7.8 Hz, 1H), 8.08 (d, J = 8.4
Hz, 1H), 7.82 (d, J = 7.2 Hz, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.62 – 7.49 (m, 2H), 7.34
(d, J = 7.8 Hz, 1H). 13C NMR (150 MHz, DMSOꢀd6) δ 171.6, 156.2, 153.6, 133.1,
132.6, 127.8, 125.6, 125.2, 123.3, 122.3, 121.6, 120.7, 117.8, 111.8, 98.6. HRMS
35
+
(ESI) calcd for C15H9 ClNO2 [M + H+] 270.0316, found 270.0323. IR (KBr, neat)
2997, 1625, 1607, 1582, 1551, 1524, 1342, 1195, 1062, 883, 751, 740 cmꢀ1.
9ꢀChlorochromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2e). Following the general procedure
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for 4 h, 2e was isolated as a white solid. Yield: 89 mg, 33%, mp > 300 ºC; H NMR
(600 MHz, DMSOꢀd6) δ 13.09 (s, 1H), 8.25 (d, J = 7.2 Hz, 1H), 8.04 (s, 1H), 7.82 (t,
J = 7.5 Hz, 1H), 7.76 (d, J = 8.4 Hz, 1H), 7.61 – 7.48 (m, 2H), 7.36 (d, J = 8.4 Hz,
1H). Unfortunately, the poor solubility of 2e prevented 13C NMR characterization.
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HRMS (ESI) calcd for C15H9 ClNO2 [M + H+] 270.0316, found 270.0321. IR (KBr,
neat) 3045, 1633, 1607, 1584, 1554, 1526, 1456, 1196, 754 cmꢀ1.
35
+
8ꢀBromochromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2f). Following the general procedure
1
for 4 h, 2f was isolated as a light gray solid. Yield: 205 mg, 65%, mp > 300 ºC; H
NMR (600 MHz, DMSOꢀd6) δ 13.12 (s, 1H), 8.25 (d, J = 7.2 Hz, 1H), 8.03 (d, J = 7.2
Hz, 1H), 7.82 (d, J = 6.6 Hz, 1H), 7.77 (d, J = 8.4 Hz, 1H), 7.68 (s, 1H), 7.56 (d, J =
7.2 Hz, 1H), 7.46 (d, J = 8.4 Hz, 1H). 13C NMR (150 MHz, DMSOꢀd6) δ 171.7, 156.1,
153.6, 133.1, 132.9, 125.6, 125.2, 124.9, 123.3, 122.0, 121.0, 117.8, 115.7, 114.5,
79
+
98.6. HRMS (ESI) calcd for C15H9 BrNO2 [M + H+] 313.9811, found 313.9811. IR
(KBr, neat) 2993, 1623, 1607, 1579, 1550, 1524, 1195, 882, 749, 738 cmꢀ1.
8ꢀMethoxychromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2g). Following the general
procedure for 5 h, 2g was isolated as a light gray solid. Yield: 184 mg, 69%, mp > 300
ºC; 1H NMR (600 MHz, DMSOꢀd6) δ 12.75 (s, 1H), 8.25 (d, J = 7.8 Hz, 1H), 7.97 (d,
J = 8.4 Hz, 1H), 7.82 – 7.76 (m, 1H), 7.73 (d, J = 8.4 Hz, 1H), 7.53 (t, J = 7.2 Hz, 1H),
13
7.01 (d, J = 1.8 Hz, 1H), 6.93 (dd, J = 8.4, 1.8 Hz, 1H), 3.83 (s, 3H). C NMR (150
MHz, DMSOꢀd6) δ 171.2, 156.9, 155.5, 153.4, 133.0, 132.6, 125.5, 124.9, 123.5,
+
121.2, 117.6, 115.4, 110.4, 98.8, 96.3, 55.4. HRMS (ESI) calcd for C16H12NO3 [M +
H+] 266.0812, found 266.0809. IR (KBr, neat) 2998, 1626, 1604, 1554, 1524, 1509,
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1195, 1151, 1101, 784, 755 cmꢀ1.
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7ꢀMethoxychromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2h). Following the general
procedure for 4 h, 2h was isolated as a white solid. Yield: 51 mg, 19%, mp > 300 ºC;
1H NMR (600 MHz, DMSOꢀd6) δ 13.10 (s, 1H), 8.25 (d, J = 7.2 Hz, 1H), 7.84 – 7.77
(m, 1H), 7.72 (dd, J = 15.6, 7.8 Hz, 2H), 7.54 (t, J = 7.5 Hz, 1H), 7.24 (t, J = 7.8 Hz,
1H), 6.98 (d, J = 7.8 Hz, 1H), 3.98 (s, 3H). 13C NMR (150 MHz, DMSOꢀd6) δ 171.8,
155.4, 153.6, 145.8, 133.0, 125.6, 124.9, 123.4, 123.1, 122.8, 121.2, 117.7, 113.0,
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+
105.3, 99.2, 55.5. HRMS (ESI) calcd for C16H12NO3 [M + H+] 266.0812, found
266.0806. IR (KBr, neat) 3422, 3117, 1623, 1609, 1545, 1525, 1505, 1214, 1026,
1004 cmꢀ1.
9ꢀMethoxychromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2h′). Following the general
procedure for 4 h, 2h′ was isolated as a white solid. Yield: 152 mg, 57%, the yield
1
ratio of 2h and 2h’ is 1:3,mp > 300 ºC; H NMR (600 MHz, DMSOꢀd6) δ 12.78 (s,
1H), 8.25 (d, J = 7.8 Hz, 1H), 7.80 (t, J = 7.5 Hz, 1H), 7.74 (d, J = 8.4 Hz, 1H), 7.63
(s, 1H), 7.54 (t, J = 7.2 Hz, 1H), 7.41 (d, J = 8.4 Hz, 1H), 6.95 (d, J = 9.0 Hz, 1H),
3.84 (s, 3H). 13C NMR (150 MHz, DMSOꢀd6) δ 171.6, 155.7, 155.3, 153.5, 132.9,
126.2, 125.5, 124.9, 123.3, 122.6, 117.7, 112.6, 112.2, 103.3, 98.9, 55.4. HRMS (ESI)
+
calcd for C16H12NO3 [M + H+] 266.0812, found 266.0810. IR (KBr, neat) 3019, 2955,
1623, 1606, 1558, 1524, 1479, 1204, 839, 755, 729 cmꢀ1.
10ꢀMethylchromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2i). Following the general
procedure for 6 h, 2i was isolated as a white solid. Yield: 120 mg, 48%, mp > 300 ºC;
1H NMR (600 MHz, DMSOꢀd6) δ 12.90 (s, 1H), 8.26 (d, J = 7.2 Hz, 1H), 7.79 (t, J =
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1H), 7.21 (t, J = 7.5 Hz, 1H), 7.04 (d, J = 7.2 Hz, 1H), 3.03 (s, 3H). C NMR (150
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+
123.6, 123.5, 121.7, 117.2, 109.0, 99.6, 22.2. HRMS (ESI) calcd for C16H12NO2 [M
+ H+] 250.0863, found 250.0863. IR (KBr, neat) 3035, 1629, 1608, 1578, 1551, 1518,
1501, 1458, 748 cmꢀ1.
3ꢀFluorochromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2j). Following the general procedure
1
for 36 h, 2j was isolated as a light gray solid. Yield: 203 mg, 80%, mp > 300 ºC; H
NMR (600 MHz, DMSOꢀd6) δ 12.99 (s, 1H), 8.29 (dd, J = 8.7, 6.9 Hz, 1H), 8.10 (d, J
= 7.2 Hz, 1H), 7.79 – 7.72 (m, 1H), 7.51 (d, J = 7.8 Hz, 1H), 7.42 (td, J = 8.4, 1.8 Hz,
1H), 7.33 (dt, J = 24.6, 7.2 Hz, 2H). 13C NMR (150 MHz, DMSOꢀd6) δ 170.9, 164.1
(d, J = 248.6 Hz), 155.9, 154.4 (d, J = 12.0 Hz), 131.8, 127.9 (d, J = 10.5 Hz), 123.8,
122.1, 121.7, 120.5, 120.4, 113.1 (d, J = 21.9 Hz), 111.9, 105.0 (d, J = 25.7 Hz), 98.6.
HRMS (ESI) calcd for C15H9FNO2 [M + H+] 254.0612, found 254.0611. IR (KBr,
+
neat) 3021, 1636, 1608, 1589, 1558, 1524, 1489, 1458, 1255, 784, 774, 741 cmꢀ1.
1ꢀChlorochromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2k). Following the general procedure
for 6 h, 2k was isolated as a gray solid. Yield: 217 mg, 80%, mp > 300 ºC; 1H NMR
(600 MHz, DMSOꢀd6) δ 12.86 (s, 1H), 8.12 (d, J = 7.2 Hz, 1H), 7.76 – 7.67 (m, 2H),
13
7.57 – 7.45 (m, 2H), 7.38 – 7.26 (m, 2H). C NMR (150 MHz, DMSOꢀd6) δ 170.8,
155.4, 154.4, 132.5, 132.3, 131.9, 128.2, 123.7, 122.0, 121.9, 120.3, 120.0, 117.6,
111.8, 99.3. HRMS (ESI) calcd for C15H9 ClNO2 [M + H+] 270.0316, found
35
+
270.0324. IR (KBr, neat) 3080, 1625, 1592, 1525, 1231, 932, 869, 800, 748 cmꢀ1.
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2ꢀBromochromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2l). Following the general procedure
for 3 h, 2l was isolated as a white solid. Yield: 271 mg, 86%, mp > 300 ºC; 1H NMR
(600 MHz, DMSOꢀd6) δ 13.03 (s, 1H), 8.29 (d, J = 2.4 Hz, 1H), 8.10 (d, J = 7.8 Hz,
1H), 7.96 (dd, J = 9.0, 2.4 Hz, 1H), 7.77 (d, J = 9.0 Hz, 1H), 7.51 (d, J = 7.8 Hz, 1H),
7.36 (t, J = 7.5 Hz, 1H), 7.31 (t, J = 7.2 Hz, 1H).
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3ꢀ(Benzyloxy)chromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2m). Following the general
procedure for 24 h, 2m was isolated as a light gray solid. Yield: 339 mg, 99%, mp >
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300 ºC; H NMR (600 MHz, DMSOꢀd6) δ 12.85 (s, 1H), 8.15 (d, J = 8.4 Hz, 1H),
8.10 (d, J = 7.2 Hz, 1H), 7.56 – 7.47 (m, 3H), 7.44 (t, J = 7.2 Hz, 2H), 7.41 – 7.26 (m,
4H), 7.19 (d, J = 8.4 Hz, 1H), 5.29 (s, 2H). 13C NMR (150 MHz, DMSOꢀd6) δ 171.5,
161.9, 155.7, 155.0, 136.2, 131.7, 128.5, 128.1, 127.9, 126.8, 123.4, 121.9, 121.9,
+
120.3, 117.1, 113.7, 111.7, 102.1, 98.3, 70.0. HRMS (ESI) calcd for C22H16NO3 [M
+ H+] 342.1125, found 342.1127. IR (KBr, neat) 3033, 1605, 1551, 1520, 1492, 1460,
1262, 1233, 740 cmꢀ1.
4ꢀMethylchromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2n). Following the general
procedure for 24 h, 2n was isolated as a light gray solid. Yield: 198 mg, 79%, mp >
300 ºC; 1H NMR (600 MHz, DMSOꢀd6) δ 12.96 (s, 1H), 8.14 – 8.06 (m, 2H), 7.65 (d,
J = 6.6 Hz, 1H), 7.49 (d, J = 7.8 Hz, 1H), 7.42 (t, J = 7.2 Hz, 1H), 7.31 (dt, J = 22.8,
7.2 Hz, 2H), 2.56 (s, 3H). 13C NMR (150 MHz, DMSOꢀd6) δ 171.9, 155.7, 152.0,
133.8, 131.9, 126.6, 124.3, 123.6, 123.3, 123.2, 121.9, 121.8, 120.4, 111.8, 98.5, 15.4.
+
HRMS (ESI) calcd for C16H12NO2 [M + H+] 250.0863, found 250.0867. IR (KBr,
neat) 3004, 1617, 1853, 1555, 1523, 1486, 1478, 1344, 849 cmꢀ1.
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Benzo[6,7]chromeno[2,3ꢀb]indolꢀ13(5H)ꢀone (2o). Following the general
procedure for 14 h, 2o was isolated as a light gray solid. Yield: 272 mg, 95%, mp >
300 ºC; 1H NMR (600 MHz, DMSOꢀd6) δ 12.99 (s, 1H), 8.91 (s, 1H), 8.30 (d, J = 9.0
Hz, 2H), 8.14 (d, J = 7.2 Hz, 2H), 7.77 – 7.67 (m, 1H), 7.67 – 7.59 (m, 1H), 7.51 (d, J
= 7.8 Hz, 1H), 7.39 – 7.27 (m, 2H). Unfortunately, the poor solubility of 2o prevented
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13C NMR characterization. HRMS (ESI) calcd for C19H12NO2 [M + H+] 286.0863,
found 286.0862. IR (KBr, neat) 3047, 1646, 1613, 1589, 1560, 1531, 1196, 1096, 838,
788, 763 cmꢀ1.
8ꢀChloroꢀ3ꢀmethoxychromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2p). Following the
general procedure for 12 h, 2p was isolated as a light gray solid. Yield: 259 mg, 86%,
1
mp > 300 ºC; H NMR (600 MHz, DMSOꢀd6) δ 13.05 (s, 1H), 8.13 (d, J = 8.4 Hz,
1H), 8.05 (d, J = 7.8 Hz, 1H), 7.53 (d, J = 1.2 Hz, 1H), 7.32 (dd, J = 8.4, 1.2 Hz, 1H),
7.28 (d, J = 1.8 Hz, 1H), 7.12 (dd, J = 8.7, 2.1 Hz, 1H), 3.93 (s, 3H). Unfortunately,
the poor solubility of 2p prevented 13C NMR characterization. HRMS (ESI) calcd for
+
C16H1135ClNO3 [M + H+] 300.0422, found 300.0421. IR (KBr, neat) 3064, 1630,
1605, 1578, 1543, 1520, 1486 1264, 1234 cmꢀ1.
8ꢀChloroꢀ4ꢀmethylchromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2q). Following the general
procedure for 48 h, 2q was isolated as a white solid. Yield: 251 mg, 88%, mp > 300
ºC; 1H NMR (600 MHz, DMSOꢀd6) δ 13.19 (s, 1H), 8.08 (t, J = 8.4 Hz, 2H), 7.68 (d,
J = 7.2 Hz, 1H), 7.52 (d, J = 1.2 Hz, 1H), 7.43 (t, J = 7.5 Hz, 1H), 7.33 (d, J = 7.2 Hz,
1H), 2.56 (s, 3H). Unfortunately, the poor solubility of 2q prevented 13C NMR
+
characterization. HRMS (ESI) calcd for C16H1135ClNO2 [M + H+] 284.0473, found
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284.0471. IR (KBr, neat) 3065, 1619, 1587, 1556, 1524, 1226, 1187, 762, 746, 665
cmꢀ1.
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3,8ꢀDimethoxychromeno[2,3ꢀb]indolꢀ11(6H)ꢀone (2r). Following the general
procedure for 14 h, 2r was isolated as a gray solid. Yield: 127 mg, 43%, mp > 300 ºC;
1H NMR (600 MHz, DMSOꢀd6) δ 12.69 (s, 1H), 8.12 (d, J = 9.0 Hz, 1H), 7.94 (d, J =
8.4 Hz, 1H), 7.24 (s, 1H), 7.10 (d, J = 8.4 Hz, 1H), 6.99 (s, 1H), 6.91 (d, J = 8.4 Hz,
1H), 3.92 (s, 3H), 3.83 (s, 3H). 13C NMR (150 MHz, DMSOꢀd6) δ 171.2, 162.7, 156.6,
155.3, 155.0, 132.8, 126.7, 121.0, 117.0, 115.4, 113.1, 110.4, 101.1, 98.3, 96.1, 56.0,
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55.3. HRMS (ESI) calcd for C17H14NO4 [M + H+] 296.0917, found 296.0917. IR
(KBr, neat) 3009, 2836, 1635, 1606, 1590, 1519, 1495, 1150, 1100, 825 cmꢀ1.
IV. Preparation of 6ꢀmethylchromeno[2,3ꢀb]indolꢀ11(6H)ꢀone.9 To a suspension
of 2a (1.0 mmol, 1.0 equiv) in DMF (5 mL) was added NaH (1.2 mmol, 1.2 equiv).
The mixture was stirred at room temperature until TLC indicated the total
consumption of 2a. The reaction mixture was treated with water (50 mL), extracted
with EtOAc (3 × 20 mL) and then washed with water (2 × 50 mL). The organic phase,
after being dried over anhydrous Na2SO4, was evaporated under reduced pressure.
The residue was purified by flash column chromatography (200−300 mesh silica gel,
EtOAc/petroleum ether = 1/4, v/v) to give the desired product. White solid, yield: 237
1
mg, 95%. H NMR (400 MHz, CDCl3) δ 8.45 (dd, J = 7.6, 1.6 Hz, 1H), 8.39 – 8.31
(m, 1H), 7.68 – 7.62 (m, 1H), 7.54 (d, J = 8.0 Hz, 1H), 7.49 – 7.41 (m, 1H), 7.39 –
7.28 (m, 3H), 3.85 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 172.6, 155.1, 153.8, 133.5,
132.3, 126.6, 125.0, 124.1, 123.8, 122.8, 121.9, 117.2, 108.9, 100.0, 99.4, 28.2.
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Acknowledgment
.
We acknowledge the National Natural Science Foundation of
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China (#21472136) and the National Basic Research Project (2014CB932201) for
financial support.
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Supporting Information Available: Spectral data for all new compounds. The
material is available free of charge via the Internet at http://pubs.acs.org.
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(8) Eiden identified chromono[2,3ꢀb]indolꢀ11(6H)ꢀone as a product in the process of
treating 3ꢀsalicylicꢀoxindolen with hydrochloride in alcohol. However, Bergman
described in another work that the structure Eiden identified is incorrect (see ref.
7). For Eiden’s work, see: Eiden, F.; Dobinsky, H. Synthesis 1970, 365.
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(9) In order to rule out the possibility that the reaction might give the angular isomer
of 2a as product, we prepared the methylated product of 2a and got it compared
with its corresponding angular isomer reported by You. The comparison results
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Lan, J.; Guo, S.; You, J. Org. Lett. 2014, 16, 5862−5865.
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