Rhodium(II)-Catalyzed [4+3] Cyclization of Triazoles with Indole Derivatives and Its Application in the Total Synthesis of (±)-Aurantioclavine

Article abstract of DOI:10.1002/cjoc.202000657

An efficient rhodium(II)-catalyzed [4+3] cyclization reaction of 1-sulfonyl-1,2-3-triazoles and indoles was developed. Azepino[5,4,3- cd]indoles, which are widely distributed in ergot alkaloids with various biological activities, could be obtained in good

Full text of DOI:10.1002/cjoc.202000657

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中
国 化 学
Cite this paper: Chin. J. Chem. 2021, 39, 1145—1152. DOI: 10.1002/cjoc.202000657
Rhodium(II)-Catalyzed [4+3] Cyclization of Triazoles with Indole
Derivatives and Its Application in the Total Synthesis of
(±)-Aurantioclavine
Shengguo Duan, Bing Xue, Hui Meng, Zihang Ye, Ze-Feng Xu, and Chuan-Ying Li*
Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, China
Keywords
Triazoles | Rhodium | Alkaloids | Cyclization | Aurantioclavine
Main observation and conclusion
An efficient rhodium(II)-catalyzed [4+3] cyclization reaction of 1-sulfonyl-1,2-3-triazoles and indoles was developed. Azepino[5,4,3-
cd]indoles, which are widely distributed in ergot alkaloids with various biological activities, could be obtained in good to excellent
yields. In addition, the total synthesis of (±)-aurantioclavine was completed in four steps from the known compound 1a adopting this
[4+3] cyclization as a key step.
Comprehensive Graphic Content
*E-mail: licy@zstu.edu.cn
View HTML Article
Supporting Information
Chin. J. Chem. 2021, 39, 1145－1152
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Duan et al.
Concise Report
Scheme 1 Previous work and our proposal
Background and Originality Content
Azepino[5,4,3-cd]indole skeleton is mainly found in some in-
dole alkaloids (Figure 1). This special unit consists of only three
rings, but the related natural products exhibited a variety of im-
portant biological activities.[1a] For example, fargesine, which was
isolated from Evodia fargesii, demonstrated inhibitory activity on
monoamine oxidase-A;[1] hyrtinadine C, isolated from the marine
sponge Hyrtios sp., showed antimicrobial activity.[2] In addition,
communesin F, which has attracted much attention due to signifi-
cant cytotoxicity and exquisite structural complexity, also contains
an azepino[5,4,3-cd]indole core.[3] Aurantioclavine, the simplest
azepinoindole alkaloid, which was isolated from Penicillium auran-
tiovirens by Kozlovskii and coworkers in 1981,[4] has been proven
to be a biosynthetic intermediate of communesins alkaloids.[5]
Thus, aurantioclavine was an attractive synthetic target for syn-
thetic chemists.[6]
Table 1 Optimization of reaction conditionsa
Figure 1 Representative natural products containing azepinoindole core.
In 2008, Gevorgyan and Fokin reported a rhodium(II)-cata-
lyzed denitrogenative transannulation reaction by converting
1-sulfonyl-1,2,3-triazoles to imidazoles via α-imino rhodium(II)
carbene intermediates (Scheme 1a).[7] On the basis of this seminal
work, α-imino carbene became one of the most important inter-
mediates, especially in the synthesis of nitrogen-containing het-
erocycles.[8] Due to the high electrophilic nature of the rhodium(II)
carbene and the nucleophilic sulfonylimine moiety, α-imino car-
bene often acts as an aza-[3C] synthon in cyclization reaction.
Meanwhile, as an excellent nucleophile, indole was used in sever-
al reactions with 1-sulfonyl-1,2,3-triazoles.[9-10] Accordingly, a ret-
rosynthesis of azepino[5,4,3-cd]indole would lead to a triazole-
derived α-imino carbene and a suitable [4C] synthon containing
indole (Scheme 1b). Herein, we report facile synthesis of azepino-
[5,4,3-cd]indoles through rhodium(II)-catalyzed [4+3] cyclization
of 1-sulfonyl-1,2,3-triazoles and indole derivatives. Furthermore,
the total synthesis of (±)-aurantioclavine was completed in four
steps adopting this [4+3] cyclization as a key step.
To simulate the substituents in the natural product, a tertiary
allyl alcohol was introduced at the 4-position of indole (Scheme 1c,
compounds 1a and 1b). It is worth noting that there are three
potential nucleophilic sites in this compound, including oxygen,
nitrogen and the C3 position of indole. From our initial hypothesis,
we thought the steric hindrance of the tertiary alcohol would
reduce the reaction of the hydroxyl attacking the rhodium car-
bene and by protecting the nitrogen with methyl would facilitate
the reaction between the C3 position of indole and carbene. If
intermediate 3aa or 3ba could be obtained, an appropriate acid
would promote the formation of a 7-membered ring in spite of
higher ring strain.
entry
1
2
3
4
5
6
7
8
[Rh]
additive
—
—
—
—
solvent
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
DCE
3ba/4bab (%)
Rh2(OAc)4
Rh2(piv)4
Rh2(oct)4
Rh2(adc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(piv)4
Rh2(oct)4
Rh2(esp)4
Rh2(adc)4
Rh2(dpf)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
Rh2(OAc)4
74/9
5/23
15/40
13/37
0/0
TsOH·H2O
PPTS
0/0
TsOH·H2Oc
PPTSc
PPTSc
PPTSc
PPTSc
PPTSc
PPTSc
PPTSc
PPTSc
PPTSc
PPTSc
PPTSc
PPTSc
0/50
0/85
0/32
0/59
0/83
0/60
0/0
0/89
0/71
0/77
0/93
0/88
0/97
9
10
11
12
13
14d
15d
16d
17d
18d
19d,e
toluene
PhCl
CHCl3
CH2Cl2
CHCl3
a Reaction conditions: 1b (0.4 mmol), 2a (0.2 mmol), [Rh] (5 mol%), addi-
tive (0.2 mmol), solvent (2 mL), N2 atmosphere, reflux, 4 h. b Isolated yield.
c After 4 h, the reaction mixture was cooled to room temperature, then the
additive was added and stirred for 0.5 h. d [Rh] (1 mol%). e Compound 1b
(0.3 mmol). PPTS: Pyridinium p-toluenesulfonate.
3aa was obtained in 46% yield. When the analogue 1b was used in
this transformation, the target product 4ba was obtained in 9%
yield (Table 1, entry 1) in addition to the uncyclized product 3ba
(74% yield).[11] Encouraged by this result, the reaction conditions
were further screened to improve the yield of 4ba. Different rho-
dium(II) catalysts were tried in this reaction (Table 1, entries 2—4),
and 4ba was obtained in low yield. Additives such as p-toluene-
sulfonic acid and pyridinium p-toluenesulfonate (PPTS) were em-
ployed to promote the cyclization. Disappointingly, the reaction
mixture was complicated, and it is believed that the decomposi-
Results and Discussion
We started our investigation with the reaction of readily
available indole 1a and triazole 2a in the presence of Rh2(OAc)4.
The reaction mixture was complicated and the uncyclized product
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Rhodium(II)-Catalyzed [4+3] Cyclization of Triazoles
Chin. J. Chem.
tion of the related compounds was observed due to the increase
in temperature and acidic conditions (Table 1, entries 5—6). We
then added the acid after the mixture was cooled to room tem-
perature. To our delight, the yield of 4ba increased to 85% yield
when using PPTS (Table 1, entry 8). A variety of rhodium(II) cata-
lysts were examined at this stage, and Rh2(OAc)4 was still the best
choice (Table 1, entries 9—13). Reducing the amount of catalyst to
1 mol% could slightly increase the yield of 4ba to 89% (Table 1,
entry 14). Various solvents were tried in this reaction, and chloro-
form gave the best results (Table 1, entries 15—18). At last, 4ba
could be obtained in 97% yield when reducing the amount of 1b
to 1.5 equivalents (Table 1, entry 19). We hypothesized this situa-
tion is probably due to the reaction between the intermediate
3ba or the product 4ba and the carbocation, which was easily
generated by tertiary alcohol under acidic conditions.
Scheme 3 The substrate scope of 1-sulfonyl-1,2,3-triazoles
With the optimal reaction conditions in hand (Table 1, entry
19), the substrate scope was investigated using a variety of in-
doles (Scheme 2). Surprisingly, the NH unprotected indole 1a gave
the product 4aa in 68% yield. Other indoles with electron donat-
ing groups, such as methyl, allyl, benzyl, and p-methoxybenzyl, led
to the corresponding products in excellent yields (4ba—4ea,
87%—99%). To test the practicality of this newly developed
method, the reaction of triazole 1b and indole 2a was carried out
in 1 mmol scale under the standard reaction conditions. The cy-
clization product 4ba was isolated in 95% yield. It is worth noting
that indoles with electron withdrawing groups, such as tert-but-
oxycarbonyl and tosyl, could not furnish the related products (4fa,
4ga).
Scheme 2 The substrate scope of indoles
Then, the studies on a series of 1-sulfonyl-1,2,3-triazoles were
carried out, and the results were summarized in Scheme 3. At first,
the cyclization reactions of triazoles 2b—2f with different sulfonyl
groups were carried out under the optimized condition. It was
found that the yield of 4bd (53%) was much lower than those of
other compounds (4bb, 4bc, 4be, 4bf, 88%—99%), which may be
because of the steric hindrance of ortho-isopropyl groups. Next,
various substituents on C-4 position of triazoles were examined.
Electronic effect of the benzene ring had marginal impact on the
results, good to excellent yields could be achieved when sub-
strates with electron donating groups (2g—2j) or electron with-
drawing groups (2k—2m) were used. The structure of 4bi was
unambiguously confirmed by X-ray crystallographic analysis.[12] In
addition, thiophene derivative (4bn) and estron derivative (4bo)
were obtained smoothly using this method. With slightly modified
conditions, alkyl substituted triazole (2p) could also be applied to
this reaction.
A plausible mechanism was proposed based on the reaction
results and previous reports[7-8] (Scheme 4). The C-3 position of
indole 1 attacked the α-imino rhodium(II) carbene, which was
generated from 1-sulfonyl-1,2,3-triazole in the presence of rho-
dium(II) catalyst, delivering uncyclized compounds 3. Then an acid
promoted intramolecular SN2’ reaction led to the formation of
final product 4.
Chin. J. Chem. 2021, 39, 1145－1152
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
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Duan et al.
Concise Report
Scheme 4 The proposed mechanism
1 h at room temperature. The mixture was filtered through a pad
of Celite and the eluent was concentrated in vacuo. The residue
was purified by silica gel column chromatography.
1-(2-Methylprop-1-en-1-yl)-4-phenyl-2-tosyl-2,6-dihydro-1H-
azepino[5,4,3-cd]indole (4aa): Brown solid, m.p. 124—125 °C;
1
61.8 mg, 68% yield; H NMR (400 MHz, CDCl3) δ: 8.18—8.08 (br,
1H), 7.52—7.46 (m, 2H), 7.43—7.35 (m, 3H), 7.30—7.26 (m, 2H),
7.18—7.09 (m, 2H), 6.97—6.92 (m, 1H), 6.72 (d, J = 8.0 Hz, 2H),
6.67 (d, J = 2.6 Hz, 1H), 6.18 (t, J = 4.4 Hz, 2H), 5.29—5.23 (m, 1H),
2.12 (s, 3H), 1.91 (s, 3H), 1.60 (s, 3H); 13C NMR (101 MHz, CDCl3) δ:
142.2, 139.9, 136.8, 136.5, 135.6, 135.5, 135.3, 129.2, 128.5,
128.2, 128.0, 126.9, 124.2, 123.4, 123.2, 122.9, 119.9, 117.8,
115.7, 110.1, 60.6, 25.9, 21.3, 18.9; ESI-HRMS m/z calcd for
C28H27N2O2S+ [M + H]+ 455.1788, found 455.1796.
6-Methyl-1-(2-methylprop-1-en-1-yl)-4-phenyl-2-tosyl-2,6-
dihydro-1H-azepino[5,4,3-cd]indole (4ba): Off-white solid, m.p.
1
65—66 °C ; 90.9 mg, 97% yield; H NMR (400 MHz, CDCl3) δ:
7.53—7.48 (m, 2H), 7.45—7.37 (m, 3H), 7.27—7.22 (m, 2H),
7.20—7.13 (m, 1H), 7.12—7.06 (m, 1H), 6.96 (d, J = 6.9 Hz, 1H),
6.69 (d, J = 8.2 Hz, 2H), 6.53 (s, 1H), 6.17 (d, J = 8.8 Hz, 1H), 6.14 (s,
1H), 5.25 (d, J = 8.8 Hz, 1H), 3.60 (s, 3H), 2.13 (s, 3H), 1.92 (s, 3H),
1.60 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 141.9, 140.0, 137.7,
136.7, 135.7, 135.4, 129.2, 128.7, 128.5, 128.1, 128.0, 126.9,
124.1, 123.2, 122.5, 119.3, 117.6, 114.3, 108.3, 60.7, 32.9, 25.9,
21.4, 18.9 (one carbon missed); ESI-HRMS m/z calcd for
C29H29N2O2S+ [M + H]+ 469.1944, found 469.1951.
6-Allyl-1-(2-methylprop-1-en-1-yl)-4-phenyl-2-tosyl-2,6-dihy-
dro-1H-azepino[5,4,3-cd]indole (4ca): Brown solid, m.p. 50—51 °C;
89.0 mg, 90% yield; 1H NMR (400 MHz, Acetone-d6) δ: 7.53—7.48
(m, 2H), 7.46—7.36 (m, 3H), 7.34—7.28 (m, 2H), 7.26—7.22 (m,
1H), 7.17—7.11 (m, 1H), 6.97 (d, J = 7.1 Hz, 1H), 6.85 (d, J = 8.1 Hz,
2H), 6.75 (s, 1H), 6.23—6.17 (m, 1H), 6.11—6.06 (m, 1H),
5.97—5.84 (m, 1H), 5.34—5.26 (m, 1H), 5.16—5.09 (m, 1H),
5.01—4.92 (m, 1H), 4.78—4.64 (m, 2H), 2.16 (s, 3H), 1.91 (s, 3H),
1.59 (d, J = 1.4 Hz, 3H); 13C NMR (101 MHz, Acetone-d6) δ: 143.4,
141.0, 138.3, 137.9, 136.3, 136.0, 135.6, 134.8, 129.9, 129.5,
129.3, 129.1, 128.8, 127.7, 125.1, 124.5, 123.1, 119.8, 118.2,
117.4, 115.0, 110.1, 61.3, 49.4, 25.9, 21.4, 18.9; ESI-HRMS m/z
calcd for C31H31N2O2S+ [M + H]+ 495.2101, found 495.2105.
To further demonstrate the utility of this reaction, the total
synthesis of (±)-aurantioclavine was completed using this [4+3]
cyclization as the key step (Scheme 5). The tricyclic compound 4aq
could be produced smoothly employing 1a and 2q as starting
materials under a slightly modified procedure. The reduction of
the double bond and hydrazinolysis of phthalimide were achieved
in one step using N2H4·H2O. At last, (±)-aurantioclavine was ob-
tained after removal of the amino[13] and tosyl group.
Scheme 5 Total synthesis of (±)-aurantioclavine
6-Benzyl-1-(2-methylprop-1-en-1-yl)-4-phenyl-2-tosyl-2,6-di-
hydro-1H-azepino[5,4,3-cd]indole (4da): Off-white solid, m.p.
1
214—215 °C; 94.8 mg, 87% yield; H NMR (400 MHz, CDCl3) δ:
7.54—7.47 (m, 2H), 7.43—7.35 (m, 3H), 7.34—7.25 (m, 5H),
7.12—6.98 (m, 4H), 6.97—6.91 (m, 1H), 6.76 (d, J = 8.0 Hz, 2H),
6.69 (s, 1H), 6.23—6.16 (m, 2H), 5.31—5.25 (m, 1H), 5.16 (d, J =
16.1 Hz, 1H), 5.10 (d, J = 16.1 Hz, 1H), 2.14 (s, 3H), 1.92 (s, 3H),
1.60 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 142.2, 140.0, 137.4,
137.0, 136.9, 135.9, 135.6, 134.7, 129.2, 128.9, 128.5, 128.3,
128.2, 128.0, 127.9, 127.0, 126.7, 124.3, 123.2, 122.6, 119.8,
117.7, 114.9, 108.9, 60.5, 50.3, 25.9, 21.5, 18.9; ESI-HRMS m/z
calcd for C35H33N2O2S+ [M + H]+ 545.2257, found 545.2260.
Conclusions
6-(4-Methoxybenzyl)-1-(2-methylprop-1-en-1-yl)-4-phenyl-2-
tosyl-2,6-dihydro-1H-azepino[5,4,3-cd]indole (4ea): White solid,
m.p. 189—190 °C; 113.8 mg, 99% yield; 1H NMR (400 MHz, CDCl3)
δ: 7.52—7.47 (m, 2H), 7.43—7.35 (m, 3H), 7.31 (d, J = 8.0 Hz, 2H),
7.12—7.03 (m, 2H), 6.99—6.91 (m, 3H), 6.84—6.78 (m, 2H), 6.75
(d, J = 8.0 Hz, 2H), 6.68—6.66 (m, 1H), 6.22—6.16 (m, 2H),
5.31—5.25 (m, 1H), 5.08 (d, J = 15.7 Hz, 1H), 5.02 (d, J = 15.7 Hz,
1H), 3.76 (s, 3H), 2.13 (s, 3H), 1.91 (s, 3H), 1.59 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ: 159.3, 142.1, 140.0, 137.3, 136.9, 135.8,
135.5, 134.7, 129.2, 128.9, 128.5, 128.3, 128.1, 128.02, 127.95,
127.0, 124.3, 123.2, 122.5, 119.6, 117.6, 114.6, 114.3, 108.9, 60.5,
55.4, 49.8, 25.9, 21.4, 18.8; ESI-HRMS m/z calcd for C36H35N2O3S+
[M + H]+ 575.2363, found 575.2370.
In conclusion, we have developed a facile rhodium(II)-cata-
lyzed [4+3] cyclization of 1-sulfonyl-1,2,3-triazoles and indoles to
synthesize azepino[5,4,3-cd]indoles under mild conditions with
good to excellent yields. In addition, by adopting this [4+3] cy-
clization as a key step, a concise total synthesis of (±)-aurantiocla-
vine was completed in four steps from the known compound 1a.
Experimental
General procedure for synthesis of 4
The mixture of 1 (0.3 mmol), 2 (0.2 mmol), and Rh2(OAc)4
(1 mol%) was heated to reflux for 4 h under N2. Then pyridinium
p-toluenesulfonate (0.2 mmol) was added to the mixture after
cooling to room temperature, and then the mixture was stirred for
6-Methyl-1-(2-methylprop-1-en-1-yl)-4-phenyl-2-(phenylsul-
fonyl)-2,6-dihydro-1H-azepino[5,4,3-cd]indole (4bb): White solid,
m.p. 214—215 °C; 81.8 mg, 90% yield; 1H NMR (400 MHz, CDCl3) δ:
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Rhodium(II)-Catalyzed [4+3] Cyclization of Triazoles
Chin. J. Chem.
7.52—7.47 (m, 2H), 7.44—7.33 (m, 5H), 7.18—7.12 (m, 1H),
7.11—7.04 (m, 2H), 6.98—6.94 (m, 1H), 6.92—6.85 (m, 2H), 6.50
(s, 1H), 6.18 (d, J = 8.7 Hz, 1H), 6.15 (s, 1H), 5.29—5.22 (m, 1H),
carbon missed); ESI-HRMS m/z calcd for C30H31N2O2S+ [M + H]+
483.2101, found 483.2106.
4-(4-(tert-Butyl)phenyl)-6-methyl-1-(2-methylprop-1-en-1-yl)-
3.57 (s, 3H), 1.93 (s, 3H), 1.60 (s, 4H); 13C NMR (101 MHz, CDCl3) δ: 2-tosyl-2,6-dihydro-1H-azepino[5,4,3-cd]indole (4bh): Light yellow
1
139.9, 139.5, 137.7, 135.8, 135.8, 135.5, 131.2, 129.2, 128.8,
128.5, 128.0, 127.5, 126.9, 124.0, 123.2, 122.4, 119.0, 117.5,
114.2, 108.4, 60.7, 32.9, 25.9, 18.8; ESI-HRMS m/z calcd for
C28H27N2O2S+ [M + H]+ 455.1788, found 455.1791.
solid, m.p. 174—175 °C; 98.6 mg, 94% yield; H NMR (400 MHz,
CDCl3) δ: 7.48—7.39 (m, 4H), 7.22 (d, J = 8.0 Hz, 2H), 7.18—7.12
(m, 1H), 7.08 (d, J = 8.2 Hz, 1H), 6.95 (d, J = 7.0 Hz, 1H), 6.66 (d, J =
8.1 Hz, 2H), 6.58 (s, 1H), 6.16 (d, J = 8.8 Hz, 1H), 6.13 (s, 1H),
5.28—5.21 (m, 1H), 3.59 (s, 3H), 2.11 (s, 3H), 1.92 (s, 3H), 1.58 (s,
3H), 1.37 (s, 9H); 13C NMR (101 MHz, CDCl3) δ: 151.1, 141.8, 137.7,
137.0, 136.6, 135.7, 135.5, 128.8, 128.0, 126.9, 125.4, 124.1,
123.3, 122.4, 119.0, 117.5, 114.2, 108.3, 60.7, 34.8, 32.9, 31.5,
25.9, 21.3, 18.9 (two carbon missed); ESI-HRMS m/z calcd for
C33H37N2O2S+ [M + H]+ 525.2570, found 525.2573.
2-((4-(tert-Butyl)phenyl)sulfonyl)-6-methyl-1-(2-methylprop-
1-en-1-yl)-4-phenyl-2,6-dihydro-1H-azepino[5,4,3-cd]indole (4bc):
1
Yellow solid, m.p. 84—85 °C; 101.1 mg, 99% yield; H NMR (400
MHz, CDCl3) δ: 7.56—7.49 (m, 2H), 7.45—7.35 (m, 3H), 7.30 (d, J =
8.5 Hz, 2H), 7.17—7.10 (m, 1H), 7.04 (d, J = 8.2 Hz, 1H), 6.94 (d, J =
7.1 Hz, 1H), 6.91—6.85 (m, 2H), 6.52 (s, 1H), 6.19—6.12 (m, 2H),
5.28—5.20 (m, 1H), 3.55 (s, 3H), 1.92 (s, 3H), 1.59 (s, 3H), 1.10 (s,
9H); 13C NMR (101 MHz, CDCl3) δ: 155.1, 140.0, 137.6, 136.3,
136.3, 135.6, 135.53, 135.46, 129.2, 128.5, 128.0, 126.7, 124.4,
123.9, 123.2, 122.4, 119.4, 117.5, 114.2, 108.3, 60.5, 34.7, 32.9,
31.0, 25.8, 18.8; ESI-HRMS m/z calcd for C32H34N2NaO2S+ [M +
Na]+ 533.2233, found 533.2236.
6-Methyl-1-(2-methylprop-1-en-1-yl)-4-phenyl-2-((2,4,6-tri-
isopropylphenyl)sulfonyl)-2,6-dihydro-1H-azepino[5,4,3-cd]indole
(4bd): White solid, m.p. 187—188 °C; 61.6 mg, 53% yield; 1H NMR
(400 MHz, CDCl3) δ: 7.37—7.31 (m, 5H), 7.21—7.14 (m, 2H), 7.02
(s, 2H), 6.92 (dd, J = 5.8, 2.2 Hz, 1H), 6.73 (s, 1H), 6.33 (d, J = 9.5
Hz, 1H), 6.23 (s, 1H), 5.49—5.42 (m, 1H), 4.07—3.96 (m, 2H), 3.70
(s, 3H), 2.88—2.77 (m, 1H), 1.93 (s, 3H), 1.61 (s, 3H), 1.19 (d, J =
6.9 Hz, 6H), 1.09 (d, J = 6.7 Hz, 6H), 0.86 (d, J = 6.7 Hz, 6H);
13C NMR (101 MHz, CDCl3) δ: 153.0, 151.5, 140.6, 137.9, 136.2,
134.2, 132.5, 130.0, 129.3, 128.4, 128.3, 127.6, 124.3, 123.7,
123.6, 122.4, 119.4, 116.8, 114.8, 108.4, 58.4, 34.2, 33.1, 29.6,
26.1, 24.71, 24.66, 23.7, 23.6, 18.9; ESI-HRMS m/z calcd for
C37H44N2NaO2S+ [M + Na]+ 603.3016, found 603.3022.
4-(4-Methoxyphenyl)-6-methyl-1-(2-methylprop-1-en-1-yl)-2-
tosyl-2,6-dihydro-1H-azepino[5,4,3-cd]indole (4bi): Off-white solid,
m.p. 211—212 °C; 86.8 mg, 87% yield; 1H NMR (400 MHz, CDCl3) δ:
7.46—7.41 (m, 2H), 7.23—7.19 (m, 2H), 7.18—7.12 (m, 1H),
7.11—7.05 (m, 1H), 6.98—6.91 (m, 3H), 6.66 (d, J = 8.1 Hz, 2H),
6.53 (s, 1H), 6.16 (d, J = 8.8 Hz, 1H), 6.09 (s, 1H), 5.24 (d, J = 8.8 Hz,
1H), 3.86 (s, 3H), 3.59 (s, 3H), 2.12 (s, 3H), 1.92 (s, 3H), 1.59 (s, 3H);
13C NMR (101 MHz, CDCl3) δ: 159.6, 141.8, 137.7, 136.6, 135.7,
135.6, 135.4, 132.3, 130.3, 128.7, 128.0, 126.8, 124.1, 123.2,
122.4, 118.5, 117.6, 114.5, 113.9, 108.2, 60.7, 55.5, 32.9, 25.9,
21.3, 18.9; ESI-HRMS m/z calcd for C30H31N2O3S+ [M + H]+
499.2050, found 499.2053.
1-(2-Methylprop-1-en-1-yl)-2-tosyl-4-(3,4,5-trimethoxyphen-
yl)-2,6-dihydro-1H-azepino[5,4,3-cd]indole (4aj): Red solid, m.p.
1
90—91 °C; 95.9 mg, 88% yield; H NMR (400 MHz, CDCl3) δ:
8.85—8.69 (br, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.18 (d, J = 8.1 Hz, 1H),
7.09 (t, J = 7.6 Hz, 1H), 6.92 (d, J = 7.1 Hz, 1H), 6.79—6.72 (m, 3H),
6.71 (s, 2H), 6.23—6.12 (m, 2H), 5.32—5.22 (m, 1H), 3.90 (s, 3H),
3.84 (s, 6H), 2.14 (s, 3H), 1.89 (s, 3H), 1.59 (s, 3H); 13C NMR (101
MHz, CDCl3) δ: 153.1, 142.5, 137.8, 136.8, 136.4, 135.7, 135.4,
135.22, 135.16, 128.3, 126.8, 124.7, 123.2, 123.0, 122.7, 119.0,
117.6, 115.0, 110.4, 106.3, 61.0, 60.7, 56.3, 25.8, 21.2, 18.8;
ESI-HRMS m/z calcd for C31H33N2O5S+ [M + H]+ 545.2105, found
545.2108.
6-Methyl-1-(2-methylprop-1-en-1-yl)-2-(naphthalen-2-ylsul-
fonyl)-4-phenyl-2,6-dihydro-1H-azepino[5,4,3-cd]indole
(4be):
1
Yellow solid, m.p. 110—111 °C; 88.8 mg, 88% yield; H NMR (400
MHz, CDCl3) δ: 7.71—7.67 (m, 1H), 7.60—7.55 (m, 1H), 7.52—
7.47 (m, 2H), 7.46—7.34 (m, 7H), 7.20 (s, 1H), 7.17—7.10 (m, 1H),
7.00 (d, J = 7.1 Hz, 1H), 6.84 (d, J = 8.3 Hz, 1H), 6.22 (d, J = 8.7 Hz,
1H), 6.18 (d, J = 12.4 Hz, 2H), 5.22 (d, J = 8.6 Hz, 1H), 3.15 (s, 3H),
1.96 (s, 3H), 1.60 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 139.8,
137.5, 137.4, 136.4, 136.1, 135.0, 134.2, 131.5, 129.3, 129.1,
128.7, 128.5, 128.13, 128.06, 127.9, 127.2, 126.8, 126.3, 123.9,
123.2, 122.8, 122.4, 118.9, 117.8, 114.0, 108.5, 61.1, 32.4, 25.9,
18.9; ESI-HRMS m/z calcd for C32H29N2O2S+ [M + H]+ 505.1944,
found 505.1943.
6-Methyl-1-(2-methylprop-1-en-1-yl)-2-tosyl-4-(3,4,5-trimeth-
oxyphenyl)-2,6-dihydro-1H-azepino[5,4,3-cd]indole (4bj): Light
1
yellow solid, m.p. 60—61 °C; 110.6 mg, 99% yield; H NMR (400
MHz, CDCl3) δ: 7.28—7.23 (m, 3H), 7.19—7.15 (m, 1H), 7.13—
7.09 (m, 1H), 6.98—6.94 (m, 1H), 6.74—6.70 (m, 4H), 6.63 (s, 1H),
6.19—6.14 (m, 2H), 5.26 (d, J = 8.8 Hz, 1H), 3.91 (s, 3H), 3.88 (s,
6H), 3.63 (s, 3H), 2.15 (s, 3H), 1.92 (s, 3H), 1.60 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ: 153.2, 142.1, 138.0, 137.7, 136.6, 135.6,
135.5, 135.3, 128.7, 128.1, 126.8, 123.9, 123.0, 122.5, 118.9,
117.6, 114.0, 108.3, 106.3, 61.0, 60.7, 56.4, 33.0, 25.9, 21.4, 18.8
6-Methyl-1-(2-methylprop-1-en-1-yl)-2-(methylsulfonyl)-4-
phenyl-2,6-dihydro-1H-azepino[5,4,3-cd]indole (4bf): White solid,
m.p. 182—183 °C; 73.0 mg, 93% yield; 1H NMR (400 MHz, CDCl3) δ: (one carbon missed); ESI-HRMS m/z calcd for C32H35N2O5S+ [M +
7.59—7.52 (m, 2H), 7.45—7.35 (m, 3H), 7.29—7.20 (m, 2H), 7.02
(d, J = 6.4 Hz, 1H), 6.85 (s, 1H), 6.15—6.09 (m, 2H), 5.31 (d, J = 8.6
Hz, 1H), 3.75 (s, 3H), 2.38 (s, 3H), 1.93 (s, 3H), 1.63 (s, 3H);
13C NMR (101 MHz, CDCl3) δ: 139.8, 137.9, 136.1, 135.9, 134.5,
129.3, 128.5, 128.1, 123.8, 123.0, 122.8, 119.5, 117.5, 114.1,
109.0, 59.9, 39.1, 33.2, 25.9, 18.8 (one carbon missed); ESI-HRMS
m/z calcd for C23H24N2NaO2S+ [M + Na]+ 415.1451, found
415.1452.
H]+ 559.2261, found 559.2265.
4-(4-Fluorophenyl)-6-methyl-1-(2-methylprop-1-en-1-yl)-2-
tosyl-2,6-dihydro-1H-azepino[5,4,3-cd]indole (4bk): White solid,
m.p. 203—204 °C; 89.5 mg, 92% yield; 1H NMR (400 MHz, CDCl3) δ:
7.49—7.43 (m, 2H), 7.24 (d, J = 8.3 Hz, 2H), 7.20—7.14 (m, 1H),
7.13—7.06 (m, 3H), 6.96 (d, J = 7.0 Hz, 1H), 6.70 (d, J = 8.1 Hz, 2H),
6.49 (s, 1H), 6.16 (d, J = 8.8 Hz, 1H), 6.10 (s, 1H), 5.22 (d, J = 8.8 Hz,
1H), 3.61 (s, 3H), 2.14 (s, 3H), 1.92 (s, 3H), 1.60 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ: 162.7 (d, J = 247.5 Hz), 142.0, 137.8, 136.7,
136.0, 135.8, 135.7, 134.4, 130.8 (d, J = 7.9 Hz), 128.5, 128.1,
126.9, 124.0, 123.1, 122.6, 119.4, 117.7, 115.4 (d, J = 21.4 Hz),
114.4, 108.4, 60.6, 32.9, 25.9, 21.4, 18.9; ESI-HRMS m/z calcd for
C29H28FN2O2S+ [M + H]+ 487.1850, found 487.1855.
6-Methyl-1-(2-methylprop-1-en-1-yl)-4-(m-tolyl)-2-tosyl-2,6-
dihydro-1H-azepino[5,4,3-cd]indole (4bg): Light yellow solid, m.p.
1
179—180 °C; 86.9 mg, 90% yield; H NMR (400 MHz, CDCl3) δ:
7.36—7.28 (m, 3H), 7.28—7.22 (m, 2H), 7.22—7.12 (m, 2H), 7.08
(d, J = 8.2 Hz, 1H), 6.95 (d, J = 7.0 Hz, 1H), 6.68 (d, J = 8.0 Hz, 2H),
6.54 (s, 1H), 6.19—6.11 (m, 2H), 5.28—5.21 (m, 1H), 3.60 (s, 3H),
2.41 (s, 3H), 2.13 (s, 3H), 1.92 (s, 3H), 1.59 (s, 3H); 13C NMR (101
MHz, CDCl3) δ: 141.9, 140.0, 138.2, 137.7, 136.7, 135.6, 129.8,
128.8, 128.7, 128.4, 128.0, 126.9, 126.3, 124.1, 123.2, 122.4,
119.1, 117.6, 114.3, 108.3, 60.7, 32.9, 25.9, 21.6, 21.4, 18.9 (two
4-(4-Bromophenyl)-6-methyl-1-(2-methylprop-1-en-1-yl)-2-
tosyl-2,6-dihydro-1H-azepino[5,4,3-cd]indole (4bl): Light yellow
1
solid, m.p. 209—210 °C; 92.0 mg, 84% yield; H NMR (400 MHz,
CDCl3) δ: 7.53 (d, J = 8.4 Hz, 2H), 7.41—7.34 (m, 2H), 7.27—7.21
(m, 2H), 7.20—7.14 (m, 1H), 7.10 (d, J = 8.2 Hz, 1H), 6.95 (d, J =
Chin. J. Chem. 2021, 39, 1145－1152
© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
www.cjc.wiley-vch.de
1149

Duan et al.
Concise Report
7.0 Hz, 1H), 6.71 (d, J = 8.0 Hz, 2H), 6.50 (s, 1H), 6.16 (d, J = 8.8 Hz,
1H), 6.12 (s, 1H), 5.21 (d, J = 8.8 Hz, 1H), 3.62 (s, 3H), 2.14 (s, 3H),
1.91 (s, 3H), 1.59 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 142.1,
139.0, 137.8, 136.6, 135.8, 135.6, 134.1, 131.7, 130.8, 128.4,
128.2, 126.8, 123.9, 123.0, 122.6, 122.0, 119.5, 117.7, 114.0,
108.4, 60.6, 33.0, 25.9, 21.4, 18.9; ESI-HRMS m/z calcd for
C29H27BrN2NaO2S+ [M + Na]+ 569.0869, found 569.0869.
concentrated in vacuo. The residue was purified by silica gel col-
umn chromatography (V(PE) : V(EtOAc) = 5 : 1 to 3 : 1) to give the
product 4aq.
2-(1-(2-Methylprop-1-en-1-yl)-2-tosyl-2,6-dihydro-1H-azepi-
no[5,4,3-cd]indol-4-yl)isoindoline-1,3-dione (4aq): Yellow solid,
m.p. 145—146 °C; 639 mg, 61% yield; 1H NMR (400 MHz, CDCl3) δ:
8.30—8.18 (br, 1H), 8.02—7.87 (m, 2H), 7.87—7.75 (m, 2H), 7.48
(d, J = 7.9 Hz, 2H), 7.12—6.95 (m, 2H), 6.88 (d, J = 6.9 Hz, 1H), 6.77
(d, J = 7.9 Hz, 2H), 6.69—6.60 (m, 1H), 6.41 (s, 1H), 6.18 (d, J = 9.0
Hz, 1H), 5.49 (d, J = 9.0 Hz, 1H), 2.08 (s, 3H), 1.91 (s, 3H), 1.65 (s,
3H); 13C NMR (101 MHz, CDCl3) δ: 167.7, 167.4, 142.6, 136.8,
136.0, 135.9, 134.6, 132.0, 128.5, 127.1, 124.1, 123.9, 123.7,
123.1, 122.7, 122.1, 121.4, 117.8, 112.4, 110.5, 60.3, 25.6, 21.3,
18.8; ESI-HRMS m/z calcd for C30H26N3O4S+ [M + H]+ 524.1639,
found 524.1639.
The solution of 4aq (639 mg, 1.22 mmol) and N2H4·H2O (50
wt%, 1.2 mL) in CH3CN (12 mL) was heated to reflux for 1 h, and a
large quantity of white solid appeared in the mixture. Then the
mixture was filtered and the eluent was concentrated in vacuo.
The residue was purified by silica gel column chromatography
(V(PE) : V(EtOAc) = 1 : 1) to give the product 5 (dr = 1.5 : 1) as a
mixture of isomers.
1-(4-(6-Methyl-1-(2-methylprop-1-en-1-yl)-2-tosyl-2,6-dihy-
dro-1H-azepino[5,4,3-cd]indol-4-yl)phenyl)ethan-1-one
(4bm):
1
Light yellow solid, m.p. 163—164 °C; 97.0 mg, 95% yield; H NMR
(400 MHz, CDCl3) δ: 8.03—7.97 (m, 2H), 7.63—7.57 (m, 2H), 7.28
(d, J = 8.2 Hz, 2H), 7.21—7.15 (m, 1H), 7.11 (d, J = 8.3 Hz, 1H), 6.96
(d, J = 6.9 Hz, 1H), 6.74 (d, J = 8.1 Hz, 2H), 6.52 (s, 1H), 6.21 (s, 1H),
6.17 (d, J = 8.8 Hz, 1H), 5.26—5.19 (m, 1H), 3.62 (s, 3H), 2.65 (s,
3H), 2.15 (s, 3H), 1.91 (s, 3H), 1.59 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ: 197.8, 145.1, 142.2, 137.8, 136.8, 136.7, 135.9, 135.6,
133.7, 129.4, 128.7, 128.34, 128.27, 126.9, 124.0, 123.0, 122.7,
120.3, 117.7, 113.7, 108.4, 60.6, 33.0, 26.8, 25.9, 21.4, 18.9;
ESI-HRMS m/z calcd for C31H31N2O3S+ [M + H]+ 511.2050, found
511.2059.
6-Methyl-1-(2-methylprop-1-en-1-yl)-4-(thiophen-3-yl)-2-tos-
yl-2,6-dihydro-1H-azepino[5,4,3-cd]indole (4bn): White solid, m.p.
1
144—145 °C; 59.8 mg, 63% yield; H NMR (400 MHz, Acetone-d6)
1-(2-Methylprop-1-en-1-yl)-2-tosyl-2,3,4,6-tetrahydro-1H-
azepino[5,4,3-cd]indol-4-amine (5): Yellow solid, m.p. 79—80 °C;
δ: 7.59—7.52 (m, 2H), 7.31—7.22 (m, 4H), 7.19—7.12 (m, 1H),
6.97—6.91 (m, 2H), 6.84 (d, J = 8.0 Hz, 2H), 6.21 (s, 1H), 6.16 (d,
J = 8.9 Hz, 1H), 5.30—5.19 (m, 1H), 3.74 (s, 3H), 2.18 (s, 3H), 1.90
(s, 3H), 1.57 (s, 3H); 13C NMR (101 MHz, Acetone-d6) δ: 143.4,
141.5, 138.9, 137.9, 136.2, 135.4, 130.6, 130.0, 129.3, 129.2,
127.7, 126.8, 125.0, 124.5, 124.2, 123.0, 119.3, 118.1, 114.2,
109.6, 61.6, 33.1, 25.9, 21.4, 18.9; ESI-HRMS m/z calcd for
C27H27N2O2S2+ [M + H]+ 475.1508, found 475.1515.
1
333 mg, 69% yield; H NMR (400 MHz, CDCl3) δ: 9.55—8.70 (m,
1H), 7.83—7.24 (m, 2H), 7.23—6.96 (m, 3H), 6.93—6.82 (m, 1H),
6.79—6.60 (m, 2H), 6.27—5.99 (m, 1H), 5.32—5.08 (m, 2H),
5.06—4.27 (m, 2H), 2.16—2.07 (m, 3H), 1.95—1.86 (m, 3H),
1.72—1.66 (m, 3H); 13C NMR (101 MHz, CDCl3) δ: 148.0, 143.9,
142.3, 142.2, 139.6, 137.8, 137.4, 136.4, 136.3, 136.0, 134.8,
128.3, 128.2, 128.1, 127.3, 127.1, 126.5, 123.3, 123.0, 122.5,
122.1, 121.9, 121.7, 119.7, 118.3, 114.4, 110.3, 110.2, 108.1, 59.2,
59.1, 51.1, 43.0, 25.9, 25.7, 21.3, 21.2, 18.61, 18.57; ESI-HRMS
m/z calcd for C22H26N3O2S+ [M + H]+ 396.1740, found 396.1722.
The B(C6F5)3 (10 mg, 0.02 mmol) was weighted in glove box
(8R,9S,13S,14S)-13-Methyl-3-(6-methyl-1-(2-methylprop-1-
en-1-yl)-2-tosyl-2,6-dihydro-1H-azepino[5,4,3-cd]indol-4-yl)-6,7,8,
9,11,12,13,14,15,16-decahydro-17H-cyclopenta[a]phenanthren-
17-one (4bo): Yellow solid, m.p. 160—161 °C; 95.4 mg, 74% yield;
1H NMR (400 MHz, CDCl3) δ: 7.37—7.27 (m, 3H), 7.23 (d, J = 7.9 Hz, and placed in sealed tube. Then compound 5 (158 mg, 0.40 mmol),
2H), 7.19—7.12 (m, 1H), 7.08 (d, J = 8.2 Hz, 1H), 6.95 (d, J = 7.0 Hz,
1H), 6.67 (d, J = 7.9 Hz, 2H), 6.62—6.55 (m, 1H), 6.15 (s, 2H), 5.23
(d, J = 8.7 Hz, 1H), 3.61 (s, 3H), 3.07—2.91 (m, 2H), 2.61—2.42 (m,
2H), 2.42—2.30 (m, 1H), 2.24—1.96 (m, 8H), 1.91 (s, 3H),
1.77—1.41 (m, 8H), 0.94 (s, 3H); 13C NMR (101 MHz, CDCl3) δ:
220.8, 141.8, 139.8, 137.7, 137.5, 136.9, 136.7, 135.7, 135.6,
135.4, 129.6, 128.7, 128.0, 126.9, 126.7, 125.4, 124.1, 123.2,
122.4, 119.1, 117.6, 114.2, 108.2, 60.7, 50.7, 48.1, 44.5, 38.4, 36.0,
32.9, 31.8, 29.6, 26.7, 25.9, 21.8, 21.4, 18.9, 14.0; ESI-HRMS m/z
calcd for C41H45N2O3S+ [M + H]+ 645.3145, found 645.3148.
phenylsilane (0.39 mL, 3.20 mmol) and 1,2-difluorobenzene (4 mL)
were added to the sealed tube under N2. The reaction mixture
produced a large quantity of white solid. The solid disappeared
after the mixture was heated to 140 °C for 36 h. The mixture was
cooled to room temperature and the solvent was evaporated in
vacuo. The residue was purified by silica gel column chromatog-
raphy (V(PE) : V(EtOAc) = 3 : 1) to give the product 6.
1-(2-Methylprop-1-en-1-yl)-2-tosyl-2,3,4,6-tetrahydro-1H-
azepino[5,4,3-cd]indole (6): Light yellow solid, m.p. 171—172 °C;
82 mg, 54% yield; 1H NMR (400 MHz, CDCl3) δ: 8.15—7.97 (br, 1H),
7.53 (d, J = 8.2 Hz, 2H), 7.14 (d, J = 8.1 Hz, 1H), 7.08—6.99 (m, 3H),
6.86 (s, 1H), 6.77 (d, J = 7.2 Hz, 1H), 6.25 (d, J = 9.0 Hz, 1H), 5.35 (d,
J = 9.1 Hz, 1H), 4.00 (dt, J = 14.8, 4.2 Hz, 1H), 3.77—3.65 (m, 1H),
3.28—3.14 (m, 1H), 3.01 (dt, J = 16.2, 3.4 Hz, 1H), 2.29 (s, 3H),
4-Butyl-6-methyl-1-(2-methylprop-1-en-1-yl)-2-tosyl-2,6-di-
hydro-1H-azepino[5,4,3-cd]indole (4bp): Yellow oil; 44.8 mg, 50%
yield; 1H NMR (400 MHz, CDCl3) δ: 7.15 (d, J = 8.0 Hz, 2H),
7.13—7.07 (m, 1H), 7.04 (d, J = 8.1 Hz, 1H), 6.87 (d, J = 6.9 Hz, 1H),
6.82 (s, 1H), 6.65 (d, J = 7.9 Hz, 2H), 6.06 (d, J = 8.5 Hz, 1H), 5.99 (s, 1.83 (s, 3H), 1.63 (s, 3H); 13C NMR (101 MHz, CDCl3) δ: 142.4,
1H), 5.12 (d, J = 8.6 Hz, 1H), 3.66 (s, 3H), 2.60—2.48 (m, 1H),
2.40—2.27 (m, 1H), 2.12 (s, 3H), 1.92 (s, 3H), 1.60 (s, 3H),
1.58—1.47 (m, 2H), 1.45—1.29 (m, 2H), 0.90 (t, J = 7.3 Hz, 3H);
13C NMR (101 MHz, CDCl3) δ: 141.7, 137.6, 136.6, 135.7, 135.5,
133.4, 127.9, 126.8, 125.8, 124.0, 123.4, 122.2, 117.8, 117.2,
113.6, 108.1, 60.0, 32.9, 32.7, 31.6, 25.8, 22.5, 21.4, 18.7, 14.0;
ESI-HRMS m/z calcd for C27H33N2O2S+ [M + H]+ 449.2257, found
449.2257.
138.5, 137.2, 136.3, 135.6, 129.0, 127.2, 124.5, 123.5, 121.8,
121.4, 118.0, 113.9, 109.5, 59.9, 44.2, 28.5, 25.9, 21.5, 18.7;
ESI-HRMS m/z calcd for C22H25N2O2S+ [M + H]+ 381.1631, found
381.1644.
To the solution of naphthalene (276 mg, 2.16 mmol) in anhy-
drous THF (2 mL) was added Na (50 mg, 2.16 mmol) at room
temperature under N2. The mixture was stirred at room temper-
ature for 10 min and the mixture turned into dark green. Then a
solution of 6 (82 mg, 0.22 mmol) in anhydrous THF (2 mL) was
added to the mixture dropwise after cooling down to –78 °C.
Ethanol was added to the mixture to quench the reaction at
–78 °C after 15 min. The mixture was diluted with water and
extracted with EtOAc 3 times. The combined organic layers were
washed with brine, dried with Na2SO4, filtered and concentrated.
The residue was purified by silica gel (basify with NaOH, pH = 8—9)
column chromatography (EtOAc) to give (±)-aurantioclavine.
Total synthesis of (±)-aurantioclavine
The mixture of 1a (604 mg, 3.0 mmol), 2q (737 mg, 2.0 mmol),
and Rh2(piv)4 (61 mg, 0.1 mmol) was heated to reflux for 1 h un-
der N2. Then pyridinium p-toluenesulfonate (251 mg, 1.0 mmol)
was added to the mixture after cooling to room temperature, and
then the mixture was stirred for 10 min at room temperature. The
mixture was filtered through a pad of Celite and the eluent was
1150
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© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
Chin. J. Chem. 2021, 39, 1145－1152

Rhodium(II)-Catalyzed [4+3] Cyclization of Triazoles
Chin. J. Chem.
(±)-Aurantioclavine: Off-white solid, m.p. 179—180 °C; 38 mg,
78% yield; H NMR (400 MHz, CDCl3) δ: 8.22—8.06 (br, 1H), 7.22
Liu, Q.; Zhang, L.; Jia, Y. Total Synthesis of Clavicipitic Acid and Au-
rantioclavine: Stereochemistry of Clavicipitic Acid Revisited. J. Org.
Chem. 2010, 75, 7626–7635; (h) Cui, Z.; Chen, Y. J.; Gao, W. Y.; Feng,
C. G.; Lin, G. Q. Enantioselective Alkenylation of Aldimines Catalyzed
by a Rhodium-Diene Complex. Org. Lett. 2014, 16, 1016–1019; (i)
Suetsugu, S.; Nishiguchi, H.; Tsukano, C.; Takemoto, Y. Asymmetric
Synthesis of (-)-Aurantioclavine Via Palladium-Catalyzed Intramolec-
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1
(d, J = 8.0 Hz, 1H), 7.09 (t, J = 7.7 Hz, 1H), 7.00 (s, 1H), 6.84 (d, J =
7.4 Hz, 1H), 5.46 (d, J = 9.2 Hz, 1H), 4.90 (d, J = 9.1 Hz, 1H),
3.61—3.49 (m, 1H), 3.18—2.96 (m, 3H), 1.85 (s, 3H), 1.84 (s, 3H);
13C NMR (101 MHz, CDCl3) δ: 138.6, 137.3, 133.4, 127.8, 125.5,
121.7, 121.1, 118.0, 115.9, 109.3, 62.8, 49.0, 31.1, 26.0, 18.5;
+
ESI-HRMS m/z calcd for C15H19N2 [M + H]+ 227.1543, found
227.1563.
Supporting Information
The supporting information for this article is available on the
WWW under https://doi.org/10.1002/cjoc.202000657.
Acknowledgement
Financial support from the National Natural Science Founda-
tion of China (Nos. 21871235, 21901230, 21801224), the Natural
Science Foundation of Zhejiang Province (No. LQ18B020009), the
Fundamental Research Funds of Zhejiang Sci-Tech University
(2019Y003), and the Science Foundation of Zhejiang Sci-Tech
University (ZSTU) under Grant No. 18062301-Y is gratefully
acknowledged.
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Manuscript received: December 2, 2020
Manuscript revised: December 29, 2020
Manuscript accepted: January 3, 2021
Accepted manuscript online: January 5, 2021
Version of record online: April 13, 2021
1152
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© 2021 SIOC, CAS, Shanghai, & WILEY-VCH GmbH
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