Gold-Catalyzed β-Regioselective Formal [3 + 2] Cycloaddition of Ynamides with Pyrido[1,2-b]indazoles: Reaction Development and Mechanistic Insights

Article abstract of DOI:10.1021/acs.joc.6b01948

Here, we report an unprecedented gold(I)-induced β-site regioselective formal [3 + 2] cycloaddition of ynamides with pyrido[1,2-b]indazoles, giving 3-amido-7-(pyrid-2′-yl)indoles in good to excellent yields. A complex of gold(I) catalyst with ynamide was isolated and characterized by X-ray diffraction analysis for the first time. Mechanistic investigations suggest the reaction pathway involves a gold-stabilized carbocation intermediate, which in turn participated in sequential C-H bond functionalization of the ortho-position of the phenyl ring.

Full text of DOI:10.1021/acs.joc.6b01948

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Featured Article
Gold-Catalyzed #-Regioselective Formal [3+2] Cycloaddition of Ynamides
with Pyrido[1,2-b]indazoles: Reaction Development and Mechanistic Insights
Yinghua Yu, Gui Chen, Lei Zhu, Yun Liao, Yufeng Wu, and Xueliang Huang
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b01948 • Publication Date (Web): 28 Aug 2016
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GoldꢀCatalyzed βꢀRegioselective Formal [3+2]
Cycloaddition of Ynamides with Pyrido[1,2ꢀ
b]indazoles: Reaction Development and Mechanistic
Insights
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Yinghua Yu,‡a Gui Chen,‡a Lei Zhu,a Yun Liao,a,b Yufeng Wu,a,b Xueliang Huang*a
a. Key Laboratory of Coal to Ethylene Glycol and Its Related Technology, Fujian Institute of
Research on the Structure of Matter, Chinese Academy of Sciences, Yangqiao west road 155#,
Fuzhou, Fujian 350002 (China)
b. College of Chemistry, Fuzhou University, Fuzhou, Fujian 350108 (China).
Keywords
Gold catalysis, ynamides, pyrido[1,2ꢀb]indazoles, βꢀsite regioselectivity, 3ꢀaminoindole
Abstract
Here we report an unprecedented gold(I) induced βꢀsite regioselective formal [3+2]
cycloaddition of ynamides with pyrido[1,2ꢀb]indazoles, giving 3ꢀamidoꢀ7ꢀ(pyridꢀ2ꞌꢀyl)indoles in
good to excellent yields. A complex of gold(I)ꢀcatalyst with ynamide was isolated and
characterized by Xꢀray diffraction analysis for the first time. Mechanistic investigations suggest
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the reaction pathway involves a goldꢀstabilized carbocation intermediate, which in turn
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participated in sequential CꢀH bond functionalization of the orthoꢀposition of the phenyl ring.
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Introduction
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Ynamides are bench stable and easily accessible starting materials. In the past decade, a large
library of nitrogenꢀcontaining molecules have been prepared via addition of nucleophiles to the
αꢀsite of ynamides (Scheme 1a).1,2 In contrast, the addition of nucleophiles at the β position of
the triple bond is comparatively less common.3,4 Very recently, Marek,3a Lam3c and others3d,3e
reported carbometallation of ynamides in presence of proper copper(I) or rhodium(I) salts, in
which the tethered carbomate functionality was crucial for the βꢀregioselectivity by acting as a
chelating group. Herein, we report the first goldꢀcatalyzed βꢀregioselective cycloaddition of
ynamides with external reagents, giving 3ꢀamidoindole derivatives in atomꢀeconomical manner
(Scheme 1b). Hashmi4a and Gagosz4b have reported goldꢀcatalyzed intramolecular cyclization of
Nꢀalkynyl tertꢀbutyloxycarbomates independently. However, to our knowledge, goldꢀcatalyzed
intermolecular cycloaddition of ynamides with other reactants features βꢀregioselectivity has
remained elusive to date.
EWG
N
Nu
E
R2
AuL+
well known
(a)
(b)
-site addition
-site addition
R2
EWG
N
R1
Nu
E
+
EWG
N
E
R2
AuL+
This work
R1
R1
Nu
Scheme 1. Goldꢀcatalyzed formal cycloaddition of ynamides.
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Goldꢀcatalyzed reactions of alkynes with nucleophiles have received considerable attention.5
Compared with the relatively well investigated approach to generate αꢀcarbonyl goldꢀcarbene,6
similar but equally appealing concept on goldꢀcatalyzed formation of αꢀimino carbene remains
underdeveloped.7 Seminal works on goldꢀcatalyzed nitrene transfer by intramolecular reaction of
alkynyl azides were first described by Toste in 2005,8 and further demonstrated by Zhang,9
Gagosz10 and others.11 Instead of azides, also anthranils and other nitreneꢀtransfer reagents have
been used as nitrene precursors.12 Intermolecular reactions of azides with ynamides have also
been realized by Ye,13 Liu14 and our group15aꢀb very recently. In conjunction with our continuing
interest in nitrogenꢀcontaining molecules synthesis via αꢀimino carbene intermediates,15 we
envisioned that goldꢀcatalyzed reaction of ynamide 1a with azide b might generate intermediate
B, which in turn undergo intramolecular cyclization with tethered pyridinyl moiety, thus
eventually leading to the formation of fused tricyclic compound 1ab (Scheme 2).
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Scheme 2. Initial attempts towards original hypothesis.
Herein, we would like to present our detailed studies towards this goal, and disclose an
unprecedented goldꢀcatalyzed annulation of ynamides with pyrido[1,2ꢀb]indazoles, providing 3ꢀ
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aminoꢀ7ꢀ(pyridꢀ2ꞌꢀyl)indoles in good to excellent yields. The regioselectivity of the current
transformation suggests an unusual βꢀsite cycloaddition of ynamide was involved. A series of
mechanistic studies were performed to get valuable information on the reaction pathways.
Moreover, a complex of gold catalyst with ynamide was isolated for the first time and
characterized by singleꢀcrystal Xꢀray analysis.
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Results and discussion
Optimization studies and substrate scope
To test our hypothesis, the reaction of ynamide 1a and 2ꢀ(2ꢀazidophenyl)pyridine b was
evaluated initially (Scheme 2). Using JohnphosAu(MeCN)SbF6 (Echavarren’s catalyst, 5 mol%)
o
as catalyst,16 azide b was completely consumed after heating at 100 C for 29 h in DCE (1,2ꢀ
dichloroethane), while most ynamide 1a remained intact, and the suspecting product 1ab was not
observed from the reaction mixture. Pyrido[1,2ꢀb]indazole 2a was obtained as the major product,
which was presumably resulting from the ring closure of b by thermolysis.17 Surprisingly, a new
compound which was identified to be 3ꢀaminoꢀ7ꢀ(pyridꢀ2ꞌꢀyl)indole 3aa18 was obtained in 5%
yield upon isolation. Unambiguous proof of structure and regioselectivity was achieved by
singleꢀcrystal Xꢀray analysis. Pleasingly, under otherwise identical conditions, replacing b with
pyrido[1,2ꢀb]indazole 2a, 3aa was obtained as the sole product in nearly quantitative yield. It is
worthwhile to mention that Hashmi12a and Ye12c reported elegant goldꢀcatalyzed annulations of
anthranils or isoxazoles with ynamides to synthesize polysubstituted pyrroles or 7ꢀacylindoles
very recently. In their report, αꢀsite regiocontrolled addition of ynamides occurred exclusively. In
contrast, the precise structure of 3aa suggests an unusual βꢀsite addition of ynamide 1a take
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place here. This observation indicates that a key reaction intermediate distinct from well
accepted ketenimium ion was involved in this novel transformation (vide infra).
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As one of the most important class of heterocycles, indole scaffolds are embedded in a wide
range of natural products and pharmaceuticals.19 Therefore, the development of efficient
methodologies to access these compounds have received long term attention.20 Compared with
normal indole moiety, the classic Fisher cyclization is not applicable to prepare 7ꢀ(pyridꢀ2ꞌꢀ
yl)indoles.21 Moreover, regarding their potential utilities in pharmaceuticals and material
science,21b,22,23 and the abnormal βꢀregioselective addition of the ynamides in current
transformation, we decided to explore the reaction of ynamides with pyrido[1,2ꢀb]indazole
systematically.
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As depicted in Table 1, a series of gold catalysts containing different counter anions and
ligands were examined. JohnphosAuNTf2 was found to be less reactive (entry 2). Other cationic
catalysts bearing simple phosphine or Nꢀheterocycliccarbene ligands including PPh3AuNTf2,
IAdAu(PhCN)SbF6 and IPrAuNTf2 were proved to be less efficient or totally inactive (entries 4ꢀ
8). AgSbF6 or HOTf showed no catalytic activity for the reaction (entries 9 and 10). The effects
of solvent were also examined (entries 11ꢀ15). CH2Cl2, toluene and CHCl3 were proper reaction
media, while low yields of indole 3aa were observed when the reactions were performed in
MeNO2 or MeCN.
With a set of efficient reaction condition established (Table 1, entry 1), the reaction scope was
explored by using pyrido[1,2ꢀb]indazole 2a as the nitrene precursor. Results are shown in Table
2. In general, both electronꢀdonating (methyl, ethyl and methoxyl, cf. 3ba-3da) and electronꢀ
withdrawing groups (Fluoro, chloro and bromo, cf. 3ea-3ia) on the phenyl ring of ynamides 1
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were tolerated, furnishing the corresponding indoles in good to excellent yields. Moreover,
ynamides bearing 1ꢀnaphthyl or 2ꢀnaphthyl at the terminal position of the triple bond were viable
substrates. 3ja and 3ka were obtained in 99% and 82% yield, respectively. Ynamide (1l) derived
from hexꢀ1ꢀyne, could participate in the reaction, albeit with 42% yield (cf. 3la). The reaction of
ynamide 1m bearing a chiral auxiliary group proceeded well, furnishing indole 3ma in 76% yield.
Given the abundance and the easy accessibility of chiral oxazolidinꢀ2ꢀones, such kind of 7ꢀ
(pyridꢀ2ꞌꢀyl)indoles may have synthetic potential in the research area of chiral bidentated anion
ligands.
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Table 1. Optimization of the reaction conditions.a
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Table 2. Reaction scope of ynamides.a
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O
R1
O
5
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O
N
HN
O
R
JohnPhosAu(MeCN)SbF6
DCE, 100 oC
N
R1
N
N
N
1, 0.2 mmol
2a, 0.24 mmol
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3ba, R = OMe, 3 h, 91%
3ca, R = Me, 3 h, 92%
3da, R = Et, 3 h, 99%
3ea, R = F, 6 h, 99%
3fa, R = Cl, 30 h, 87%b
3ga, R = Br, 29 h, 73%b
O
O
N
HN
N
X-ray of 3ca
Cl
O
O
O
Cl
O
O
O
N
N
N
HN
HN
HN
N
N
N
3ha, 30 h, 93%b
3ja, 4 h, 99%
3ia, 21 h, 88%
Me
O
O
O
O
O
O
N
N
N
HN
HN
HN
N
N
N
Bn
3la, 24 h, 42 %b
3ma, 24 h, 76%b
3ka, 5 h, 82%
aAll reaction was carried out in 0.2 mmol scale with 5 mol% of JohnphosAu(MeCN)SbF6 as
catalsyt at 100 oC in DCE, [1] = 0.1 M. b10 mol% of catalyst was employed.
Subsequently, the generality and limitation of pyrido[1,2ꢀb]indazoles for the reaction with
ynamide 1a was investigated under the standard reaction condition. As depicted in Table 3, a
broad set of substituents on pyrido[1,2ꢀb]indazole were proved to be compatible (3ab-3ap).
Notably, electronꢀwithdrawing groups (R2) trended to speed up the reaction and afford the
corresponding products in higher yields (Table 3 and Scheme S1 in Supporting Information).
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Table 3. Reaction scope of pyrido[1,2ꢀb]indazole.a
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Mechanistic studies
Detection and Characterization of Reaction Intermediates
The unusual regioselectivity of goldꢀcatalyzed annulation between ynamides and pyrido[1,2ꢀ
b]indazoles is intriguing. To get deeper understanding on the reaction mechanism, a series of
experiments were subsequently conducted. The stoichiometric reactions of 1a and 2a with
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catalyst JohnphosAu(MeCN)SbF6 were monitored by P NMR spectroscopy in CDCl3 at room
temperature (Figure 1 and Figure S1 in Supporting Information). Treatment of 1a with
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JohnphosAu(MeCN)SbF6 generated a new species with 31P NMR shift at 64.28 ppm (Figure 1c),
which has been identified to be the adduct of 1a with the cationic gold catalyst. The structure of
this complex was confirmed by Xꢀray crystallography,24 which contained a fused bicyclic fiveꢀ
memberedꢀring system (Figure 2). Compared with the extensive studies on goldꢀcatalyzed formal
cycloaddition of ynamides in recent years, current outcome is noteworthy. As the well accepted
keteniminium ion intermediate which would commonly lead to αꢀsite selective cycloaddition
product was not observed. More importantly, in previous reports, the activation mode of goldꢀ
catalyst with ynamide is somewhat speculative. No direct evidences for the actual reaction
intermediate have been described. The adduct obtained here represents the first isolated gold
complex with ynamide, and it well explained the unusual βꢀsite regioselective addition observed
in current transformation. Encouraged by this discovery, further systematical examinations on
the complexation of gold catalysts with other ynamides will be the subject of our future studies.
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Figure 1. The 31P NMR spectroscopy of (a) 10 mmol JohnposAu(MeCN)SbF6, (b) mixture of 10
mmol JohnposAu(MeCN)SbF6 and 10 mmol 2a, (c) mixture of 10 mmol
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JohnposAu(MeCN)SbF6 and 20 mmol 1a, (d) mixture of 10 mmol JohnposAu(MeCN)SbF6, 20
mmol 1a and 20 mmol 2a in 0.5 mL CDCl3.
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Figure 2. Xꢀray structure of JohnphosAu(1a)SbF6. Hydrogen atoms have been omitted for
clarity.
On the other hand, the reaction of 2a with JohnphosAu(MeCN)SbF6 gave
JohnphosAu(2a)SbF6. The structure of this complex was also confirmed by Xꢀray
crystallography (Figure 3), and the corresponding 31P NMR showing a chemical shift at 59.03
ppm (Figure 1b). Interestingly, upon addition of 2a to the mixture of JohnphosAu(MeCN)SbF6
and 1a, the peak for JohnphosAu(1a)SbF6 disappeared with concomitant formation of a new
species showing a chemical shift at 64.63 ppm (Figure 1d). Although attempts to crystallize the
corresponding threeꢀcomponent adduct was not successful, a new species was detected by high
resolution mass spectrometry (HRꢀMS, m/z: 850.2901, Figure S2 In Supporting Information),
which could be assigned to a complex of gold catalyst with 1a and 2a, namely
JohnphosAu(1a)(2a)SbF6.
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Figure 3. Xꢀray structure of JohnphosAu(2a)SbF6. Hydrogen atoms have been omitted for
clarity.
Kinetic studies for the goldꢀcatalyzed reaction of 1a and 2a were further carried out to get
better understanding of the reaction mechanism. The reaction was found to be firstꢀorder in
JohnphosAu(MeCN)SbF6 (Figure 4 and Figure S3 in Supporting Information) and zeroꢀorder in
both 1a and 2a (Figure S4 and S5 in Supporting Information). Increasing the concentration of 2a
slightly depressed reaction rates, suggesting that 2a may partially poison the gold catalyst.
Varying temperature from 313 to 335 K (Figure 5 and Figure S6 in Supporting Information),
activation parameters ∆H‡ = 16.8 kcal mol−1 and ∆S‡ = ꢀ19.1 cal molꢀ1 Kꢀ1 were obtained from
Eyring plots. The negative ∆S‡ value is consistent with our NMR experiments. Kinetics for the
reactions of various paraꢀsubstituted ynamides 1 with 2a was also carried out. A fairly linear
Hammett correlation between log(kX/kH) and σ was obtained with a reaction constant of ρ = ꢀ
2.15 (Figure 6 and Figure S7 in Supporting Information), The large negative ρ value suggests
that the transition state of the reaction is polarized with positive charge at the reaction center.
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-8.0
-8.5
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-10.0
-10.5
-11.0
y = 1.0117x - 3.7141, R2 = 0.9892
-7.0
-6.5
-6.0
-5.5
-5.0
-4.5
In[Au]
Figure 4. Plot of ln(initial rate) vs ln([Au]). y = 1.0117x – 3.7141, R2 = 0.9892. The slope of the
line is approximately 1, indicating that the rate for the reaction is firstꢀorder in
JohnphosAu(MeCN)SbF6.
-15.6
-16.0
-16.4
-16.8
y = -8506.9x + 10.033, R2 = 0.9993
-17.2
0.00300 0.00305 0.00310 0.00315 0.00320
1/T
(
K-1
)
Figure 5. Plot of ln(initial rate/T) vs 1/T for the reaction between 1a and 2a in CDCl3, [1a] =
0.10 M, [2a] = 60 mM, [Au] = 2.5 mM. Slope = ꢀ8.51 × 103, yꢀintercept = 1.00 × 10, R2 = 0.999.
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MeO
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0.0
H
-0.2
-0.4
F
Cl
Br
y = -2.1534x + 0.1118, R2 = 0.9666
σ0.0
-0.3
-0.2
-0.1
0.1
0.2
0.3
Figure 6. Hammett plot of log(kX/kH) vs σ for the reaction of 2a with paraꢀsubstituted ynamides
1 in CDCl3 at 60 oC, [1a] = 0.10 M, [2a] = 60 mM, [Au] = 2.5 mM. Slope = ꢀ2.15, yꢀintercept =
0.11, R2 = 0.967.
Scheme 3. Kinetic isotope effect experiments.
As CꢀH bond functionalization of the aromatic ring was involved in current transformation. To
identify whether cleavage of the CꢀH bond at the orthoꢀposition of pyrido[1,2ꢀb]indazoles 2a is
involved as the rateꢀdetermined step, kinetic isotope effect of parallel experiments were carried
out (Scheme 3 and Figure 7). As depicted, no significant kinetic isotope effect (kH/kD = 1.07)
was observed, suggesting that CꢀH bond cleavage was not involved in the rateꢀdetermined step.
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2a-H ( )
y = 0.000107x + 0.001819, R2 = 0.989885
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2a-D (y = 0.000100x + 0.003082, R2 = 0.997241)
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Time / min
Figure 7. Kinetic profiles for the goldꢀcatalyzed annulation of ynamides 1a with pyrido[1,2ꢀ
b]indazoles 2a-H (black) and 2a-D (red). Yields were obtained by 1H MNR using
dibromomethane as internal standard. Standard reaction conditions: [1a] = 0.10 M, [2a] = 0.12
M, [Au] = 5 mM in 2.0 mL CDCl3 under argon at 60 oC.
Collectively, plausible mechanistic rationales for current indole synthesis were outlined in
Scheme 4. Coordination of ynamide 1a to the gold catalyst C would generate intermediate E
bearing a transient fiveꢀmembered ring. A nucleophilic attack of E by 2a gave F. Ring opening
of the pyrido[1,2ꢀb]indazole (b ring) led to the formation of intermediate G. Intramolecular sp2
CꢀH bond functionalization taking place (G→H), followed by protodeauration and isomerization,
would furnish the final product 3ꢀaminoindole 3aa. Since enhanced reaction rate and efficiency
were observed by setting up electronꢀwithdrawing groups onto a ring (Table 3 and Scheme S1 in
Supporting Information),25 pathways akin to FriedelꢀCraftꢀtype alkylation or CꢀH bond insertion
of gold carbene intermediate were unlikely.
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Scheme 4. Mechanistic Rationale.
During the testing of the scope of ynamides, we found that the reaction of ynamides bearing
sulfonyl protecting group on the nitrogen atom led to no formation of corresponding 3ꢀ
amidoindoles (results not shown). Notably, when ynamide 4, possessing a Cbz (benzyl
carbomate) protected amide moiety, was employed instead of 1a, the target indole was not
obtained either (Scheme 5). These observations further highlight the critical role of oxazolidinꢀ2ꢀ
onyl moiety for current βꢀregioselective formal cycloaddition.
Scheme 5. The reaction of ynamide 4 with 2a.
Conclusions
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In summary, we have demonstrated a novel goldꢀcatalyzed formal [3+2] cycloaddition of
ynamides with pyrido[1,2ꢀb]indazoles, furnishing 3ꢀamidoꢀ7ꢀ(pyridꢀ2ꞌꢀyl)indoles in good to
excellent yields. Compared with previous relatively extensive studies on goldꢀcatalyzed reactions
of ynamides, current transformation has showcased an unusual βꢀsite regioselective formal
cycloadditon of pyrido[1,2ꢀb]indazoles 2 to ynamides 1, thus leading 3ꢀamidoindoles exclusively.
According to this activation mode, we believe that a number of new reactions which feature βꢀ
site regioselective addition of ynamides will be uncovered in the near future.
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EXPERIMENTAL SECTION
General Information. JohnphosAu(MeCN)SbF6,16 ynamides 126 and pyrido[1,2ꢀb]indazoles
217 were prepared according to literature methods. All reactions were carried out with standard
Schlenk techniques under argon. All reagents were used as received from commercial suppliers
unless otherwise stated. All solvents were purified by distillation following standard procedures.
Reaction progress was monitored by thin layer chromatography (TLC) and components were
visualized by observation under UV light at 254 nm. Flash column chromatography was
performed using silica gel 60 (200ꢀ300 mesh). High resolution mass spectrometry was performed
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on UHR TOF LC/MS Mass Spectrometry. All H NMR, C NMR and P NMR spectra were
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recorded on a 400 MHz spectrometer (1H 400 MHz, C 100 MHz, P 162 MHz) using CDCl3
1
as solvent. Chemical shifts were reported in parts per million (ppm, δ). H NMR spectra are
referenced to the peak of tetramethylsilane (δ = 0.00) and reported as follows: chemical shift
(ppm), multiplicity (s = singlet, t = triplet, q = quartet, m = multiplet) and coupling constant
31
(Hz). 13C NMR spectra are referenced to the solvent center peak of CDCl3 (δ = 77.0). P NMR
spectra are referenced to the peak of H3PO4 (δ = 0.00).
Synthesis of pyrido[1,2-b]indazole 2
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A solution of 2ꢀphenylpyridine (2 mmol), [Cp*RhCl2]2 (4 mol %), PhI(OAc)2 (1.5 equiv) and pꢀ
TsOH⋅H2O (1.5 equiv) in 15 mL acetone was stirred at room temperature for 15 min. After
addition of NaN3 (6 mmol), the reaction mixture was stirred at 50 °C for 16 h. Then the solvent
was removed under reduced pressure and the residue was purified by silica gel chromatography
using EA/PE as eluent to afford the azidation product 2ꢀ(2ꢀazidophenyl)–pyridine b in 88%
yield. 2ꢀ(2ꢀAzidophenyl)pyridine b and dry dioxane (5 mL) were charged into a pressure tube
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o
under nitrogen. After stirred at 125 C for 8 ꢀ 20 h, the solvent was removed on a rotary
evaporator and the residue was purified by column chromatography on silica gel (ethyl
acetate/petroleum ether = 10 : 1), affording the product pyrido[1,2ꢀb]indazole 2a.
1H and 13C NMR Spectra data for the prepared substrates
2-(2-azidophenyl)pyridine (b)
1H NMR (400 MHz, CDCl3) δ 8.71 (d, J = 4.4 Hz, 1H), 7.74ꢀ7.65 (m, 3H), 7.43 (t, J = 7.2 Hz, 1H), 7.26ꢀ
7.22 (m, 3H); 13C{H}NMR (100 MHz, CDCl3) δ155.7, 149.4, 137.1, 135.8, 132.1, 131.4, 129.8, 125.0,
124.8, 122.1, 118.7.
pyrido[1,2-b]indazole (2a)
1H NMR (400 MHz, CDCl3) δ 8.77 (d, J = 6.8 Hz, 1H), 8.08 (t, J = 6.8 Hz, 2H), 7.85 (d, J = 8.4 Hz, 1H),
7.56 (t, J = 7.6 Hz, 1H), 7.32 (t, J = 7.6 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.15 (t, J = 6.8 Hz, 1H);
13C{H}NMR (100 MHz, CDCl3) δ 149.6, 135.3, 128.4, 127.9, 121.9, 119.8, 119.7, 117.9, 116.2, 115.5,
115.1.
3-fluoropyrido[1,2-b]indazole (2b)
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1H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 6.8 Hz, 1H), 8.02ꢀ8.96 (m, 2H), 7.41ꢀ7.27 (m, 2H), 7.16ꢀ7.12
(m, 1H), 7.00ꢀ6.94 (m, 1H); 13C{H}NMR (100 MHz, CDCl3) δ 163.3 (d, J = 244 Hz), 150.2 (d, J = 13
Hz), 135.5, 128.1, 122.9, 121.5 (d, J = 11 Hz), 117.5, 116.0, 112.1, 110.4 (d, J = 27 Hz), 99.4 (d, J = 24
Hz).
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3-chloropyrido[1,2-b]indazole (2c)
1H NMR (400 MHz, CDCl3) δ 8.77 (d, J = 6.8 Hz, 1H), 8.09 (d, J = 8.8 Hz, 1H), 8.00 (d, J = 8.8 Hz,
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1H), 7.81 (s, 1H), 7.41 (t, J = 8.0 Hz, 1H), 7.23ꢀ7.16 (m, 2H); C{H}NMR (100 MHz, CDCl3) δ 150.0,
135.4, 134.3, 128.2, 122.8, 121.0, 120.9, 117.9, 116.6, 114.7, 113.6.
3-bromopyrido[1,2-b]indazole (2d)
1H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 6.8 Hz, 1H), 8.02 (d, J = 8.4 Hz, 1H), 7.96 (s, 1H), 7.87 (d, J =
8.4 Hz, 1H), 7.36 (t, J = 7.2 Hz, 1H), 7.27ꢀ7.17 (m, 2H); 13C{H}NMR (100 MHz, CDCl3) δ 150.3, 135.3,
128.1, 123.1, 122.8, 122.4, 121.1, 117.9, 117.8, 116.6, 113.8.
3-methylpyrido[1,2-b]indazole (2e)
1H NMR (400 MHz, CDCl3) δ 8.76 (d, J = 5.6 Hz, 1H), 8.07 (d, J = 8.2 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H),
7.60 (s, 1H), 7.33 (t, J = 7.2 Hz, 1H), 7.16ꢀ7.06 (m, 2H), 2.57 (s, 3H); 13C{H}NMR (100 MHz, CDCl3) δ
150.3, 138.6, 135.3, 127.9, 122.4, 121.9, 119.3, 117.6, 115.7, 114.3, 113.3, 22.4.
3-methoxypyrido[1,2-b]indazole (2f)
Pale yellow solid; Yield: 244 mg, 61 %; mp: 102ꢀ104 oC; 1H NMR (400 MHz, CDCl3) δ 8.72 (d, J =
6.8 Hz, 1H), 8.00 (d, J = 8.8 Hz, 1H), 7.93 (d, J = 8.8 Hz, 1H), 7.33 (t, J = 7.6 Hz, 1H), 7.12 – 7.07 (m,
2H), 6.90 (d, J = 8.8 Hz, 1H), 3.94 (s, 4H); 13C{H}NMR (100 MHz, CDCl3) δ 160.7, 151.2, 135.4, 127.9,
122.3, 120.6, 117.1, 114.9, 113.5, 110.0, 93.8, 55.3; IR (KBr): ṽ = 1649.0, 1604.5, 1557.7, 1475.2,
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1431.5, 1324.5, 1290.3, 1214.9, 1197.9, 1163.3, 801.9, 758.7, 740.6 cmꢀ1; HRMS (EI) m/z: [M + H]+
calcd for C12H11N2O, 199.0871; found: 199.0866.
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methylpyrido[1,2-b]indazole-3-carboxylate (2g)
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Pale yellow solid; Yield: 80.0 mg, 15 %; mp: 180ꢀ182 oC; 1H NMR (400 MHz, CDCl3) δ 8.83 (d, J
= 6.4 Hz, 1H), 8.61 (s, 1H), 8.15 (dd, J = 16.0, 8.4 Hz, 2H), 7.87 (d, J = 8.0 Hz, 1H), 7.42 (t, J = 7.2 Hz,
1H), 7.27 (s, 1H), 4.00 (s, 3H); 13C{H}NMR (100 MHz, CDCl3) δ 167.5, 149.0, 135.3, 130.1, 128.2,
122.5, 119.9, 119.7, 118.9, 118.6, 117.6, 117.2, 52.3; IR (KBr): ṽ = 1715.2, 1432.8, 1366.5, 1303.1,
1219.8, 1144.2, 1081.6, 751.7, 720.6 cmꢀ1; HRMS (ESI) m/z: [M + H]+ calcd for C13H11N2O2, 227.0821;
found: 227.0815.
3-phenylpyrido[1,2-b]indazole (2h)
Pale yellow solid; Yield: 297 mg, 61 %; mp: 120ꢀ121 oC; 1H NMR (400 MHz, CDCl3) δ 8.80 (d, J =
6.4 Hz, 1H), 8.15 (d, J = 7.2 Hz, 2H), 8.03 (s, 1H), 7.75 (d, J = 7.2 Hz, 2H), 7.52ꢀ7.36 (m, 5H), 7.21ꢀ7.18
(t, J = 6.0 Hz, 1H); 13C{H}NMR (100 MHz, CDCl3) δ 150.3, 141.7, 141.6, 135.3, 128.8, 128.0, 127.6,
127.4, 122.1, 120.14, 120.07, 117.9, 116.2, 114.4, 113.4; IR (KBr): ṽ = 1644.7, 1596.9, 1533.4, 1507.6,
1421.1, 1362.7, 1339.1, 1212.6, 753.8, 741.3, 722.0 cmꢀ1; HRMS (ESI) m/z: [M + H]+ calcd for
C17H13N2, 245.1079; found: 245.1073.
2-chloropyrido[1,2-b]indazole (2i)
1H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 6.8 Hz, 1H), 8.00ꢀ7.98 (m,2H), 7.74 (d, J = 9.2 Hz, 1H), 7.46
(dd, J = 9.2, 2.0 Hz, 1H), 7.34ꢀ7.30 (m, 1H), 7.18ꢀ7.15 (m, 1H); 13C{H}NMR (100 MHz, CDCl3) δ 147.9,
134.7, 129.3, 128.0, 125.0, 122.3, 118.8, 118.0, 117.0, 116.6, 115.6.
2-bromopyrido[1,2-b]indazole (2j)
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1H NMR (400 MHz, CDCl3) δ 8.77 (d, J = 6.4 Hz, 1H), 8.23 (s, 1H), 8.08 (d, J = 8.4 Hz, 1H), 7.67 (dd, J
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1-methylpyrido[1,2-b]indazole (2k)
Pale yellow oil; Yield: 96.0 mg, 26 %; 1H NMR (400 MHz, CDCl3) δ 8.77 (d, J = 6.4 Hz, 1H), 8.13
(d, J = 8.8 Hz, 1H), 7.69 (d, J = 8.8 Hz, 1H), 7.47ꢀ7.25 (m, 2H), 7.14 – 6.96 (m, 2H), 2.80 (s, 3H);
13C{H}NMR (100 MHz, CDCl3) δ 149.7, 135.6, 132.1, 128.3, 127.8, 121.8, 120.2, 119.5, 115.6, 114.8,
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cmꢀ1; HRMS (ESI) m/z: [M + H]+ calcd for C12H11N2, 183.0922; found: 183.0917.
1-chloropyrido[1,2-b]indazole (2l)
Pale yellow solid; Yield:132 mg, 32 %; mp: 90ꢀ91 oC; 1H NMR (400 MHz, CDCl3) δ 8.76 (d, J = 6.8
Hz, 1H), 8.53 (d, J = 8.8 Hz, 1H), 7.72 (d, J = 8.4 Hz, 1H), 7.46ꢀ7.36 (m, 2H), 7.22ꢀ7.17 (m, 2H);
13C{H}NMR (100 MHz, CDCl3) δ 150.5, 135.1, 128.6, 127.9, 127.0, 122.7, 120.1, 119.7, 116.8, 114.1,
113.3; IR (KBr): ṽ = 1642.0, 1600.3, 1511.5, 1436.4, 1408.6, 1358.9, 1215.7, 1137.4, 950.9, 784.2, 740.7,
712.9 cmꢀ1; HRMS (ESI) m/z: [M + H]+ calcd for C11H8ClN2, 203.0376; found: 203.0371.
8-methylpyrido[1,2-b]indazole (2m)
1H NMR (400 MHz, CDCl3) δ 8.59 (s, 1H), 8.03 (dd, J = 16, 8.4 Hz, 2H), 7.82 (d, J = 8.8 Hz, 1H), 7.54
(t, J = 7.6 Hz, 1H), 7.22ꢀ7.19 (m, 2H), 2.49 (s, 3H); 13C{H}NMR (100 MHz, CDCl3) δ 149.5, 133.7,
127.9, 126.5, 126.2, 124.7, 119.5, 119.4, 117.1, 115.4, 115.1, 18.58.
8-chloropyrido[1,2-b]indazole (2n)
Pale yellow solid; Yield: 110 mg, 27 %; mp: 157ꢀ159 oC; 1H NMR (400 MHz, CDCl3) δ 8.77 (d, J =
0.8 Hz, 1H), 7.99 (dd, J = 12.4, 8.4 Hz, 2H), 7.83 (d, J = 8.8 Hz, 1H), 7.58ꢀ7.54 (m, 1H), 7.28ꢀ7.22 (m,
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115.9, 115.2; IR (KBr): ṽ = 1598.8, 1511.6, 1436.8, 1354.1, 1329.0, 1315.2, 1074.6, 798.7, 740.6, 710.4
cmꢀ1; HRMS (ESI) m/z: [M + H]+ calcd for C11H8ClN2, 203.0376; found: 203.0371.
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1H NMR (400 MHz, CDCl3) δ 8.64 (d, J = 7.2 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.84ꢀ7.78 (m, 2H), 7.53
(t, J = 7.6 Hz, 1H), 7.17 (t, J = 7.6 Hz, 1H), 6.98ꢀ6.97(m, 1H), 2.51 (s, 3H); 13C{H}NMR (100 MHz,
CDCl3) δ 150.0, 135.4, 133.0, 128.3, 127.2, 119.8, 119.1, 118.5, 116.8, 115.3, 114.5, 21.2.
pyrimido[1,2-b]indazole (2p)
1H NMR (400 MHz, CDCl3) δ 8.98 (dd, J = 6.8, 1.2 Hz, 1H), 8.63 (d, J = 2.4 Hz, 1H), 8.33 (d, J = 8.0 Hz,
1H), 7.85 (d, J = 8.4 Hz, 1H), 7.66 (t, J = 7.2 Hz, 1H), 7.34 (t, J = 7.2 Hz, 1H), 7.21 (dd, J = 6.8, 4.0 Hz,
1H); 13C{H}NMR (100 MHz, CDCl3) δ 151.3, 145.2, 143.8, 133.7, 130.0, 121.1, 120.7, 116.1, 113.3,
111.6.
Au-catalyzed cycloaddition of ynamides 1 with pyrido[1,2-b]indazoles 2
General method: A pressure tube equipped with a magnetic stirrer bar was charged with
JohnphosAu(MeCN)SbF6 (5 mol %), ynamide 1 (0.2 mmol), pyrido[1,2ꢀb]indazole 2 (0.24
o
mmol) and solvent (1 mL). The reaction was stirred for 11 h at 100 C. Then the solvent was
removed under vacuum, and the residue was purified by column chromatography on silica gel
(ethyl acetate/petroleum ether = 2 : 1), providing the desired compound 3.
Method for 3fa, 3ga, 3ha, 3ma:
To a solution of JohnphosAu(MeCN)SbF6 (5 mol %) in dry DCE was added ynamide 1 (0.2
mmol) and pyrido[1,2ꢀb]indazole 2 (0.24 mmol). The reaction mixture was stirred 4 h at 100 oC,
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then another portion of JohnphosAu(MeCN)SbF6 (5 mol%) was added. After the reaction was
complete (detected by TLC), the solvent was removed under vacuum, and the residue was
purified by column chromatography using PE/EA as eluent to provide the desired compound.
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1H and 13C NMR Spectra data for the prepared products
3-(2-phenyl-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one (3aa)
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1
Pale yellow solid; Yield: 67.4 mg, 95 %; mp 142ꢀ143 C; Rf = 0.30 (PE/EA = 2:1); H NMR
(400 MHz, CDCl3) δ 11.67 (s, 1H), 8.73ꢀ8.71 (m, 1H), 8.03 (d, J = 8.0 Hz, 1H), 7.83ꢀ7.75 (m,
4H), 7.63 (d, J = 8.0 Hz, 1H), 7.52 (t, J = 7.6 Hz, 2H), 7.44ꢀ7.41 (m, 1H), 7.28ꢀ7.22 (m, 2H),
4.53 (d, J = 8.0 Hz,2H), 3.85 (d, J = 8.0 Hz,2H); 13C{H}NMR (100 MHz, CDCl3) δ 158.1, 157.4,
148.6, 136.7, 134.2, 133.16, 131.2, 129.2, 128.5, 127.2, 126.3, 121.6, 121.0, 120.4, 120.3, 119.9,
119.5, 110.1, 62.6, 47.6; IR (KBr): ṽ = 3686, 3308, 1750, 1590, 1438, 1271, 1110, 778, 689 cmꢀ
1; HRMS (ESI) m/z: [M + H]+ calcd for C22H18N3O2, 356.1399; found: 356.1394.
3-(2-(4-methoxyphenyl)-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one (3ba)
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Pale yellow solid; Yield: 70.5 mg, 91 %; mp: 170ꢀ171 C; Rf = 0.15 (PE/EA = 2:1); H NMR
(400 MHz, CDCl3) δ 11.57 (s, 1H), 8.69 (d, J = 4.0 Hz, 1H), 7.99 (d, J = 8.4 Hz, 1H), 7.78ꢀ7.75
(m, 2H), 7.68 (d, J = 8.4 Hz, 2H), 7.59 (d, J = 7.6 Hz, 1H), 7.25ꢀ7.19 (m, 2H), 7.04 (d, J = 8.4
Hz, 2H), 4.50 (t, J = 8.0 Hz, 2H), 3.86 (s, 3H), 3.82 (t, J = 8.0 Hz, 2H);13C{H}NMR (100 MHz,
CDCl3) δ 159.8, 158.1, 157.4, 148.5, 136.7, 134.2, 132.9, 128.5, 126.4, 123.6, 121.5, 120.7,
120.3, 120.0, 119.8, 119.1, 114.5, 109.2, 62.5, 55.3, 47.4; IR (KBr): ṽ = 3295, 1746, 1590, 1513,
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1262, 1032, 775 cmꢀ1; HRMS (ESI) m/z: [M + H]+ calcd for C23H20N3O3, 386.1505; found:
386.1499.
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3-(7-(pyridin-2-yl)-2-(p-tolyl)-1H-indol-3-yl)oxazolidin-2-one (3ca)
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White solid; Yield: 68.1 mg, 92 %; mp: 237ꢀ238 C; Rf = 0.33 (PE/EA = 2:1); H NMR (400
MHz, CDCl3) 11.63 (s, 1H), 8.71 (d, J = 3.6 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.82ꢀ7.78 (m,
2H), 7.66ꢀ7.61 (m, 3H), 7.34ꢀ7.21 (m, 4H), 4.53 (t, J = 8.0 Hz, 2H), 3.84 (t, J = 8.0 Hz, 2H), 2.44
(s, 3H);13C{H}NMR (100 MHz, CDCl3) δ 158.1, 157.4, 148.6, 138.5, 136.7, 134.4, 133.0, 129.8,
128.3, 127.1, 126.4, 121.5, 120.9, 120.4, 120.1, 119.9, 119.3, 109.7, 62.6, 47.5, 21.4; IR (KBr): ṽ
= 3327, 1745, 1413, 1268, 1032, 817, 777, 656 cmꢀ1; HRMS (ESI) m/z: [M + H]+ calcd for
C23H20N3O2, 370.1556; found: 370.1550.
3-(2-(4-ethylphenyl)-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one (3da)
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Pale yellow solid; Yield, 76.4 mg, 99 %; mp: 127ꢀ128 C; Rf = 0.25 (PE/EA = 2:1); H NMR
(400 MHz, CDCl3) δ 11.63 (s, 1H), 8.68 (d, J = 4.0 Hz, 1H), 7.99 (d, J = 7.6 Hz, 1H), 7.78ꢀ
7.59(m, 5H), 7.36ꢀ7.19 (m, 4H), 4.51 (t, J = 8.0 Hz, 2H), 3.83 (t, J = 8.0 Hz, 2H), 2.72 (q, J = 7.6
Hz, 2H), 1.30 (t, J = 7.6 Hz, 3H); 13C{H}NMR (100 MHz, CDCl3) δ 158.1, 157.4, 148.5, 144.7,
136.7, 134.3, 133.0, 128.6, 128.5, 127.1, 126.4, 121.5, 120.8, 120.3, 120.1, 119.8, 119.3, 109.7,
62.5, 47.5, 28.7, 15.4; IR (KBr): ṽ = 3327, 2965, 1742, 1588, 1415, 1268, 1102, 773, 638 cmꢀ1;
HRMS (ESI) m/z: [M + H]+ calcd for C24H22N3O2, 384.1712; found: 384.1707.
3-(2-(4-fluorophenyl)-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one(3ea)
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Pale yellow solid, Yield, 74.2 mg, 99 %; mp: 183ꢀ184 C; Rf = 0.33 (PE/EA = 2:1); H NMR
(400 MHz, CDCl3) δ 11.63 (s, 1H), 8.69 (d, J = 3.6 Hz, 1H), 7.99 (d, J = 8.0 Hz, 1H), 7.79ꢀ7.70
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(m, 4H), 7.59 (d, J = 7.6 Hz, 1H), 7.26ꢀ7.18 (m, 4H), 4.51 (t, J = 8.0 Hz, 2H), 3.82 (t, J = 8.0 Hz,
2H); 13C{H}NMR (100 MHz, CDCl3) δ 162.7 (d, J =248 Hz), 158.1, 157.2, 148.5, 136.7, 133.4,
133.0, 129.0 (d, J = 8.0 Hz), 127.3 (d, J = 3.0 Hz), 126.2, 121.6, 120.9, 120.5, 120.3, 119.8,
119.3, 116.2 (d, J = 21.0 Hz), 110.0, 62.5, 47.5. 19F NMR (376 MHz, CDCl3) δ ꢀ112.4; IR (KBr):
ṽ = 3308, 1746, 1507, 1412, 1230, 1113, 1032, 775, 661 cmꢀ1; HRMS (ESI) m/z: [M + H]+ calcd
for C22H17FN3O2, 374.1305; found: 374.1299.
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3-(2-(4-chlorophenyl)-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one (3fa)
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White solid; Yield: 67.7 mg, 87 %; mp: 215ꢀ216 C; Rf = 0.33 (PE/EA = 2:1); H NMR (400
MHz, CDCl3) δ 11.68 (s, 1H), 8.71 (d, J = 4.0 Hz, 1H), 8.02 (d, J = 8.4 Hz, 1H), 7.81ꢀ7.79 (m,
2H), 7.68 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 7.6 Hz, 1H), 7.48 (d, J = 8.4 Hz, 2H), 7.28ꢀ7.22 (m,
2H), 4.53 (t, J = 8.0 Hz, 2H), 3.84 (t, J = 8.0 Hz, 2H); 13C{H}NMR (100 MHz, CDCl3) δ 158.1,
157.3, 148.6, 136.8, 134.4, 133.2, 133.1, 129.6, 129.4, 128.4, 126.2, 121.7, 121.0, 120.6, 120.5,
119.9, 119.4, 110.5, 62.6, 47.6; IR (KBr): ṽ = 3369, 1758, 1742, 1493, 1408, 1271, 1252, 1118,
773, 592 cmꢀ1; HRMS (ESI) m/z: [M + H]+ calcd for C22H17ClN3O2, 390.1009; found: 390.1004.
3-(2-(4-bromophenyl)-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one (3ga)
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Pale yellow solid; Yield: 63.6 mg, 73 %; mp: 198ꢀ199 C; Rf = 0.33 (PE/EA = 2:1); H NMR
(400 MHz, CDCl3) δ 11.68 (s, 1H), 8.71 (d, J = 3.6 Hz, 1H), 8.02 (d, J = 8.0 Hz, 1H), 7.82ꢀ7.79
(m, 2H), 7.65ꢀ7.60 (m, 5H), 7.28ꢀ7.22 (m, 2H), 4.53 (t, J = 8.0 Hz, 2H), 3.84 (t, J = 8.0 Hz, 2H);
13C{H}NMR (100 MHz, CDCl3) δ 158.1, 157.3, 148.6, 136.8, 133.3, 133.1, 132.3, 130.0, 128.7,
126.2, 122.6, 121.7, 121.0, 120.62, 120.57,, 119.9, 119.5, 110.5, 62.6, 47.6; IR (KBr): ṽ = 3373,
1739, 1592, 1414, 1271, 1034, 769, 745, 582 cmꢀ1; HRMS (ESI) m/z: [M + H]+ calcd for
C22H17BrN3O2, 434.0504; found: 434.0499.
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3-(2-(3-chlorophenyl)-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one(3ha)
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White solid; Yield, 72.6 mg, 93 %; mp: 192ꢀ193 C; Rf = 0.33 (PE/EA = 2:1); H NMR (400
MHz, CDCl3) δ 11.71 (s, 1H), 8.76ꢀ8.74 (m, 1H), 8.04 (d, J = 8.4 Hz, 1H), 7.85ꢀ7.80 (m, 2H),
7.73 (t, J = 2.0 Hz, 1H), 7.67ꢀ7.62 (m, 2H), 7.47ꢀ7.38 (m, 2H), 7.30ꢀ7.24 (m, 2H), 4.58ꢀ4.54 (m,
2H), 3.89ꢀ3.85 (m, 2H); 13C{H}NMR (100 MHz, CDCl3) δ 158.0, 157.2, 148.6, 136.8, 135.1,
133.3, 132.9, 132.6, 130.5, 128.4, 127.0, 126.1, 125.4, 121.7, 121.1, 120.70, 120.65, 119.9,
119.6, 110.9, 62.6, 47.6;IR (KBr): ṽ = 3676, 3336, 3055, 2909, 1739, 1594, 1424, 1272, 1119,
769, 676 cmꢀ1; HRMS (ESI) m/z: [M + H]+ calcd for C22H17ClN3O2, 390.1009; found: 390.1004.
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3-(2-(2-chlorophenyl)-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one (3ia)
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Pale yellow solid; Yield: 68.5 mg, 88 %; mp: 144ꢀ145 C; Rf = 0.33 (PE/EA = 2:1); H NMR
(400 MHz, CDCl3) δ 11.78 (s, 1H), 8.67 (d, J = 3.2 Hz, 1H), 8.03 (d, J = 8.0 Hz, 1H), 7.84ꢀ7.66
(m, 4H), 7.57ꢀ7.54 (m, 1H), 7.41ꢀ7.39 (m, 2H), 7.30ꢀ7.20 (m, 2H), 4.44 (t, J = 8.0 Hz, 2H), 3.80
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(t, J = 8.0 Hz, 2H); C{H}NMR (100 MHz, CDCl3) δ 157.7, 157.2, 148.5, 136.6, 133.1, 132.9,
132.1, 131.1, 130.2, 130.1, 130.0, 127.2, 125.2, 121.5, 121.0, 120.4, 120.3, 119.79, 119.76,
111.9, 62.5, 47.5; IR (KBr): ṽ = 3357, 1744, 1430, 1399, 1221, 1034, 767, 744 cmꢀ1; HRMS
(ESI) m/z: [M + H]+ calcd for C22H17ClN3O2, 390.1009; found: 390.1004.
3-(2-(naphthalen-1-yl)-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one (3ja)
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White solid, Yield: 80.9 mg, 99 %; mp: 123ꢀ124 C; Rf = 0.33 (PE/EA = 2:1); H NMR (400 MHz,
CDCl3) δ 11.63 (s, 1H), 8.57 (d, J = 4.4 Hz, 1H), 8.05 (d, J = 8.0 Hz, 2H), 8.00ꢀ7.95 (m, 2H), 7.86 (d, J =
7.2 Hz, 1H), 7.81ꢀ7.73 (m, 3H), 7.63ꢀ7.49 (m, 3H), 7.32 (t, J = 7.6 Hz, 1H), 7.19ꢀ7.16 (m, 1H), 4.21 (t, J
= 8.0 Hz, 2H), 3.53 (d, J = 8.0 Hz, 2H); 13C{H}NMR (100 MHz, CDCl3) δ 157.6, 157.4, 148.5, 136.7,
133.6, 133.2, 132.7, 131.8, 129.4, 128.8, 128.5, 128.4, 127.1, 126.4, 125.6, 125.5, 121.5, 121.0, 120.4,
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120.3, 119.9, 119.8, 112.3, 62.3, 47.4; IR (KBr): ṽ = 3337, 1749, 1589, 1397, 1270, 1103, 772, 656 cmꢀ1;
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HRMS (ESI) m/z: [M + H]+ calcd for C26H20N3O2, 406.1556; found: 406.1550
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Pale yellow solid; Yield, 66.1 mg, 82 %; mp: 115ꢀ116 C; Rf = 0.30 (PE/EA = 2:1); H NMR
(400 MHz, CDCl3) δ 11.76 (s, 1H), 8.71 (d, J = 4.0 Hz, 1H), 8.18 (s, 1H), 8.00ꢀ7.75 (m, 7H),
7.64 (d, J = 7.6 Hz, 1H), 7.56ꢀ7.50 (m, 2H), 7.28ꢀ7.19 (m, 2H), 4.49 (t, J = 8.0 Hz, 2H), 3.80 (t, J
= 8.0 Hz, 2H); 13C{H}NMR (100 MHz, CDCl3) δ 158.1, 157.3, 148.6, 136.7, 134.1, 133.4,
133.3, 133.0, 128.9, 128.5, 128.3, 127.7, 126.7, 126.6, 126.33, 126.26, 124.7, 121.6, 120.9,
120.5, 120.4, 119.9, 119.5, 110.5, 62.6, 47.5; IR (KBr): ṽ = 3336, 1749, 1590, 1398, 1270, 1110,
771, 747,643 cmꢀ1; HRMS (ESI) m/z: [M + H]+ calcd for C26H20N3O2, 406.1556; found:
406.1550.
3-(2-butyl-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one (3la)
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Pale yellow solid; Yield: 27.9 mg, 42 %; mp: 142ꢀ143 C; Rf = 0.30 (PE/EA = 2:1); H NMR
(400 MHz, CDCl3) δ 11.21 (s, 1H), 8.72 (d, J = 3.6 Hz, 1H), 8.00 (d, J = 8.0 Hz, 1H), 7.81ꢀ7.77
(m, 1H), 7.72 (d, J = 7.2 Hz, 1H), 7.50 (d, J = 7.6 Hz, 1H), 7.24ꢀ7.19 (m, 2H), 4.58 (t, J = 8.0
Hz, 2H), 4.01 (t, J = 8.0 Hz, 2H), 2.83 (t, J = 8.0 Hz, 2H), 1.80ꢀ1.72 (m, 2H), 1.52ꢀ1.42 (m, 2H),
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0.98 (t, J = 7.6 Hz, 3H); C{H}NMR (100 MHz, CDCl3) δ 157.7, 157.6, 148.5, 137.0, 136.6,
132.5, 125.7, 121.4, 120.4, 120.0, 119.9, 119.7, 119.1, 118.4, 109.6, 62.3, 48.3, 31.0, 25.6, 22.6,
13.8; IR (KBr): ṽ = 3364, 2921, 1750, 1467, 1404, 1263, 771 cmꢀ1; HRMS (ESI) m/z: [M + H]+
calcd for C20H22N3O2, 336.1712; found: 336.1707.
(S)-4-benzyl-3-(2-phenyl-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one (3ma)
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White solid; Yield: 67.7 mg, 76 %; mp: 86ꢀ87 oC; Rf = 0.50 (PE/EA = 2:1); 1H NMR (400 MHz,
CDCl3) δ 11.69 (s, 1H), 8.73 (d, J = 4.4 Hz, 1H), 8.04 (d, J = 8.0 Hz, 1H), 7.80 (dd, J = 15.6, 7.6
Hz, 3H), 7.66 (d, J = 7.6 Hz, 1H), 7.55ꢀ7.42 (m, 3H), 7.31ꢀ7.22 (m, 2H), 7.15ꢀ7.13 (m, 3H), 6.85
(d, J = 6.0 Hz, 2H), 4.37ꢀ4.21 (m, 3H), 2.86 (d, J = 12.8 Hz, 1H), 2.50 (s, 1H); 13C{H}NMR (100
MHz, CDCl3) δ 157.4, 148.6, 136.8, 135.6, 133.3, 131.3, 129.1, 128.8, 128.6, 128.6, 127.6,
126.8, 121.6, 121.0, 120.6, 120.4, 120.0, 119.6, 108.7, 67.9, 59.7, 39.2; IR (KBr): ṽ = 3339,
2924, 1757, 1590, 1439, 1396, 1270, 1119, 769, 698 cmꢀ1; HRMS (ESI) m/z: [M + H]+ calcd for
C29H24N3O2, 446.1869; found: 446.1863.
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3-(4-fluoro-2-phenyl-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one(3ab)
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Pale yellow solid, Yield: 74.0 mg, 99 %; mp: 186ꢀ187 C; Rf = 0.30 (PE/EA = 2:1); H NMR
(400 MHz, CD3CN) δ 12.02 (s, 1H), 8.78 (d, J = 4.0 Hz, 1H),8.08 (d, J = 8.4 Hz, 1H), 7.92ꢀ7.82
(m, 4H), 7.59ꢀ7.55 (m, 2H), 7.50ꢀ7.46 (m, 1H), 7.35ꢀ7.32 (m, 1H), 6.99ꢀ6.94 (m, 1H), 4.56ꢀ4.49
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(m, 2H), 4.04ꢀ3.98 (m, 1H), 3.86ꢀ3.81 (m, 1H); C{H}NMR (100 MHz, CDCl3) δ 158.6, 156.6,
156.4 (d, J = 248 Hz), 148.4, 136.8, 135.8 (d, J = 11.0 Hz), 135.1, 130.5, 129.1, 128.7, 127.2,
121.4, 121.1 (d, J = 8.0 Hz), 119.6, 117.5 (d, J = 4.0 Hz), 114.9 (d, J = 20.0 Hz), 108.3, 105.9 (d,
J = 20.0 Hz), 62.6, 48.6 (d, J = 3.0 Hz); 19F NMR (376 MHz, CDCl3) δ ꢀ120.2; IR (KBr): ṽ =
3321, 1754, 1593, 1468, 1270, 1124, 760, 694 cmꢀ1; HRMS (ESI) m/z: [M + H]+ calcd for
C22H17FN3O2, 374.1305; found: 374.1299.
3-(4-chloro-2-phenyl-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one (3ac)
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Pale yellow solid, Yield: 76.2 mg, 97 %; mp: 231ꢀ232 C; Rf = 0.33 (PE/EA = 2:1); H NMR
(400 MHz, CDCl3) δ 11.95 (s, 1H), 8.66 (d, J = 3.6 Hz, 1H), 7.94 (d,J = 8.4 Hz, 1H), 7.77ꢀ7.64
(m, 4H), 7.54ꢀ7.43 (m, 3H), 7.23ꢀ7.17 (m, 2H), 4.62ꢀ4.56 (m, 1H), 4.49ꢀ4.42 (m, 1H), 4.09ꢀ4.02
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(m, 1H), 3.75ꢀ3.70 (m, 1H); 13C{H}NMR (100 MHz, CDCl3) δ 159.0, 156.6, 148.5, 136.9, 136.6,
134.5, 130.5, 129.2, 128.9, 127.4, 125.8, 123.4, 121.8, 121.4, 120.7, 120.0, 119.5, 109.4, 62.5,
49.1; IR (KBr): ṽ = 3311, 1751, 1603, 1407, 1244, 1122, 760, 694cmꢀ1; HRMS (ESI) m/z: [M +
H]+ calcd for C22H17ClN3O2, 390.1009; found: 390.1004.
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3-(4-bromo-2-phenyl-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one (3ad)
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White solid; Yield: 82.0 mg, 94 %; mp: 254ꢀ255 C; Rf = 0.33 (PE/EA = 2:1); H NMR (400
MHz, CDCl3) δ 11.98 (s, 1H), 8.66 (d, J = 4.0 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.79ꢀ7.75 (m,
3H), 7.59ꢀ7.43 (m, 4H), 7.36 (d, J = 8.0 Hz, 1H), 7.23ꢀ7.20 (m, 1H), 4.63ꢀ4.57 (m, 1H), 4.48ꢀ
4.42 (m, 1H), 4.10ꢀ4.04 (m, 1H), 3.73ꢀ3.67 (m, 1H); 13C{H}NMR (100 MHz, CDCl3) δ 159.0,
156.5, 148.5, 136.9, 136.8, 134.3, 130.4, 129.2, 128.9, 127.4, 124.8, 124.6, 121.8, 121.0, 120.0,
119.9, 113.6, 109.7, 62.4, 49.0; IR (KBr): ṽ = 3272, 1751, 1602, 1409, 1120, 776, 692 cmꢀ1;
HRMS (ESI) m/z: [M + H]+ calcd for C22H17BrN3O2, 434.0504; found: 434.0499.
3-(4-methyl-2-phenyl-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one (3ae)
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Pale yellow solid; Yield: 64.0 mg, 87 %; mp: 168ꢀ169 C; Rf = 0.33 (PE/EA = 2:1); H NMR
(400 MHz, CDCl3) δ 11.89 (s, 1H), 8.66 (d, J = 4.0 Hz, 1H), 7.97 (d, J = 8.0 Hz, 1H), 7.78ꢀ7.66
(m, 4H), 7.54ꢀ7.41 (m, 3H), 7.20ꢀ7.17 (m, 1H), 6.98 (d, J = 7.6 Hz, 1H), 4.55ꢀ4.38 (m, 2H),
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3.87ꢀ3.65 (m, 2H), 2.68 (s, 3H); C{H}NMR (100 MHz, CDCl3) δ 158.8, 157.5, 148.4, 136.6,
134.7, 133.4, 131.3, 131.1, 129.2, 128.4, 127.3, 125.5, 122.2, 121.2, 120.4, 119.6, 118.7, 110.1,
62.3, 48.8, 18.6; IR (KBr): ṽ = 3264, 1744, 1604, 1405, 1220, 1125, 1030, 764, 693 cmꢀ1; HRMS
(ESI) m/z: [M + H]+ calcd for C23H20N3O2, 370.1556; found: 370.1550.
3-(4-methoxy-2-phenyl-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one (3af)
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White solid; Yield: 58.8 mg, 76 %; mp: 185ꢀ186 C; Rf = 0.15 (PE/EA = 2:1); H NMR (400
MHz, CDCl3) δ 11.77 (s, 1H), 8.65 (d, J = 4.0 Hz, 1H), 7.92ꢀ7.70 (m, 4H), 7.52ꢀ7.38 (m, 3H),
7.17ꢀ7.14(m, 1H), 6.63 (d, J = 8.4 Hz, 1H), 4.57ꢀ4.42 (m, 2H), 4.10ꢀ4.03 (m, 1H), 4.00 (s, 3H),
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3.76ꢀ3.71 (m, 1H); C{H}NMR (100 MHz, CDCl3) δ 159.4, 157.4, 154.6, 148.4, 136.5, 134.9,
133.6, 131.1, 129.0, 128.1, 127.1, 121.7, 120.6, 119.1, 116.0, 114.7, 110.2, 100.8, 62.7, 55.8,
49.3; IR (KBr): ṽ = 3323, 1738, 1600, 1466, 1259, 1108, 788, 764, 656 cmꢀ1; HRMS (ESI) m/z:
[M + H]+ calcd for C23H20N3O3, 386.1505; found: 386.1499.
Methyl3-(2-oxooxazolidin-3-yl)-2-phenyl-7-(pyridin-2-yl)-1H-indole-4-carboxylate (3ag)
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Yellow solid; Yield: 83.6 mg, 99 %; mp: 170ꢀ171 C; Rf = 0.10 (PE/EA = 2:1); H NMR (400
MHz, CDCl3) δ 12.18 (s, 1H), 8.69 (d, J = 4.8 Hz, 1H), 8.03 (d, J = 8.4 Hz, 1H), 7.86ꢀ7.73 (m,
5H), 7.55ꢀ7.43 (m, 3H), 7.27ꢀ7.24 (m, 1H), 4.65ꢀ4.60 (m, 1H), 4.43ꢀ4.37 (m, 1H), 4.07ꢀ4.01 (m,
1H), 3.98 (s, 3H), 3.64ꢀ3.59 (m, 1H); 13C{H}NMR (100 MHz, CDCl3) δ 167.4, 159.1, 156.3,
148.5, 137.3, 137.0, 134.3, 130.9, 129.1, 128.8, 127.5, 124.2, 124.0, 123.9, 123.8, 122.3, 120.8,
119.0, 110.3, 62.6, 52.4, 47.9; IR (KBr): ṽ = 3297, 2919, 1749, 1410, 1265, 1130, 768, 696 cmꢀ1;
HRMS (ESI) m/z: [M + H]+ calcd for C24H20N3O4, 414.1454; found: 414.1444.
3-(2,4-diphenyl-7-(pyridin-2-yl)-1H-indol-3-yl)oxazolidin-2-one (3ah)
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White solid; Yield: 72.7 mg, 84 %; mp: 220ꢀ221 C; Rf = 0.40 (DCM/PE = 2:1); H NMR (400
MHz, CDCl3) δ 12.05 (s, 1H), 8.72 (d, J = 4.0 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H), 7.86ꢀ7.73 (m,
4H), 7.62ꢀ7.39 (m, 8H), 7.25ꢀ7.15 (m, 2H), 4.04ꢀ3.97 (m, 1H), 3.40ꢀ3.29 (m, 2H), 2.91ꢀ2.84 (m,
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1H); C{H}NMR (100 MHz, CDCl3) δ 157.9, 157.3, 148.6, 140.4, 136.8, 136.0, 135.7, 133.7,
131.1, 129.1, 128.9, 128.5, 128.1, 127.5, 127.3, 124.1, 122.0, 121.6, 120.1, 120.0, 119.8, 109.4,
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