Rh(III)-Catalyzed Csp2?Csp3 Bond Cleavage/Carbonylethylation of α-Indolyl Alcohols

Article abstract of DOI:10.1002/adsc.202001430

A Rh(III)-catalyzed Csp²?Csp³ bond cleavage/carbonylethylation of α-indolyl alcohols with allylic alcohols has been reported. This transformation involved a cascade C?C bond cleavage/C?C bond formation, and provides a novel approach to assemble 2-carbonylethylindole skeletons. (Figure presented.).

Full text of DOI:10.1002/adsc.202001430

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DOI: 10.1002/adsc.202001430
Rh(III)-Catalyzed Csp2À Csp3 Bond Cleavage/Carbonylethylation
of α-Indolyl Alcohols
Zhipeng Liu,a Xinwei Hu,a Can Yang,a Haisheng Xie,a Huanfeng Jiang,a and
Wei Zenga,*
a
Key Laboratory of Functional Molecular Engineering of Guangdong Province, School of Chemistry and Chemical Engineering,
South China University of Technology, Guangzhou 510641, People’s Republic of China
Fax: (+86)-20-2223-6337
E-mail: zengwei@scut.edu.cn
Manuscript received: November 17, 2020; Revised manuscript received: January 19, 2021;
Version of record online: Februar 4, 2021
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.202001430
Abstract: A Rh(III)-catalyzed Csp2À Csp3 bond cleavage/carbonylethylation of α-indolyl alcohols with allylic
alcohols has been reported. This transformation involved a cascade CÀ C bond cleavage/CÀ C bond formation,
and provides a novel approach to assemble 2-carbonylethylindole skeletons.
Keywords: Rh(III)-Catalysis; Carbonylethylation; α-Indolyl alcohols; Allylic alcohols; CÀ C bond cleavage
Introduction
Indoles are often encountered in many natural products
and bioactive small molecules.[1] Therefore, various
methods have been developed in incorporating partic-
ular functional group into indole rings.[2] Among them,
2-carbonylethylindoles belong to versatile synthetic
building blocks, which could be further converted into
indole-fused polycyclic systems.[3] However, the syn-
thetic access to 2-carbonylethylindoles has been rarely
reported, the existed protocols mainly focus on the
direct Csp2À H and Csp2À Br bond carbonylethylation.
For examples, traditional transition metal-catalyzed
cross-coupling of 2-bromoindoles with α,β-unsaturated
ketones could efficiently install carbonylethyl group
into 2-position of highly congested and substituted
indoles (Scheme 1a).[3b,4] As for simple-structure in-
doles, ligand-directed coupling reaction of indolyl
Csp2À H with cyclopropanols[5] or diazo compounds[6]
Scheme 1. Carbonylethylation strategies of indoles.
may regioselectively realize indolyl C2-carbonylethy-
lation (Scheme 1b). Driven by the indole-based skel-
eton diversity, the development of new indolyl C2- hydroxymethenyl,[8] acyl,[9] aryl,[10] allyl[11], and alkyl[12]
carbonylethylation is therefore desirable.
group into alkenyl, aryl, alkyl, alkenyl, and aryl group,
Recently, ligand-directed unstrained carbon-carbon respectively. More recently, we reported a direct
σ bond activation provides a straightforward approach amination of ketones via pyridine-directed Csp2À Csp2
to reorganizing complex carbon skeletons.[7] To date, single bond activation, in which β-aryl elimination
this carbon-carbon cleavage strategy has been succes- derived from enol-based cyclometallation process
sively explored by Shi, Ackermann, Douglas, Kakiu- played a key role in this carbon-carbon bond cleavage/
chi, and Dong, et al., to regioselectively switch amination (Scheme 1c).[13] This work implied that
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hydroxyl group of α-indolyl alcohols could play a catalysts did not enable this transformation at all
similar role of enol to activate Csp2À Csp3 bond to (entries 1–2). Mn(CO)5Br and [Rh(COD)Cl]2 catalysts
enable carbon-carbon bond cleavage/functionalization. only cleavaged the indolyl Csp2À Csp3 bond of α-
If so, once allylic alcohols are used as coupling indolyl alcohol 1a, producing 2-unsubstituted indole
partners to react with α-indolyl alcohols, a novel 3–1a in 54% and 48% yields, respectively, and no
carbon-carbon σ bond cleavage/carbonylethylation desired 2-carbonylethylindole 3a was observed (entries
could be possibly achieved (Scheme 1d).
3–4). By contrast, Rh(III)-catalyst [Cp*RhCl2]2 simul-
taneously afforded 2-unsubstituted indole 3–1a (18%
yield) and 2-carbonylethylindole 3a (42% yield)
(entry 5). This result encouraged us to evaluate various
Results and Discussion
To explore the feasibility of this transformation, the oxidants by employing [Cp*RhCl2]2 as catalysts for
direct carbon-carbon bond cleavage/carbonylethylation further increasing the chemical selectivity (entries 6–
of N-(2-pyridyl) indolylalkyl alcohol 1a with but-3-en- 11). Gratifyingly, it was found that the use of Ag2CO3
2-ol 2a was carried out by employing CH3OH as led to the high-selective formation of C2-carbon-
solvent to screen different catalysts in the presence of ylethylindole 3a with 78% yield (entries 7–10 vs 11).
MnO2 (2.0 equiv.)/AgSbF6 (20 mol%) under air atmos- Changing solvent system and reaction temperature did
°
phere at 85 C. As shown by the representative results not produce any positive results (entries 12–16 vs 11).
listed in entries 1–5 of Table 1, extensive catalyst Meanwhile, lowering the Rh(III) catalyst-loading to
screening indicated that [Cp*IrCl2]2 and Cp*Co(CO)I2 2.5 mol% could not improve the reaction conversion
(entry 11 vs 17) [see the Supporting Information (SI)
for screening conditions].
The substrate scope is presented in Table 2. As in
the case of 3-phenylindoles, electron-donating (4-Me,
Table 1. Optimization of the reaction parameters.[a]
4-tBu, 4-MeO) and electron-withdrawing (4-Cl, 4-CF3)
groups on the benzene ring of indolyl skeleton have
important effects on the CÀ C σ bond cleavage/carbon-
ylethylation. Among them, electron-rich phenyl sub-
Entry
Catalysts
Oxidant
3–1a/3a[b]
stituents produced 70–83% yields of the products (3a~
3d), electron-deficient phenyl substituents made the
transformation a little sluggish and gave 40–54%
yields of 3e and 3f. Meanwhile, 3-methylindole and 3-
unsubstituted indole were also well-tolerated in this
reaction system, affording good yields of 3-carbon-
ylethylindoles 3g (78%) and 3h (64%), respectively.
Similarly, this transformation is also apparently sensi-
tive to the electronic effect of substituents at C5-
position of indoles, 5-alkyl, 5-alkoxyl, and 5-halo-
substituted indolyl alcohols could be efficiently con-
verted to 2-carbonylethylindoles (3i~3l) in 73–83%
yields. On the contrary, 5-trifluoromethylindolyl alco-
hol only furnished 38% yield of 3m. Regretfully, the
N-substituted pyridine-containing α-indolyl alcohols
gave inferior conversions (24–47% yields for 3n~3r)
possibly due to the combined effects of electron and
steric hindrance. It should be noted that N-pyrimidine-
substituted α-indolylalcohol and ortho-pyridyl-substi-
tuted α-phenylalcohol were not allowed for this
reaction system, and all the starting materials were
almost completely recovered (3s and 3t).
1
2
3
4
5
6
7
8
[Cp*IrCl2]2
MnO2
MnO2
MnO2
MnO2
MnO2
AgOAc
O2
AgClO4
Cu(OAc)2
AgOCOCF3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
Ag2CO3
0/0
0/0
Cp*Co(CO)I2
Mn(CO)5Br
[Rh(COD)Cl]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
[Cp*RhCl2]2
54/0
48/0
18/42
36/0
0/0
0/0
9
0/34
51/36
0/78
0/50[c]
0/41[d]
0/0[e]
0/47[f]
0/67[g]
0/44 [h]
10
11
12
13
14
15
16
17
[a] Unless otherwise noted, all the reactions were performed
using α-indolyl alcohol 1a (0.20 mmol), but-3-en-2-ol 2a
(0.60 mmol), AgSbF6 (20 mol%), and oxidant (0.4 mmol)
°
with catalysts (5 mol%) in MeOH (1.5 mL) at 85 C for 24 h
under air in a sealed tube, followed by flash chromatography
Subsequently, the effect of alkyl chain length from
alkyl alcohols on this reaction was also evaluated
(Table 3). It was found that reactivity of α-indolyl
methanol (38% yield of 3a from 1u) was lower than
ethyl alcohol (63% yield of 3a from 1v), propyl
alcohol (70% yield of 3a from 1w) and benzyl alcohol
(68% yield of 3a from 1w).
on SiO2.
[b] Isolated yield.
[c] Using DCE as solvent.
[d] Using THF as solvent.
[e] Using DMF as solvent.
[f]
°
The temperature was lowered to 50 C
The temperature was increased to 100 C
[g]
°
[h] The [Cp*RhCl2]2-loading was lowered to 2.5 mol%.
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More importantly, indole-fused cycloalcohols 4 ylethylation to furnish the corresponding 2-carbon-
such as 12-, 7-, and 6-membered cycloalcohols also ylethylindoles 5a, 5b, and 5c in acceptable yields
smoothly underwent Csp2À Csp3 bond cleavage/carbon- (42%–58%), in which the alcohol moieties were
converted into aldehydes or esters (Table 4).
Finally, the allylic alcohols 2 were explored
(Table 5). α-linear alkyl (R6)-substituted allylic alco-
hols (71% yield of 6a, 75% yield of 6c), α-cyclohexyl
(R6)-substituted allylic alcohol (86% yield of 6b), α-
benzyl (R6)-substituted allylic alcohols (79% yield of
6d, 69% yield of 6f), and even phenylethyl (R6)-
substituted allylic alcohol (87% yield of 6e) could
efficiently react with N-(2-pyridyl) indolylalkyl alcohol
1a to furnish different 2-carbonylethylindoles with
good to excellent yields. Notably, when homoallylic
alcohol was subjected to the catalytic reaction system,
2-(3-hydroxylbutenyl)indole 6h could be obtained in
38% yield. Unfortunately, employing internal allylic
Table 2. Substrate Scope.[a,b]
Table 4. Cycloalcohol Scope.[a,b]
[a] All the reactions were performed using indole-fused
cycloalcohols 4 (0.20 mmol), allylic alcohol 2a (0.60 mmol),
AgSbF6 (20 mol %), and Ag2CO3 (0.4 mmol) with
°
[Cp*RhCl2]2 (5 mol%) in MeOH (1.5 mL) at 85 C for
[a] All the reactions were performed using α-indolyl alcohols 1
(0.20 mmol), allylic alcohol 2 a (0.60 mmol), AgSbF6
(20 mol%), and Ag2CO3 (0.4 mmol) with [Cp*RhCl2]2
24 h under air in a sealed tube, followed by flash
chromatography on SiO2.
[b] Isolated yield.
°
(5 mol%) in MeOH (1.5 mL) at 85 C for 24 h under air in
[c] Using H2O as solvent and without Ag2CO3.
a sealed tube, followed by flash chromatography on SiO2.
[b] Isolated yield.
[c] Large-scale reaction of 1a (0.8 mmol).
[d] Using H2O as solvent and without Ag2CO3.
Table 5. Allylic Alcohol Scope.[a,b]
Table 3. Substrate Scope.[a,b]
[a] All the reactions were performed using α-indolyl alcohols 1
(0.20 mmol), allylic alcohol 2 a (0.60 mmol), AgSbF6
(20 mol%), and Ag2CO3 (0.4 mmol) with [Cp*RhCl2]2
[a] All the reactions were performed using α-indolyl alcohol 1a
(0.20 mmol), allylic alcohols 2 (0.60 mmol), AgSbF6
(20 mol%), and Ag2CO3 (0.4 mmol) with [Cp*RhCl2]2
°
°
(5 mol%) in MeOH (1.5 mL) at 85 C for 24 h under air in
(5 mol%) in MeOH (1.5 mL) at 85 C for 24 h under air in
a sealed tube, followed by flash chromatography on SiO2.
a sealed tube, followed by flash chromatography on SiO2.
[b] Isolated yield.
[b] Isolated yield.
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Scheme 2. Synthetic applications.
alcohol, 1,1-disubstituted allylic alcohols as substrates
could not give the corresponding products 6g, 6i and
6j.
In addition, 2-carbonylethylindole 3h could react
with ethyl carbonocyanidate 7 via nuclephilic reaction
to afford indole-tethered nitrile 8 (52%), followed by
Figure 1. Possible mechanism for the transformation.
an intramolecular cyclization in the presence of Pd- 1x was detected (Scheme 3c). These results indicated
(OAc)2 catalysts to rapidly assemble 4,5-dihydro-3aH- that pyridine played a key chelation-assisted role in the
oxazolo[5,4-c]carbazol-2(6H)-one 9 in 79% yield cleavage of Csp2À Csp3 σ bond, and a hydroxyl group-
(Scheme 2a).[14] Meanwhile, the Rh(II)-catalyzed cou- based CÀ C bond cleavage of α-indolyl alcohol possibly
pling-cyclization of 3h with diazo compound 10 could triggered this reaction. Finally, the Rh(III)-catalyzed
still produce 2,3,4,9-tetrahydro-1H-carbazole deriva- coupling reaction of 2-unsubstituted indole 3–1a with
tive 11 in 72% yield (Scheme 2b).[15]
2a under the same reaction system gave 53% yield of
To gain insight into this transformation, α-indolyl- 2-carbonylethylindole 3a, implying that 2-unsubsti-
α-phenylalcohol 1x was first subjected to react with tuted indole 3–1a was the possible intermediates of
but-3-en-2-ol 2a for 24 h, benzoic acid 12 which was Csp2À Csp3
σ
bond
cleavage/functionalization
possibly derived from the oxidation of benzaldehyde, (Scheme 3d).
could be detected and characterized by GC-MS
On the basis of the previous reports[13,16] and control
spectrum (Scheme 3a). Then, using N-phenyl-indole experiments, a plausible reaction mechanism has been
13 as a substrate did not lead to the formation of 2- proposed in Figure 1. The reaction starts with the
carbonylethylindole 14 (Scheme 3b). Meanwhile, the coordination of Rh(III) catalyst with pyridine “nitro-
reaction α-indolyl-α-phenylalcohol 1x with D2O in the gen” and alcoholic hydroxyl group to produce the
absence of allylic alcohol 2a under our standard cyclometallated rhodium(III) complexes A. Then, the
condition only produced 2-unsubstituted indole d1-3– CÀ C cleavage via β-aryl elimination[17] from A
1a, in which the incorporation of deuterium into C2- produces the corresponding Rh-aledehyde complex B,
position at the indole ring (14% D) was observed, and in which benzaldehyde could be further oxidized by
no H/D exchange (0% D) of α-CÀ H of the alcohol d1- Ag2CO3/O2 system to benzoic acid 12 (Scheme 3a).
Scheme 3. Control experiments.
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and stirred for 24~48 h at room temperature. The reaction was
monitored by TLC to achieve full conversion, then quenched by
saturated NH4Cl (aq), extracted by EtOAc for three times (3×
5 mL), dried over Na2SO4, and evaporated in vacuum to afford
the crude products, which were further purified by flash
chromatography on silica gel with petroleum ether/EtOAc
(20:1~5:1) to give excellent yields of the corresponding
alcohols 1 and 13.
Subsequently, coordination of allylic alcohol 2a to the
rhodium center via ligand exchange is followed by
migratory insertion to form a Rh(III)-complex D.
Finally, the rhodium complex D undergoes a β-H
elimination and keto-enol isomerization to give the
desired 2-carbonylethylindole 3a with the release of
the Rh(I) species, which could be further oxidized to
Rh(III) catalysts by Ag2CO3.
1-(3-Phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)butan-1-ol
1
(1a):[22] 975 mg, 95%; H NMR (400 MHz, CDCl3) δ 8.63 (d,
Conclusion
J=3.6 Hz, 1H), 8.04 (t, J=7.4 Hz, 1H), 7.76 (d, J=8.0 Hz,
1H), 7.66 (dd, J=14.7, 7.5 Hz, 3H), 7.53 (t, J=7.6 Hz, 3H),
7.40 (dd, J=13.3, 6.9 Hz, 2H), 7.26 (dd, J=14.8, 7.2 Hz, 2H),
6.41 (d, J=10.4 Hz, 1H), 5.02–4.90 (m, 1H), 1.51–1.39 (m,
1H), 1.25–1.13 (m, 2H), 1.03 (dd, J=20.2, 11.8 Hz, 1H), 0.62
(t, J=6.7 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 152.2, 148.7,
139.4, 138.4, 136.2, 134.2, 130.5, 128.6, 126.9, 123.5, 122.0,
121.6, 120.4, 120.2, 120.1, 119.0, 110.0, 66.7, 37.9, 19.4, 13.7.
In summary, we have disclosed a novel Rh(III)-
catalyzed Csp2À Csp3 bond cleavage/functionalization
of α-indoyl alcohols via carbon-carbon cleavage,
affording diversified 2-carbonylethylindoles. This pro-
tocol exhibited excellent functional group tolerance
which rendered this reaction synthetic values for rapid
assembly of highly congested and complex indoles
skeletons.
1-(1-(Pyridin-2-yl)-3-(p–tolyl)-1H-indol-2-yl)butan-1-ol (1b):
1
°
white solid; 833 mg, 78% yield; m.p. 80.4–81.7 C; H NMR
(500 MHz, CDCl3) δ 8.63 (dd, J=4.9, 1.2 Hz, 1H), 8.03 (m,
1H), 7.75 (d, J=8.1 Hz, 1H), 7.68 (d, J=7.7 Hz, 1H), 7.54 (d,
J=8.0 Hz, 3H), 7.40–7.37 (m, 1H), 7.34 (d, J=7.8 Hz, 2H),
7.28 (dd, J=5.4, 4.2 Hz, 1H), 7.23 (dd, J=11.0, 3.9 Hz, 1H),
6.37 (d, J=10.5 Hz, 1H), 4.97 (dd, J=7.7, 2.7 Hz, 1H), 2.47
(s, 3H), 1.48–1.41 (m, 1H), 1.23–1.15 (m, 2H), 1.07–0.99 (m,
1H), 0.62 (t, J=7.2 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ
152.2, 148.7, 139.4, 138.3, 136.6, 136.2, 131.2, 130.3, 129.3,
128.7, 123.5, 122.0, 121.6, 120.5, 120.2, 120.1, 110.0, 66.7,
37.9, 21.4, 19.5, 13.7; HR-MS (ESI) calcd for [M+H]+:
C24H25N2O: 357.1961, found: 357.1990; IR (KBr): 3290, 3026,
2953, 2863, 1589, 1475, 1435, 1361, 1219, 1014, 825, 741,
647 cmÀ 1.
Experimental Section
General Information
All reactions were carried out in flame-dried sealed tubes with
magnetic stirring. Unless otherwise noted, all experiments were
performed under argon atmosphere. Reagents were purchased
from Accela, Acros, Aladdin, Adamas, Energy Chemical or
TCI. Solvents were treated with 4 Å molecular sieves or sodium
and distilled prior to use. Purifications of reaction products
were carried out by flash chromatography using Qingdao
Haiyang Chemical Co. Ltd silica gel (400–630 mesh). Infrared
spectra (IR) were recorded on a Brucker TENSOR 27 FTIR
spectrophotometer and are reported as wavelength numbers
(cmÀ 1). Infrared spectra were recorded by preparing a KBr
1-(3-(4-(tert-Butyl)phenyl)-1-(pyridin-2-yl)-1H-indol-2-yl)
butan-1-ol (1c): white solid; 1051 mg, 88% yield; m.p. 159.9–
1
pellet containing the title compounds. H NMR and 13C NMR
1
°
162.2 C; H NMR (400 MHz, CDCl3) δ 8.63 (d, J=3.5 Hz,
spectra were recorded with tetramethylsilane (TMS) as internal
standard at ambient temperature on a Bruker Avance III
1H), 8.03 (t, J=7.2 Hz, 1H), 7.74 (dd, J=16.7, 7.8 Hz, 2H),
7.55 (t, J=6.4 Hz, 5H), 7.42–7.35 (m, 1H), 7.26 (m, 2H), 6.40
(d, J=10.3 Hz, 1H), 4.99 (d, J=9.0 Hz, 1H), 1.44 (s, 10H),
1.20 (s, 2H), 1.04 (dd, J=16.5, 8.2 Hz, 1H), 0.63 (t, J=6.7 Hz,
3H); 13C NMR (101 MHz, CDCl3) δ 152.2, 149.7, 148.7, 139.4,
138.4, 136.3, 131.2, 130.1, 128.7, 125.5, 123.5, 122.0, 121.5,
120.6, 120.2, 120.1, 110.0, 66.7, 38.0, 34.7, 31.5, 19.5, 13.8;
HR-MS (ESI) calcd for [M+H]+: C27H31N2O: 399.2431, found:
399.2503; IR (KBr): 3316, 3057, 2956, 2867, 1588, 1474, 1458,
1424, 1370, 1319, 1045, 1023, 779, 744 cmÀ 1.
1
400 MHz or 500 MHz for H NMR and 100 MHz or 126 MHz
for 13C NMR. Chemical shifts are reported in parts per million
(ppm) and coupling constants are reported as Hertz (Hz).
Splitting patterns are designated as singlet (s), doublet (d),
triplet (t), doublet of doublet (dd), quartet (q). Splitting patterns
that could not be interpreted or easily visualized are designated
as multiple (m). High resolution mass spectra (HRMS) were
recorded on an IF-TOF spectrometer (Micromass) and Thermo
Scientific Q Exactive. 1-Cyclohexylprop-2-en-1-ol 2c,[18] 1-
phenylbut-3-en-2-ol 2e,[18] 5-phenylpent-1-en-3-ol 2f,[19] 4-
phenylpent-1-en-3-ol 2g,[19] (E)-pent-3-en-2-ol 2h[20] and
phenyl(2-(pyridin-2-yl)phenyl)methanol 1t[21] were prepared
according to the previous literatures.
1-(3-(4-Methoxyphenyl)-1-(pyridin-2-yl)-1H-indol-2-yl)
butan-1-ol (1d): colorless solid; 1071 mg, 96% yield; m.p.
1
°
143.1–144.6 C; H NMR (400 MHz, CDCl3) δ 8.62 (dd, J=
4.9, 1.2 Hz, 1H), 8.02 (m, 1H), 7.75 (d, J=8.1 Hz, 1H), 7.67
(d, J=7.3 Hz, 1H), 7.56 (dd, J=13.7, 8.4 Hz, 3H), 7.38 (dd,
J=7.0, 5.3 Hz, 1H), 7.31–7.20 (m, 2H), 7.09 (d, J=8.7 Hz,
2H), 6.39 (d, J=10.4 Hz, 1H), 4.96 (dd, J=17.6, 7.5 Hz, 1H),
3.92 (s, 3H), 1.47 (m, 1H), 1.24–1.15 (m, 2H), 1.04 (m, 1H),
0.63 (t, J=7.1 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 158.7,
152.2, 148.7, 139.4, 138.2, 136.2, 131.5, 128.8, 126.5, 123.5,
121.9, 121.5, 120.4, 120.2, 119.8, 114.1, 110.0, 66.7, 55.3, 37.9,
19.5, 13.7; HR-MS (ESI) calcd for [M+H]+: C24H25N2O2:
373.1911, found: 373.1968; IR (KBr): 3320, 3049, 2950, 2862,
Procedure for the Synthesis of Secondary Alcohol
Substrates 1a~1r, 1v~1x, and 13
The secondary alcohols 1a~1r, 1v~1x and 13 were prepared
from ketones S1, which were synthesized according to the
previous literature.[13] Ketones S1 (3.0 mmol) were dissolved in
THF (20 mL), then NaBH4 (15.0 mol) was added in portions,
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1588, 1556, 1506, 1473, 1373, 1282, 1245, 1172, 1104, 1019,
998, 837, 791, 740 cmÀ 1.
(500 MHz, CDCl3) δ 8.65–8.57 (m, 1H), 8.02 (m, 1H), 7.74 (d,
J=8.1 Hz, 1H), 7.63 (dd, J=8.0, 1.1 Hz, 2H), 7.53 (t, J=
7.7 Hz, 2H), 7.46–7.35 (m, 4H), 7.11 (dd, J=8.5, 1.2 Hz, 1H),
6.43 (d, J=10.5 Hz, 1H), 4.94 (m, 1H), 2.46 (s, 3H), 1.49–1.41
(m, 1H), 1.22–1.10 (m, 2H), 1.06–0.96 (m, 1H), 0.61 (t, J=
7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 152.3, 148.6,
139.4, 138.5, 134.5, 134.4, 131.1, 130.5, 128.8, 128.6, 126.9,
125.0, 121.8, 120.1, 120.0, 119.9, 109.8, 66.7, 37.9, 21.4, 19.4,
13.7; HR-MS (ESI) calcd for [MÀ H]À : C24H23N2O: 355.1816,
found: 355.1816; IR (KBr): 3565, 3064, 2959, 1867, 1747,
1681, 1516, 1506, 1372, 1261, 1100, 799, 744 cmÀ 1.
1-(3-(4-Chlorophenyl)-1-(pyridin-2-yl)-1H-indol-2-yl)butan-
1-ol (1e): light yellow solid; 812 mg, 72% yield; m.p. 171.9–
173.0 C; 1H NMR (500 MHz, CDCl3) δ 8.64 (dd, J=4.9,
°
1.2 Hz, 1H), 8.04 (m, 1H), 7.76 (dd, J=8.0, 4.5 Hz, 1H), 7.63
(d, J=7.4 Hz, 1H), 7.54 (m, 5H), 7.42–7.39 (m, 1H), 7.31–7.27
(m, 1H), 7.24 (dd, J=10.9, 3.9 Hz, 1H), 6.31 (d, J=10.3 Hz,
1H), 4.90 (dd, J=17.6, 7.5 Hz, 1H), 1.46 (m, 1H), 1.22–1.12
(m, 2H), 1.07–0.98 (m, 1H), 0.62 (t, J=7.2 Hz, 3H); 13C NMR
(126 MHz, CDCl3) δ 152.0, 148.8, 139.5, 138.5, 136.2, 132.8,
131.7, 130.5, 128.8, 128.2, 123.7, 122.2, 121.8, 120.2, 120.1,
118.8, 110.1, 66.6, 37.8, 19.4, 13.7. HR-MS (ESI) calcd for [M
+H]+: C23H22N2OCl: 377.1415, found: 377.1409; IR (KBr):
3310, 3061, 2954, 2861,1587, 1566, 1472, 1455, 1435, 1365,
1314, 1215, 1088, 1014, 1000, 832, 779, 746, 716 cmÀ 1.
1-(5-Methoxy-3-phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)
butan-1-ol (1j): colorless oily liquid; 770 mg, 69% yield; H
1
NMR (500 MHz, CDCl3) δ 8.61 (dd, J=5.0, 1.2 Hz, 1H), 8.02
(m, 1H), 7.72 (d, J=8.1 Hz, 1H), 7.65–7.60 (m, 2H), 7.53 (t,
J=7.7 Hz, 2H), 7.45–7.39 (m, 2H), 7.37 (m, 1H), 7.10 (d, J=
2.5 Hz, 1H), 6.92 (dd, J=9.0, 2.5 Hz, 1H), 6.45 (s, 1H), 4.92 (t,
J=7.5 Hz, 1H), 3.84 (s, 3H), 1.48–1.39 (m, 1H), 1.22–1.13 (m,
2H), 1.07–0.98 (m, 1H), 0.61 (t, J=7.2 Hz, 3H); 13C NMR
(126 MHz, CDCl3) δ 155.5, 152.2, 148.6, 139.4, 139.0, 134.4,
131.2, 130.4, 129.2, 128.6, 126.9, 121.8, 120.0, 119.9, 113.3,
110.9, 102.0, 66.7, 55.9, 37.9, 19.4, 13.7; HR-MS (ESI) calcd
for [M+H]+: C24H25N2O2: 373.1911, found: 373.1902; IR
(KBr): 3260, 3036, 3011, 2988, 2953, 2863, 1473, 1441, 1206,
1150, 1069, 965, 703, 521 cmÀ 1.
1-(1-(Pyridin-2-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indol-
2-yl)butan-1-ol (1f): colorless solid; 984 mg, 80% yield; m.p.
1
°
110.5–111.3 C; H NMR (400 MHz, CDCl3) δ 8.65 (dd, J=
4.9, 1.3 Hz, 1H), 8.06 (m, 1H), 7.86–7.74 (m, 5H), 7.68 (d, J=
7.5 Hz, 1H), 7.56 (d, J=8.2 Hz, 1H), 7.42 (dd, J=7.3, 5.0 Hz,
1H), 7.36–7.25 (m, 2H), 6.38 (d, J=10.5 Hz, 1H), 4.95 (m,
1H), 1.53–1.44 (m, 1H), 1.22–1.18 (m, 1H), 1.05 (m, 1H),
0.95–0.89 (m, 1H), 0.65 (t, J=7.1 Hz, 3H); 13C NMR
(101 MHz, CDCl3) δ 151.9, 148.8, 139.6, 139.0, 138.3, 136.3,
2
130.7, 129.0(q, J=32.3 Hz, JCF), 128.0, 125.5(q, J=4.0 Hz,
1-(5-Fluoro-3-phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)butan-
3JCF), 124.5(d, J=273.7 Hz, JCF), 123.9, 122.4, 122.0, 120.3,
1-ol (1k): colorless solid; 972 mg, 90% yield; m.p. 94.3–
1
95.9 C; 1H NMR (500 MHz, CDCl3) δ 8.61 (dd, J=4.9,
°
120.0, 118.7, 110.2, 66.7, 37.8, 19.5, 13.7; HR-MS (ESI) calcd
for [MÀ H]À : C24H20F3N2O: 409.1533, found: 409.1532; IR
(KBr): 3456, 3057, 2926, 2860, 1618, 1589, 1474, 1458, 1438,
1371, 1323, 1123, 1068, 1021, 843, 782, 741 cmÀ 1.
1.1 Hz, 1H), 8.01 (m, 1H), 7.68 (d, J=8.1 Hz, 1H), 7.57 (d, J=
7.4 Hz, 2H), 7.50 (t, J=7.7 Hz, 2H), 7.39 (m, 3H), 7.28 (dd,
J=9.3, 2.5 Hz, 1H), 6.97 (m, 1H), 6.28 (d, J=10.5 Hz, 1H),
4.91 (m, 1H), 1.43–1.36 (m, 1H), 1.20–1.10 (m, 2H), 0.99 (m,
1H), 0.59 (t, J=7.2 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ
1-(3-Methyl-1-(pyridin-2-yl)-1H-indol-2-yl)butan-1-ol (1g):
1
colorless oily liquid; 756 mg, 90% yield; H NMR (500 MHz,
1
159.0 (d, J=238.1 Hz, JCF), 152.0, 148.8, 140.0, 139.6, 133.8,
CDCl3) δ 8.57 (m, 1H), 8.00–7.94 (m, 1H), 7.66 (d, J=8.1 Hz,
1H), 7.64–7.61 (m, 1H), 7.50–7.45 (m, 1H), 7.33 (m, 1H),
7.27–7.20 (m, 2H), 6.54 (d, J=10.1 Hz, 1H), 5.06–4.97 (m,
1H), 2.44 (s, 3H), 1.64–1.56 (m, 1H), 1.32–1.27 (m, 2H), 1.17–
1.08 (m, 1H), 0.77 (t, J=7.2 Hz, 3H); 13C NMR (126 MHz,
CDCl3) δ 152.3, 148.4, 139.3, 138.0, 136.1, 129.8, 123.1, 121.6,
120.9, 120.0, 119.5, 112.6, 109.9, 66.1, 38.2, 19.6, 13.8, 9.2;
HR-MS (ESI) calcd for [MÀ H]À : C18H19N2O: 279.1503, found:
279.1503; IR (KBr): 3690, 3062, 2956, 2868, 1867, 1747, 1730,
1515, 1361, 1222, 780, 741 cmÀ 1.
3
132.7, 130.3, 129.2 (d, J=10.1 Hz, JCF), 128.7, 127.1, 122.3,
2
120.1, 119.9, 111.6 (d, J=26.5 Hz, JCF), 110.9 (d, J=8.8 Hz,
2
3JCF), 105.4 (d, J=23.9 Hz, JCF), 66.6, 37.7, 19.4, 13.7; HR-
MS (ESI) calcd for [M+H]+: C23H22N2OF: 361.1711, found:
361.1761; IR (KBr): 3379, 3305, 3082, 2961, 2927, 2866, 1588,
1472, 1444, 1370, 1137, 1024, 811, 774, 700 cmÀ 1.
1-(5-Chloro-3-phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)butan-
°
1-ol (1l): white solid; 959 mg, 85% yield; m.p. 102.4–104.8 C;
1H NMR (400 MHz, CDCl3) δ 8.64 (d, J=4.8 Hz, 1H), 8.05 (t,
J=7.7 Hz, 1H), 7.70 (d, J=8.1 Hz, 1H), 7.63–7.58 (m, 3H),
7.54 (t, J=7.5 Hz, 2H), 7.45–7.40 (m, 3H), 7.22 (d, J=8.8 Hz,
1H), 6.29 (d, J=10.5 Hz, 1H), 4.94 (dd, J=17.8, 7.6 Hz, 1H),
1.46–1.39 (m, 1H), 1.18 (m, 2H), 1.02 (dd, J=16.8, 7.7 Hz,
1H), 0.62 (t, J=7.0 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ
151.8, 148.8, 139.7, 139.6, 134.6, 133.6, 130.3, 129.7, 128.7,
127.2, 123.7, 122.4, 120.1, 119.8, 119.5, 111.2, 66.6, 37.7, 19.4,
13.7; HR-MS (ESI) calcd for [MÀ H]À : C23H20ClN2O: 375.1270,
found: 375.1269; IR (KBr): 3352, 3053, 2955, 2862, 1866,
1747, 1472, 1442, 1368, 1262, 1042, 1016, 799, 704 cmÀ 1.
1-(1-(Pyridin-2-yl)-1H-indol-2-yl)butan-1-ol (1h): white sol-
1
°
id; 758 mg, 95% yield; m.p. 60.7–63.3 C; H NMR (400 MHz,
CDCl3) δ 8.61 (d, J=4.8 Hz, 1H), 7.98 (t, J=7.7 Hz, 1H),
7.71–7.65 (m, 2H), 7.51 (d, J=7.6 Hz, 1H), 7.38–7.33 (m, 1H),
7.26–7.20 (m, 2H), 6.71 (s, 1H), 6.11 (d, J=2.1 Hz, 1H), 4.63
(s, 1H), 2.09–2.01 (m, 1H), 1.90 (m, 1H), 1.60 (dd, J=14.5,
7.1 Hz, 1H), 1.45 (dd, J=15.8, 7.2 Hz, 1H), 0.97 (t, J=7.4 Hz,
3H); 13C NMR (101 MHz, CDCl3) δ 151.4, 148.7, 143.9, 139.1,
136.6, 128.8, 122.8, 121.7, 121.3, 121.3, 120.1, 110.3, 102.8,
65.7, 36.4, 19.7, 14.1; HR-MS (ESI) calcd for [MÀ H]À :
C17H17N2O: 265.1346, found: 265.1345; IR (KBr): 3317, 3059,
2955, 2922, 2867, 1591, 1474, 1454, 1345, 1154, 1031, 1021,
803, 746, 523 cmÀ 1.
1-(3-Phenyl-1-(pyridin-2-yl)-5-(trifluoromethyl)-1H-indol-2-
yl)butan-1-ol (1m): colorless oily liquid; 1033 mg, 84% yield;
1H NMR (500 MHz, CDCl3) δ 8.67 (m, 1H), 8.09 (m, 1H), 7.93
(s, 1H), 7.73 (d, J=8.1 Hz, 1H), 7.63–7.60 (m, 2H), 7.59–7.53
(m, 3H), 7.51 (dd, J=8.7, 1.4 Hz, 1H), 7.48–7.43 (m, 2H), 6.16
(d, J=10.4 Hz, 1H), 4.96 (m, 1H), 1.44 (m, 1H), 1.21–1.13 (m,
1-(5-Methyl-3-phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)butan-
1
1-ol (1i): colorless oily liquid; 940 mg, 88% yield; H NMR
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2H), 1.08–0.99 (m, 1H), 0.62 (t, J=7.2 Hz, 3H); 13C NMR
421.0910, found: 421.0915; IR (KBr): 3305, 3039, 2953, 2922,
1571, 1454, 1470, 1458, 1034, 1012, 775, 753, 703 cmÀ 1.
(101 MHz, CDCl3) δ 151.6, 149.0, 140.2, 139.7, 137.7, 133.3,
1
130.4, 128.8, 128.1, 127.4, 125.0(d, J=272.7 Hz, JCF), 124.0
1-(3-Phenyl-1-(5-(trifluoromethyl)pyridin-2-yl)-1H-indol-2-
2
(q, J=32.3 Hz, JCF), 122.8, 120.4, 120.3, 120.2 (q, J=4.0 Hz,
yl)butan-1-ol (1r): colorless solid; 935 mg, 76% yield; m.p.
3
3JCF), 118.0 (q, J=5.0 Hz, JCF), 110.4, 66.6, 37.7, 19.4, 13.6;
72.8–73.9 C; 1H NMR (500 MHz, CDCl3) δ 8.92 (d, J=
°
HR-MS (ESI) calcd for [M+H]+: C24H22F3N2O: 411.1679,
found: 411.1673; IR (KBr): 3437, 3056, 2961, 1473, 1442,
1325, 1272, 1162, 1115, 1000, 896, 774, 617 cmÀ 1.
0.8 Hz, 1H), 8.27 (dd, J=8.5, 2.3 Hz, 1H), 7.91 (d, J=8.5 Hz,
1H), 7.67 (d, J=7.6 Hz, 1H), 7.65–7.61 (m, 2H), 7.54 (dd, J=
15.0, 7.7 Hz, 3H), 7.46–7.40 (m, 1H), 7.34–7.30 (m, 1H), 7.28–
7.24 (m, 1H), 5.85 (d, J=10.3 Hz, 1H), 4.96 (m, 1H), 1.51–
1.44 (m, 1H), 1.25–1.14 (m, 2H), 1.08–1.00 (m, 1H), 0.63 (t,
J=7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 154.8, 146.0 (q,
1-(1-(5-Methylpyridin-2-yl)-3-phenyl-1H-indol-2-yl)butan-1-
1
°
ol (1n): white solid; 854 mg, 80% yield; m.p. 96.2–97.2 C; H
NMR (500 MHz, CDCl3) δ 8.48–8.42 (m, 1H), 7.84 (dd, J=
8.1, 2.3 Hz, 1H), 7.68–7.62 (m, 4H), 7.54–7.48 (m, 3H), 7.44–
7.36 (m, 1H), 7.26 (m, 1H), 7.24–7.19 (m, 1H), 6.37 (d, J=
9.0 Hz, 1H), 4.95 (d, J=7.1 Hz, 1H), 2.50 (s, 3H), 1.48–1.40
(m, 1H), 1.22–1.13 (m, 2H), 1.07–0.99 (m, 1H), 0.62 (t, J=
7.2 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 149.8, 148.7,
140.0, 138.3, 136.3, 134.3, 132.0, 130.5, 128.5, 128.4, 126.8,
123.4, 121.4, 120.3, 119.7, 119.7, 110.0, 66.7, 37.9, 19.5, 18.1,
13.7; HR-MS (ESI) calcd for [M+H]+: C24H25N2O: 357.1961,
found: 357.1992; IR (KBr): 3265, 3047, 2954, 2926, 1599,
1484, 1455, 1390, 1219, 1012, 961, 745, 704 cmÀ 1.
3
3
J=4.0 Hz, JCF), 138.2, 136.7 (q, J=4.0 Hz, JCF), 136.1,
133.7, 130.4, 129.0, 128.7, 127.3, 124.2, 124.1(q, J=24.2 Hz,
2JCF), 123.3 (d, J=272.7 Hz, JCF), 122.4, 121.6, 120.8, 119.7,
1
109.9, 66.7, 38.0, 19.4, 13.6; HR-MS (ESI) calcd for [MÀ H]À :
C24H20F3N2O: 409.1533, found: 409.1533; IR (KBr): 3364,
3052, 2956, 2867, 1602, 1489, 1456, 14325, 1169, 1133, 1081,
1019, 749, 702 cmÀ 1.
1-(3-Phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)ethan-1-ol (1v):
1
°
light yellow solid; 829 mg, 88% yield; m.p. 148.5–150.6 C; H
NMR (500 MHz, CDCl3) δ 8.68–8.62 (m, 1H), 8.04 (m, 1H),
7.78 (d, J=8.1 Hz, 1H), 7.69 (d, J=7.6 Hz, 1H), 7.65 (dd, J=
8.0, 1.1 Hz, 2H), 7.56–7.52 (m, 3H), 7.44–7.38 (m, 2H), 7.29
(m, 1H), 7.25–7.22 (m, 1H), 6.52 (s, 1H), 5.20 (s, 1H), 1.15 (d,
J=7.0 Hz, 3H); 13C NMR (126 MHz, CDCl3) δ 152.1, 148.7,
139.4, 139.3, 136.2, 134.2, 130.5, 128.6, 128.5, 127.0, 123.6,
122.0, 121.7, 120.5, 120.3, 119.1, 110.0, 62.4, 22.2; HR-MS
(ESI) calcd for [M+H]+: C21H19N2O: 315.1492, found:
315.1510; IR (KBr): 3211, 3025, 2959, 1867, 1747, 1730, 1506,
1539, 1361, 1224, 094, 1018, 771, 748 cmÀ 1.
1-(1-(4-Methylpyridin-2-yl)-3-phenyl-1H-indol-2-yl)butan-1-
°
ol (1o): colorless solid; 929 mg, 87% yield; m.p. 84.6–86.2 C;
1H NMR (500 MHz, CDCl3) δ 8.47 (d, J=5.2 Hz, 1H), 7.69–
7.62 (m, 3H), 7.57–7.50 (m, 4H), 7.43–7.39 (m, 1H), 7.27 (m,
1H), 7.24–7.20 (m, 2H), 6.53 (d, J=10.1 Hz, 1H), 4.95 (d, J=
9.6 Hz, 1H), 2.58 (s, 3H), 1.44 (m, 1H), 1.25–1.14 (m, 2H),
1.09–0.99 (m, 1H), 0.63 (t, J=7.2 Hz, 3H); 13C NMR
(126 MHz, CDCl3) δ 152.1, 151.2, 148.2, 138.5, 136.2, 134.3,
130.5, 128.5, 126.9, 123.4, 123.2, 121.5, 120.7, 120.4, 119.9,
110.1, 66.6, 37.9, 21.5, 19.5, 13.7; HR-MS (ESI) calcd for [M
+H]+: C24H25N2O: 357.1961, found: 357.1989; IR (KBr):
3516, 2978, 2960, 2866, 1752, 1735, 1700, 1654, 1457, 1220,
1068, 746, 699 cmÀ 1.
1-(3-Phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)propan-1-ol (1w):
colorless liquid; 925 mg, 94% yield; 1H NMR (500 MHz,
CDCl3) δ 8.65–8.60 (m, 1H), 8.03 (m, 1H), 7.76 (d, J=8.1 Hz,
1H), 7.67 (dd, J=15.0, 7.4 Hz, 3H), 7.54 (t, J=7.8 Hz, 3H),
7.44–7.37 (m, 2H), 7.31–7.27 (m, 1H), 7.24 (t, J=7.4 Hz, 1H),
6.38 (d, J=10.4 Hz, 1H), 4.87 (dd, J=18.0, 7.9 Hz, 1H), 1.53–
1.45 (m, 1H), 1.28–1.21 (m, 1H), 0.68 (t, J=7.4 Hz, 3H); 13C
NMR (126 MHz, CDCl3) δ 152.1, 148.7, 139.4, 138.2, 136.2,
134.3, 130.5, 128.6, 127.0, 123.6, 122.0, 121.6, 120.4, 120.3,
120.2, 110.0, 68.4, 28.8, 10.7; HR-MS (ESI) calcd for [M+H]+
: C22H21N2O: 329.1648, found: 329.1669; IR (KBr): 3674, 3026,
2967, 2922, 2869, 1867, 1588, 1471, 1439, 1222, 1091, 1962,
741, 703 cmÀ 1.
1-(1-(5-Chloropyridin-2-yl)-3-phenyl-1H-indol-2-yl)butan-1-
ol (1p): colorless solid; 1038 mg, 92% yield; m.p. 128.7–
1
°
129.9 C; H NMR (500 MHz, CDCl3) δ 8.60 (d, J=2.4 Hz,
1H), 8.00 (dd, J=8.6, 2.6 Hz, 1H), 7.72 (d, J=8.6 Hz, 1H),
7.68 (d, J=7.8 Hz, 1H), 7.66–7.63 (m, 2H), 7.54 (t, J=7.7 Hz,
2H), 7.49 (d, J=8.2 Hz, 1H), 7.43 (t, J=7.4 Hz, 1H), 7.33–
7.29 (m, 1H), 7.27–7.23 (m, 1H), 5.78 (d, J=9.8 Hz, 1H), 4.97
(q, J=7.8 Hz, 1H), 1.53–1.46 (m, 1H), 1.22 (m, 2H), 1.09–1.02
(m, 1H), 0.65 (t, J=7.3 Hz, 3H); 13C NMR (126 MHz, CDCl3)
δ 150.4, 147.6, 139.2, 138.1, 136.2, 134.0, 130.4, 129.9, 128.6,
127.1, 123.8, 121.9, 121.1, 120.6, 109.8, 66.7, 37.9, 19.5, 13.7;
HR-MS (ESI) calcd for [M+H]+: C23H22ClN2O: 377.1415,
found: 377.1419; IR (KBr): 3297, 3043, 2953, 2862, 1576,
1459, 1390, 1361, 1110, 1035, 776, 747 cmÀ 1.
Phenyl(3-phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)methanol
1
°
(1x): white power; 948 mg, 84% yield; m.p. 167.0–168.1 C; H
NMR (500 MHz, CDCl3) δ 8.43 (dd, J=5.0, 1.2 Hz, 1H), 7.86–
7.78 (m, 3H), 7.64 (m, 1H), 7.57 (t, J=7.7 Hz, 2H), 7.49 (dd,
J=7.0, 1.5 Hz, 1H), 7.44 (t, J=7.4 Hz, 1H), 7.34–7.25 (m,
3H), 7.10 (m, 1H), 7.09–7.05 (m, 2H), 7.00 (dd, J=16.2,
9.3 Hz, 3H), 6.94 (t, J=7.2 Hz, 1H), 6.27 (d, J=11.1 Hz, 1H);
13C NMR (126 MHz, CDCl3) δ 151.5, 148.1, 142.8, 138.9,
138.3, 136.2, 134.0, 130.3, 128.8, 128.1, 127.4, 127.2, 126.1,
125.2, 123.8, 121.7, 121.6, 121.2, 120.6, 120.2, 110.2, 67.4;
HR-MS (ESI) calcd for [M+H]+: C26H21N2O: 377.1648, found:
377.1675; IR (KBr): 3409, 3026, 2927, 1589, 1488, 1434, 1367,
1149, 1039, 774, 756, 609 cmÀ 1.
1-(1-(5-Bromopyridin-2-yl)-3-phenyl-1H-indol-2-yl)butan-1-
ol (1q): light yellow solid; 844 mg, 67% yield; m.p. 111.2–
1
°
112.3 C; H NMR (500 MHz, CDCl3) δ 8.69 (d, J=1.8 Hz,
1H), 8.12 (dd, J=8.4, 1.9 Hz, 1H), 7.68 (dd, J=15.0, 8.1 Hz,
4H), 7.55 (t, J=7.5 Hz, 2H), 7.50 (d, J=8.2 Hz, 1H), 7.44 (t,
J=7.3 Hz, 1H), 7.33–7.24 (m, 2H), 5.82 (d, J=10.2 Hz, 1H),
5.06–4.88 (m, 1H), 1.58–1.47 (m, 1H), 1.31–1.17 (m, 2H), 1.07
(m, 1H), 0.67 (t, J=7.2 Hz, 3H); 13C NMR (126 MHz, CDCl3)
δ 150.8, 149.8, 142.1, 138.1, 136.2, 134.1, 130.5, 128.7, 127.1,
123.9, 122.0, 121.4, 120.7, 120.6, 118.0, 109.9, 66.7, 37.9, 19.5,
13.7; HR-MS (ESI) calcd for [M+H]+: C23H22BrN2O:
1-(3-Methyl-1-phenyl-1H-indol-2-yl)ethan-1-ol (13): light
yellow power; 685 mg, 91% yield; m.p. 122.3–124.0 C; 1H
°
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NMR (400 MHz, CDCl3) δ 7.66 (m, 1H), 7.59–7.47 (m, 3H),
7.41 (d, J=7.5 Hz, 2H), 7.25–7.14 (m, 2H), 7.08–7.01 (m, 1H),
5.06 (q, J=6.8 Hz, 1H), 2.56 (s, 3H), 1.56 (d, J=6.8 Hz, 3H);
13C NMR (101 MHz, CDCl3) δ 138.5, 138.3, 137.8, 129.5,
128.9, 128.8, 128.1, 122.3, 119.8, 118.6, 110.3, 109.0, 63.6,
22.9, 9.1; HR-MS (ESI) calcd for [M+H]+: C17H18NO:
252.1383, found: 252.1374; IR (KBr): 3436, 3067, 2966, 1923,
1637, 1498, 1454, 1370, 1110, 1070, 760, 742, 700 cmÀ 1.
5-(Pyridin-2-yl)-7,8,9,10-tetrahydrocyclohepta[b]indol-
6(5H)-one (S3): white solid; 432 mg, 55% yield; m.p. 108.7–
1
°
110.0 C; H NMR (400 MHz, CDCl3) δ 8.60 (d, J=4.0 Hz,
1H), 7.87 (m, 1H), 7.75 (d, J=8.0 Hz, 1H), 7.39–7.30 (m, 4H),
7.27–7.21 (m, 1H), 3.24–3.16 (m, 2H), 2.89–2.84 (m, 2H),
2.09–1.99 (m, 4H); 13C NMR (101 MHz, CDCl3) δ 194.6,
152.3, 149.2, 139.4, 138.0, 134.8, 128.3, 127.4, 126.9, 122.2,
121.6, 121.2, 121.0, 111.3, 42.9, 25.8, 24.0, 22.3; HR-MS [ESI-
MS(+)] calcd for [M+H]+: C18H17N2O: 277.1335, found:
277.1332; IR (KBr): 3465, 3051, 2926, 2854, 1747, 1704, 1649,
1589, 1468, 1220, 1150, 1135, 1049, 778, 744, 684 cmÀ 1.
Procedure for the Synthesis of Primary Alcohols 1s
and 1u
Compounds 4a, 4b, 4c was prepared from the compound S3
according to the procedure for the synthesis of compound 1b.
The alcohols 1s and 1u were prepared from ketones S2, which
were synthesized according to the previous literature.[13] To a
35 mL pressure tube equipped with a stirring bar were added
[Mn(CO)5Br] (2 mg, 0.005 mmol), (CH2O)n (90.0 mg,
3.0 mmol), NaOAc (8.0 mg, 0.10 mmol) and ketones
(1.0 mmol) under air. The reaction vessel was evacuated and
backfilled with argon for three times. Dioxane (1.0 mL) was
added under an argon atmosphere, the tube was sealed and the
5-(Pyridin-2-yl)-6,7,8,9,10,11,12,13,14,15-decahydro-5H-cy-
clododeca[b]indol-6-ol (4a): white power; 564 mg, 54% yield;
1
°
m.p. 122.2–124.7 C; H NMR (400 MHz, CDCl3) δ 8.63–8.52
(m, 1H), 7.99 (m, 1H), 7.73–7.61 (m, 2H), 7.51–7.45 (m, 1H),
7.34 (dd, J=7.3, 5.1 Hz, 1H), 7.27–7.19 (m, 2H), 6.57 (d, J=
10.7 Hz, 1H), 5.17 (m, 1H), 3.05–2.91 (m, 2H), 2.02–1.93 (m,
1H), 1.82 (m, 2H), 1.60 (m, 2H), 1.44–1.32 (m, 4H), 1.28–1.09
(m, 6H), 0.92–0.88 (m, 1H); 13C NMR (101 MHz, CDCl3) δ
152.5, 148.3, 140.1, 139.3, 136.7, 129.1, 123.1, 121.6, 120.9,
120.2, 120.0, 116.8, 109.9, 62.4, 32.7, 28.0, 25.9, 23.7, 23.6,
22.9, 22.0, 21.7, 20.9; HR-MS (ESI) calcd for [MÀ H]À :
C23H27N2O: 347.2129, found: 347.2127; IR (KBr): 3289, 3050,
2925, 2850, 1588, 1567, 1474, 1437, 1212, 992, 935, 786, 743,
681 cmÀ 1.
°
reaction was stirred for 15 h at 80 C. The mixture was cooled
to room temperature and concentrated afterwards. Purification
by column chromatography on silica gel (eluent: pentane/ethyl
acetate=15:1) afforded the pure desired products 1s and 1u.
(3-Phenyl-1-(pyrimidin-2-yl)-1H-indol-2-yl)methanol (1s):
°
light yellow power; 200 mg, 66% yield; m.p. 138.1–138.9 C;
1H NMR (400 MHz, CDCl3) δ 8.80 (d, J=4.9 Hz, 2H), 8.59 (d,
J=8.4 Hz, 1H), 7.75 (dd, J=8.1, 1.3 Hz, 3H), 7.58 (dd, J=
10.5, 4.7 Hz, 2H), 7.48–7.37 (m, 2H), 7.37–7.29 (m, 1H), 7.15
(t, J=4.9 Hz, 1H), 5.50 (t, J=7.3 Hz, 1H), 4.74 (d, J=7.3 Hz,
2H); 13C NMR (101 MHz, CDCl3) δ 158.4, 157.8, 136.1, 135.7,
133.6, 130.2, 128.9, 128.7, 127.3, 124.7, 123.0, 122.8, 120.1,
116.8, 115.1, 55.7; HR-MS (ESI) calcd for [MÀ H]À :
C19H14N3O: 300.1142, found: 300.1142; IR (KBr): 3262, 3042,
2929, 2883, 1565, 1453, 1430, 1268, 1231, 1010, 783,
728 cmÀ 1.
5-(Pyridin-2-yl)-5,6,7,8,9,10-hexahydrocyclohepta[b]indol-6-
ol (4b): white power; 150 mg, 54% yield; m.p. 98.7–99.0 C;
°
1H NMR (400 MHz, CDCl3) δ 8.55 (d, J=4.6 Hz, 1H), 7.92–
7.86 (m, 1H), 7.71–7.65 (m, 1H), 7.62 (d, J=8.1 Hz, 1H),
7.53–7.46 (m, 1H), 7.26 (dd, J=7.9, 4.7 Hz, 3H), 5.61 (s, 1H),
4.97–4.85 (m, 1H), 3.13–2.95 (m, 2H), 2.42–2.18 (m, 3H), 2.05
(t, J=12.9 Hz, 1H), 1.98–1.86 (m, 2H); 13C NMR (101 MHz,
CDCl3) δ 151.4, 148.9, 139.4, 139.0, 135.3, 129.3, 123.0, 121.5,
120.9, 120.2, 119.3, 117.9, 110.0, 65.0, 32.1, 27.6, 23.1; HR-
MS [ESI-MS(+)] calcd for [M+H]+: C18H19N2O: 279.1492,
found: 279.1490; IR (KBr): 3451, 2928, 1634, 1591, 1475,
1457, 1367, 1218, 1095, 1002, 775, 739 cmÀ 1.
(3-Phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)methanol
(1u):
white power; 210 mg, 70% yield; m.p. 104.3–105.7 C; 1H
NMR (400 MHz, CDCl3) δ 8.56 (d, J=4.2 Hz, 1H), 7.95–7.87
(m, 1H), 7.77 (d, J=7.6 Hz, 1H), 7.69 (t, J=9.0 Hz, 3H), 7.57
(d, J=8.1 Hz, 1H), 7.51 (t, J=7.6 Hz, 2H), 7.37 (t, J=7.4 Hz,
1H), 7.29–7.19 (m, 3H), 5.68 (t, J=6.8 Hz, 1H), 4.58 (d, J=
6.6 Hz, 2H); 13C NMR (101 MHz, CDCl3) δ 151.3, 148.9,
139.2, 136.6, 135.6, 134.1, 130.0, 128.8, 128.3, 126.9, 123.8,
121.9, 121.6, 120.6, 119.7, 119.6, 110.5, 55.1; HR-MS (ESI)
calcd for [MÀ H]À : C20H15N2O: 299.1190, found: 299.1190; IR
(KBr): 3325, 3018, 2925, 2855, 1592, 1473, 1439, 1367, 1233,
1199, 1077, 1055, 924, 727, 704, 649 cmÀ 1.
°
9-(Pyridin-2-yl)-2,3,4,9-tetrahydro-1H-carbazol-1-ol
(4c):
1
°
white power; 180 mg, 68% yield; m.p.105.2–107.0 C; H NMR
(400 MHz, CDCl3) δ 8.56 (dd, J=4.9, 1.1 Hz, 1H), 7.94 (m,
1H), 7.70 (d, J=8.2 Hz, 1H), 7.65–7.58 (m, 2H), 7.31–7.22 (m,
3H), 6.25 (s, 1H), 4.76 (s, 1H), 2.96 (m, 1H), 2.73–2.62 (m,
1H), 2.31 (dd, J=12.3, 2.3 Hz, 1H), 2.26–2.13 (m, 1H), 2.01–
1.86 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 151.3, 148.6,
139.0, 137.7, 135.5, 128.7, 123.2, 121.1, 120.7, 119.4, 118.5,
115.2, 110.4, 60.5, 31.0, 21.5, 18.0; HR-MS [ESI-MS(+)] calcd
for [M+H]+: C17H17N2O: 265.1335, found: 265.1331; IR
(KBr): 3296, 2946, 2920, 2852, 1590, 1474, 1444, 1371, 1308,
1227, 1168, 983, 756, 743 cmÀ 1.
Procedure for the Synthesis of Indole-Fused Cyclo-
alcohols 4a, 4b and 4c
General procedure for the synthesis of arylalkylketone S3:
Indole (3.0 mmol) was coupled with 2-bromopyridine (569 mg,
3.6 mmol) using K3PO4 ·3H2O (1.68 g, 6.3 mmol), CuI (29 mg,
1.5 mmol), and N, N-dimethylcyclohexane-1,2-diamine (85 mg,
6.0 mmol). Flash chromatography on silica gel (petroleum
ether: ethyl acetate=20:1) provided of the desired product
S3.[13,23]
Procedure for the Synthesis of Allylic Alcohol 2j
Synthesis of 2-benzylacrylaldehyde S4: To a solution of
formaldehyde (10 mmol, 37% in water) and 3-phenylpropanal
(10 mmol, 100 mol%) in i-PrOH (1 mL/mmol) was added
propionic acid (1 mmol, 10 mol%) and pyrrolidine (1 mmol,
°
10 mol%). The reaction mixture was stirred at 45 C for
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20 hours. NaHCO3 (3 mL/mmol) was added and the mixture
was extracted with CH2Cl2 (3×2 mL/mmol). The combined
organic extracts were washed with brine (3 mL/mmol), dried
(Na2SO4), and concentrated in vacuo. Purification of the residue
by flash chromatography (petroleum ether: ethyl acetate=
30:1), afforded the corresponding aldehyde.[24]
raphy on silica gel using ethyl acetate/petroleum ether (1:10~
1:5) as eluent to afford the desired products.
4-(3-Phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)butan-2-one (3a):
1
yellow oil; 53 mg, 78% yield; H NMR (400 MHz, CDCl3) δ
8.69 (d, J=3.4 Hz, 1H), 7.96 (m, 1H), 7.63 (d, J=6.8 Hz, 1H),
7.58–7.49 (m, 5H), 7.38 (dd, J=10.8, 6.2 Hz, 3H), 7.24–7.16
(m, 2H), 3.31–3.19 (m, 2H), 2.65–2.51 (m, 2H), 1.96 (s, 3H);
13C NMR (101 MHz, CDCl3) δ 207.4, 151.4, 149.8, 138.6,
136.7, 135.9, 134.8, 129.9, 128.7, 128.3, 126.6, 122.6, 122.4,
121.4, 121.1, 119.2, 117.7, 110.1, 43.6, 29.6, 19.7; HR-MS
(ESI) calcd for [M+H]+: C23H21N2O: 341.1640, found:
341.1648; IR (KBr): 3474, 1747, 1715, 1705, 1647, 1506, 1275,
1261, 898, 749 cmÀ 1.
2-Benzylacrylaldehyde (S4):[24] yellow oil; 1.21 g, 83% yield;
1H NMR (400 MHz, CDCl3) δ 9.64 (s, 1H), 7.36–7.18 (m, 5H),
6.12 (d, J=15.5 Hz, 2H), 3.60 (s, 2H); 13C NMR (101 MHz,
CDCl3) δ 194.0, 149.8, 138.2, 135.2, 129.2, 128.6, 126.5, 34.2.
Synthesis of 3-benzylbut-3-en-2-ol 2j: To a solution of MeLi
(6.0 mL, 1.6 M in Et2O, 9.6 mmol) in anhydrous THF (5 mL) at
°
0 C was added a solution of the 2-benzylacrylaldehyde S4
(876 mg, 6 mmol) in anhydrous THF (5 mL) dropwise. The
reaction mixture was stirred at room temperature for 1 hour
before addition of saturated aqueous NH4Cl (20 mL). The
resulting phases were separated, and the aqueous phase was
extracted with Et2O (2×20 mL). The combined organic phases
were dried over Na2SO4 and concentrated in vacuo to afford the
title compound.[25]
4-(1-(Pyridin-2-yl)-3-(p–tolyl)-1H-indol-2-yl)butan-2-one
1
°
(3b): colorless solid; 52 mg, 74% yield; m.p. 89.0–92.8 C; H
NMR (400 MHz, CDCl3) δ 8.69 (dd, J=4.8, 1.3 Hz, 1H), 7.95
(dd, J=7.7, 1.9 Hz, 1H), 7.62 (dd, J=6.7, 1.9 Hz, 1H), 7.57–
7.54 (m, 1H), 7.44 (d, J=8.0 Hz, 2H), 7.40–7.35 (m, 2H), 7.32
(d, J=7.8 Hz, 2H), 7.23–7.15 (m, 2H), 3.28–3.19 (m, 2H),
2.61–2.53 (m, 2H), 2.46 (s, 3H), 1.96 (s, 3H); 13C NMR
(101 MHz, CDCl3) δ 207.5, 151.4, 149.8, 138.6, 136.7, 136.2,
135.7, 131.7, 129.8, 129.4, 128.4, 122.5, 122.4, 121.4, 121.0,
119.3, 117.6, 110.1, 43.6, 29.6, 21.3, 19.7; HR-MS (ESI) calcd
for [M+H]+: C24H23N2O: 355.1799, found: 355.1805; IR
(KBr): 3818, 3617, 2314, 1715, 1470, 1437, 1369, 742 cmÀ 1.
3-Benzylbut-3-en-2-ol (2j):[25] yellow oil; 923 mg, 95% yield;
1H NMR (400 MHz, CDCl3) δ 7.38–7.30 (m, 2H), 7.25 (t, J=
6.7 Hz, 3H), 5.18 (s, 1H), 4.78 (s, 1H), 4.28 (q, J=6.3 Hz, 1H),
3.51 (d, J=15.5 Hz, 1H), 3.39 (d, J=15.5 Hz, 1H), 1.68 (s,
1H), 1.34 (d, J=6.5 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ
152.7, 139.5, 129.2, 128.4, 126.2, 110.9, 70.2, 39.0, 22.2.
4-(3-(4-(tert-Butyl)phenyl)-1-(pyridin-2-yl)-1H-indol-2-yl)
butan-2-one (3c): yellow oil; 66 mg, 83% yield. 1H NMR
(400 MHz, CDCl3) δ 8.74–8.65 (m, 1H), 7.96 (m, 1H), 7.69–
7.64 (m, 1H), 7.55 (dd, J=13.3, 8.2 Hz, 3H), 7.48 (d, J=
8.3 Hz, 2H), 7.41–7.36 (m, 2H), 7.23–7.16 (m, 2H), 3.30–3.22
(m, 2H), 2.62–2.55 (m, 2H), 1.97 (s, 3H), 1.43 (s, 9H); 13C
NMR (101 MHz, CDCl3) δ 207.5, 151.5, 149.8, 149.3, 138.6,
136.7, 135.8, 131.6, 129.5, 128.4, 125.6, 122.5, 122.3, 121.3,
121.0, 119.4, 117.6, 110.0, 43.7, 34.6, 31.5, 29.6, 19.8; HR-MS
(ESI) calcd for [M+H]+: C27H29N2O: 397.2268, found:
397.2274; IR (KBr): 3901, 3565, 1799, 1747, 1714, 1689, 1516,
1456, 742 cmÀ 1.
Procedure for the Synthesis of Compound 3–1a
An oven-dried sealed tube charged 1a (0.20 mmol), 2a
(0.40 mmol), AgSbF6 (20 mol%), MnO2 (0.4 mmol), Mn-
(CO)5Br (5 mol%), and MeOH (1.5 mL) was added under air
atmosphere. The reaction mixture was then allowed to stir at
°
85 C for 24 h. The mixture was then cooled down and filtrated.
The corresponding filtrate was further concentrated under
reduced pressure. The residue was purified by flash chromatog-
raphy on silica gel using ethyl acetate/petroleum ether (1:6) as
eluent to afford the desired product 3–1a.
4-(3-(4-Methoxyphenyl)-1-(pyridin-2-yl)-1H-indol-2-yl)
butan-2-one (3d): brown oil; 52 mg, 70% yield; 1H NMR
(400 MHz, CDCl3) δ 8.69 (d, J=4.5 Hz, 1H), 7.96 (t, J=
7.6 Hz, 1H), 7.58 (dd, J=15.7, 7.7 Hz, 2H), 7.46 (d, J=8.2 Hz,
2H), 7.41–7.35 (m, 2H), 7.23–7.16 (m, 2H), 7.06 (d, J=8.2 Hz,
2H), 3.91 (s, 3H), 3.29–3.16 (m, 2H), 2.59–2.51 (m, 2H), 1.97
(s, 3H); 13C NMR (101 MHz, CDCl3) δ 207.5, 158.4, 151.4,
149.8, 138.6, 136.6, 135.6, 131.0, 128.5, 127.0, 122.5, 122.3,
121.3, 121.0, 119.2, 117.3, 114.2, 110.1, 55.3, 43.6, 29.6, 19.7;
HR-MS (ESI) calcd for [M+H]+: C24H23N2O2: 371.1754,
found: 371.1750; IR (KBr): 3853, 3728, 2925, 1716, 1585,
1470, 1369, 1245, 835 cmÀ 1.
3-Phenyl-1-(pyridin-2-yl)-1H-indole 3-1a:[13] 29 mg, 54%
1
yield; H NMR (400 MHz, CDCl3) δ 8.63 (dd, J=4.8, 0.9 Hz,
1H), 8.31 (d, J=8.3 Hz, 1H), 8.01 (d, J=7.9 Hz, 1H), 7.93 (s,
1H), 7.85 (m, J=8.2, 1.8 Hz, 1H), 7.79 (d, J=7.8 Hz, 2H),
7.60–7.51 (m, 3H), 7.40 (q, J=6.8 Hz, 2H), 7.34 (t, J=7.5 Hz,
1H), 7.21 (dd, J=7.3, 4.9 Hz, 1H). 13C NMR (101 MHz,
CDCl3) δ 152.3, 149.1, 138.5, 135.9, 134.8, 128.9, 128.6, 127.9,
126.6, 123.6, 123.5, 121.8, 120.8, 120.2, 120.2, 114.7, 113.3.
Procedure for the Synthesis of Compounds 3a~3f,
3i~3r, 5c, 6a~6f and 6h
4-(3-(4-Chlorophenyl)-1-(pyridin-2-yl)-1H-indol-2-yl)butan-
An oven-dried sealed tube charged 1 or 4 (0.20 mmol), 2
(0.40 mmol), AgSbF6 (20 mol%), Ag2CO3 (0.4 mmol),
[Cp*RhCl2]2 (5 mol%), and MeOH (1.5 mL) was added under
air atmosphere. The reaction mixture was then allowed to stir at
2-one (3e): colorless solid; 40 mg, 54% yield; m.p. 101.4–
1
°
103.8 C; H NMR (400 MHz, CDCl3) δ 8.69 (d, J=4.7 Hz,
1H), 7.97 (t, J=7.7 Hz, 1H), 7.57 (t, J=7.9 Hz, 2H), 7.48 (s,
4H), 7.43–7.34 (m, 2H), 7.25–7.16 (m, 2H), 3.30–3.16 (m, 2H),
2.62–2.48 (m, 2H), 1.98 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
207.2, 151.2, 149.9, 138.7, 136.7, 136.1, 133.3, 132.5, 131.1,
128.9, 128.0, 122.7, 122.6, 121.4, 121.3, 118.9, 116.4, 110.2,
43.4, 29.7, 19.6; HR-MS (ESI) calcd for [M+H]+:
°
85 C for 24 h. The mixture was then cooled down and filtrated.
The corresponding filtrate was further concentrated under
reduced pressure. The residue was purified by flash chromatog-
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C23H20ClN2O: 375.1252, found: 375.1259; IR (KBr): 3595,
1716, 1586, 1469, 1437, 1369, 1235, 1089, 1012, 831,
742 cmÀ 1.
J=4.3 Hz, 1H), 7.15 (d, J=8.7 Hz, 1H), 3.25–3.15 (m, 2H),
2.59–2.52 (m, 2H), 1.96 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
207.1, 151.0, 150.0, 138.8, 137.3, 135.1, 134.1, 129.8, 129.4,
128.8, 126.9, 126.8, 122.8, 122.7, 121.4, 118.7, 117.2, 111.2,
43.3, 29.6, 19.7; HR-MS (ESI) calcd for [M+H]+:
C23H20ClN2O: 375.1251, found: 375.1259; IR (KBr): 3500,
1715, 1586, 1471, 1453, 1440, 1368, 1267, 1179, 1070, 954,
796, 768, 703 cmÀ 1.
4-(1-(Pyridin-2-yl)-3-(4-(trifluoromethyl)phenyl)-1H-indol-
1
2-yl)butan-2-one (3f): yellow oil; 33 mg, 40% yield; H NMR
(400 MHz, CDCl3) δ 8.70 (dd, J=4.8, 1.2 Hz, 1H), 7.99 (m,
1H), 7.77 (d, J=8.1 Hz, 2H), 7.67 (d, J=8.0 Hz, 2H), 7.64–
7.54 (m, 2H), 7.42 (dd, J=7.0, 5.3 Hz, 1H), 7.39–7.33 (m, 1H),
7.23 (m, 2H), 3.29–3.16 (m, 2H), 2.63–2.47 (m, 2H), 1.97 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 207.0, 151.1, 149.9, 138.8,
4-(3-Phenyl-1-(pyridin-2-yl)-5-(trifluoromethyl)-1H-indol-2-
1
yl)butan-2-one (3m): yellow oil; 31 mg, 38% yield; H NMR
2
138.7, 136.8, 136.5, 130.0, 128.6 (q, J=32.3 Hz, JCF), 127.8,
(400 MHz, CDCl3) δ 8.72 (d, J=3.2 Hz, 1H), 8.00 (m, 1H),
7.87 (s, 1H), 7.53 (m, 5H), 7.46–7.38 (m, 4H), 3.26–3.18 (m,
2H), 2.60–2.51 (m, 2H), 1.95 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 207.0, 150.8, 150.1, 138.9, 138.0, 137.8, 133.8, 129.8,
3
1
125.7 (q, J=4.0 Hz, JCF), 124.4 (d, J=282.8 Hz, JCF), 122.9,
122.7, 121.5, 121.4, 118.9, 116.3, 110.3, 43.4, 29.6, 19.6; HR-
MS (ESI) calcd for [M+H]+: C24H20F3N2O: 409.1522, found:
409.1520; IR (KBr): 3839, 3713, 3565, 1867, 1715, 1516, 1338,
1266, 953, 742 cmÀ 1.
1
128.9, 127.8, 127.1, 124.3(d, J=277.8 Hz, JCF), 123.5 (q, J=
2
3
32.3 Hz, JCF), 123.1, 121.6, 119.3 (q, J=3.0 Hz, JCF), 118.1,
3
116.9 (q, J=4.0 Hz, JCF), 110.4, 43.2, 29.6, 19.6; HR-MS
4-(5-Methyl-3-phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)butan-
2-one (3i): colorless solid; 57 mg, 81% yield; m.p. 90.1–
(ESI) calcd for [M+H]+: C24H20F3N2O: 409.1522, found:
409.1514; IR (KBr): 3605, 2922, 2854, 1716, 1584, 1470, 1440,
1370, 1325, 1275, 1160, 1112, 1057, 767, 701 cmÀ 1.
1
°
93.4 C; H NMR (400 MHz, CDCl3) δ 8.68 (d, J=4.7 Hz, 1H),
7.95 (m, 1H), 7.53 (dd, J=16.2, 8.0 Hz, 5H), 7.43–7.34 (m,
3H), 7.30–7.27 (m, 1H), 7.05 (d, J=8.4 Hz, 1H), 3.25 (dd, J=
10.2, 5.6 Hz, 2H), 2.61–2.55 (m, 2H), 2.46 (s, 3H), 1.96 (s,
3H); 13C NMR (101 MHz, CDCl3) δ 207.5, 151.5, 149.8, 138.6,
136.0, 135.0, 134.9, 130.5, 130.0, 128.7, 128.5, 126.6, 124.0,
122.2, 121.2, 118.9, 117.4, 109.8, 43.6, 29.6, 21.5, 19.8; HR-
MS (ESI) calcd for [M+H]+: C24H23N2.lO: 355.1799, found:
355.1805; IR (KBr): 3491, 1715, 1686, 1588, 1471, 1438, 1370,
770, 745, 702 cmÀ 1.
4-(1-(5-Methylpyridin-2-yl)-3-phenyl-1H-indol-2-yl)butan-2-
one (3n): colorless solid; 33 mg, 47% yield; m.p. 137.7–
1
°
141.1 C; H NMR (400 MHz, CDCl3) δ 8.51 (s, 1H), 7.76 (d,
J=8.0 Hz, 1H), 7.63 (d, J=7.7 Hz, 1H), 7.57–7.49 (m, 4H),
7.44 (d, J=8.0 Hz, 1H), 7.38 (t, J=7.1 Hz, 1H), 7.33–7.28 (m,
1H), 7.23–7.15 (m, 2H), 3.25–3.16 (m, 2H), 2.62–2.55 (m, 2H),
2.48 (s, 3H), 1.97 (s, 3H); 13C NMR (101 MHz, CDCl3) δ
207.5, 150.1, 148.9, 139.2, 136.9, 135.9, 134.9, 132.3, 129.9,
128.7, 128.1, 126.5, 122.4, 121.0, 120.9, 119.1, 117.2, 110.1,
43.6, 29.7, 19.7, 18.1; HR-MS (ESI) calcd for [M+H]+:
C24H23N2O: 355.1798, found: 355.1805; IR (KBr): 3624, 2925,
1716, 1483, 1458, 1397, 1363, 1238, 1189, 836, 775, 744,
703 cmÀ 1.
4-(5-Methoxy-3-phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)
butan-2-one (3j): colorless solid; 61 mg, 83% yield; m.p.
1
°
80.2–83.6 C; H NMR (500 MHz, CDCl3) δ 8.67 (dd, J=4.9,
1.2 Hz, 1H), 7.94 (m, 1H), 7.57–7.48 (m, 5H), 7.38 (m, 2H),
7.29–7.27 (m, 1H), 7.07 (d, J=2.4 Hz, 1H), 6.86 (dd, J=8.9,
2.5 Hz, 1H), 3.83 (s, 3H), 3.22 (dd, J=8.8, 7.0 Hz, 2H), 2.61–
2.49 (m, 2H), 1.95 (s, 3H); 13C NMR (126 MHz, CDCl3) δ
207.5, 155.3, 151.5, 149.8, 138.6, 136.5, 134.9, 131.8, 129.8,
128.8, 126.6, 122.2, 121.1, 117.5, 112.3, 111.0, 101.1, 55.9,
43.6, 29.6, 19.8; HR-MS (ESI) calcd for [M+H]+:
C24H23N2O2: 371.1749, found: 371.1754; IR (KBr): 3648, 2923,
1715, 1582, 1472, 1440, 1370, 1271, 1208, 1162, 796, 770,
703 cmÀ 1.
4-(1-(4-Methylpyridin-2-yl)-3-phenyl-1H-indol-2-yl)butan-2-
1
one (3o): yellow oil; 31 mg, 44% yield; H NMR (400 MHz,
CDCl3) δ 8.55 (d, J=5.0 Hz, 1H), 7.64 (d, J=7.6 Hz, 1H),
7.54 (m, 4H), 7.38 (dd, J=13.7, 7.6 Hz, 3H), 7.26–7.15 (m,
3H), 3.36–3.12 (m, 2H), 2.67–2.55 (m, 2H), 2.53 (s, 3H), 1.98
(s, 3H); 13C NMR (101 MHz, CDCl3) δ 207.5, 151.4, 150.2,
149.4, 136.8, 135.9, 134.9, 129.9, 128.7, 128.2, 126.6, 123.7,
122.5, 122.1, 121.0, 119.2, 117.4, 110.2, 43.7, 29.6, 21.2, 19.8;
HR-MS (ESI) calcd for [M+H]+: C24H23N2O: 355.1798, found:
355.1805; IR (KBr): 3853, 3701, 1716, 1601, 1560, 1459, 1443,
1421, 1358, 1241, 1166, 829, 775, 745, 703 cmÀ 1.
4-(5-Fluoro-3-phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)butan-
1
2-one (3k): brown oil; 57 mg, 80% yield; H NMR (400 MHz,
CDCl3) δ 8.69 (d, J=4.7 Hz, 1H), 7.97 (t, J=7.7 Hz, 1H), 7.52
(t, J=6.3 Hz, 5H), 7.41–7.37 (m, 2H), 7.30–7.26 (m, 2H), 6.93
(dd, J=12.5, 5.4 Hz, 1H), 3.28–3.16 (m, 2H), 2.62–2.54 (m,
2H), 1.96 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 207.2, 158.9
(d, J=236.3 Hz, 1JCF), 151.2, 149.9, 138.8, 137.5, 134.3, 133.2,
4-(1-(5-Chloropyridin-2-yl)-3-phenyl-1H-indol-2-yl)butan-2-
one (3p): colorless solid; 31 mg, 42% yield; m.p. 150.2–
1
°
152.1 C; H NMR (500 MHz, CDCl3) δ 8.63 (d, J=2.6 Hz,
1H), 7.93 (dd, J=8.5, 2.6 Hz, 1H), 7.61 (dd, J=7.1, 1.3 Hz,
1H), 7.55–7.48 (m, 5H), 7.42–7.37 (m, 1H), 7.35 (d, J=7.5 Hz,
1H), 7.21 (m, 2H), 3.21 (dd, J=8.7, 7.0 Hz, 2H), 2.63–2.55 (m,
2H), 1.98 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 207.2, 149.6,
148.6, 138.4, 136.5, 135.8, 134.5, 130.4, 129.9, 128.7, 128.4,
126.8, 122.8, 121.9, 121.4, 119.4, 118.1, 110.1, 43.6, 29.7, 19.6;
HR-MS (ESI) calcd for [M+H]+: C23H20ClN2O: 375.1252,
found: 375.1259; IR (KBr): 3505, 1713, 1647, 1395, 1354,
1188, 1111, 1012, 771 cmÀ 1.
3
129.7, 128.8, 128.7 (d, J=8.1 Hz, JCF), 126.8, 122.7, 121.3,
3
2
117.6, 110.9 (d, J=10.1 Hz, JCF), 110.6 (d, J=26.3 Hz, JCF),
2
104.3 (d, J=24.2 Hz, JCF), 43.4, 29.6, 19.8; HR-MS (ESI)
calcd for [M+H]+: C23H20FN2O: 359.1546, found: 359.1554;
IR (KBr): 3627, 2923, 1716, 1584, 1472, 1441, 1372, 1265,
1139, 795, 742, 702 cmÀ 1.
4-(5-Chloro-3-phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)butan-
1
2-one (3l): yellow oil; 55 mg, 73% yield; H NMR (400 MHz,
CDCl3) δ 8.70 (d, J=4.6 Hz, 1H), 7.98 (t, J=7.7 Hz, 1H), 7.57
(s, 1H), 7.52 (d, J=11.7 Hz, 5H), 7.44–7.38 (m, 2H), 7.28 (d,
4-(1-(5-Bromopyridin-2-yl)-3-phenyl-1H-indol-2-yl)butan-2-
one (3q): colorless solid; 20 mg, 24% yield; m.p. 160.3–
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1
°
163.8 C; H NMR (500 MHz, CDCl3) δ 8.73 (d, J=2.1 Hz,
1H), 8.07 (dd, J=8.4, 2.5 Hz, 1H), 7.61 (dd, J=7.1, 1.3 Hz,
1H), 7.55–7.46 (m, 5H), 7.41–7.35 (m, 2H), 7.25–7.17 (m, 2H),
3.22 (dd, J=8.7, 7.0 Hz, 2H), 2.63–2.56 (m, 2H), 1.98 (s, 3H);
13C NMR (126 MHz, CDCl3) δ 207.2, 150.8, 150.0, 141.2,
136.5, 135.8, 134.5, 129.9, 128.7, 128.5, 126.8, 122.8, 122.4,
121.4, 119.4, 118.7, 118.2, 110.0, 43.6, 29.7, 19.7; HR-MS
(ESI) calcd for [M+H]+: C23H20BrN2O: 419.0745, found:
419.0754; IR (KBr): 3648, 3612, 3566, 1747, 1713, 1465, 1361,
1189, 836, 742, 702 cmÀ 1.
122.5, 122.4, 121.5, 121.1, 119.2, 117.5, 110.1, 50.5, 40.5, 28.4,
25.8, 25.6, 19.7; HR-MS (ESI) calcd for [M+H]+: C28H29N2O:
409.2274, found: 409.2263; IR (KBr): 3819, 3648, 2929, 2852,
1705, 1586, 1470, 1371, 1318, 1147, 988, 771, 742, 702 cmÀ 1.
1-(3-Phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)octan-3-one (6c):
1
yellow oil; 59 mg, 75% yield; H NMR (400 MHz, CDCl3) δ
8.69 (d, J=4.4 Hz, 1H), 7.96 (t, J=7.7 Hz, 1H), 7.64 (d, J=
7.5 Hz, 1H), 7.60–7.54 (m, 3H), 7.51 (t, J=7.5 Hz, 2H), 7.39
(t, J=7.3 Hz, 3H), 7.25–7.16 (m, 2H), 3.32–3.16 (m, 2H),
2.59–2.49 (m, 2H), 2.19 (t, J=7.4 Hz, 2H), 1.45 (dd, J=15.0,
7.5 Hz, 2H), 1.28–1.22 (m, 2H), 1.19–1.12 (m, 2H), 0.88 (t, J=
7.2 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 209.9, 151.4,
149.8, 138.6, 136.7, 136.1, 134.8, 129.9, 128.7, 128.3, 126.6,
122.5, 122.4, 121.4, 121.1, 119.2, 117.6, 110.1, 42.5, 31.3, 23.6,
22.4, 19.7, 13.9; HR-MS (ESI) calcd for [M+H]+: C27H29N2O:
397.2274, found: 397.2269; IR (KBr): 3901, 3672, 2929, 2862,
1748, 1714, 1682, 1471, 1371, 1266, 1189, 770, 741, 703 cmÀ 1.
4-(3-Phenyl-1-(5-(trifluoromethyl)pyridin-2-yl)-1H-indol-2-
yl)butan-2-one (3r): yellow solid; 35 mg, 43% yield; m.p.
143.5–145.3 C; H NMR (400 MHz, CDCl3) δ 8.94 (s, 1H),
8.19 (dd, J=8.4, 2.2 Hz, 1H), 7.73 (d, J=8.4 Hz, 1H), 7.64–
7.60 (m, 1H), 7.57–7.49 (m, 4H), 7.46 (d, J=7.4 Hz, 1H), 7.41
(m, 1H), 7.24 (m, 2H), 3.32–3.20 (m, 2H), 2.66–2.56 (m, 2H),
1.99 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 207.1, 154.2, 146.9
(q, J=4.0 Hz, JCF), 136.3, 135.9, 135.9 (q, J=6.1 Hz, JCF),
134.3, 129.9, 128.9, 128.8, 127.0, 124.6 (q, J=27.3 Hz, JCF),
1
°
3
3
1-Phenyl-4-(3-phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)butan-
2
1
2-one (6d): brown oil; 66 mg, 79% yield; H NMR (400 MHz,
1
123.4 (d, J=279.8 Hz, JCF), 123.1, 121.8, 120.4, 119.5, 119.1,
CDCl3) δ 8.55 (d, J=3.8 Hz, 1H), 7.90 (m, 1H), 7.62 (d, J=
6.9 Hz, 1H), 7.52–7.44 (m, 5H), 7.38 (dd, J=8.7, 3.8 Hz, 1H),
7.33 (t, J=6.6 Hz, 2H), 7.27 (d, J=8.7 Hz, 3H), 7.23–7.15 (m,
2H), 7.08–6.94 (m, 2H), 3.49 (s, 2H), 3.25–3.12 (m, 2H), 2.68–
2.56 (m, 2H); 13C NMR (101 MHz, CDCl3) δ 206.9, 151.3,
149.8, 138.5, 136.7, 135.9, 134.7, 134.1, 129.9, 129.3, 128.7,
128.7, 128.2, 127.0, 126.6, 122.6, 122.4, 121.3, 121.1, 119.2,
117.6, 110.1, 49.9, 41.9, 19.7; HR-MS (ESI) calcd for [M+H]+
: C29H25N2O: 417.1961, found: 417.1951; IR (KBr): 3500, 3055,
2922, 1714, 1644, 1494, 1470, 1370, 1236, 1187, 743,
700 cmÀ 1.
110.1, 43.6, 29.6, 19.8; HR-MS (ESI) calcd for [M+H]+:
C24H20F3N2O: 409.1522, found: 409.1522; IR (KBr): 3866,
3612, 2308, 1867, 1713, 1465, 1375, 1189, 836, 770, 742,
703 cmÀ 1.
Methyl
4-(2-(3-oxobutyl)-1-(pyridin-2-yl)-1H-indol-3-yl)
butanoate (5c): yellow oil; 31 mg, 42% yield; 1H NMR
(400 MHz, CDCl3) δ 8.64 (d, J=4.7 Hz, 1H), 7.92 (m, 1H),
7.63–7.56 (m, 1H), 7.47 (d, J=8.0 Hz, 1H), 7.33 (dd, J=10.5,
5.4 Hz, 2H), 7.21–7.11 (m, 2H), 3.69 (s, 3H), 3.16–3.04 (m,
2H), 2.87–2.76 (m, 2H), 2.72–2.61 (m, 2H), 2.44 (t, J=7.3 Hz,
2H), 2.07 (s, 3H), 2.05–1.99 (m, 2H); 13C NMR (101 MHz,
CDCl3) δ 207.7, 174.1, 151.5, 149.7, 138.4, 136.7, 135.9, 128.6,
122.1, 122.0, 121.0, 120.4, 118.6, 114.1, 110.0, 51.5, 43.8, 33.7,
29.8, 25.8, 23.6, 19.3; HR-MS (ESI) calcd for [M+H]+:
C22H25N2O3: 365.1860, found: 365.1856; IR (KBr): 3649, 3553,
1747, 1705, 1689, 1681, 1647, 1567, 1516, 1266, 899,
742 cmÀ 1.
1-Phenyl-5-(3-phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)pentan-
3-one (6e): colorless solid; 75 mg, 87% yield; m.p. 84.6–
1
°
85.3 C; H NMR (400 MHz, CDCl3) δ 8.65 (d, J=3.9 Hz, 1H),
7.95 (t, J=7.2 Hz, 1H), 7.65 (d, J=7.1 Hz, 1H), 7.53 (dd, J=
17.0, 7.7 Hz, 5H), 7.43–7.35 (m, 3H), 7.26 (dd, J=17.9,
10.6 Hz, 5H), 7.10 (d, J=7.1 Hz, 2H), 3.31–3.20 (m, 2H), 2.78
(t, J=7.5 Hz, 2H), 2.55 (dd, J=17.3, 9.6 Hz, 4H); 13C NMR
(101 MHz, CDCl3) δ 208.6, 151.3, 149.8, 140.9, 138.7, 138.6,
136.7, 135.9, 134.8, 129.9, 128.7, 128.5, 128.3, 126.6, 126.1,
122.6, 122.4, 121.4, 121.1, 119.2, 117.6, 110.1, 44.0, 42.7, 29.7,
19.7; HR-MS (ESI) calcd for [M+H]+: C30H27N2O: 431.2118,
found: 431.2110; IR (KBr): 3905, 3598, 1712, 1654, 1560,
1470, 1370, 1319, 1192, 1094, 771, 744, 701 cmÀ 1.
1-(3-Phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)pentan-3-one
(6a): colorless solid; 50 mg, 71% yield; m.p. 87.4–89.7 C; H
1
°
NMR (400 MHz, CDCl3) δ 8.69 (d, J=4.6 Hz, 1H), 7.96 (t, J=
7.7 Hz, 1H), 7.64 (d, J=7.6 Hz, 1H), 7.58–7.54 (m, 3H), 7.51
(t, J=7.5 Hz, 2H), 7.39 (t, J=7.6 Hz, 3H), 7.24–7.17 (m, 2H),
3.29–3.21 (m, 2H), 2.58–2.52 (m, 2H), 2.22 (q, J=7.3 Hz, 2H),
0.94 (t, J=7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3) δ 210.1,
151.4, 149.8, 138.6, 136.7, 136.1, 134.8, 129.9, 128.7, 128.3,
126.6, 122.5, 122.4, 121.4, 121.1, 119.2, 117.6, 110.1, 42.1,
35.6, 19.8, 7.8; HR-MS (ESI) calcd for [M+H]+: C24H23N2O:
355.1805, found: 355.1803; IR (KBr): 3734, 3489, 1713, 1660,
1647, 1586, 1470, 1457, 1436, 1371, 1318, 1236, 1189, 771,
742, 703 cmÀ 1.
4-Phenyl-1-(3-phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)pentan-
1
3-one (6f): yellow oil; 59 mg, 69% yield; H NMR (400 MHz,
CDCl3) δ 8.50 (d, J=4.6 Hz, 1H), 7.86 (t, J=7.7 Hz, 1H), 7.62
(d, J=7.7 Hz, 1H), 7.52–7.43 (m, 4H), 7.42 (d, J=8.0 Hz, 1H),
7.39–7.33 (m, 1H), 7.34–7.23 (m, 5H), 7.23–7.15 (m, 2H),
7.07–6.99 (m, 2H), 3.56 (q, J=6.9 Hz, 1H), 3.31–3.18 (m, 1H),
3.18–3.02 (m, 1H), 2.67–2.42 (m, 2H), 1.30 (d, J=7.0 Hz, 3H);
13C NMR (101 MHz, CDCl3) δ 209.3, 151.2, 149.7, 140.5,
138.4, 136.7, 136.0, 134.7, 129.8, 128.9, 128.6, 128.2, 127.7,
127.0, 126.5, 122.5, 122.3, 121.2, 121.0, 119.2, 117.5, 110.1,
52.7, 41.0, 19.9, 17.2; HR-MS (ESI) calcd for [M+H]+:
C30H27N2O: 431.2118, found: 431.2104; IR (KBr): 3571, 3055,
2973, 2930, 1713, 1601, 1493, 1318, 1286, 1023, 990, 771,
744 cmÀ 1.
1-Cyclohexyl-3-(3-phenyl-1-(pyridin-2-yl)-1H-inden-2-yl)
propan-1-one (6b): colorless solid; 70 mg, 86% yield; m.p.
92.4–93.9 C; 1H NMR (400 MHz, CDCl3) δ 8.69 (d, J=
°
3.8 Hz, 1H), 7.95 (m, 1H), 7.68–7.63 (m, 1H), 7.60–7.55 (m,
3H), 7.52 (t, J=7.6 Hz, 2H), 7.39 (dd, J=12.2, 5.3 Hz, 3H),
7.25–7.16 (m, 2H), 3.23 (dd, J=10.4, 5.5 Hz, 2H), 2.71–2.56
(m, 2H), 2.14 (s, 1H), 1.68 (d, J=24.7 Hz, 5H), 1.19 (d, J=
4.0 Hz, 5H); 13C NMR (101 MHz, CDCl3) δ 212.6, 151.4,
149.8, 138.6, 136.8, 136.4, 134.9, 129.9, 128.7, 128.3, 126.6,
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(E)-4-(3-Phenyl-1-(pyridin-2-yl)-1H-indol-2-yl)but-3-en-1-ol
(6h): yellow oil; 26 mg, 38% yield; 1H NMR (400 MHz,
CDCl3) δ 8.70 (d, J=3.9 Hz, 1H), 7.93 (t, J=7.8 Hz, 1H), 7.68
(d, J=7.1 Hz, 1H), 7.57 (d, J=7.5 Hz, 2H), 7.51 (dd, J=12.7,
7.7 Hz, 3H), 7.42–7.35 (m, 3H), 7.25–7.17 (m, 2H), 5.59–5.19
(m, 2H), 3.86–3.76 (m, 4H); 13C NMR (101 MHz, CDCl3) δ
151.5, 149.7, 138.3, 136.9, 134.8, 134.5, 130.5, 130.0, 129.3,
128.5, 128.0, 126.5, 122.6, 122.4, 121.6, 121.0, 119.3, 117.9,
110.0, 63.2, 28.2; HR-MS (ESI) calcd for [M+H]+:
C23H20N2O: 341.1648, found: 341.1640; IR (KBr): 3929, 3825,
3082, 2906, 1583, 1507, 1375, 1190, 1087, 745, 702 cmÀ 1.
5-(2-(3-Oxobutyl)-1-(pyridin-2-yl)-1H-indol-3-yl)pentanal
(5b): brown oil; 40 mg, 58% yield; 1H NMR (400 MHz,
CDCl3) δ 9.79 (s, 1H), 8.64 (d, J=3.2 Hz, 1H), 7.91 (m, 1H),
7.58–7.54 (m, 1H), 7.47 (d, J=7.9 Hz, 1H), 7.33 (dd, J=6.8,
4.7 Hz, 2H), 7.19–7.14 (m, 2H), 3.16–3.07 (m, 2H), 2.81 (t, J=
7.0 Hz, 2H), 2.67–2.62 (m, 2H), 2.50 (t, J=6.2 Hz, 2H), 2.06
(s, 3H), 1.75 (d, J=5.7 Hz, 4H); 13C NMR (101 MHz, CDCl3) δ
207.7, 202.6, 151.6, 149.7, 138.4, 136.7, 135.6, 128.6, 122.1,
122.0, 120.9, 120.4, 118.5, 114.6, 110.0, 43.9, 43.8, 30.3, 29.9,
24.1, 22.2, 19.3; HR-MS (ESI) calcd for [M+H]+:
C22H25N2O2: 349.1911, found: 349.1912; IR (KBr): 3839, 3650,
3612, 3565, 1867, 1747, 1705, 1689, 1515, 1266, 905,
742 cmÀ 1.
Procedure for the Synthesis of Compounds 3g, 3h,
5a and 5b
Chemical Transformation of 3h
Coupling-cyclization of 3h with ethyl carbonocyanidate:[14] To
An oven-dried sealed tube charged 1 or 4(0.20 mmol), 2a
(0.40 mmol), AgSbF6 (20 mol%), [Cp*RhCl2]2 (5 mol%), and
H2O (1.5 mL) was added under air atmosphere. The reaction
a
mixture of 3h (106 mg, 0.4 mmol) and Et3N (4 mg,
0.04 mmol), ethyl carbonocyanidate 7 (44 mg, 0.44 mmol) was
slowly added at rt. Upon completion, the reaction was
concentrated in vacuum. The residue was purified by column
chromatography (silica gel, EtOAc/Petroleum ether=5:1) to
give product 8 (76 mg, 52% yield).
°
mixture was then allowed to stir at 85 C for 24 h. The
corresponding reaction mixture was then cooled down and
filtrated. The corresponding filtrate was further concentrated
under reduced pressure. The residue was purified by flash
chromatography on silica gel using ethyl acetate/petroleum
ether (1:10~1:5) as eluent to afford the desired products 3 or 5.
A mixture of substrate 8 (73 mg, 0.2 mmol), Pd(OAc)2 (2 mg,
5 mol%) and 2,2’-bipyridine (2 mg, 6 mol%) in HOAc/NMA
4-(3-Methyl-1-(pyridin-2-yl)-1H-indol-2-yl)butan-2-one (3g):
brown oil; 43 mg, 78% yield. H NMR (400 MHz, CDCl3) δ
1
°
(v/v=1/3, 0.5 mL) was stirred at 120 C. Upon completion, the
mixture was cooled to room temperature, and then NaHCO3
was added until no CO2 bubbles were generated. The resulting
mixture was extracted with DCM three times. The combined
organic layers were dried over Na2SO4, filtered, and concen-
trated under reduced pressure. The residue was purified by flash
column chromatography on a silica gel using petroleum ether/
EtOAc (3:1 to 1:1) as the eluent to give the desired product 9
(50 mg, 79% yield).
8.64 (dd, J=4.8, 1.3 Hz, 1H), 7.91 (m, 1H), 7.57 (dd, J=5.6,
3.3 Hz, 1H), 7.47 (d, J=8.0 Hz, 1H), 7.36–7.29 (m, 2H), 7.22–
7.12 (m, 2H), 3.14 (dd, J=9.9, 5.7 Hz, 2H), 2.70 (dd, J=10.1,
5.5 Hz, 2H), 2.35 (s, 3H), 2.08 (s, 3H); 13C NMR (101 MHz,
CDCl3) δ 208.0, 151.6, 149.6, 138.4, 136.5, 135.5, 129.4, 122.1,
121.8, 120.8, 120.4, 118.4, 110.3, 109.9, 43.5, 29.9, 19.5, 8.7;
HR-MS (ESI) calcd for [M+H]+: C18H19N2O: 279.1492, found:
279.1494; IR (KBr): 3455, 2921, 1714, 1586, 1471, 1459, 1437,
1362, 1317, 1224, 1163, 993, 777, 741 cmÀ 1.
2-Cyano-4-(1-(pyridin-2-yl)-1H-indol-2-yl)butan-2-yl ethyl
carbonate (8): colorless oil; 76 mg, 52% yield; 1H NMR
(400 MHz, CDCl3) δ 8.70 (dd, J=4.9, 1.2 Hz, 1H), 7.94 (m,
1H), 7.66–7.57 (m, 1H), 7.52 (d, J=8.0 Hz, 1H), 7.41–7.31 (m,
2H), 7.21–7.14 (m, 2H), 6.52 (s, 1H), 4.28–4.19 (m, 2H), 3.17
(m, 2H), 2.36 (m, 2H), 1.78 (s, 3H), 1.34 (t, J=7.1 Hz, 3H);
13C NMR (126 MHz, CDCl3) δ 152.5, 151.1, 149.8, 138.7,
138.5, 137.1, 128.4, 122.2, 122.2, 120.9, 120.7, 120.2, 118.1,
110.2, 103.1, 73.5, 64.9, 39.2, 24.5, 22.4, 14.1; HR-MS (ESI)
calcd for [M+H]+: C21H22N3O3: 364.1653, found: 364.1656;
IR (KBr): 2951, 1753, 1456, 1389, 1214, 1017, 673, 579 cmÀ 1.
4-(1-(Pyridin-2-yl)-1H-indol-2-yl)butan-2-one (3h): yellow
oil; 34 mg, 64% yield. H NMR (400 MHz, CDCl3) δ 8.68 (dd,
1
J=4.8, 1.2 Hz, 1H), 7.92 (m, 1H), 7.59 (m, 1H), 7.49 (d, J=
8.0 Hz, 1H), 7.35 (dd, J=7.8, 4.8 Hz, 2H), 7.16 (dd, J=6.0,
3.1 Hz, 2H), 6.45 (s, 1H), 3.15–3.09 (m, 2H), 2.88–2.83 (m,
2H), 2.16 (s, 3H); 13C NMR (101 MHz, CDCl3) δ 207.6, 151.3,
149.7, 140.0, 138.5, 137.3, 128.5, 122.2, 121.9, 121.1, 120.8,
120.1, 110.2, 102.3, 42.8, 30.0, 21.7; HR-MS (ESI) calcd for
[M+H]+: C17H17N2O: 265.1335, found: 265.1335; IR (KBr):
3738, 3005, 1713, 1469, 1456, 1436, 1344, 1266, 1212, 917,
741 cmÀ 1.
3a-Methyl-6-(pyridin-2-yl)-3a,4,5,6-tetrahydro-2H-oxazolo
1
[5,4-c]carbazol-2-one (9): yellow oil; 50 mg, 79% yield; H
10-(2-(3-Oxobutyl)-1-(pyridin-2-yl)-1H-indol-3-yl)decanal
(5a): yellow oil; 38 mg, 45% yield; 1H NMR (400 MHz,
CDCl3) δ 9.78 (s, 1H), 8.66–8.59 (m, 1H), 7.91 (m, 1H), 7.61–
7.55 (m, 1H), 7.47 (d, J=8.0 Hz, 1H), 7.33 (m, 2H), 7.16 (m,
2H), 3.16–3.07 (m, 2H), 2.80–2.73 (m, 2H), 2.70–2.60 (m, 2H),
2.43 (m, 2H), 2.06 (s, 3H), 1.72–1.63 (m, 4H), 1.47–1.40 (m,
2H), 1.33 (s, 8H); 13C NMR (126 MHz, CDCl3) δ 207.8, 203.0,
151.6, 149.6, 138.4, 136.6, 135.4, 128.8, 121.9, 121.9, 120.9,
120.3, 118.6, 115.5, 109.9, 43.9, 30.9, 29.9, 29.8, 29.5, 29.4,
29.2, 24.4, 22.1, 19.4; HR-MS (ESI) calcd for [M+H]+:
C27H35N2O2: 419.2684, found: 419.2693; IR (KBr): 3727, 3628,
2924, 1720, 1587, 1470, 1454, 1437, 1380, 1226, 1099, 740,
697 cmÀ 1.
NMR (400 MHz, CDCl3) δ 8.73 (d, J=3.3 Hz, 1H), 8.19 (d,
J=7.6 Hz, 1H), 8.04 (t, J=7.6 Hz, 1H), 7.61 (d, J=7.9 Hz,
1H), 7.49 (dd, J=12.1, 7.5 Hz, 2H), 7.43–7.34 (m, 2H), 3.48–
3.34 (m, 1H), 3.10 (dd, J=18.6, 5.4 Hz, 1H), 2.54 (dd, J=
12.4, 5.1 Hz, 1H), 2.28 (dd, J=12.1, 6.0 Hz, 1H), 1.69 (s, 3H);
13C NMR (126 MHz, CDCl3) δ 192.1, 167.7, 150.1, 149.3,
149.1, 139.1, 138.1, 124.9, 124.1, 123.7, 121.8, 120.2, 111.2,
107.7, 85.3, 34.5, 29.7, 23.1, 23.1; HR-MS (ESI) calcd for [M
+H]+: C19H16N3O2: 318.1232, found: 318.1237; IR (KBr):
3728, 3628, 2930, 1583, 1456, 1380, 1162, 1078 cmÀ 1.
Coupling-cyclization of 3-1h with methyl 2-diazo-2-
phenylacetate:[15] To an oven-dried sealed tube charged 3h
Adv. Synth. Catal. 2021, 363, 1672–1684
1683
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FULL PAPER
asc.wiley-vch.de
(53 mg, 0.20 mmol), 10 (70 mg, 0.40 mmol), Rh2(OAc)4 (3 mg,
5 mol%) and CH2Cl2 (1.5 mL) was added under Ar atmosphere.
[4] H. X. Huang, S. J. Jin, J. Gong, D. Zhang, H. Song, Y.
Qin, Chem. Eur. J. 2015, 21, 13284.
°
The reaction mixture was then allowed to stir at 40 C for 1 h.
[5] X. Zhou, S. Yu, L. Kong, X. Li, ACS Catal. 2016, 6, 647.
[6] Q. Lu, S. Mondal, S. Cembellin, F. Glorius, Angew.
Chem. Int. Ed. 2018, 57, 10732.
The corresponding reaction mixture was then cooled down and
filtrated. The corresponding filtrate was further concentrated
under reduced pressure. The residue was purified by flash
chromatography on silica gel using ethyl acetate/petroleum
ether (1:10~1:5) as eluent to afford the desired products 11
(59 mg, 72% yield).
[7] For selected reviews, see: a) F. Song, T. Gou, B. Q.
Wang, Z. J. Shi, Chem. Soc. Rev. 2018, 47, 7078; b) Y. J.
Park, J. W. Park, C. H. Jun, Acc. Chem. Res. 2008, 41,
222; c) K. Ruhland, Eur. J. Org. Chem. 2012, 2012,
2683; d) C. H. Jun, C. W. Moon, D. Y. Lee, Chem. Eur.
J. 2002, 8, 2422; e) P. H. Chen, B. A. Billett, T.
Tsukamoto, G. Dong, ACS Catal. 2017, 7, 1340.
[8] H. Li, Y. Li, X. S. Zhang, K. Chen, X. Wang, Z. J. Shi, J.
Am. Chem. Soc. 2011, 133, 15244.
[9] M. Moselage, J. Li, F. Kramm, L. Ackermann, Angew.
Chem. Int. Ed. 2017, 56, 5341.
[10] A. M. Dreis, C. J. Douglas, J. Am. Chem. Soc. 2009, 131,
412.
[11] S. Onodera, S. Ishikawa, T. Kochi, F. Kakiuchi, J. Am.
Chem. Soc. 2018, 140, 9788.
[12] Y. Xia, J. Wang, G. Dong, J. Am. Chem. Soc. 2018, 140,
5347.
[13] X. W. Hu, Y. Shao, H. S. Xie, X. Chen, F. Chen, Z. F.
Ke, H. F. Jiang, W. Zeng, ACS Catal. 2020, 10, 8402.
[14] T. T. Wang, L. Zhao, Y. J. Zhang, W. W. Liao, Org. Lett.
2016, 18, 5002.
Methyl-3-hydroxy-3-methyl-4-phenyl-9-(pyridin-2-yl)-
2,3,4,9-tetrahydro-1H-carbazole-4-carboxylate (11): yellow
oil; 59 mg, 72% yield; H NMR (400 MHz, CDCl3) δ 8.70 (dd,
1
J=4.8, 1.1 Hz, 1H), 7.94 (m, 1H), 7.53 (d, J=8.0 Hz, 1H),
7.44 (d, J=8.2 Hz, 1H), 7.39–7.29 (m, 4H), 7.26 (s, 2H), 7.14
(t, J=7.6 Hz, 1H), 7.06 (d, J=7.9 Hz, 1H), 6.98 (t, J=7.3 Hz,
1H), 4.69 (s, 1H), 3.63 (s, 3H), 3.19–3.02 (m, 1H), 2.90 (dd,
J=17.6, 4.7 Hz, 1H), 2.74 (m, 1H), 2.04 (dd, J=12.8, 4.9 Hz,
1H), 0.90 (s, 3H); 13C NMR (126 MHz, CDCl3) δ 176.8, 150.9,
149.6, 138.4, 137.4, 137.3, 137.3, 129.8, 127.7, 127.1, 126.9,
123.4, 122.1, 121.8, 120.6, 120.0, 111.5, 110.0, 74.5, 60.6, 52.1,
35.4, 23.4, 22.6; HR-MS (ESI) calcd for [M+H]+:
C26H25N2O3: 413.1854, found: 413.1860; IR (KBr): 2944, 1705,
1587, 1471, 1439, 1361, 1243, 1151, 1041, 910, 738, 443 cmÀ 1.
Acknowledgements
The authors thank NKRDPC (No. 2016YFA0602900), the NSFC
(No. 21871097), KARDPGP (No. 2020B010188001), NSFGP
(No. 2018B030308007, 2019 A1515011790), CPSF (No.
2019 M662887), and STPG (No. 201904010113) for financial
support.
[15] L. L. Song, D. Ni, S. Jia, R. Pi, S. Dong, F. Yang, J.
Tang, S. Liu, Org. Lett. 2020, 22, 1846.
[16] a) F. Chen, T. Wang, N. Jiao, Chem. Rev. 2014, 114,
8613; b) S. Vásquez-Céspedes, X. Wang, F. Glorius,
ACS Catal. 2018, 8, 242.
[17] For selected examples, see: P. Zhao, C. D. Incarvito, J. F.
Hartwig, J. Am. Chem. Soc. 2006, 128, 3124.
[18] A. Ramdular, K. A. Woerpel, Org. Lett. 2020, 22, 4113.
[19] S. T. Handy, J. Org. Chem. 2006, 71, 4659.
[20] J. B. Langlois, A. Alexakis, Angew. Chem. Int. Ed. 2011,
50, 1877.
References
[1] For selected reviews, see: a) F. E. Chen, J. Huang, Chem.
Rev. 2005, 105, 4671; b) A. Ramírez, S. García-Rŭbio,
Curr. Med. Chem. 2003, 10, 1891.
[21] H. Li, Y. Li, X. S. Zhang, K. Chen, X. Wang, Z. J. Shi, J.
Am. Chem. Soc. 2011, 133, 15244.
[22] X. Hu, X. Chen, Y. Zhu, Y. Deng, H. Zhang, H. F. Jiang,
W. Zeng, Org. Lett. 2017, 19, 3474.
[23] S. Bai, X. Chen, X. Hu, Y. Deng, H. F. Jiang, W. Zeng,
Org. Biomol. Chem. 2017, 15, 3638.
[24] A. Faulkner, J. S. Scott, J. F. Bower, J. Am. Chem. Soc.
2015, 137, 7224.
[2] For selected reviews, see: a) S. Liu, F. Zhao, X. Chen,
G. J. Deng, H. Huang, Adv. Synth. Catal. 2020, 362,
3795; b) M. S. Christodoulou, E. M. Beccalli, F. Foschi,
S. Giofre, Synthesis 2020, 52, 2731; c) B. Deka, M. L.
Deb, P. K. Baruah, Top. Curr. Chem. 2020, 378, 22;
d) M. Petrini, Adv. Synth. Catal. 2020, 362, 1214;
e) X. Y. Liu, Y. Qin, Acc. Chem. Res. 2019, 52, 1877.
[3] For selected examples, see: a) L. Shen, M. Zhang, Y.
Wu, Y. Qin, Angew. Chem. Int. Ed. 2008, 47, 3618;
b) S. J. Jin, J. Gong, Y. Qin, Angew. Chem. Int. Ed. 2015,
54, 2228; c) M. Zhang, X. Huang, L. Shen, Y. Qin, J.
Am. Chem. Soc. 2009, 131, 6013.
[25] X. Ma, I. R. Hazelden, T. Langer, R. H. Munday, J. F.
Bower, J. Am. Chem. Soc. 2019, 141, 3356.
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