Ligand-Free and Reusable Palladium Nanoparticles-Catalyzed Alkylation of 2-Alkylazaarenes with Activated Ketones under Neutral Conditions

Article abstract of DOI:10.1002/adsc.201900447

A mild, efficient, and stable binaphthyl-stabilized palladium nanoparticles (Pd?BNP) catalyzed (sp³)C?H reaction of 2-alkylazaarenes with activated carbonyl compounds was developed. Various activated carbonyl compounds such as α-keto amide, isatin, 1,2-diketone, α-keto ester, trifluoromethyl ketone, and phenylglyoxal derivatives were examined and most of the compounds underwent the reaction smoothly to provide the corresponding products in moderate to excellent yields. Moreover, chemoselective reactions of α-keto amides in the presence of simple ketones were achieved. Also, the model reaction was extended to a gram-scale synthesis and some of the products were utilized for derivatization to form the corresponding N-oxides, acryl amides and 1,2-diol, respectively. The major advantages of the protocol are neutral reaction conditions, no additional requirement of external ligand, and successful reusability of the Pd?BNP catalyst up to five cycles without losing its activity and yield. Hg-poisoning and hot filtration tests confirmed the heterogeneity of the Pd?BNP catalyst. (Figure presented.).

Full text of DOI:10.1002/adsc.201900447

Title: Ligand-Free and Reusable Palladium Nanoparticles-Catalyzed
Alkylation of 2-Alkylazaarenes with Activated Ketones under
Neutral Conditions
Authors: Naziya Parveen, Alagesan Muthukumar, and Govindasamy
Sekar
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10.1002/adsc.201900447
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Ligand-Free and Reusable Palladium Nanoparticles-Catalyzed
Alkylation of 2-Alkylazaarenes with Activated Ketones under
Neutral Conditions
Naziya Parveen,a Alagesan Muthukumar,a and Govindasamy Sekara*
a
Department of Chemistry, Indian Institute of Technology Madras, Chennai – 600036, India
Fax: (+91)-44-2257-4202; phone: (+91)-44-2257-4229; e-mail: gsekar@iitm.ac.in
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. A mild, efficient, and stable binaphthyl-stabilized scale synthesis and some of the products were utilized for
palladium nanoparticles (Pd-BNP) catalyzed (sp3)C-H derivatization to form the corresponding N-oxides, acryl
reaction of 2-alkylazaarenes with activated carbonyl amides and 1,2-diol, respectively. The major advantages of
compounds was developed. Various activated carbonyl the protocol are neutral reaction conditions, no additional
compounds such as -keto amide, isatin, 1,2-diketone, - requirement of external ligand, and successful reusability of
keto ester, trifluoromethyl ketone, and phenylglyoxal the Pd-BNP catalyst up to five cycles without losing its
derivatives were examined and most of the compounds activity and yield. Hg-poisoning and hot filtration tests
underwent the reaction smoothly to provide the confirmed the heterogeneity of the Pd-BNP catalyst.
corresponding products in moderate to excellent yields.
Moreover, chemoselective reactions of -keto amides in the
presence of simple ketones were achieved. Also, the model
reaction wass extended to a gram-
Keywords: palladium nanoparticles; ligand-free; C-H
functionalization; 2-alkylazaarenes; activated carbonyls
heteroatom multiple bond containing compounds is
an example of redox-neutral C-C bond forming
transformation.[2] Conventionally, the reaction is
carried out by treating picoline or quinaldine with an
organolithium base to generate the anion which upon
treatment with an electrophile provides the
corresponding product (Scheme 1a).[3] However,
shortcomings, such as the use of pyrophoric base and
the need of cryogenic temperature, associated with
this approach were first overcome by Huang and co-
workers by treating 2-methylazaarenes with N-
sulfonyl aldimines using Pd(OAc)2/1,10-phen catalyst
(Scheme 1b).[4]
Introduction
C-2 Alkylated azaarenes such as quinoline and
pyridine are found in many natural products and have
numerous applications in biology as drugs and in
chemistry as precursors, ligands, materials, etc.[1] For
instance, chimanine A, galipine and cusparine are
quinoline alkaloids. Pyridine-containing molecules
such as carbinoxamine and rabeprazole show
distinctive biological properties and pyridoxine is
known as vitamin B6.
Afterwards, both Brønsted acid[5] and Lewis acid[6-
7]
catalyzed transformations, as well as transition
metal-free[8] and asymmetric[9] approaches have been
reported by varying the electrophiles (Scheme 1c).
Although these transformations have many benefits,
they require the use of corrosive Brønsted acid and
homogeneous Lewis acid catalysts and external
ligand, and most of the reports were not focused on
the recovery of the catalysts. In 2017, our group
reported Zn(OTf)2 catalyzed reaction of 2-
alkylazaarenes with -keto amides in chemoselective
fashion. Though the methodology has advantages
over the classical procedure, it has the drawbacks
such as the use of hygroscopic catalyst, failure of the
substrate such as 2-methylquinoxaline due to the
Lewis acidity of Zn(OTf)2, less reactivity of 2-alkyl
pyridines and importantly, failure of cyclic -keto
Figure 1. Selective examples of bioactive 2-
alkylquinolines and pyridines
In general, 2-methylazaarene is used as the
precursor for the synthesis of higher C-2 alkylated
analogues. Reaction of 2-methylazaarene with C-
1
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10.1002/adsc.201900447
Advanced Synthesis & Catalysis
amide i.e., isatin.[10] Thus, the search for a mild and
reusable catalyst remains desirable.
2-hydroxy-N,2-diphenyl-3-(quinolin-2-
yl)propanamide 3a was isolated (entry 1). Followed
i
Metal nanoparticles (NPs) have been drawing
attention over the past two decades in catalysis as
they have the properties such as low catalyst loading,
high activity, more selectivity and catalyst reusability
and importantly, the use of external ligands can be
completely avoided.[11] In a more specific scenario,
Pd-nanoparticles (Pd-NPs) have received more
attention due to the multifarious catalytic properties
in coupling reactions, hydrogenation reactions etc.[12]
Recently, our group has developed binaphthyl
supported Pd nanoparticles (Pd-BNPs) catalyzed
transformations for C-C and C-O bonds forming and
reduction reactions.[13]
by this, other polar protic solvents such as PrOH,
t
EtOH and BuOH were screened and none of them
gave better yield than MeOH (entries 2-4). Next, the
screening of polar aprotic solvents such as EtOAc,
THF and 1,4-dioxane revealed that THF solvent was
superior than the other two solvents as it gave 68%
yield of the product. The use of chlorinated solvents
such as DCE and TCE and non-polar solvent such as
toluene did not increase the product yield (entries 8-
10). When PEG 200 was used as the solvent, it
rendered the product in 77% yield (entry 11). Thus,
PEG 200 was found to be a better solvent for the
transformation.
Reactions of activated ketone containing molecules
are always of interest due to high electrophilicity of
the keto group in comparison with the simple keto
group. Over a decade, plenty of methods involving
the reactions of activated carbonyls such as isatin, -
keto amide, -keto ester, -keto phosphonate,
trifluoromethyl ketone, etc were reported so far.[14]
We are also interested in the synthesis and
functionalization of activated ketone containing
moieties.[15] By considering the shortcomings of
previous reports and in continuation of our interest in
the functionalization of activated carbonyl
compounds, we herein describe a ligand-free,
recoverable and reusable Pd-BNP catalyzed the
reaction of 2-alkylquinolines and pyridines with
activated ketones under neutral conditions (Scheme
1d). To the best of our knowledge, this is the first
report on nanoparticles catalyzed C(sp3)-H
functionalization of 2-alkylazaarenes.
In order to improve the yield of product, the
reaction temperature was varied from 60-90 oC.
However, the variation of temperature did not favour
the increase in yield (entries 12-14). Then, the Pd-
BNP catalyst loading was reduced to 2 and 1 mol%
(entries 15 and 16). To our surprise, the reaction with
2 mol% of Pd-BNP provided the maximum yield
(90%) of product 3a (entry 15). Meanwhile, when the
role of other PEG solvents with higher molecular
weight such as PEG 400 and 600 was tested, they
provided the product 3a in 70% and 42% yields,
respectively (entries 17 and 18). Finally, the
heterogeneous Pd-BNP catalyst was compared with
Pd on carbon (Pd/C) catalyst which is also
heterogeneous in nature. However, the yield of
reaction was much lower than the reaction of Pd-BNP
catalyst (entry 19).
Table 1. Optimization of reaction conditions[a]
Pd-BNP
(mol%)
Temp.
(oC)
70
70
70
70
70
70
70
70
70
70
70
80
90
60
70
Yield
(%)[b]
65
56
42
51
51
68
39
50
54
31
77
57
39
56
90
Entry
Solvent
1
2
3
4
5
6
7
8
3
3
3
3
3
3
3
3
3
3
3
3
3
3
2
1
2
2
-
MeOH
iPrOH
EtOH
tBuOH
EtOAc
THF
1,4-Dioxane
DCE
TCE
Toluene
PEG 200
PEG 200
PEG 200
PEG 200
PEG 200
PEG 200
PEG 400
PEG 600
PEG 200
9
10
11
12
13
14
15
16
17
18
19c
Scheme 1. Functionalization of 2-alkylazaarenes
Results and Discussion
70
70
70
70
61
70
42
38
The optimization studies were begun with 1.5 mmol
of quinaldine 1a and 0.5 mmol of -keto amide 2-
oxo-N-2-diphenylacetamide 2a as the model
substrates and the results are depicted in Table 1.
Initially, 3 mol% of Pd-BNP was used as the catalyst
[a]Reaction conditions: 1a (1.5 mmol) and 2a (0.5 mmol)
were used in 2 mL of solvent. [b]Isolated yield. [c]2 mol% of
o
in MeOH solvent at 70 C temperature. To our
delight, 65% of the quinaldine incorporated product
2
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10.1002/adsc.201900447
Advanced Synthesis & Catalysis
commercially available Pd/C (10 wt. %) was used as
the catalyst for 36 h.
Next, the scope of the transformation was tested with
various -keto amides and 2-methylazaarenes and the
results are shown in Table 2. Electron donating
groups such as sterically hindered ortho-methyl and
para-methyl substituted -keto amides paved the
corresponding quinaldine incorporated products 3b
and 3c in 65% and 81% yields, respectively (entries 2
and 3). Electron donating methoxy group substituted
at para position of benzoyl ring provided the addition
product 3d in 78% yield (entry 4). When weak donor
chloro group substituted at meta and para positions
of -keto amides, gave the corresponding products 3e
and 3f in 67% and 88% yields, respectively (entries 5
and 6). In the case of electron withdrawing
trifluoromethyl group containing -keto amide, the
reaction yielded 87% of the product 3g (entry 7).
Likewise, meta-nitro substituted -keto amide also
gave the corresponding product 3h in 67% yield
(entry 8). When aliphatic -keto amide was tested
under the standard conditions, the reaction was slow
and 56% of 3i was obtained in 48 h (entry 9).
Similarly, the reaction with aliphatic amine derived
-keto amide was slow and 62% of 3j was isolated in
48 h (entry 10). Noteworthy, 4-aminopyridine
derived -keto amide rendered the respective product
3k in 58% yield (entry 11).
Then the scope of 2-methylazaarene was initiated
with 6-bromoquinaldine and the reaction yielded 92%
of the corresponding product 3l (entry 12). The
reaction of 2a with 8-hydroxyquinaldine gave the
respective addition product 3m in 71% yield (entry
13). It is important to mention that 2-
methylquinoxaline
failed
to
provide
the
corresponding product in our previous work due to
the Lewis acidity of Zn(OTf)2 catalyst. Whereas in
this work, the same reaction with Pd-BNP catalyst
yielded 49% of the product 3n which reveals the mild
nature of Pd-BNP catalyst (entry 14). In the case of 3-
methylbenzo[f]quinoline, the reaction provided the
corresponding product 3o in 36% yield (entry 15).
Due to the acidity factor, the reactivity of 2-
alkylpyridines is lesser than 2-aklylquinolines. This
was consistent with the reactions of 2a with 2-
methylpyridines such as 2-picoline, 2,6-lutidine and
2,4,6-collidine as they yielded the corresponding
products 3p-3r in 35-42% yields in 48 h (entries 16-
18).
Table 2. Scope of -keto amide[a], [b]
[a]Reaction conditions: 1 (1.5 mmol) and 2 (0.5 mmol)
were used in 2 mL of PEG 200. [b]Isolated yield.
The chemoselective reaction of the keto group of
-keto amide was further studied with acetyl and
benzoyl substituted -keto amides with 2-methyl
azaarenes and the results are given in Table 3. In the
3
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10.1002/adsc.201900447
Advanced Synthesis & Catalysis
case of sterically hindered ortho-acetyl substituted -
keto amide, 53% of 3s was isolated (entry 1).
However, the meta- and para-iosmers provided the
corresponding products 3t and 3u in higher yields
(entries 2 and 3). When para-benzoyl -keto amide
was treated under the standard conditions, it yielded
the corresponding product 3v in 86% yield (entry 4).
Finally, when ortho-acetyl substituted -keto amide
was treated with 2,6-lutidine, the reaction provided
56% of 3w in 48 h (entry 5). In all the cases, the
chemoselectivity was perfect as the reactions gave
only selective addition products.
methylquinoxaline and 3-methylbenzo[f]quinoline
rendered the products 5i and 5j in excellent yields
(entries 9 and 10). As mentioned before, the reactions
of 2,4,6-collidine and 2-picoline provided moderate
to good yields of products 5k and 5l (entries 11 and
12). However, a good improvement in the yield of
product 5m was observed in the case of 2,6-lutidine
(entry 13) and the structure of 5m was further
confirmed using single crystal X-ray analysis (CCDC
No. 1903391) (Figure 5).[16] In the case of 2-ethyl
pyridine, 1:1 ratio of distereomers of 5n was obtained
in 80% yield (entry 14). Also in the case of 2-
benzylpyridine, 3:1 ratio of diastereomers of 5o was
isolated in 72% yield (entry 15).
Table 3. Chemoselective reaction of -keto amide[a], [b]
Table 4. Scope of isatin[a], [b]
[a]Reaction conditions: 1 (1.5 mmol) and 2 (0.5 mmol)
were used in 2 mL of PEG 200. [b]Isolated yield.
Next, our focus shifted towards the reactivity of 2-
alkylazaarenes with other activated carbonyl group
containing molecule known as isatin and the results
are shown in Table 4. To our delight, the reactions
proceeded smoothly and provided the corresponding
products in moderate to excellent yields. When N-
allyl isatin was treated with quinaldine 1a, 96% of the
product 5a was obtained (entry 1). Similarly, N-
benzyl isatin paved the corresponding product 5b in
94% yield (entry 2). In addition, N-ethyl and methyl
protected isatins also worked well and the respective
products 5c and 5d were isolated in 90% and 96%
yields (entry 3 and 4). However, in the case of N-
acetyl isatin, yield of the product 5e got reduced to
45% (entry 5). When Isatin was treated with 1a, the
reaction delivered the addition product 5f in 60%
yield (entry 6).
Furthermore, the scope of 2-alkylazaarene was
carried out by treating them with N-allyl isatin. In the
case of 6-bromoquinaldine, 90% of 5g was obtained
(entry 7). 8-Hydroxyquinaldine also yielded the
product 5h in 95% yield (entry 8). Both 2-
4
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10.1002/adsc.201900447
Advanced Synthesis & Catalysis
transformation. For this purpose, phenylglyoxal and
its derivatives were used as the precursors and the
results are given in Table 5. In all the examples the
reaction selectively took place at more reactive
aldehyde functionality without affecting the keto
group. When phenylglyoxal was used, 72% of the
product 15a was obtained (entry 1). Also the electron
donating groups such as methyl and methoxy
substituted para to the benzoyl ring were well
tolerated and provided the products 15b and 15c in
good yields (entries 2 and 3). Also, the reaction of
meta-nitrophenylglyoxal resulted in 75% of the
product 15d (entry 4).
Table 5. Scope of phenylglyoxal[a], [b]
[a]Reaction conditions: 1 (1.5 mmol) and 4 (0.5 mmol)
were used in 2 mL of PEG 200. [b]Isolated yield.
In order to understand the reactivity of the other
activated ketones such as 1,2-diketone, -keto ester
and trifluoromethyl ketone, they were tested with
quinaldine 1a under the standard reaction conditions
(Scheme 2). In the case of linear 1,2-diketone i.e.,
benzil 6, no product formation was observed (Scheme
2a). Interestingly, when cyclic 1,2-diketone i.e.,
acenaphthoquinone 8 was treated, the reaction
resulted in 88% of the corresponding (sp3)C-H
[a]Reaction conditions: 1a (1.5 mmol) and 14 (0.5 mmol)
were used in 2 mL of PEG 200. [b]Isolated yield.
addition product
9
(Scheme 2b). To our
disappointment, the reactions of 1a with -keto ester
10 and 2,2,2-trifluoro-1-(1H-indol-3-yl)ethanone 12
failed to afford the respective products 11 and 13
(Scheme 2c and 2d).
Next, the scalability of optimized transformation
was performed with a gram scale reaction. For this
purpose, 6.6 mmol of quinaldine 1a was treated with
4.4 mmol of -keto amide 2a in 10 mL of PEG 200
solvent (Scheme 3). The reaction led to the formation
of 3a in 87% yield (1.4 g).
Scheme 3. Gram-scale synthesis
A plausible reaction mechanism for (sp3)C-H
addition of 2-alkylazaarene is proposed (Scheme 4).
Initially, Pd-BNP catalyst A interacted with 2-
methylazaarene B to produce the complex C. Next,
interaction of activated ketone D with complex C
could form E. Proton transfer from 2-methylazaarene
Scheme 2. Reaction of quinaldine with activated ketones
to
activated
ketone
furnished
Pd-enamide
intermediate F. Finally, the reaction of enamide with
protonated ketone resulted in the formation of
product G.
In addition, the role of activated aldehyde was
examined in this quinaldine (sp3)C-H addition
5
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10.1002/adsc.201900447
Advanced Synthesis & Catalysis
Figure 3. (i) HR-TEM images: (a) freshly prepared Pd-
BNP and (b) Pd-BNP after fifth catalytic cycle. (ii) Particle
size distribution: (c) freshly prepared Pd-BNP and (d)
recovered Pd-BNP.
To understand about the leaching of Pd-BNP
catalyst, the hot filtration test was performed. A
couple of reactions were carried out separately and
the reaction mixtures were filtered off at 4 h (25%
NMR yield) and 7 h (32% NMR yield) reaction time
intervals, respectively. The filtrates were further
allowed for reaction up to 24 h. However, no
improvement in the yields was observed in both cases.
This confirms that no leaching of Pd-BNP catalyst
was observed during the course of reactions. Also,
the activity of Pd-BNP residue was similar to that of
freshly prepared Pd-BNP catalyst (Figure 4).
Scheme 4. Plausible reaction mechanism
In order to test the efficacy of Pd-BNP catalyst,
catalyst recyclability study was carried out. The
catalyst was centrifuged and reused for five
successive recycles. The reaction yields of 3a were
excellent and the catalyst was recovered back without
any major loss (Figure 2).
Figure 4. Hot filtration test and effect on the yield of 3a
Furthermore, Hg-poisoning test was carried out to
confirm heterogeneity and no leaching of the Pd-BNP
catalyst. For this purpose, 2 mol% of Pd-BNP
catalyst and 30 equiv. of Hg were stirred at room
temperature for 2 h. Next, 1.5 mmol of 1a and 0.5
mmol of 2a were added in PEG 200 solvent and the
Figure 2. Recovery of Pd-BNP catalyst and yield of 3a
Moreover, the particle size of freshly prepared Pd-
BNP catalyst and after fifth cycle was compared. No
change in the particle size and no agglomeration of
the catalyst were observed (Figure 3). This
observation confirms that the catalyst is well active
up to five cycles.
o
mixture was allowed to stir at 70 C for 24 h. No
product formation confirms that the activity of
heterogeneous Pd-BNP catalyst was completely
inhibited by Hg (Scheme 5).
Scheme 5. Hg-poisoning test
6
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10.1002/adsc.201900447
Advanced Synthesis & Catalysis
To show synthetic utility of the protocol, some
derivatizations of the products were carried out
(Scheme 6). Initially, the compounds 3a and 5a were
treated with mCPBA. The corresponding N-oxides 16
and 17 were isolated in 88% and 91% yields,
respectively (Scheme 6a and 6b). Also, they were
treated with triflic acid. In the case of 3a, 82% of the
eliminated acrylamide derivative 18 was isolated as a
single isomer in 91% yield (Scheme 6c). Similarly,
when 5a was treated with triflic acid, it yielded the
eliminated product 19a in 60% yield, which again
reacted with 5a to form an interesting dimer 19b in
18% yield (Scheme 6d). The reason for the formation
of dimer is that, initially, the N atom of quinoline is
protonated in the acidic medium. The third position
of isatin is electrophilic in nature. Similarly, the fifth
position becomes nucleophilic in nature. Thus, the
fifth position of the isatin ring of compound 19b
underwent SEAr reaction with the third position of
another molecule 19a leading to the formation of
dimer 19b. The compound 19b was confirmed by X-
ray analysis (CCDC No. 1904526) (Figure 5).[16]
Finally, the compound 15a obtained from the reaction
of phenylglyoxal was treated with NaBH4 which
resulted in the formation of diol 20 as 3:2 ratios of
diastereomers (Scheme 6e).
Figure 5. Single crystal X-ray structures of 5m (CCDC No.
1903391) and 19b (CCDC No. 1904526)
Conclusion
A ligand-free approach of (sp3)C-H addition of 2-
alkylquinolines and pyridines to activated carbonyl
compounds catalyzed by using stable and reusable
binaphthyl stabilized Pd-nanoparticles (Pd-BNP) has
been developed. The reactivity of activated carbonyls
such as -keto amide, isatin, 1,2-diketone, -keto
ester, trifluoromethyl ketone, and phenylglyoxal
derivatives were studied. Most of the reactants
underwent reactions smoothly and provided the
corresponding products in moderate to excellent
yields. Moreover, chemoselective addition of 2-
methylquinoline and pyridine derivatives to keto
group of -keto amide in the presence of isolated
ketone was successfully achieved. In order to show
the utility of the transformation, a gram-scale reaction
and derivatization of respective products into N-
oxides, acryl amides and 1,2-diol were successfully
carried out. The Pd-BNP catalyst was well active up
to five recycles with no change in particle size. The
heterogeneousness of Pd-BNP was confirmed by the
hot filtration and Hg-poisoning tests. The key
advantages such as external ligand-free, low catalyst
loading, reusability of the catalyst and neutral
reaction conditions determine that the process is mild
and economic.
Experimental Section
General experimental procedure for (sp3)C-H
incorporation of 2-alkylazaarenes to activated carbonyl
compound
A mixture of activated carbonyl compound (0.5 mmol), 2-
alkylazaarene (1.5 mmol) and Pd-BNP (2 mol%) in
polyethylene glycol (PEG 200) (2.0 mL) was taken in an
oven dried reaction tube equipped with a magnetic bar and
the reaction tube was closed with a glass stopper. The
reaction mixture was kept in a pre-heated oil bath at 70 °C
and stirred for the given time. The progress of the reaction
was monitored by TLC. Upon completion of reaction, the
mixture was cooled down to room temperature and
extracted with EtOAc and water. The organic layer was
separated and solvent was removed under reduced pressure.
The crude mixture was purified by column
chromatography (eluents, hexanes:ethyl acetate, 80:20) to
obtain pure product.
Scheme 6. Synthetic utility
2-Hydroxy-N,2-diphenyl-3-(quinolin-2-yl)propanamide
(3a):
90% yield (165.6 mg); White solid; mp 159-160 °C (Lit.[10]
mp 158–160 °C); Rf = 0.27 (10% ethyl acetate in hexanes);
7
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10.1002/adsc.201900447
Advanced Synthesis & Catalysis
1H NMR (400 MHz, CDCl3):  = 3.53 (d, J = 15.2 Hz, 1H), 8.4 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 8.90 (s, 1H), 8.98 (s,
4.04 (d, J = 15.6 Hz, 1H), 7.00 (t, J = 7.6 Hz, 1H), 7.18-
7.36 (m, 4H), 7.45 (d, J = 8.4 Hz, 2H), 7.51 (t, J = 7.6 Hz,
1H), 7.69 (t, J = 8.0 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.84
(d, J = 7.6 Hz, 2H), 7.98 (d, J = 8.4 Hz, 1H), 8.10 (d, J =
8.4 Hz, 1H), 8.82 (bs, 1H), 8.95 (s, 1H) ppm; 13C NMR
(100 MHz, CDCl3):  = 44.9, 80.1, 120.8, 122.9, 125.2,
126.6, 127.1, 127.8, 127.9, 128.2, 128.5, 128.9, 129.1,
130.2, 136.4, 142.1, 146.3, 159.8, 172.5 ppm; FTIR (KBr):
ν = 3432, 3055, 2980, 1679, 1522, 1431, 738 cm-1; HRMS
(m/z): [M+H]+ calcd for C24H21O2N2: 369.1603; found:
369.1656.
1H) ppm; 13C NMR (100 MHz, CDCl3):  = 44.8, 80.1,
117.4, 119.6, 122.9, 124.2, 125.2, 126.6, 127.1, 127.9,
127.9, 128.2, 128.5, 129.9, 130.2, 134.6, 137.8, 138.9,
142.0, 146.3, 159.7, 172.6 ppm; FTIR (KBr): ν = 3372,
3059, 2917, 1686, 1591, 1517, 1196, 776 cm-1; HRMS
(m/z): [M+Na]+ calcd for C24H19O2N2ClNa: 425.1025;
found: 425.1030.
N-(4-Chlorophenyl)-2-hydroxy-2-phenyl-3-(quinolin-2-
yl)propanamide (3f):
88% yield (176.8 mg); White solid; mp 158–160 °C
(Lit.[10] mp 157–159 °C); Rf = 0.6 (20% ethyl acetate in
2-Hydroxy-2-phenyl-3-(quinolin-2-yl)-N-(o-
1
tolyl)propanamide (3b):
hexanes); H NMR (400 MHz, CDCl3):  = 3.54 (d, J =
15.2 Hz, 1H), 4.02 (d, J = 15.2 Hz, 1H), 7.17 (dt, J = 8.8,
3.2 Hz, 2H), 7.29 (dt, J = 7.2, 2.0 Hz, 1H), 7.32–7.43 (m,
5H), 7.45-7.55 (m, 1H), 7.66–7.73 (m, 1H), 7.77 (d, J =
8.4 Hz, 1H), 7.80-7.87 (m, 2H), 7.97 (d, J = 8.0 Hz, 1H),
65% yield (124.1 mg); White solid; mp 130-132 °C; Rf =
1
0.34 (10% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  = 2.09 (s, 3H), 3.54 (d, J = 15.2 Hz, 1H), 4.08
(d, J = 15.2 Hz, 1H), 6.95 (t, J = 7.6 Hz, 1H), 7.02-7.17 (m, 8.09 (d, J = 8.0 Hz, 1H), 8.82 (s, 1H), 8.97 (s, 1H) ppm;
2H), 7.22-7.34 (m, 1H), 7.34-7.46 (m, 3H), 7.46-7.60 (m,
1H), 7.63-7.85 (m, 3H), 7.89 (d, J = 7.6 Hz, 2H), 7.99 (d, J
= 8.4 Hz, 1H), 8.10 (d, J = 8.4 Hz, 1H), 8.97 (d, J = 14.4
Hz, 2H) ppm; 13C NMR (100 MHz, CDCl3):  = 17.5,
44.8, 80.4, 122.0, 123.0, 124.7, 125.2, 126.5, 126.6, 127.1,
127.7, 127.9, 128.1, 128.4, 128.6, 130.2, 130.3, 135.5,
137.6, 142.4, 146.2, 160.0, 172.4 ppm; FTIR (KBr): ν =
3388, 3054, 2925, 1686, 1588, 1521, 756 cm-1; HRMS
(m/z): [M+H]+ calcd for C25H23N2O2: 383.1759; found:
383.1760.
13C NMR (100 MHz, CDCl3):  = 44.9, 80.1, 120.8, 122.9,
125.2, 126.6, 127.1, 127.8, 127.9, 128.2, 128.5, 128.9,
129.1, 130.2, 136.4, 142.1, 146.3, 159.8, 172.5 cm-1;
HRMS (m/z): [M+Na]+ calcd for C24H19O2N2ClNa:
425.1027; found: 425.1032. FTIR (KBr): ν = 3349, 3055,
2965, 1662, 1510, 1263, 742 cm-1;
2-Hydroxy-2-phenyl-3-(quinolin-2-yl)-N-(4-
(trifluoromethyl)phenyl)propanamide (3g):
87% yield (189.7 mg); Colorless solid; mp 149-151 °C
(Lit.[10] mp 163-165 °C); Rf = 0.8 (30% ethyl acetate in
2-Hydroxy-2-phenyl-3-(quinolin-2-yl)-N-(p-
tolyl)propanamide (3c):
1
hexanes); H NMR (400 MHz, CDCl3):  = 3.54 (d, J =
15.2 Hz, 1H), 4.03 (d, J = 15.2 Hz, 1H), 7.23-7.33 (m, 1H),
7.33-7.43 (m, 3H), 7.43-7.55 (m, 3H), 7.59 (d, J = 8.4 Hz,
2H), 7.70 (t, J = 7.6 Hz, 1H), 7.78 (d, J = 8.0 Hz, 1H), 7.83
(d, J = 7.6 Hz, 2H), 7.97 (d, J = 8.4 Hz, 1H), 8.11 (d, J =
8.4 Hz, 1H), 8.93 (s, 1H), 9.12 (s, 1H) ppm; 13C NMR (100
MHz, CDCl3):  = 44.8, 80.1, 119.2, 122.8, 125.2, 126.2,
126.2, 126.7, 127.1, 127.9, 128.2, 128.5, 130.3, 137.8,
140.8, 141.9, 146.3, 159.7 and 172.9 ppm; FTIR (KBr): ν
= 3128, 2944, 2891, 1647, 1517, 1408, 1321, 1262, 1172,
1117, 820, 749 cm-1; HRMS (m/z): [M+H]+ calcd for
C25H20O2N2F3: 437.1477; found: 437.1475.
81% yield (154.7 mg); Colorless solid; mp 162-164 °C
(Lit.[10] mp 163-165 °C); Rf = 0.72 (30% ethyl acetate in
1
hexanes); H NMR (400 MHz, CDCl3):  = 2.22 (s, 3H),
3.52 (d, J = 15.2 Hz, 1H), 4.03 (d, J = 15.2 Hz, 1H), 7.01
(d, J = 8.0 Hz, 2H), 7.21-7.39 (m, 1H), 7.30-7.40 (m, 5H),
7.45-7.53 (m, 1H), 7.68 (td, J = 8.8, 1.6 Hz, 1H), 7.75 (d, J
= 8.0 Hz, 1H), 7.80-7.88(m, 2H), 7.97 (d, J = 8.4 Hz, 1H),
8.08 (d, J = 8.4 Hz, 1H), 8.72 (s, 1H), 8.89 (s, 1H) ppm;
13C NMR (100 MHz, CDCl3):  = 20.9, 44.9, 80.1, 119.5,
122.9, 125.3, 126.5, 127.1, 127.7, 127.9, 128.3, 128.4,
129.4, 130.1, 133.7, 135.2, 137.6, 142.4, 146.3, 159.9 and
172.2 ppm; FTIR (KBr): ν = 3393, 3204, 3064, 2955, 2821,
1625, 1515, 1413, 1263, 742 cm-1; HRMS (m/z): [M+H]+
calcd for C25H23O2N2: 383.1760; found: 383.1766.
2-Hydroxy-N-(3-nitrophenyl)-2-phenyl-3-(quinolin-2-
yl)propanamide (3h):
67% yield (138.3 mg); Yellow solid; mp 179-181 °C
(Lit.[10] mp 178–180 °C); Rf = 0.66 (30% ethyl acetate in
2-Hydroxy-2-(4-methoxyphenyl)-N-phenyl-3-(quinolin-
2-yl)propanamide (3d):
1
hexanes); H NMR (400 MHz, CDCl3):  = 3.54 (d, J =
15.2 Hz, 1H), 4.04 (d, J = 15.6 Hz, 1H), 7.20-7.45 (m, 5H),
7.51 (t, J = 7.6 Hz, 1H), 7.69 (t, J = 7.6 Hz, 1H), 7.77 (d, J
= 7.6 Hz, 2H), 7.84 (d, J = 8.0 Hz, 3H), 7.97 (d, J = 8.4 Hz,
1H), 8.11 (d, J = 8.4 Hz, 1H), 8.40 (s, 1H), 8.96 (s, 1H),
9.19 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3):  = 44.7,
80.1, 114.3, 118.7, 122.8, 125.1, 125.2, 126.7, 127.1, 127.9,
128.1, 128.2, 128.6, 129.7, 130.3, 137.8, 138.9, 141.8,
146.3, 148.6, 159.6 and 173.1 ppm; FTIR (KBr): ν = 3381,
3055, 2980, 1679, 1525, 1431, 1263, 729 cm-1; HRMS
(m/z): [M+H]+ calcd for C24H20O4N3: 414.1448; found:
414.1447.
78% yield (155.2 mg); Colourless solid; mp 144-145 °C
(Lit.[10] mp 143–145 °C); Rf = 0.67 (30% ethyl acetate in
1
hexanes); H NMR (400 MHz, CDCl3):  = 3.52 (d, J =
15.2 Hz, 1H), 3.78 (s, 3H), 4.01 (d, J = 15.6 Hz, 1H), 6.89
(d, J = 8.4 Hz, 2H), 7.01 (t, J = 7.6 Hz, 1H), 7.22 (t, J = 8.0
Hz, 2H), 7.36 (d, J = 8.4 Hz, 1H), 7.43-7.55 (m, 3H), 7.69
(t, J = 8.0 Hz, 1H), 7.76 (t, J = 8.8 Hz, 3H), 7.98 (d, J = 8.4
Hz, 1H), 8.09 (d, J = 8.4 Hz, 1H), 8.78 (s, 1H), 8.96 (s,
1H) ppm; 13C NMR (100 MHz, CDCl3):  = 45.0, 55.4,
79.8, 113.7, 119.5, 123.0, 124.1, 126.5, 126.5, 127.1, 127.9,
128.3, 128.9, 130.1, 134.5, 137.6, 137.8, 146.3, 159.2,
159.9 and 172.6 ppm; FTIR (KBr): ν = 3425, 3228, 2918,
1648, 1506, 1385, 1185, 817 cm-1; HRMS (m/z): [M+H]+
calcd for C25H23O3N2: 399.1708; found: 399.1712.
2-Hydroxy-N-phenyl-2-(quinolin-2-
ylmethyl)butanamide (3i):
56% yield (89.6 mg); Colourless solid; mp 136-137 °C
(Lit.[10] mp 135–137 °C); Rf = 0.63 (30% ethyl acetate in
hexanes); 1H NMR (400 MHz, CDCl3):  = 1.02 (t, J = 7.2
Hz, 3H), 1.60-1.86 (m, 1H), 1.92-2.13 (m, 1H), 3.25 (d, J
= 15.2 Hz, 1H), 3.62 (d, J = 14.8 Hz, 1H), 7.03 (t, J = 7.2
Hz, 1H), 7.24 (t, J = 7.6 Hz, 2H), 7.34 (d, J = 8.4 Hz, 1H),
N-(3-Chlorophenyl)-2-hydroxy-2-phenyl-3-(quinolin-2
yl)propanamide (3e):
67% yield (134.7 mg); White solid; mp 161-163 °C (Lit.[10]
mp 162–164 °C); Rf = 0.62 (30% ethyl acetate in hexanes);
1H NMR (400 MHz, CDCl3):  = 3.52 (d, J = 15.6 Hz, 1H), 7.40-7.57 (m, 3H), 7.69 (t, J = 8.0 Hz, 1H), 7.78 (t, J = 8.0
4.02 (d, J = 15.6 Hz, 1H), 6.94-7.02 (m, 1H), 7.12 (t, J =
8.0 Hz, 1H), 7.21–7.32 (m, 2H), 7.32-7.42 (m, 3H), 7.46–
7.56 (m, 1H), 7.64 (t, J = 2.0 Hz, 1H), 7.66-7.74 (m, 1H),
7.77 (d, J = 8.0 Hz, 1H), 7.81-7.89 (m, 2H), 7.97 (d, J =
Hz, 1H), 7.87 (bs, 1H), 7.97 (d, J = 8.4 Hz, 1H), 8.10 (d, J
= 8.4 Hz, 1H), 8.95 (s, 1H) ppm; 13C NMR (100 MHz,
CDCl3):  = 8.0, 33.0, 42.9, 79.6, 119.6, 122.9, 124.2,
126.5, 127.1, 127.9, 128.3, 129.0, 130.1, 137.6, 146.5,
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900447
Advanced Synthesis & Catalysis
159.9, 173.8 ppm; FTIR (KBr): ν = 3369, 3054, 2961,
2922, 1677, 1598, 1523, 1428, 753 cm-1; HRMS (m/z):
[M+H]+ calcd for C20H21O2N2: 321.1603; found: 321.1607.
CDCl3):  = 3.59 (d, J = 15.6 Hz, 1H), 4.11 (d, J = 15.6 Hz,
1H), 6.52-7.08 (m, 1H), 7.18-7.33 (m, 3H), 7.33-7.42 (m,
2H), 7.42-7.50 (m, 2H), 7.55 (s, 1H), 7.70-7.79 (m, 2H),
7.79-7.85 (m, 2H), 7.95-8.02 (m, 1H), 8.05-8.12 (m, 1H),
8.83 (s, 2H) ppm; 13C NMR (100 MHz, CDCl3):  = 42.7,
80.2, 119.6, 124.4, 125.1, 128.1, 128.3, 128.6, 129.0, 129.7,
129.9, 130.8, 137.5, 140.0, 141.6, 141.8, 146.7, 154.4,
171.7 ppm; FTIR (KBr): ν = 3372, 3058, 2921, 1601, 1529,
1442, 753 cm-1; HRMS (m/z): [M+Na]+ calcd for
C23H19O2N3Na: 392.1369; found: 392.1368.
N-Butyl-2-hydroxy-2-phenyl-3-(quinolin-2-
yl)propanamide (3j):
62% yield (107.9 mg); Yellow solid; mp 62-63 °C; (Rf =
1
0.18 (10% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  = 0.59 (t, J = 7.6 Hz, 3H), 0.90-1.02 (m, 2H),
1.14-1.24 (m, 2H), 2.87-3.01 (m, 1H), 3.05-3.25 (m, 1H),
3.43 (d, J = 15.2 Hz, 1H), 3.96 (d, J = 15.2 Hz, 1H), 7.11 (t,
5.6 Hz, 1H) 7.21-7.29 (m, 1H), 7.30-7.31 (m, 3H), 7.49 (t,
J = 7.6 Hz, 1H), 7.64-7.72 (m, 1H), 7.76 (d, J = 8.0 Hz,
1H), 7.80 (d, J = 7.6 Hz, 2H), 7.96 (d, J = 8.4 Hz, 1H),
8.07 (d, J = 8.0 Hz, 1H), 8.41 (bs, 1H) ppm; 13C NMR
(100 MHz, CDCl3):  = 13.5, 19.7, 31.5, 38.7, 45.3, 76.8,
123.1, 125.2, 126.4, 127.0, 127.5, 127.8, 128.2, 128.2,
129.9, 137.3, 142.8, 146.3, 160.1, 174.0, ppm; FTIR
(KBr): ν = 3411, 3058, 2957, 2928, 1666, 1518 cm-1;
HRMS (m/z): [M+H]+ calcd for C22H25O2N2: 349.1911;
found: 349.1904.
3-(Benzo[f]quinolin-3-yl)-2-hydroxy-N,2-
diphenylpropanamide (3o):
36% yield (75.2 mg); Colorless solid; mp 189-191°C
(Lit.[10] mp 191–193 °C); Rf = 0.75 (30% ethyl acetate in
1
hexanes); H NMR (400 MHz, CDCl3):  = 3.59 (d, J =
15.2 Hz, 1H), 4.06 (d, J = 15.2 Hz, 1H), 6.99 (t, J = 7.6 Hz,
1H), 7.20 (t, J = 8.0 Hz, 2H), 7.21-7.31 (m, 2H), 7.36 (t, J
= 8.0 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.52 (d, J = 8.4 Hz,
1H), 7.59-7.78 (m, 2H), 7.78-8.01 (m, 5H), 8.55 (d, J =
8.0 Hz, 1H), 8.87 (d, J = 8.4 Hz, 1H), 8.97 (s, 1H) ppm;
13C NMR (100 MHz, CDCl3):  = 44.7, 76.8, 119.5, 122.6,
123.0, 124.2, 124.2, 125.3, 127.0, 127.5, 127.5, 127.8,
128.4, 128.9, 128.9, 129.5, 131.6, 131.7, 132.3, 137.7,
142.3, 146.4, 158.8 ppm; FTIR (KBr): ν = 3349, 3294,
3050, 1666, 1439, 827 cm-1; HRMS (m/z): [M+H]+ calcd
for C28H23O2N2: 419.1759; found: 419.1777.
2-Hydroxy-2-phenyl-N-(pyridin-4-yl)-3-(quinolin-2-
yl)propanamide (3k):
58% yield (107.0 mg); White solid; Rf = 0.62 (30% ethyl
acetate in hexanes); 1H NMR (400 MHz, CDCl3):  = 3.53
(d, J = 15.6 Hz, 1H), 4.02 (d, J = 15.6 Hz, 1H), 7.28 (t, J =
8.8 Hz, 2H), 7.32-7.45 (m, 5H), 7.50 (t, J = 7.2 Hz, 1H),
7.69 (t, J = 8.4 Hz, 1H), 7.72-7.88 (m, 3H), 7.95 (d, J = 8.4
Hz, 1H), 8.10 (d, J = 8.4 Hz, 1H), 8.38 (d, J = 5.6 Hz, 2H),
9.11 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3):  = 44.7,
2-Hydroxy-N,2-diphenyl-3-(pyridin-2-yl)propanamide
(3p):
35% yield (55.6 mg); Colourless solid; mp 132-134 °C
80.2, 113.5, 122.7, 125.1, 126.7, 127.1, 127.9, 128.0, 128.1, (Lit.[10] mp 131–133 °C); Rf = 0.31 (10% ethyl acetate in
1
128.6, 130.3, 137.8, 141.6, 144.6, 146.2, 150.5, 159.5,
hexanes); H NMR (400 MHz, CDCl3):  = 3.37 (d, J =
173.5 ppm; FTIR (KBr): ν = 3377, 3059, 2988, 1698, 1588, 15.2 Hz, 1H), 3.81 (d, J = 14.8 Hz, 1H), 7.03 (t, J = 7.6 Hz,
1502, 1263, 721 cm-1; HRMS (m/z): [M+H]+ calcd for
1H), 7.10-7.20 (m, 1H), 7.19-7.31(m, 4H), 7.35 (t, J = 8.0
Hz, 2H), 7.47 (d, J = 7.6 Hz, 2H), 7.62 (td, J = 8.0, 1.6 Hz,
1H), 7.79 (d, J = 7.2 Hz, 2H), 8.41 (d, J = 4.4 Hz, 1H),
8.51 (bs, 1H), 8.94 (s, 1H), ppm; 13C NMR (100 MHz,
CDCl3):  = 44.3, 76.8, 119.5, 122.2, 124.2, 125.0, 125.3,
127.7, 128.4, 129.0, 137.7, 137.8, 142.3, 147.7, 158.7,
172.3 ppm; FTIR (KBr): ν = 3347, 3352, 1666, 1591, cm-1;
HRMS (m/z): [M+H]+ calcd for C20H19O2N2: 319.1446;
found: 319.1450.
C23H20O2N3: 370.1556; found: 370.1534.
3-(6-Bromoquinolin-2-yl)-2-hydroxy-N,2-
diphenylpropanamide (3l):
92% yield (206.2 mg); Colorless solid; mp 158–160 °C
(Lit.[10] mp 159–161 °C); Rf = 0.77 (20% ethyl acetate in
1
hexanes); H NMR (400 MHz, CDCl3):  = 3.50 (d, J =
15.2 Hz, 1H), 4.02 (d, J = 15.6 Hz, 1H), 7.00 (t, J = 7.6 Hz,
1H), 7.21 (t, J = 8.0 Hz, 2H), 7.27 (t, J = 7.2 Hz, 1H),
7.31-7.40 (m, 3H), 7.44 (d, J = 8.0 Hz, 2H), 7.74 (d, J =
9.0 Hz, 1H), 7.84 (t, J = 8.0 Hz, 3H), 7.91 (s, 1H), 7.99 (d,
J = 8.4 Hz, 1H), 8.30-8.60 (m, 1H) 8.90 (s, 1H) ppm; 13C
NMR (100 MHz, CDCl3):  = 46.2, 79.4, 111.6, 118.6,
119.7, 123.9, 124.5, 125.2, 127.5, 127.7, 128.0, 128.7,
129.0, 137.0, 137.4, 137.9, 141.6, 151.2, 157.1 and 171.6
2-Hydroxy-3-(6-methylpyridin-2-yl)-N,2-
diphenylpropanamide (3q):
42% yield (69.7 mg); Colorless solid; mp 137-138 °C
(Lit.[10] mp 136–138°C); Rf = 0.73(30% ethyl acetate in
1
hexanes); H NMR (400 MHz, CDCl3):  = 2.49 (s, 3H),
3.32 (d, J = 14.8 Hz, 1H), 3.77 (d, J = 14.8 Hz, 1H), 6.92-
ppm; FTIR (KBr): ν = 3381, 3051, 2988, 1683, 1596, 1525, 7.10 (m, 3H), 7.18-7.30 (m, 3H), 7.30-7.40 (m, 2H), 7.43-
1431, 1267, 729 cm-1.
7.54 (m, 3H), 7.74-7.86 (m, 2H), 8.85 (bs, 1H), 8.96 (s,
1H), ppm; 13C NMR (100 MHz, CDCl3):  = 24.2, 44.1,
79.8, 119.4, 121.7, 121.8, 124.1, 125.3, 127.6, 128.3, 128.9,
137.8, 142.4, 156.6, 157.8, 172.4 ppm; FTIR (KBr): ν =
3347, 3050, 2988, 1591, 1517, 749 cm-1; HRMS (m/z):
[M+H]+ calcd for C21H21O2N2: 333.1603; found: 333.1599.
2-Hydroxy-3-(8-hydroxyquinolin-2-yl)-N,2-
diphenylpropanamide (3m):
71% yield (136.3 mg); Orange solid; mp 177-179 °C
(Lit.[10] mp 176–178 °C); orenge solid, Rf = 0.65 (10%
ethyl acetate in hexanes); 1H NMR (400 MHz, CDCl3):  =
3.57 (d, J = 14.8 Hz, 1H), 4.14 (d, J = 14.8 Hz, 1H), 6.01
(s, 1H), 7.69-7.07(m, 1H) 7.15-7.50 (m, 12H) 7.75-7.87 (m,
2H), 8.07 (d, J = 8.4 Hz, 1H), 8.77 (s, 1H), ppm; 13C NMR
(100 MHz, CDCl3):  = 46.2, 79.4, 111.6, 118.6, 119.7,
123.9, 124.5, 125.2, 127.5, 127.7, 128.0, 128.7, 129.0,
137.0, 137.4, 137.9, 141.6, 151.2, 157.1 and 171.6 ppm;
FTIR (KBr): ν = 3436, 3055, 2988, 1659, 1514, 1262, 753
cm-1; HRMS (m/z): [M+H]+ calcd for C24H21O3N2:
385.1552; found: 385.1556.
3-(4,6-Dimethylpyridin-2-yl)-2-hydroxy-N,2
diphenylpropanamide (3r):
35% yield (60.5 mg); Colourless solid; mp 136-138 °C
(Lit.[10] mp 135-137 °C); Rf = 0.40 (10% ethyl acetate in
1
hexanes); H NMR (400 MHz, CDCl3):  = 2.22 (s, 3H),
2.43 (s, 3H), 3.25 (d, J = 15.2 Hz, 1H), 3.73 (d, J = 15.2
Hz, 1H), 6.79 (s, 1H), 6.86 (s, 1H), 7.01 (t, J = 7.6 Hz,
1H), 7.24 (dd, J = 15.6, 8.4 Hz, 3H), 7.34 (t, J = 8.0 Hz,
2H), 7.48 (d, J = 8.0 Hz, 2H), 7.80 (d, J = 8.8 Hz, 2H),
8.99 (s, 1H), 9.13 (bs, 1H), ppm; 13C NMR (100 MHz,
CDCl3):  = 21.1, 24.0, 43.9, 79.8, 119.4, 122.7, 124.0,
125.3, 127.6, 128.3, 128.9, 137.8, 142.6, 149.1, 156.2,
157.5, 172.6 ppm; FTIR (KBr): ν = 3352, 3058, 2917,
1686, 1603, 1521, 1439, 756 cm-1; HRMS (m/z): [M+H]+
calcd for C22H23O2N2: 347.1760; found: 347.1790.
2-Hydroxy-N,2-diphenyl-3-(quinoxalin-2-
yl)propanamide (3n):
49% yield (90.4 mg); Orange solid; mp 136-138 °C; Rf =
1
0.36 (30% ethyl acetate in hexanes); H NMR (400 MHz,
9
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900447
Advanced Synthesis & Catalysis
N-(2-Acetylphenyl)-2-hydroxy-2-phenyl-3-(quinolin-2-
yl)propanamide (3s):
56% yield (104.7 mg); Colourless solid; mp 156-157 °C
(Lit.[10] mp 155-157 °C); Rf = 0.53 (30% ethyl acetate in
1
hexanes); H NMR (400 MHz, CDCl3):  = 2.46 (s, 3H),
2.63 (s, 3H), 3.43 (d, J = 14.8 Hz, 1H), 3.77 (d, J = 15.2
Hz, 1H), 6.93 (d, J = 7.6 Hz, 1H), 6.97-7.10 (m, 2H), 7.22
(t, J = 6.8 Hz, 1H), 7.32 (t, J = 7.2 Hz, 2H), 7.39-7.51 (m,
2H), 7.84 (t, J = 8.8 Hz, 3H), 8.65 (d, J = 7.2 Hz, 2H),
12.69 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3):  = 24.2,
28.6, 44.1, 79.9, 120.7, 121.5, 122.5, 121.7, 122.9, 125.5,
127.4, 128.2, 131.5, 134.7, 137.6, 140.4, 142.6, 156.9,
157.9, 174.4 and 201.8 ppm; FTIR (KBr): ν = 3485, 3056,
2921, 2852, 1681, 1662, 1576, 1515, 1445, 1359, 1309,
1260, 956, 749 cm-1; HRMS (m/z): [M+H]+ calcd for
C24H24O3N: 375.1708; found: 375.1709.
53% yield (108.6 mg); Colourless solid; mp 183-186 °C
(Lit.[10] mp 184–186 °C); Rf = 0.47 (30% ethyl acetate in
1
hexanes); H NMR (400 MHz, CDCl3):  = 2.59 (s, 3H),
3.60 (d, J = 15.6 Hz, 1H), 4.05 (d, J = 15.6 Hz, 1H), 6.92-
7.04 (m, 1H), 7.17-7.28 (m, 1H), 7.28-7.50 (m, 5H), 7.58-
7.67 (m, 1H), 7.70 (d, J = 8.6 Hz, 1H), 7.72-7.81 (m, 1H),
7.90 (d, J = 8.4 Hz, 2H), 7.96 (d, J = 8.4 Hz, 1H), 8.03 (d,
J = 8.4 Hz, 1H), 8.59 (dd, J = 8.8, 1.2 Hz, 1H), 8.68 (s,
1H), 12.76 (s, 1H) ppm;13C NMR (100 MHz, CDCl3):  =
28.6, 44.8, 80.1, 120.7, 122.5, 122.8, 122.8, 125.4, 126.4,
126.4, 127.5, 127.7, 128.3, 128.4, 129.9, 131.5, 134.6,
137.3, 140.3, 142.5, 146.3, 159.8, 174.3, 201.8 ppm; FTIR
(KBr): ν = 3251, 3055, 2988, 1666, 1514, 1444, 1267, 742
cm-1; HRMS (m/z): [M+H]+ calcd for C26H23O3N2:
411.1709; found: 411.1737.
1-Allyl-3-hydroxy-3-(quinolin-2-ylmethyl)indolin-2-one
(5a):
o
96% yield (158.4 mg); Pale yellow solid, mp 102-103 C;
1
N-(3-Acetylphenyl)-2-hydroxy-2-phenyl-3-(quinolin-2-
yl)propanamide (3t):
Rf = 0.53 (50% ethyl acetate in hexanes); H NMR (400
MHz, CDCl3):  = 3.35 (d, J = 14.8 Hz, 1H), 3.66 (d, J =
14.8 Hz, 1H), 4.03-4.51 (m, 2H), 5.21-5.41 (m, 2H), 5.79-
6.04 (m, 1H), 6.83-7.05 (m, 3H), 7.18-7.40 (m, 2H), 7.59-
7.53 (m, 1H), 7.84 (td, J = 7.2, 1.2 Hz, 1H), 7.93 (d, J =
8.0 Hz, 1H), 8.01 (bs, 1H), 8.20 (q, J = 8.4 Hz, 2H) ppm;
13C NMR (100 MHz, CDCl3):  = 42.4, 43.3, 76.4, 109.3,
117.8, 122.8, 122.9, 124.2, 126.7, 127.1, 127.3, 128.8,
129.4, 130.0, 131.2, 131.4, 137.3, 142.3, 146.7, 158.6,
176.5 ppm; FTIR (KBr): ν = 3364, 3050, 2921, 1721, 1611,
1466, 1356, 749 cm-1; HRMS (m/z): [M+H]+ calcd for
C21H19O2N2: 331.1441; found: 331.1438.
65% yield (133.2 mg); Yellow solid; mp 172-174 °C
(Lit.[10] mp 169–171 °C); Rf = 0.54 (30% ethyl acetate in
1
hexanes); H NMR (400 MHz, CDCl3):  = 2.53 (s, 3H),
3.57 (d, J = 15.6 Hz, 1H), 4.05 (d, J = 15.6 Hz, 1H), 7.23-
7.42 (m, 6H), 7.45-7.55 (m, 1H), 7.55-7.62 (m, 1H), 7.65-
7.81 (m, 3H), 7.81-7.89 (m, 2H), 7.95-8.06 (m, 2H), 8.11
(d, J = 8.4 Hz, 1H), 9.12 (s, 1H) ppm; 13C NMR (100 MHz,
CDCl3):  = 26.8, 44.7, 80.0, 119.2, 122.9, 123.9, 124.0,
125.2, 126.6, 127.1, 127.9, 128.2, 128.5, 129.2, 130.2,
137.8, 138.2, 142.0, 146.2, 159.7, 172.8, 198.0 ppm; FTIR
(KBr): ν = 3381, 3055, 2988, 1679, 1592, 1522, 1423,
1263, 749 cm-1; HRMS (m/z): [M+H]+ calcd for
C26H23O3N2: 411.1703; found: 411.1695.
1-Benzyl-3-hydroxy-3-(quinolin-2-ylmethyl)indolin-2-
one (5b):
94% yield (178.6 mg); Yellow solid; mp 140-142°C; Rf =
1
N-(4-Acetylphenyl)-2-hydroxy-2-phenyl-3-(quinolin-2-
0.37 (50% ethyl acetate in hexanes); H NMR (400 MHz,
yl)propanamide (3u):
CDCl3):  = 3.30 (d, J = 14.8 Hz, 1H), 3.53-3.79 (m, 2H),
4.81 (d, J = 16.0 Hz, 1H), 4.49 (d, J = 15.6 Hz, 1H), 6.69
(d, J = 7.6 Hz, 1H), 6.80-6.95 (m, 2H), 7.13 (t, J = 7.2 Hz,
1H), 7.19 (d, J = 8.4 Hz, 1H), 7.20-7.38 (m, 4H), 7.57 (t, J
= 7.6 Hz, 1H), 7.76 (t, J = 8.0 Hz, 1H), 7.84 (d, J = 8.4 Hz,
2H), 8.04-8.18 (m, 2H) ppm; 13C NMR (100 MHz,
CDCl3):  = 43.5, 43.9, 76.5, 109.5, 122.8, 123.0, 124.2,
126.7, 127.2, 127.4, 127.7, 127.8, 128.9, 129.4, 130.3,
131.3, 135.8, 137.3, 142.2, 146.8, 158.5, 176.9 ppm; FTIR
(KBr): ν = 3348, 3058, 2917, 1717, 1612, 1364, 745 cm-1.
71% yield (145.5 mg); Colourless solid; mp 169-170 °C
(Lit.[10] mp 168–170 °C); Rf = 0.57 (30% ethyl acetate in
1
hexanes); H NMR (400 MHz, CDCl3):  = 2.50 (s, 3H),
3.54 (d, J = 15.6 Hz, 1H), 4.03 (d, J = 15.6 Hz, 1H), 7.22-
7.32 (m, 1H), 7.32-7.42 (m, 3H), 7.50 (t, J = 7.6 Hz, 1H),
7.56 (d, J = 8.8 Hz, 2H), 7.65-7.73 (m, 1H), 7.76 (d, J =
8.0 Hz, 1H), 7.83 (d, J = 8.4 Hz, 4H), 7.96 (d, J = 8.4 Hz,
1H), 8.09 (d, J = 8.4 Hz, 1H), 8.93 (s, 1H) 9.16 (s, 1H)
ppm; 13C NMR (100 MHz, CDCl3):  = 26.5, 44.8, 80.1,
118.8, 122.8, 125.2, 126.7, 127.1, 127.9, 127.9, 128.2,
128.5, 129.7, 130.2, 132.8, 137.7, 141.9, 142.0, 146.2,
159.6, 172.9, 196.9 ppm; FTIR (KBr): ν = 3381, 3055,
2992, 1683, 1596, 1518, 1416, 1267, 742 cm-1; HRMS
(m/z): [M+H]+ calcd for C26H23O3N2: 411.1703; found:
411.1695.
1-Ethyl-3-hydroxy-3-(quinolin-2-ylmethyl)indolin-2-
one (5c):
90% yield (143.1 mg); Pale brown solid; mp 183-184 °C
(Lit.[10] mp 182-184 °C); Rf = 0.15 (30% ethyl acetate in
hexanes); 1H NMR (400 MHz, CDCl3):  = 1.26 (t, J = 7.2
Hz, 3H), 3.23 (d, J = 14.8 Hz, 1H), 3.56 (d, J = 14.2 Hz,
1H), 3.66-3.83 (m, 2H), 6.79-6.91 (m, 3H), 7.17 (d, J = 8.0
Hz, 1H), 7.23 (d, J = 7.6 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H),
7.70-7.80 (m, 2H), 7.83 (d, J = 8.0 Hz, 1H), 8.05-8.17 (m,
2H) ppm; 13C NMR (100 MHz, CDCl3):  = 12.7, 34.8,
43.4, 76.4, 108.5, 122.7, 122.8, 124.4, 126.7, 127.2, 127.8,
128.9, 129.4, 130.2, 131.5, 137.2, 142.2, 146.8, 158.7 and
176.4 ppm; FTIR (KBr): ν = 3481, 3056, 2932, 2845, 1681,
1662, 1576, 1515, 1446, 1357, 1309, 1260, 956, 749 cm-1;
HRMS (m/z): [M+H]+ calcd for C20H19O2N2: 319.1446;
found: 319.1444.
N-(4-Benzoylphenyl)-2-hydroxy-2-phenyl-3-(quinolin-
2-yl)propanamide (3v):
86% yield (153.4 mg); Pale brown solid; mp 183-184 °C
(Lit.[10] mp 182-184 °C); Rf = 0.53 (30% ethyl acetate in
1
hexanes); H NMR (400 MHz, CDCl3):  = 3.55 (d, J =
15.2 Hz, 1H), 4.05 (d, J = 15.2 Hz, 1H), 7.26-7.33 (m, 1H),
7.33-7.47 (m, 5H), 7.47-7.57 (m, 2H), 7.59 (d, J = 8.4 Hz,
2H), 7.71 (t, J = 8.8 Hz, 5H), 7.78 (d, J = 8.4 Hz, 1H), 7.84
(d, J = 7.6 Hz, 2H), 7.98 (d, J = 8.4 Hz, 1H), 8.12 (d, J =
8.4 Hz, 1H), 8.95 (s, 1H), 9.18 (s, 1H) ppm; 13C NMR (100
MHz, CDCl3):  = 44.8, 80.2, 118.6, 122.8, 125.2, 126.7,
127.1, 127.9, 128.2, 128.3, 128.5, 130.0, 130.2, 131.6,
132.2, 132.9, 137.8, 138.0, 141.6, 141.9, 146.3, 159.7,
173.0 and 195.7 ppm; FTIR (KBr): ν = 3481, 3056, 2932,
2845, 1681, 1662, 1576, 1515, 1446, 1357, 1309, 1260,
956, 749 cm-1; HRMS (m/z): [M+H]+ calcd for
C31H25O3N2: 473.1865; found: 473.1875.
3-Hydroxy-1-methyl-3-(quinolin-2-ylmethyl)indolin-2-
one (5d):
96% yield (145.9 mg); Brown solid; mp 140 -142°C; Rf =
1
0.59 (50% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  = 3.20 (s, 3H), 3.23 (d, J = 15.2 Hz, 1H), 3.56 (d,
J = 15.2 Hz, 1H), 6.78-6.85 (m, 2H), 6.85-6.93 (m, 1H),
7.17 (d, J = 8.4 Hz, 1H), 7.21-7.31 (m, 1H), 7.52-7.62 (m,
1H) 7.75 (td, J = 8.4, 1.2 Hz, 1H), 7.84 (d, J = 8.0 Hz, 1H),
7.91 (s, 1H), 8.11 (dd, J = 16.4, 8.4 Hz, 2H) ppm; 13C
NMR (100 MHz, CDCl3):  = 26.3, 43.2, 76.4, 108.4,
N-(2-Acetylphenyl)-2-hydroxy-2-phenyl-3-(m-
tolyl)propanamide (3w):
10
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900447
Advanced Synthesis & Catalysis
122.8, 122.9, 124.1, 126.7, 127.2, 127.8, 128.9, 129.5,
130.3, 131.3, 137.3, 143.1, 146.7, 158.7, 176.8 ppm; FTIR
(KBr): ν = 3372, 3054, 2961, 1709, 1607,1766 1086, 745
cm-1; HRMS (m/z): [M+H]+ calcd for C19H17O2N2.
305.1261; found: 305.1290.
1H), 6.94 (t, J = 7.6 Hz, 1H), 7.08 (d, J = 7.2 Hz, 1H),
7.12-7-26 (m, 1H), 7.64-7.79 (m, 2H), 7.90-8.10 (m, 2H),
8.60 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3):  = 42.3,
42.7, 76.0, 109.3, 117.8, 122.9, 124.2, 128.8, 129.0, 129.7,
129.7, 130.3, 130.9, 141.2, 141.2, 142.2, 146.2, 152.1,
176.6 ppm; FTIR (KBr): ν = 3368, 3059, 2980, 1717, 1607,
1490, 1364, 744 cm-1; HRMS (m/z): [M+Na]+ calcd for
C20H17O2N3Na: 354.1213; found: 354.1215.
1-Acetyl-3-hydroxy-3-(quinolin-2-ylmethyl)indolin-2-
one (5e):
1-Allyl-3-(benzo[h]isoquinolin-3-ylmethyl)-3-
hydroxyindolin-2-one (5j):
45% yield (74.7 mg); Brown solid; mp 116-118 °C; Rf =
1
0.37 (3% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  = 2.65 (s, 3H), 3.46 (s, 2H), 7.05-7.13 (m, 2H),
7.15 (d, J = 8.4 Hz, 1H), 7.29-7.38 (m, 1H), 7.56 (t, J = 8.0
Hz, 1H), 7.71-7.78 (m, 1H), 7.83 (d, J = 8.4 Hz, 1H), 8.04
(d, J = 8.4 Hz, 1H), 8.14 (d, J = 8.4 Hz, 1H), 8.23 (d, J =
8.4 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3):  = 26.7,
43.9, 76.2, 116.8, 122.4, 123.8, 125.6, 126.9, 127.2, 127.9,
128.7, 130.0, 130.3, 130.4, 137.5, 139.5, 146.6, 157.6,
171.0, 177.8 ppm; FTIR (KBr): ν = 3686, 3062, 2988,
1765, 1713, 1600, 1440, 1279, 898, 749 cm-1.
o
95% yield (180.5 mg); Pale yellow solid, mp 134-136 C;
1
Rf = 0.59 (50% ethyl acetate in hexanes); H NMR (400
MHz, CDCl3):  = 3.27 (d, J = 14.4 Hz, 1H), 3.59 (d, J =
14.4 Hz, 1H), 4.10-4.30 (m, 1H), 4.30-4.50 (m, 1H), 5.05-
5.30 (m, 2H), 5.67-5.92 (m, 1H), 6.70-6.92 (m, 3H), 7.10-
7.32 (m, 1H), 7.23-7.33 (m, 1H), 7.54-7.71 (m, 2H), 7.80-
8.02 (m, 4H), 8.50 (d, J = 8.0 Hz, 1H), 8.79 (d, J = 8.8 Hz,
1H) ppm; 13C NMR (100 MHz, CDCl3):  = 42.2, 43.1,
76.3, 110.2, 117.6, 122.5, 122.6, 122.7, 124.0, 124.1, 127.3,
127.3, 128.7, 129.2, 129.3, 131.0, 131.2, 131.4, 131.5,
131.8, 142.1, 146.6, 157.5, 176.5 ppm; FTIR (KBr): ν =
3302, 3054, 2913, 1717, 1604, 1486, 1361, 744 cm-1;
HRMS (m/z): [M+H]+ calcd for C25H21O2N2: 381.1603;
found: 381.1612.
3-Hydroxy-3-(quinolin-2-ylmethyl)indolin-2-one (5f):
60% yield (87.0 mg); Yellow solid; mp 176 -178°C Rf =
1
0.31 (50% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  = 3.25 (d, J = 14.8 Hz, 1H), 3.57 (d, J = 14.8 Hz,
1H), 6.71-6.92 (m, 4H), 7.08-7.24 (m, 2H), 7.51-7.64 (m,
1H), 7.70-7.82 (m, 1H), 7.86 (d, J = 0.8 Hz, 1H), 8.12 (t, J
= 8.8 Hz, 2H), 8.54 (s, 1H) ppm; 13C NMR (100 MHz,
CDCl3):  = 43.2, 110.4, 114.0, 122.9, 124.5, 126.8, 127.2,
127.8, 127.9, 128.9, 129.5, 130.3, 131.7, 137.3, 140.2,
146.7, 158.6, 179.1 ppm; FTIR (KBr): ν = 3183, 2965,
2929, 1717, 756 cm-1; HRMS (m/z): [M+H]+ calcd for
C18H15O2N2: 291.1134; found: 291.1131.
1-Allyl-3-(4,6-dimethylpyridin-2-yl)methyl)-3-
hydroxyindolin-2-one (5k):
o
40% yield (61.6 mg); Yellow solid, mp 88-91 C; Rf =
0.59 (50% ethyl acetate in hexanes); H NMR (400 MHz,
1
CDCl3):  = 2.27 (s, 3H), 2.55 (s, 3H), 2.95 (d, J = 14.8 Hz,
1H), 3.27 (d, J = 14.8 Hz, 1H), 4.16-4.45 (m, 2H), 5.14-
5.31 (m, 2H), 5.73-5.92 (m, 1H), 6.67 (s, 1H), 6.74-6.86
(m, 2H), 6.86-7.00 (m, 2H), 7.14-7.25 (m, 1H) ppm; 13C
NMR (100 MHz, CDCl3):  = 21.1, 24.1, 44.3, 44.3, 76.3,
109.2, 117.6, 122.6, 122.7, 123.0, 124.0, 129.2, 131.4,
131.5, 142.1, 148.7, 156.7, 156.9, 176.7 ppm; FTIR (KBr):
ν = 3380, 2921, 1721, 1607, 1466, 749 cm-1; HRMS (m/z):
[M+H]+ calcd for C19H21O2N2: 309.1598; found: 309.1600.
1-Allyl-3-((6-bromoquinolin-2-yl)methyl)-3-
hydroxyindolin-2-one (5g):
90% yield (183.6 mg); White solid; mp 150-152 °C; Rf =
1
0.65 (50% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  = 3.38 (d, J = 14.8 Hz, 1H), 3.59 (d, J = 14.8 Hz,
1H), 4.20-4.55 (m, 2H), 5.16-5.40 (m, 2H), 5.74-6.01 (m,
1H), 6.87 (td, J = 8.0 Hz, 1H), 6.97 (d, J = 4.0 Hz, 2H),
7.20-7.40 (m, 2H), 7.45 (bs, 1H), 7.86 (dd, J = 8.8, 2.2 Hz,
1H), 7.93-8.18 (m, 3H) ppm; 13C NMR (100 MHz,
CDCl3):  = 42.4, 43.7, 76.3, 109.3, 117.8, 120.5, 122.8,
123.7, 124.1, 128.2, 129.5, 129.8, 130.5, 130.8, 131.2,
133.6, 136.1, 142.2, 145.3, 158.8, 176.5 ppm; FTIR (KBr):
ν = 3372, 3054, 2921, 1721, 1607, 1364 cm-1; HRMS
(m/z): [M+H]+ calcd for C21H18O2BrN2: 409.0552; found:
409.0544.
1-Allyl-3-hydroxy-3-(pyridin-2-ylmethyl)indolin-2-one
(5l):
o
60% yield (84.0 mg); Yellow solid, mp 106-108 C; Rf =
1
0.4 (50% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  = 3.12 (d, J = 14.8 Hz, 1H), 3.36 (d, J = 14.8 Hz,
1H), 4.10-4.30 (m, 1H), 4.30-4.50 (m, 1H), 5.16-5.35 (m,
2H), 5.70-5.93 (m, 1H), 6.72-6.89 (m, 2H), 6.93 (t, J = 7.2
Hz, 1H), 7.06 (d, J = 7.6 Hz, 1H), 7.15-7.36 (m, 2H), 7.65
(td, J = 7.6, 1.6 Hz, 1H), 8.75 (d, J = 4.0 Hz, 1H) ppm; 13
C
NMR (100 MHz, CDCl3):  = 42.3, 43.0, 76.3, 109.3,
117.7, 122.4, 122.8, 124.0, 124.7, 129.4, 131.0, 131.4,
137.3, 142.2, 148.3, 157.6 ppm; FTIR (KBr): ν = 3399,
2961, 2929, 1721, 1612, 1458 cm-1; HRMS (m/z): [M+H]+
calcd for C17H17O2N2: 281.1290; found: 281.1293.
1-Allyl-3-hydroxy-3-((8-hydroxyquinolin-2-
yl)methyl)indolin-2-one (5h):
95% yield (164.3 mg); Pale yellow solid; mp 160-162 °C;
1
Rf = 0.6 (50% ethyl acetate in hexanes); H NMR (400
MHz, CDCl3):  = 3.63 (d, J = 13.6 Hz, 1H), 3.71 (d, J =
13.2 Hz, 1H), 4.05-4.21 (m, 1H), 4.21-4.37 (m, 1H), 4.81-
5.06 (m, 2H), 5.44-5.66 (m, 1H), 6.69 (d, J = 7.6 Hz, 1H),
7.04 (t, J = 7.6 Hz, 1H), 7.10 (dd, J = 7.6, 0.8 Hz, 1H),
7.14-7.31 (m, 4H), 7.37 (d, J = 8.0 Hz, 1H), 7.96 (d, J =
8.4 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3):  = 42.4,
46.1, 76.6, 109.5, 110.4, 117.7, 123.1, 123.6, 124.5, 127.2,
127.5, 129.8, 129.8, 130.8, 136.5, 137.5, 142.4, 151.9,
154.0, 177.5 ppm; FTIR (KBr): ν = 3407, 2929, 2855,
1709, 1619, 1027 cm-1; HRMS (m/z): [M+H]+ calcd for
C21H19O3N2: 347.1390 found: 347.1390.
1-Allyl-3-hydroxy-3-((6-methylpyridin-2-
yl)methyl)indolin-2-one (5m):
o
87% yield (127.9 mg); Yellow solid, mp 68-70 C; Rf =
1
0.53 (50% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  = 2.58 (s, 3H), 3.02 (d, J = 14.4 Hz, 1H), 3.31 (d,
J = 14.4 Hz, 1H), 4.05-4.50 (m, 2H), 5.10-5.39 (m, 2H),
5.62-6.00 (m, 1H), 6.79 (t, J = 7.2 Hz, 2H), 6.85 (d, J = 7.6
Hz, 1H), 6.91 (t, J = 8.0 Hz, 1H), 7.12 (d, J = 8.0 Hz, 1H),
7.16-7.27 (m, 1H), 7.54 (t, J = 8.0 Hz, 1H) 8.05 (bs, 1H)
ppm; 13C NMR (100 MHz, CDCl3):  = 24.3, 44.3, 42.5,
76.1, 109.1, 117.6, 121.5, 121.9, 122.6, 123.9, 129.2, 131.2,
131.3, 137.4, 142.0, 156.8, 157.2, 176.6 ppm; FTIR (KBr):
ν = 3356, 3058, 2925, 1725, 1612, 760 cm-1; HRMS
(m/z): [M+H]+ calcd for C18H19O2N2: 295.1446; found:
295.1442
1-Allyl-3-hydroxy-3-(quinoxalin-2-ylmethyl)indolin-2-
one (5i):
95% yield (157.2 mg); Orange solid; mp 105-107 oC; Rf =
1
0.5 (50% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  = 3.51 (d, J = 14.0 Hz, 1H), 3.63 (d, J = 14.0 Hz,
1H), 4.01-4.02 (m, 1H), 4.20-4.35 (m, 1H), 4.90-5.52 (m,
2H), 5.50-5.53 (m, 1H), 6.18 (s, 1H), 6.71 (d, J = 8.0 Hz,
1-Allyl-3-hydroxy-3-(1-(quinolin-2-yl)ethyl)indolin-2-
one (5n):
11
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900447
Advanced Synthesis & Catalysis
Isolated as a mixture of diastereomers with a 1:1 ratio. (the
data of 1;1 mixture is given below). 80% yield (137.6 mg);
CDCl3):  = 3.27 (q, J = 8.0 Hz, 1H), 3.54 (dd, J = 15.2,
3.6 Hz, 1H), 3.58 (s, 3H), 5.28 (q, J = 4.4 Hz, 1H), 7.14
(dd, J = 8.0, 2.0 Hz, 1H), 7.29 (d, J = 8.4 Hz, 1H), 7.39 (t,
J = 8.0 Hz, 1H), 7.49 (t, J = 8.0 Hz, 1H), 7.58 (t, J = 2.4
Hz, 1H), 7.65-7.72 (m, 2H), 7.78 (d, J = 8.0 Hz, 1H), 7.99
(d, J = 8.4 Hz, 1H), 8.07 (d, J = 8.4 Hz, 1H) ppm; 13C
NMR (100 MHz, CDCl3):  = 42.9, 55.6, 73.6, 113.2,
120.3, 121.6, 122.4, 126.4, 127.1, 127.7, 128.8, 129.7,
129.9, 135.7, 136.7, 147.5, 158.8, 159.9, 200.7 ppm; FTIR
(KBr): ν = 3062, 2984, 1423, 1271, 114, 894, 729 cm-1;
HRMS (m/z): [M+H]+ calcd for C19H18O3N: 308.1286;
found: 308.1290.
1
Yellow solid; Rf = 0.34 (30% ethyl acetate in hexanes); H
NMR (400 MHz, CDCl3):  = 1.21 (d, J = 6.8 Hz, 3H),
1.34 (d, J = 7.2 Hz, 3H), 3.41 (q, J = 7.2 Hz, 1H), 3.53 (q,
J = 7.2 Hz, 1H), 4.72 (t, J = 15.2 Hz, 2H), 4.90 (q, J = 15.2
Hz, 1H), 5.02 (d, J = 15.2 Hz, 1H), 6.48 (d, J = 7.2 Hz,
1H), 6.67 (q, J = 8.4 Hz, 2H), 6.82 (t, J = 7.6 Hz, 1H),
6.95 (t, J = 7.2 Hz, 1H), 7.01 (d, J = 7.2 Hz, 1H), 7.69-
7.20 (m, 4H), 7.20-7.37 (m, 12H), 7.62-7.76 (m, 2H), 8.57
(dd, J = 18.4, 4.4 Hz, 2H) ppm; 13C NMR (100 MHz,
CDCl3):  = 13.6, 13.8, 43.7, 43.9, 44.4, 45.4, 79.2, 79.6,
109.3, 122.3, 122.4, 122.5, 122.6, 122.8, 123.0, 123.9,
124.9, 127.0, 127.1, 127.4, 127.6, 127.7, 128.7, 128.7,
128.8, 128.8, 128.9, 129.3, 129.3, 131.0, 132.6, 135.8,
137.4, 142.7, 143.0, 147.8, 147.9, 161.8, 161.9, 176.8 and
177.4 ppm; FTIR (KBr): ν = 3690, 3051, 2988, 1721,
1440, 1263, 729 cm-1; HRMS (m/z): [M+H]+ calcd for
C24H21O2N2: 345.1524; found: 345.1611.
2-Hydroxy-1-(3-nitrophenyl)-3-(quinolin-2-yl)propan-
1-one (15d):
75% yield (120.7 mg); Orange solid; mp 78-80 °C; Rf =
1
0.31 (30% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  = 3.45-3.60 (m, 2H), 5.52 (dd, J = 6.8, 4.4 Hz,
1H), 7.35 (d, J = 8.4 Hz, 1H), 7.51 (t, J = 7.6 Hz, 1H),
7.63-7.72 (m, 2H), 7.79 (d, J = 8.0 Hz, 1H), 7.91 (d, J =
8.4 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 8.32-8.47 (m, 2H),
8.95 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3):  = 40.4,
74.3, 122.3, 124.4, 126.5, 127.0, 127.5, 127.8, 128.5, 129.8,
130.0, 135.0, 137.2, 147.0, 148.4, 159.0 and 198.7 ppm;
FTIR (KBr): ν = 3062, 2984, 1423, 1271, 114, 894, 729
cm-1; HRMS (m/z): [M+H]+ calcd for C18H15O4N2:
323.1031; found: 323.1040.
1-Benzyl-3-hydroxy-3-(phenyl(pyridin-2-
yl)methyl)indolin-2-one (5o):
Isolated as a mixture of diastereomers with a 3 : 1 ratio.
72% yield (146.2 mg); Brown semi solid; Rf = 0.46 (30%
ethyl acetate in hexanes); 1H NMR (400 MHz, CDCl3):  =
4.41 (d, J = 15.6 Hz, 1H), 4.68 (d, J = 6.8 Hz, 0.5H), 4.76
(s, 1H), 4.92 (d, J = 16.0 Hz, 1H), 6.39-6.49 (m, 1H), 6.65-
6.75 (m, 3H), 6.79 (t, J = 7.6 Hz, 1H), 6.88-6.96 (m, 2H),
6.89-7.19 (m, 1H), 7.20-7.35 (m, 5H), 7.52-7.63 (m, 1H),
8.60 (d, J = 4.4 Hz, 0.3H), 8.65 (d, J = 4.4 Hz, 1H) ppm;
13C NMR (100 MHz, CDCl3):  = 43.7, 44.1, 56.5, 56.9,
80.3, 80.5, 108.9, 109.3, 122.1, 122.4, 122.7, 124.1, 124.6,
124.7, 125.6, 126.8, 127.2, 127.5, 127.8, 128.3, 128.6,
129.4, 129.8, 130.5, 130.8, 135.4, 136.3, 136.4, 137.2,
137.5, 142.6, 143.1, 146.9, 147.2, 161.3, 161.8, 176.0,
177.0 ppm; FTIR (KBr): ν = 3686, 3051, 2984, 1721,
1436, 1271, 742 cm-1; HRMS (m/z): [M+H]+ calcd for
C27H23O2N2: 407.1759; found: 407.1768.
2-Hydroxy-2-(quinolin-2-ylmethyl)acenaphthylen-
1(2H)-one (9):
88% yield (143.0 mg); Brown solid; mp 116-118 °C ; Rf =
1
0.34 (30% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  = 3.30 (d, J = 15.2 Hz, 1H), 3.66 (d, J = 15.2 Hz,
1H), 7.05 (d, J = 6.8 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H),
7.45 (d, J = 7.6 Hz, 1H), 7.58 (t, J = 7.6 Hz, 1H), 7.71-7.80
(m, 2H), 7.80-7.88 (m, 2H), 7.99 (d, J = 6.8 Hz, 1H), 8.18
(t, J = 7.6 Hz, 3H), ppm; 13C NMR (100 MHz, CDCl3): 
= 43.2, 80.2, 120.7, 122.4, 122.8, 125.2, 126.7, 127.2,
127.8, 128.4, 128.7, 128.9, 130.3, 130.8, 130.8, 132.0,
137.3, 140.9, 141.0, 146.8, 159.2 ppm; FTIR (KBr): ν =
3686, 3070, 2980, 1730, 1431, 1267, 894, 738 cm-1;
HRMS (m/z): [M+H]+ calcd for C22H16O2N: 326.1181;
found: 326.1195.
2-Hydroxy-1-phenyl-3-(quinolin-2-yl)propan-1-one
(15a):
72% yield (99.7 mg); Deep brown semi solid; Rf = 0.23
(20% ethyl acetate in hexanes); 1H NMR (400 MHz,
CDCl3):  = 3.28 (q, J = 8.0 Hz, 1H), 3.53 (dd, J = 15.2,
3.2 Hz, 1H), 5.64 (q, J = 3.2 Hz, 1H), 7.31 (d, J = 8.4 Hz,
1H), 7.49 (t, J = 7.6 Hz, 3H), 7.59 (t, J = 7.2 Hz, 1H), 7.68
(t, J = 7.6 Hz, 1H), 7.77 (d, J = 8.0 Hz, 1H), 7.99 (d, J =
8.4 Hz, 1H), 8.04-8.14 (m, 3H) ppm; 13C NMR (100 MHz,
CDCl3):  = 42.7, 73.5, 126.5, 126.2, 127.1, 127.7, 128.8,
129.1, 129.7, 133.7, 134.5, 136.7, 147.5, 158.9, 200.9 ppm;
FTIR (KBr): ν = 3059, 2984, 1604, 1436, 1271, 1110, 905,
742 cm-1; HRMS (m/z): [M+H]+ calcd for C18H16O2N:
278.1181; found: 278.1185.
Experimental procedure to synthesize N-oxide
To a solution of compound 3a (0.25 mmol) in dry CH2Cl2
(1.0 mL), m-CPBA (0.5 mmol) was added and the mixture
was stirred at room temperature for 12 h. After the
completion of reaction, the organic layer was washed with
saturated NaHCO3 solution (2 × 10 mL). The organic layer
was separated, washed with water (2 × 10 mL), dried over
Na2SO4 and evaporated under reduced pressure. The solid
residue was purified by silica gel column chromatography
to afford the titled compound.
2-Hydroxy-3-(quinolin-2-yl)-1-(p-tolyl)propan-1-
one(15b):
2-(2-Hydroxy-3-oxo-2-phenyl-3-
66% yield (96.0 mg); Brown semi solid; Rf = 0.21 (20%
ethyl acetate in hexanes); 1H NMR (400 MHz, CDCl3):  =
2.41 (s, 3H), 3.25 (q, J = 8.4 Hz, 1H), 3.52 (dd, J = 14.8,
3.2 Hz, 1H), 5.63 (dd, J = 8.0, 3.2 Hz, 1H), 7.27-7.36 (m,
3H), 7.49 (t, J = 7.6 Hz, 1H), 7.68 (t, J = 7.6 Hz, 1H), 7.77
(d, J = 8.0 Hz, 1H), 8.00 (t, J = 8.0 Hz, 3H), 8.07 (d, J =
8.4 Hz, 1H), ppm; 13C NMR (100 MHz, CDCl3):  = 21.8,
43.2, 73.3, 122.5, 126.2, 127.0, 127.6, 128.8, 129.2, 129.6,
129,6, 131.7, 136.6, 144.8, 147.5, 158.9 and 200.4 ppm;
FTIR (neat): ν = 3059, 2980, 1675, 1604, 1427, 1263, 1110,
890, 738 cm-1; HRMS (m/z): [M+H]+ calcd for C19H18O2N:
292.1338; found: 292.1349.
(phenylamino)propyl)quinoline 1-oxide (16):
88% yield (84.5 mg); White solid; mp 123-125 °C (Lit.[10]
mp 122-124 °C); Rf = 0.47 (30% ethyl acetate in hexanes);
1H NMR (400 MHz, CDCl3):  = 4.13 (s, 2H) 6.80-7.08 (m,
1H), 7.19-7.31 (m, 3H), 7.31–7.42 (m, 3H), 7.48 (dd, J =
8.8, 1.2 Hz, 2H), 7.59-7.69 (m, 1H), 7.72 (d, J = 8.8 Hz,
1H), 7.78-7.88 (m, 2H), 7.88-7.96 (m, 2H), 8.76 (d, J = 9.2
Hz, 1H), 9.15 (s, 1H), 9.57 (s, 1H), ppm; 13C NMR (100
MHz, CDCl3):  = 43.3, 76.8, 119.6, 124.2, 125.1, 125.5,
127.9, 128.2, 128.4, 128.6, 128.8, 129.0, 129.6, 131.4,
137.6, 140.6, 142.5, 146.3, 172.0 ppm; FTIR (KBr): ν =
3353, 3046, 2921, 1662, 1509, 1435 cm-1.
2-Hydroxy-1-(4-methoxyphenyl)-3-(quinolin-2-
yl)propan-1-one (15c):
2-((1-Ethyl-3-hydroxy-2-oxoindolin-3-
yl)methyl)quinoline 1-oxide (17):
63% yield (96.7 mg); Brown solid; mp 74-76 °C; Rf =
1
0.27 (20% ethyl acetate in hexanes); H NMR (400 MHz,
12
This article is protected by copyright. All rights reserved.

10.1002/adsc.201900447
Advanced Synthesis & Catalysis
91% yield (75.9 mg); Brown solid; mp 164-166 °C; Rf =
3060, 2982, 2687, 1706, 1610, 1443, 1263, 895, 758 cm-1;
HRMS (m/z): [M+H]+ calcd for C40H33O2N4: 601.2603;
found: 601.2450.
1
0.53 (30% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  = 1.26 (t, J = 7.2 Hz, 3H), 3.61-3.81 (m, 4H),
6.85 (d, J = 7.6 Hz, 1H), 6.98 (td, J = 7.4, 0.8 Hz, 1H),
7.10 (d, J = 8.4 Hz, 1H), 7.15 (dd, J = 7.2, 0.8Hz, 1H),
7.28 (td, J = 7.8, 1.2 Hz, 1H), 7.62-7.69 (m, 1H), 7.72-7.84
(m, 2H), 7.87 (d, J = 8.0 Hz, 1H), 8.78 (d, J = 8.8 Hz, 1H),
9.17 (s, 1H) ppm; 13C NMR (100 MHz, CDCl3):  = 12.7,
34.7, 40.9, 78.5, 108.5, 119.5, 122.7, 124.0, 124.5, 127.9,
128.1, 128.7, 129.6, 129.9, 131.2, 131.3, 140.9, 141.7,
145.1 and 176.6 ppm; FTIR (KBr): ν = 3679, 3070, 2984,
1717, 1612, 1419, 1361, 1259, 890, 742 cm-1; HRMS
(m/z): [M+H]+ calcd for C20H19O3N2: 335.1395; found:
335.1402.
Experimental procedure to 1,2-diol
Sodium borohydride (0.37 mmol) was added portionwise
to the solution containing the compound 15a (0.25 mmol)
in MeOH (1.0 mL) at 0 °C. The reaction progress was
monitored by TLC. After the complete consumption of 15a,
the reaction mixture was poured to crushed ice and
neutralized using NH4Cl solution. The aqueous layer was
extracted with EtOAc (3 × 10 mL). The organic layer was
dried over Na2SO4 and evaporated under reduced pressure.
The crude mixture was purified by silica gel column
chromatography to afford the titled compound as yellow
solid.
Experimental procedure to synthesize acryl amide
Triflic acid (1 mL) was added dropwise to the solution
containing the compound 3a (0.25 mmol) in dry CHCl3
(1.0 mL) at 0 °C under nitrogen atmosphere and the
reaction mixture was slowly brought to room temperature.
The reaction progress was monitored by TLC. After the
complete consumption of 3a, the reaction mixture was
poured to crushed ice and neutralized using 2 N NaOH
solution. The aqueous layer was extracted with CHCl3 (3 ×
10 mL). The organic layer was dried over Na2SO4 and
evaporated under reduced pressure. The crude mixture was
purified by silica gel column chromatography to afford the
titled compound.
1-Phenyl-3-(quinolin-2-yl)propane-1,2-diol (20):
Isolated as a mixture of diastereomers with a 3:2 ratio.
95% yield (66.2 mg).Yellow solid; mp 88-90 °C; Rf = 0.42
(20% ethyl acetate in hexanes); 1H NMR (400 MHz,
CDCl3):  = 2.91 (dd, J = 16.0, 2.4 Hz, 1H), 3.01 (d, J =
5.6 Hz, 0.4H), 3.17 (q, J = 6.8 Hz, 1H), 4.28 (q, J = 6.4 Hz,
0.3H), 4.36-4.45 (m, 1H), 4.61 (d, J = 6.8 Hz, 0.4H), 4.96
(d, J = 4.4 Hz, 1H), 7.10-7.18 (m, 1H), 7.23-7.32 (m, 1H),
7.33-7.42 (m, 3H), 7.42-7.53 (m, 3H), 7.62-7.71 (m, 1H),
7.72-7.78 (m, 1H), 7.93-7.99 (m, 1H), 7.99-8.02 (m, 1H)
ppm; 13C NMR (100 MHz, CDCl3):  = 37.1, 39.3, 74.7,
75.3, 76.1, 77.5, 122.3, 126.3, 126.5, 126.8, 127.2, 127.5,
127.7, 128.0, 128.4, 128.5, 129.9, 130.0, 136.9, 137.0,
140.8, 140.9, 146.7, 146.9, 160.4 and 160.9 ppm; FTIR
(KBr): ν = 3691, 3063, 2989, 2684, 1730, 1607, 1505,
1435, 1267 cm-1; HRMS (m/z): [M+H]+ calcd for
C18H18O2N: 280.1337; found: 280.1333.
N,2-Diphenyl-3-(quinolin-2-yl)acrylamide (18):
82% yield (71.7 mg); Colourless solid; mp 131-133 °C
(Lit.[10] mp 132-134 °C); Rf = 0.53 (30% ethyl acetate in
1
hexanes); H NMR (400 MHz, CDCl3):  = 6.93-7.12 (m,
2H), 7.13-7.41 (m, 7H), 7.41-7.59 (m, 5H), 7.59-7.79 (m,
2H), 7.95 (d, J = 8.4 Hz, 1H), 8.37 (s, 1H), ppm; 13C NMR
(100 MHz, CDCl3):  = 120.3, 121.9, 124.6, 126.9, 127.2,
127.5, 128.3, 129.0, 129.2, 129.5, 130.0, 136.8, 142.5,
147.9, 154.1 and 167.5 ppm; FTIR (KBr): ν = 3051, 2988,
1675, 1596, 1514, 1436, 1259, 729 cm-1; HRMS (m/z):
[M+H]+ calcd for C24H19ON2: 351.1492; found: 351.1505.
Acknowledgements
G.S. thanks IIT Madras for the IRDA project (CHY/17-
18/847/RFIR/GSEK). N.P. thanks UGC, New Delhi for the Senior
Research Fellowship, and A.L.M. thanks CSIR, New Delhi for the
Senior Research Fellowship.
1-Ethyl-3-(quinolin-2-ylmethylene)indolin-2-one (19a):
60% yield (45 mg); Pale brown solid; mp 88-90 °C; Rf =
1
0.65 (30% ethyl acetate in hexanes); H NMR (400 MHz,
CDCl3):  = 1.31 (t, J = 7.2 Hz, 3H), 3.79-3.90 (m, 2H),
6.85 (d, J = 7.6 Hz, 1H), 7.08 (d, J = 7.6 Hz, 1H), 7.32 (d,
J = 7.6 Hz, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.66 (d, J = 7.6
Hz, 1H), 7.69-7.75 (m, 1H), 7.82-7.91 (m, 2H), 8.11 (d, J
= 8.4 Hz, 1H), 8.22 (d, J = 8.8 Hz, 1H), 9.09 (d, J = 8.8 Hz,
1H) ppm; 13C NMR (100 MHz, CDCl3):  = 12.9, 34.7,
108.3, 120.5, 122.3, 124.0, 124.2, 127.5, 127.6, 128.0,
129.6, 129.8, 130.0, 130.1, 135.9, 136.6, 142.2, 148.3,
153.8 and 165.6 ppm; FTIR (KBr): ν = 3686, 3066, 2988,
1706, 1600, 1427, 1255, 898, 734 cm-1; HRMS (m/z):
[M+H]+ calcd for C20H17ON2: 301.1340; found: 301.1355.
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14
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10.1002/adsc.201900447
Advanced Synthesis & Catalysis
2014, 7451. h) N. C. Mamillapalli, G. Sekar, Chem.
Commun. 2014, 50, 7881.
[16] CCDC-1903391 (5m) and 1904526 (19b) contain the
supplementary crystallographic data for this paper.
These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
15
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10.1002/adsc.201900447
Advanced Synthesis & Catalysis
FULL PAPER
Ligand-Free and Reusable Palladium Nanoparticles
Catalyzed Alkylation of 2-Alkylazaarenes with
Activated Ketones under Neutral Conditions
Adv. Synth. Catal. Year, Volume, Page – Page
Naziya Parveen, Alagesan Muthukumar, and
G.Sekar*
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