Formation of Tertiary Alcohol via Chelation-Assisted Nickel(II)-Catalyzed Addition of Arylboronic Acids to Unactivated 1-(Quinolin-8-yl)ethan-1-one

Article abstract of DOI:10.1002/adsc.201800943

The synthesis of tertiary alcohol via chelation-assisted nickel-catalyzed addition of arylboronic acids to unactivated ketones was reported in this study. A series of substituted arylboronic acids was reacted with 1-(quinolin-8-yl)ethan-1-one and its derivatives to provide various substituted 1-aryl-1-(quinolin-8-yl)ethan-1-ols and relevant compounds in medium to good yields. The N-directing group is essential for the addition reaction of arylboronic acids to these unactivated ketones. Nickel(II) acetylacetonate (10.0 mol%) in combination with sodium iodide (2 equiv.) and potassium carbonate (0.8 equiv.) was identified as the optimal catalytic system for the current transformations. (Figure presented.).

Full text of DOI:10.1002/adsc.201800943

Title: Formation of Tertiary Alcohol via Chelation-Assisted Nickel(II)-
Catalyzed Addition of Arylboronic Acids to Unactivated 1-
(Quinolin-8-yl)ethan-1-one
Authors: Shutao Wu, Weijie Guo, Tao Wang, Qingxiao Xie, Jianhui
Wang, and Guiyan Liu
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201800943
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10.1002/adsc.201800943
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Formation of Tertiary Alcohol via Chelation-Assisted
Nickel(II)-Catalyzed Addition of Arylboronic Acids to
Unactivated 1-(Quinolin-8-yl)ethan-1-one
Shutao Wu,a Weijie Guo,b Tao Wang,c Qingxiao Xie,d Jianhui Wang,*,a Guiyan Liu*,b
a
Department of Chemistry, College of Science, Tianjin University, Tianjin 300350, P. R. China.
E-mail (J. Wang): wjh@tju.edu.cn
Tianjin Key Laboratory of Structure and Performance for Functional Molecules; Key Laboratory of Inorganic-Organic
b
hybrid Functional Material Chemistry; College of Chemistry, Tianjin Normal University, Tianjin, 300387, P. R. China
E-mail (G. Liu): hxxylgy@tjnu.edu.cn.
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. The synthesis of tertiary alcohol via chelation-
assisted nickel-catalyzed addition of arylboronic acids to
unactivated ketones was reported in this study. A series of
substituted arylboronic acids was reacted with 1-(quinolin-8-
yl)ethan-1-one and its derivatives to provide various
substituted 1-aryl-1-(quinolin-8-yl)ethan-1-ols and relevant
compounds in medium to good yields. The N-directing
group is essential for the addition reaction of arylboronic
acids to these unactivated ketones.
Nickel(II) acetylacetonate (10.0 mol.%) in combination
with sodium iodide (2 equiv.) and potassium carbonate (0.8
equiv.) was identified as the optimal catalytic system for
the current transformations.
Keywords: Tertiary alcohol; Chelation-assisted；
Arylboronic acids; Unactivated ketones; Addition reaction.
the reported unactivated ketones. For example, the
Introduction
intramolecular
enantioselective
additions
of
arylboronic acids to unactivated ketones yield ring
Tertiary alcohol moieties exist in a number of
therapeutic agents and natural products.[1] Thus, rapid
achievement of tertiary alcohol moieties via
transformation of readily available feedstocks has
been the continuous goal in synthetic organic
chemistry. Traditionally, tertiary alcohol moieties can
be constructed through addition of carbon
nucleophiles, such as Grignard and organozinc
reagents to ketones. However, the functional group
compatibilities of these reactions are poor owing to
high reactivity of these reagents. By contrast, boronic
acids are attractive carbon nucleophiles because these
reagents are mild air- and moisture-stable species,
with reactions tolerating a broad range of functional
groups.[2] Boronic acids have been applied in addition
to carbonyl compounds over rhodium catalysts.[3, 4]
The Rh-catalyzed addition of boronic acids to α, β-
unsaturated carbonyl compounds via 1, 4-addition
and aldehydes are well characterized. [5] The additions
of organoboron compounds to activated ketones, such
tertiary alcohols over palladium or rhodium catalysts
[9]
in the presence of chiral ligands.
A number of
unactivated ketones were identified to undergo
addition with sodium tetraphenylborate by rhodium
catalysis.[10] The intermolecular addition of
arylboronic acids to unactivated ketones was first
achieved in a low yield by a rhodium catalyst
containing an electron-poor biphosphane ligand.[11]
Then, boroxines can react with unactivated ketones to
provide tertiary alcohols over a rhodium(I)/diene
catalyst[12] and were further used to efficiently
synthesize of escitalopram via rhodium-catalyzed
enantioselective addition to aryl ketones (Scheme 1,
a).[13] Among the reported intermolecular addition of
organoborons to unactivated ketones, and aryl-
boroxines, which are generally not commercially
available reagents, were used as a stabilized form of
the corresponding boronic acids for the
transformation. Besides, rhodium or palladium
catalysts are the dominant catalysts for these
transformations. Only one report used nickel as
catalyst to promote the intermolecular addition of
arylboronate esters to unactivated ketones (Scheme 1,
b).[14] Substitution of arylboronate esters to
arylboronic acids in the reaction results in a low yield
of the desired product. [14] Overall, the use of precious
[6]
as ketoesters, trifluoromethyl [7], and difluorinated
[8]
ketones,
to provide tertiary alcohols have been
reported recently. However, the additions of
organoboron to unactivated ketones are
underdeveloped owing to low reactivity of these
unactivated ketones. Only a few examples are
available for the additions of aryl boronic esters onto
1
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10.1002/adsc.201800943
Advanced Synthesis & Catalysis
2-phenyl-1,3,2-dioxaborinane(PhBO2C5H10), PhBF3K,
(PhBO)3, produced the desired product in low yields
(0%–5%). Replacement of the Ni(acac)2 catalyst with
other simple nickel compounds, such as NiF2,
.
.
NiCl2 6H2O, NiI2, or Ni(OAc)2 4H2O, resulted in 0%–
78% yields of the product. This reaction required
both K2CO3 and NaI to give high product yield. The
use of other bases, namely, K3PO4 and Cs2CO3,
produced 61% and 64% yields, respectively.
However, these values were lower than that of K2CO3.
Other additives, such as CuCl, CuBr, Cu(OAc)2, and
I2, completely terminated the reaction, whereas CuI
gave low yields (72%). When the reaction time is
shortened to 36 hours, the yield reaches only 63 %.
The addition reaction also proceeded slowly at
temperature lower than 100 °C to provide the desired
3a in low yield.
Scheme 1. The reaction of unactivated ketones and ar-
ylboronic acids under different catalyst.
metal catalysts and commercially unavailable
boroxines seriously hamper the further application of
this reaction.
In our laboratory, we are interested in using readily
available transition metal complexes for the reactions
of arylborons with carbonyl-containing compounds
via carbon –carbon bond cleavage.[15] We recently
documented a direct exchange of a methyl or aryl
group in a quinolinyl ketone to another aryl group via
chelation-assisted rhodium-mediated C-C bond
activation.[15] In addition, the C-H bond activation
[16a-d]
[16e-g]
reaction
and alkyl addition reaction
via
chelation-assisted catalysis of quinolinyl groups have
also been reported continuously. During these studies,
we attempted to employ nickel complexes as catalysts
for exchange reactions. Unexpectedly, we observed
high yield of tertiary alcohol moieties (Scheme 1, c)
in our attempts to use nickel complexes as catalysts
for such exchange reactions. Here, we report the
synthesis of tertiary alcohol via chelation-assisted
nickel-catalyzed addition of arylboronic acids to
ketones with N-directing group.
Table 1. Influence of parameters for nickel-catalyzed
additions of phenylboronic acid (2a) onto ketone (1a).[a]
With the optimized catalytic system in hand, the
effects of various substituted groups on the
arylboronic acids to the addition reactions were
investigated. The results are shown in Table 2. When
1a was reacted with phenylboronic acids with a
methyl group at o-, m-, or p-position, the desired
product 3b, 3c, or 3d was obtained in 37%, 80%, or
74% yields, respectively. The 2,5-Me2-substituted
phenylboronic acid also produced the desired product
3e in a low yield (42%). These findings showed that
increasing steric hindrance of phenylboronic acids
decreased the product yield. Phenylboronic acids with
an n-Bu- or t-Bu substitution reacted with 1a to
produce the corresponding tertiary alcohols 3f and 3g
in 84% and 89% yields, respectively. m-MeO- and p-
MeO- substituted phenylboronic acids can also react
with 1a to produce the corresponding products of 3i
and 3j, respectively, in 72% and 65% yields. By
Results and Discussion
1-(Quinolin-8-yl)ethan-1-one (1a) and phenylboronic
acid (2a) were selected for optimizing reaction
conditions under nickel catalysts. We found that 1a
could smoothly react with 2a in xylene at 130 °C in
the presence of Ni(acac)2 (10 mol.%), K2CO3 (0.8
equiv.), and NaI (2.0 equiv.) to provide the tertiary
alcohol product 3a in a high yield (83%) (Table 1).
Under these conditions, neither direct exchange of the
methyl of 1a with phenyl group nor homocoupling of
2a occurred. Several examples of variations from the
standard conditions (see the Supporting information
for an extensive list of reaction conditions) are listed
in Table 1. Other nucleophiles, such as 5, 5-dimethyl-
2
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10.1002/adsc.201800943
Advanced Synthesis & Catalysis
Table 2. Synthesis of tertiary alcohol via chelation-assisted nickel(II)-catalyzed addition of arylboronic acids (2) to 1-
(quinolin-8-yl)ethan-1-one (1).[a,b]
Table 3. Chelation-assisted nickel(II)-catalyzed addition of phenylboronic acids (2) to quinoline derivates (1).[a,b]
contrast, the reaction of phenylboronic acids with the
Substitution with other electron-withdrawing
MeO- group at o-position with 1a did not offer any groups, such as CF3 or –OCF3 at p-position of the
desired product (3h). The phenylboronic acids with phenylboronic acids, gave 3q and 3r 87% and 84%
Cl, Br, and F also reacted with 1a to produce the yields, respectively. The naphthalen-2-ylboronic acid
desired products 3l, 3m, and 3n in medium to high also reacted with 1a to generate product 3s in 90%
yields (58%–83%). The electron effect also has a yield. Furthermore, thiophen-2-ylboronic acid was
marked impact on the reaction system. For example, used to react with 1a, but no product was isolated.
the reaction of 1a with phenylboronic acids with an This may be due to the fact that both the thiophene
electron-withdrawing group, such as –COCH3, or – sulfur atom and the nitrogen atom of the directing
COOEt at p-position, produced the corresponding group can coordinate with the transition metal, and
tertiary alcohols 3o, or 3p in 45% and 42% yield, there is a competitive complexation. Subsequently,
respectively, which is significantly lower than those the effects of different substitution groups on the
phenylboronic acids having an electron-donating quinoline ring were investigated.
A
6-MeO-
group.
substituted quinoline produced the desired product in
3
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10.1002/adsc.201800943
Advanced Synthesis & Catalysis
17]
carbonyl group yields intermediate IIIA.[14,
70% yield. This value was slightly lower than that of
1a. An electron withdrawing group substitution on the
quinoline rings, such as 5-MeOOC- and 5-Cl-, gave
the corresponding product in 82% and 87% yields,
respectively. These yields were comparable or higher
than that of 1a. 1-(Benzo[f]quinolin-5-yl)ethan-1-one
was also reacted with phenylboronic acid smoothly to
produce the desired product 4d in 90% yield.
However, ethyl and 2-Ph-ethyl ketones generated the
desired products 4e and 4f in 43% and 37% yields,
respectively. By-products through aldol condensation
were observed in this reaction system. This finding
significantly decreased the product yield. The
addition reaction with quinoline-8-carbaldehyde as a
substrate also gave a high yield of 85 %. No product
was obtained in the reaction with PhB(OH)2 under
similar reaction conditions when the quinoline ring
was replaced with a naphthalene ring. This result
indicated the importance of the N-directing group for
the addition of the phenyl group to the ketones. Other
ketones containing the N-directing groups, such as 1-
(2-methylbenzo [d]oxazol-4-yl)ethan-1-one, also
generated no product under similar reaction
conditions. This finding implied that the nickel metal
center has to be placed in the proximity of the (O)C–
C bond to ensure the occurrence of addition reaction.
Phenylboronic acids further undergo transmetallation
to the metal center, thereby producing intermediate
IVA, which contains a Ni – Ph bond. Finally, the
ligand exchange of IVA with 1a releases a borate
ester of a tertiary alcohol, thereby generating 3a after
hydrolysis while regenerating I that enters another
catalytic cycle. During this catalytic process, the
intramolecular phenyl migration and insertion
reaction (I→IIIA), which result in the conversion of
the metal center from the five-coordinated pyramid
form to the four-coordinated (square planar or
tetrahedral structure) mode, is the key transform step.
The other possible mechanism (Scheme 2, Path B)
includes similar steps except the coordination of
iodide: first, I is converted to an increasingly active
catalyst, namely, intermediate II, through the further
coordination
of
iodide.
Subsequently,
the
intramolecular insertion of the carbonyl group, which
is moved next to the metal center through the
directing group, into the Ni – Ph bond results in
intermediate IIIB.[18] The I→IIIB process may occur
more easily than the corresponding I→IIIA process
in Path A because the metal center transfers from the
six-coordinated octahedral mode, which is
a
comparatively crowded structure, to the five-
coordinated pyramid form. The crowded structure of
II facilitates the migration and insertion of
intramolecular phenyl by tension release. This
outcome is consistent with the observation that the
addition of iodide to the reaction system can
accelerate the reaction and improve product yields.
Next, further transmetallation of phenylboronic acids
to the metal center forms intermediate IVB. Finally,
the ligand exchange of IVB with 1a releases a borate
ester of a tertiary alcohol, generating tertiary alcohol
3a after hydrolysis while regenerating intermediate II
as a catalyst that enters another catalytic cycle. The
coordination of iodide can convert the coordination
model of the nickel center from pyramidal
coordination to octahedral coordination. This
condition is essential for the insertion of the carbonyl
100
90
80
70
60
50
40
Scheme 2. A plausible mechanism for addition of
arylboronic acid to ketone via chelation-assisted nickel-
catalysis.
0
1
2
3
4
5
6
7
8
9
10
Two possible pathways of the formation of tertiary
alcohol 3a are proposed on the basis of these
experiments and previous reports on the catalytic
addition of ketones (Scheme 2). One possible
mechanism (Scheme 2, Path A) includes the
following steps: the precursor of Ni(acac)2 is
converted to catalytic intermediate I through the
transmetallation of phenylboronic acids and the
subsequent coordination of 1a. Then, the
intramolecular insertion of the Ph group to the
equivalents of NaI
group to the Ni–Ph bond.
Figure 1. The amount of NaI influences the
efficiency of the reaction.
4
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10.1002/adsc.201800943
Advanced Synthesis & Catalysis
as the internal standard. The chemical shifts are reported in
ppm relative to CDCl3 (δ = 7.26) for H NMR and relative
Although direct observation of the iodide
1
coordinated anionic nickel complex intermediates of
II, IIB, and IVB is difficult, there are some
experiments to support the proposed mechanism.
Firstly, the effect of NaI amounts on reaction
efficiency is shown in Figure 1. A significantly lower
yield of 3a was produced using NaI less than 1.0
equivalent. Surprisingly, the addition of up to 3.0
equivalent of NaI does not further improve the
reaction yield, and 2.0 equivalent has been the most
appropriate. In the absence of NaI, the 1-(quinolin-8-
yl)ethan-1-one (1a) reacts very slowly with the
phenylboronic acid, and the product yield is very low
(55%). Secondly, our further study show that the
coordination of CuCN and NaSCN to the catalytic
metal intermediates also gain high product yields.[19]
Thirdly, some reports have demonstrated that the
addition of alkali metal halides as an additive could
increase the product yields, and the possible
mechanism involving anionic nickel complex
to the central CDCl3 resonance (δ = 77.0) for 13C NMR. In
addition, the (trifluoromethyl)benzene was used as an
external standard for 19F NMR. NMR data of known
compounds is in agreement with literature values. Coupling
constants (J) are quoted in Hz at 400 MHz for 1H.
Multiplicities are reported as follows: singlet (s), doublet
(d), doublet of doublets (dd), triplet (t), quartet (q), and
multiplet (m). Infrared spectra were recorded on a Perkin-
Elmer Model 1600 FT-IR spectrophotometer and Nicolet
Magna 550 FT-IR spectrophotometer. High resolution
mass spectra (HRMS) were obtained on a JEOL JMS-
DX303 instrument. Elemental analyses were performed by
the Elemental Analysis Section of Tianjin University.
Materials and Methods: Unless otherwise noted, the
reaction was monitored by analytical thin layer
chromatography on a 0.20 mm silica gel plate and spot
detected by UV absorbance. Flash chromatography was
performed using silica gel (200-300 mesh) (from Yantai
Huagong Chemical Co., Ltd.). The starting materials for
the various substitutions 1 were synthesized and purified
according to literature procedures. Various substituted
phenylboronic acids and other chemicals or reagents are
intermediates has also been studied.[20a-c] For example,
[20c]
Doyle et al
reported a nickel-catalyzed C-C bond
forming reaction between simple alkyl aziridines and
organozinc reagents. LiCl is an important additive to
improve the product yield. The initial reduction of
Ni(II) to Ni(0) in the presence of LiCl may generate obtained from commercial sources.
an anionic [Ni(0)-Cl]- complex primed for oxidative
addition. In fact, the coordination of halides to form
catalytically active anionic metal complexes is very
common.[20d-j] The above experiments and studies
indicate that NaI may have some interactions with the
key transformation intermediates to decrease the
activation energy of this reaction.
General Experimental Procedure for the Ni-Catalyzed
Synthesis of Tertiary Alcohol: To an oven-dried screwed
vial were added substituted 1-(quinolin-8-yl)ethan-1-one
(or quinoline-8-carbaldehyde) (0.1 mmol), substituted
phenylboronic acid (0.25 mmol), Ni(acac)2 (2.57 mg, 0.01
mmol), NaI (2.0 eq.), K2CO3 (0.8 eq.), and dry xylene (0.4
mL). The mixture was vigorously stirred at 130 oC under
N2 atmosphere for 48 hours to the end of the reaction.
Organic solvents were removed, and then the residue was
purified by a silica gel column chromatography to give the
desired product.
Conclusion
In conclusion, we developed a new synthetic method
for tertiary alcohol via chelation-assisted nickel(II)-
catalyzed addition of arylboronic acids to unactivated
ketones. In the presence of Ni(acac)2 (10.0 mol.%)
with NaI (2 equiv.) and K2CO3 (0.8 equiv.), a series
of substituted phenylboronic acids was reacted with
1-(quinolin-8-yl)ethan-1-one or its derivative to
generate various tertiary alcohols in medium to good
yields. Various functionalities were tolerated under
the standard reaction conditions. The N-directing
group is essential for the addition reaction of
arylboronic acids to the unactivated ketones. A
plausible catalytic mechanism was proposed to
explain the production of tertiary alcohol derivatives.
Further studies on the applications of this reaction are
currently undergoing in this lab.
Characterization data of all products:
1-phenyl-1-(quinolin-8-yl)ethan-1-ol (3a): Purified by
column chromatography to provide a white solid (20.6 mg,
o
1
yield: 83%). mp 112-114 C. H NMR (400 MHz, CDCl3):
δ 8.59 (dd, J = 4.2, 1.7 Hz, 1H), 8.42 (s, 1H), 8.04 (dd, J =
8.3, 1.8 Hz, 1H), 7.67 (t, J = 7.3 Hz, 2H), 7.45 (t, J = 7.7
Hz, 1H), 7.36 (d, J = 7.7 Hz, 2H), 7.22 (dd, J = 8.3, 4.3 Hz,
1H), 7.15 (t, J = 7.6 Hz, 2H), 7.06 (t, J = 7.3 Hz, 1H), 1.96
(s, 3H); 13C NMR (101 MHz, CDCl3): δ 149.81, 147.73,
146.25, 143.14, 137.23, 129.02, 127.65, 127.60, 127.33,
126.15, 126.04, 125.27, 120.64, 77.68, 31.11; IR (KBr): ν
3228, 2988, 2930, 1596, 1493, 1437, 1368,1311, 1201,
1108, 1058, 799, 696 cm-1; ESI-MS [M+Na]+ calcd for
C17H15NO: 249.1154, found: 272.1047; Analytical Data.
Found (calcd) for: C17H15NO C, 81.88 (81.90); H, 6.05
(6.06); N, 5.63 (5.62).
Experimental Section
General information: Melting points were determined on
1
a SGWX-4B melting point apparatus. H NMR, 13C NMR
1-(quinolin-8-yl)-1-(o-tolyl)ethan-1-ol (3b): Purified by
and 19F NMR were recorded on Bruker AV 400 MHz
spectrometer with CDCl3 as solvent and tetramethylsilane
column chromatography to provide a white solid (9.7 mg,
o
1
yield: 37%). mp 138-141 C. H NMR (400 MHz, CDCl3):
5
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10.1002/adsc.201800943
Advanced Synthesis & Catalysis
for: C19H19NO C, 82.25 (82.28); H, 6.91 (6.90); N, 5.05
(5.05).
δ 9.06 (s, 1H), 8.84 (dd, J = 3.8, 2.1 Hz, 1H), 8.27 – 8.19
(m, 1H), 7.72 (d, J = 8.1 Hz, 1H), 7.60 – 7.53 (m, 1H), 7.44
(dd, J = 8.3, 4.3 Hz, 1H), 7.36 (t, J = 7.7 Hz, 1H), 7.25 –
7.19 (m, 2H), 7.19 – 7.12 (m, 2H), 2.15 (d, J = 8.1 Hz, 6H);
13C NMR (101 MHz, CDCl3): δ 147.41, 146.48, 144.73,
144.18, 138.00, 137.48, 132.39, 128.97, 127.44, 127.26,
126.92, 126.45, 126.31, 125.00, 120.59, 79.48, 32.11,
21.99; IR (KBr): ν 3323, 2924, 2854, 1596, 1495, 1461,
1348, 1177, 1097, 823, 792, 749, 673, 479 cm-1; ESI-MS
[M+Na]+ calcd for C18H17NO: 263.1310, found: 286.1211;
Analytical Data. Found (calcd) for: C18H17NO C, 82.16
(82.10); H, 6.52 (6.51); N, 5.31 (5.32).
1-(4-butylphenyl)-1-(quinolin-8-yl)ethan-1-ol
(3f):
Purified by column chromatography to provide a white
o
1
solid (25.6 mg, yield: 84%). mp 53-55 C. H NMR (400
MHz, CDCl3): δ 8.68 (dd, J = 4.2, 1.6 Hz, 1H), 8.64 (s, 1H),
8.12 (dd, J = 8.3, 1.7 Hz, 1H), 7.74 (t, J = 7.4 Hz, 2H), 7.54
(t, J = 7.7 Hz, 1H), 7.39 (d, J = 7.8 Hz, 2H), 7.29 (dd, J =
8.3, 4.3 Hz, 1H), 7.09 (d, J = 7.8 Hz, 2H), 2.56 (t, J = 7.8
Hz, 2H), 2.08 (s, 3H), 1.62 - 1.51 (m, 2H), 1.40 - 1.29 (m,
2H), 0.91 (t, J = 7.4 Hz, 3H); 13C NMR (101 MHz, CDCl3):
δ 147.58, 146.91, 146.28, 143.36, 140.60, 137.17, 128.97,
127.65, 127.44, 127.33, 126.01, 125.21, 120.53, 77.69,
35.10, 33.46, 31.19, 22.36, 13.90; IR (KBr): ν 3303, 2927,
2862, 1602, 1498, 1371, 1102, 1053, 919, 828, 796, 683,
580 cm-1; ESI-MS [M+Na]+ calcd for C21H23NO: 305.1780,
found: 328.1669; Analytical Data. Found (calcd) for:
C21H23NO C, 82.56 (82.58); H, 7.61 (7.59); N, 4.58 (4.59).
1-(quinolin-8-yl)-1-(m-tolyl)ethan-1-ol (3c): Purified by
column chromatography to provide a white solid (21 mg,
o
yield: 80%). mp 86-88 C. 1H NMR (400 MHz, CDCl3): δ
8.71 (dd, J = 4.3, 1.7 Hz, 1H), 8.55 (s, 1H), 8.16 (dd, J =
8.3, 1.7 Hz, 1H), 7.76 (d, J = 7.6 Hz, 2H), 7.56 (t, J = 7.7
Hz, 1H), 7.37 – 7.30 (m, 2H), 7.19 (d, J = 7.9 Hz, 1H), 7.12
(t, J = 7.6 Hz, 1H), 6.98 (d, J = 7.4 Hz, 1H), 2.29 (s, 3H),
2.04 (s, 3H). 13C NMR (101 MHz, CDCl3): δ 149.68,
147.73, 146.29, 143.22, 137.25, 137.18, 129.03, 127.54,
127.49, 127.40, 126.98, 126.08, 126.06, 122.38, 120.63,
77.71, 31.23, 21.61; IR (KBr): ν 3299, 3043, 2978, 2927,
1600, 1594, 1409, 1366, 1162, 1059, 793, 706, 686 cm-1;
ESI-MS [M+Na]+ calcd for C18H17NO: 263.1310, found:
286.1208; Analytical Data. Found (calcd) for: C18H17NO C,
82.15 (82.10); H, 6.50 (6.51); N, 5.32 (5.32).
1-(4-(tert-butyl)phenyl)-1-(quinolin-8-yl)ethan-1-ol (3g):
Purified by column chromatography to provide a white
solid (27.1 mg, yield: 89%). mp 141-142 oC. 1H NMR (400
MHz, CDCl3): δ 8.72 (dd, J = 4.3, 1.7 Hz, 1H), 8.64 (s, 1H),
8.16 (dd, J = 8.4, 1.8 Hz, 1H), 7.74 (t, J = 7.8 Hz, 2H), 7.54
(t, J = 7.7 Hz, 1H), 7.35 (dd, J = 8.3, 3.4 Hz, 3H), 7.25 (d, J
= 8.5 Hz, 2H), 2.04 (s, 3H), 1.26 (s, 9H); 13C NMR (101
MHz, CDCl3): δ 148.77, 147.56, 146.55, 146.37, 143.42,
137.19, 129.00, 127.42, 126.05, 125.05, 124.54, 120.53,
77.73, 34.22, 31.31, 31.20; IR (KBr): ν 3244, 2957, 2865,
1595, 1576, 1494, 1450, 1365, 1266, 1105, 1017, 933, 832,
798, 712, 548 cm-1; ESI-MS [M+Na]+ calcd for C21H23NO:
305.1780, found: 328.1673; Analytical Data. Found (calcd)
for: C21H23NO C, 82.57 (82.58); H, 7.60 (7.59); N, 4.58
(4.59).
1-(quinolin-8-yl)-1-(p-tolyl)ethan-1-ol (3d): Purified by
column chromatography to provide a white solid (19.4 mg,
yield: 74%).mp 118-120 oC. 1H NMR (400 MHz, CDCl3): δ
8.62 (dd, J = 4.2, 1.8 Hz, 1H), 8.54 (d, J = 3.8 Hz, 1H),
8.06 (dd, J = 8.3, 1.8 Hz, 1H), 7.76 – 7.64 (m, 2H), 7.49 (t,
J = 7.7 Hz, 1H), 7.33 (dt, J = 8.3, 2.0 Hz, 2H), 7.23 (dd, J =
8.3, 4.3 Hz, 1H), 7.03 (d, J = 7.8 Hz, 2H), 2.24 (s, 3H),
2.03 (d, J = 1.6 Hz, 3H); 13C NMR (101 MHz, CDCl3): δ
147.58, 146.84, 146.20, 143.24, 137.13, 135.52, 128.93,
128.31, 127.44, 127.21, 125.97, 125.17, 120.50, 77.56,
31.15, 20.85; IR (KBr): ν 3235, 2980, 2931, 1598, 1500,
1441, 1369, 1102, 1059, 930, 817, 798, 706, 517cm-1; ESI-
MS [M+Na]+ calcd for C18H17NO: 263.1310, found:
286.1206; Analytical Data. Found (calcd) for: C18H17NO C,
82.17 (82.10); H, 6.52 (6.51); N, 5.32 (5.32).
1-(3-methoxyphenyl)-1-(quinolin-8-yl)ethan-1-ol
(3i):
Purified by column chromatography to provide a white
o
1
solid (20.1 mg, yield: 72%). mp 97-99 C. H NMR (400
MHz, CDCl3): δ 8.50 (dq, J = 4.1, 1.9 Hz, 1H), 8.44 (d, J =
2.8 Hz, 1H), 7.94 (dt, J = 8.2, 1.6 Hz, 1H), 7.67 – 7.54 (m,
2H), 7.43 – 7.35 (m, 1H), 7.11 (ddq, J = 8.3, 4.3, 2.7, 1.5
Hz, 1H), 7.02 – 6.96 (m, 2H), 6.87 – 6.80 (m, 1H), 6.56 (dd,
J = 8.2, 2.5 Hz, 1H), 3.60 (s, 3H), 1.92 (d, J = 1.6 Hz, 3H);
13C NMR (101 MHz, CDCl3): δ 159.04, 151.65, 147.60,
146.11, 142.83, 137.12, 128.88, 128.48, 127.53, 127.22,
125.94, 120.51, 117.77, 111.36, 111.12, 77.58, 54.94,
30.98; IR (KBr): ν 3273, 2961, 2938, 2835, 1606, 1578,
1496, 1480, 1430, 1371, 1313, 1049, 932, 882, 780,
707,550 cm-1; ESI-MS [M+Na]+ calcd for C18H17NO2:
279.1259, found: 302.1154; Analytical Data. Found (calcd)
for: C18H17NO2 C, 77.42 (77.40); H, 6.14 (6.13); N, 5.02
(5.01).
1-(2,5-dimethylphenyl)-1-(quinolin-8-yl)ethan-1-ol (3e):
Purified by column chromatography to provide a white
solid (11.6 mg, yield: 42%). mp 151-153 oC. 1H NMR (400
MHz, CDCl3) δ 9.06 (s, 1H), 8.84 (dd, J = 4.3, 1.8 Hz, 1H),
8.22 (dd, J = 8.4, 1.8 Hz, 1H), 7.74 – 7.67 (m, 1H), 7.47 –
7.40 (m, 2H), 7.36 (t, J = 7.7 Hz, 1H), 7.18 (dd, J = 7.3, 1.4
Hz, 1H), 7.05 (s, 2H), 2.38 (s, 3H), 2.14 (s, 3H), 2.09 (s,
3H); 13C NMR (101 MHz, CDCl3): δ 147.36, 146.46,
144.43, 144.23, 137.45, 134.70, 134.14, 132.25, 128.92,
127.77, 127.49, 127.30, 126.84, 126.29, 120.53,
79.40,32.21, 21.50, 21.26; IR (KBr): ν 3200, 2975, 2922,
1601, 1488, 1456, 1368, 1310, 1166, 1103, 1050, 1000,
792, 686, 626 cm-1; ESI-MS [M+Na]+ calcd for C19H19NO:
277.1467, found: 300.1361; Analytical Data. Found (calcd)
1-(4-methoxyphenyl)-1-(quinolin-8-yl)ethan-1-ol
(3j):
Purified by column chromatography to provide a white
solid (18.1 mg, yield: 65%). mp 104-106 oC. 1H NMR (400
MHz, CDCl3) δ 8.72 (dd, J = 4.3, 1.8 Hz, 1H), 8.54 (s, 1H),
8.17 (dd, J = 8.3, 1.8 Hz, 1H), 7.73 (ddd, J = 18.8, 7.7, 1.4
Hz, 2H), 7.53 (dd, J = 8.2, 7.3 Hz, 1H), 7.35 (dd, J = 8.6,
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800943
Advanced Synthesis & Catalysis
4.6 Hz, 3H), 6.81 – 6.75 (m, 2H), 3.75 (s, 3H), 2.04 (s, 3H); solid (22.2 mg, yield: 83%). mp 105-107 oC. 1H NMR (400
13C NMR (101 MHz, CDCl3): δ 157.96, 147.68, 146.41, MHz, CDCl3): δ 8.58 – 8.53 (m, 1H), 8.42 (s, 1H), 8.02 (dd,
143.56, 142.05, 137.29, 129.11, 127.51, 127.40, 126.59, J = 8.4, 1.7 Hz, 1H), 7.66 – 7.58 (m, 2H), 7.42 (t, J = 7.7
126.09, 120.63, 113.03, 77.57, 55.13, 31.26; IR (KBr): ν Hz, 1H), 7.29 (dd, J = 8.5, 5.5 Hz, 2H), 7.20 (dd, J = 8.3,
3289, 2929, 2837, 1605, 1504, 1459, 1368, 1248, 1176, 4.3 Hz, 1H), 6.79 (t, J = 8.6 Hz, 2H), 1.92 (s, 3H); 13C
1100, 1031, 832, 797, 586 cm-1; ESI-MS [M+Na]+ calcd NMR (101 MHz, CDCl3): δ 161.27(d, J=242 Hz), 147.71,
for C18H17NO2: 279.1259, found: 302.1157; Analytical 146.14, 145.58 (d, J=3Hz), 142.89, 137.27, 129.02, 127.70,
Data. Found (calcd) for: C18H17NO2 C, 77.43 (77.40); H, 127.24, 126.98, 126.90, 126.02, 120.67, 114.30 (d,
6.14 (6.13); N, 5.00 (5.01).
J=21Hz), 77.38, 31.14; 19F NMR (376 MHz, CDCl3): δ -
117.37 (s,1F); IR (KBr): ν 3214, 2976, 2928, 1597, 1502,
1444, 1367, 1211, 1074, 1010, 931, 836, 796, 765, 720,
522 cm-1;ESI-MS [M+Na]+ calcd for C17H14FNO: 267.1059,
found: 290.0958; Analytical Data. Found (calcd) for:
C17H14FNO C, 76.41 (76.39); H, 5.29 (5.28); N, 5.25 (5.24).
1-(3,4-dimethoxyphenyl)-1-(quinolin-8-yl)ethan-1-ol
(3k): Purified by column chromatography to provide a
white solid (14.2 mg, yield: 46%). mp 88-90 C. H NMR
(400 MHz, CDCl3): δ 8.75 – 8.68 (m, 2H), 8.17 (dd, J = 8.3,
1.7 Hz, 1H), 7.79 – 7.73 (m, 1H), 7.71 – 7.63 (m, 1H), 7.52
o
1
(t, J = 7.7 Hz, 1H), 7.36 (dd, J = 8.3, 4.3 Hz, 1H), 7.22 (d, J 1-(4-(1-hydroxy-1-(quinolin-8-yl) ethyl)phenyl)ethan-1-
= 2.0 Hz, 1H), 6.78 – 6.63 (m, 2H), 3.82 (d, J = 13.9 Hz, one (3o): Purified by column chromatography to provide a
o
1
6H), 2.05 (s, 3H); 13C NMR (101 MHz, CDCl3): δ 148.33, white solid (13.1 mg, yield: 45%). mp 175-177 C. H
147.66, 147.30, 146.31, 143.21, 142.39, 137.30, 129.02, NMR (400 MHz, CDCl3): δ 8.68 (dd, J = 4.3, 1.8 Hz, 1H),
127.54, 127.43, 126.03, 120.62, 117.49, 110.04, 109.25, 8.40 (s, 1H), 8.18 (dd, J = 8.3, 1.8 Hz, 1H), 7.86 – 7.77 (m,
77.76, 55.73, 55.68, 31.15; IR (KBr): ν 3372, 2927, 2857, 4H), 7.59 (t, J = 7.7 Hz, 1H), 7.55 – 7.48 (m, 2H), 7.36 (dd,
1595, 1508, 1445, 1407, 1367, 1257, 1229, 1133, 1026 , J = 8.3, 4.3 Hz, 1H), 2.53 (s, 3H), 2.03 (s, 3H); 13C NMR
801, 765, 652 cm-1; ESI-MS [M+Na]+ calcd for C19H19NO3: (101 MHz, CDCl3): δ 197.83, 155.57, 147.93, 146.14,
309.1365, found: 332.1258; Analytical Data. Found (calcd) 142.43, 137.35, 135.23, 129.12, 127.97, 127.25, 126.16,
for: C19H19NO3 C, 73.75 (73.77); H, 6.18 (6.19); N, 4.54 125.46, 120.85, 77.58, 30.67, 26.55; IR (KBr): ν 3221,
(4.53).
2971, 2920, 1674, 1600, 1495, 1403, 1369, 1270, 1208,
1098, 836, 798, 653, 601 cm-1; ESI-MS [M+Na]+ calcd for
C19H17NO2: 291.1259, found: 314.1152; Analytical Data.
Found (calcd) for: C19H17NO2 C, 78.30 (78.33); H, 5.88
(5.88); N, 4.80 (4.81).
1-(4-chlorophenyl)-1-(quinolin-8-yl)ethan-1-ol
(3l):
Purified by column chromatography to provide a white
solid (22.0 mg, yield: 78%). mp 110-112 oC. 1H NMR (400
MHz, CDCl3): δ 8.57 (dd, J = 4.2, 1.8 Hz, 1H), 8.37 (s, 1H),
8.05 (dd, J = 8.3, 1.8 Hz, 1H), 7.66 (dd, J = 7.8, 4.5 Hz, Ethyl 4-(1-hydroxy-1-(quinolin-8-yl)ethyl)benzoate (3p):
2H), 7.45 (t, J = 7.7 Hz, 1H), 7.29 – 7.20 (m, 3H), 7.12 – Purified by column chromatography to provide a yellow
o
1
7.05 (m, 2H), 1.92 (s, 3H); 13C NMR (101 MHz, CDCl3): δ solid (13.5 mg, yield: 42%). mp 86-88 C. H NMR (400
148.52, 147.70, 146.07, 142.62, 137.21, 131.80, 128.99, MHz, CDCl3): δ 8.59 (dd, J = 4.3, 1.9 Hz, 1H), 8.32 (s, 1H),
127.73, 127.69, 127.16, 126.76, 126.00, 120.65, 77.31, 8.08 (dd, J = 8.4, 1.8 Hz, 1H), 7.85 – 7.78 (m, 2H), 7.72 (t,
30.90; IR (KBr): ν 3212, 2926, 2854, 1600, 1487, 1437, J = 8.1 Hz, 2H), 7.50 (t, J = 7.8 Hz, 1H), 7.41 (d, J = 8.4
1369, 1204, 1092, 1051, 818,797, 674 cm-1; ESI-MS Hz, 2H), 7.26 (dd, J = 8.4, 4.2 Hz, 1H), 4.24 (q, J = 7.1 Hz,
[M+Na]+ calcd for C17H14ClNO: 283.0764, found: 2H), 1.95 (s, 3H), 1.26 (t, J = 7.1 Hz, 3H); 13C NMR (101
306.0665; Analytical Data. Found (calcd) for: C17H14ClNO MHz, CDCl3): δ 166.54, 155.18, 147.87, 146.13, 142.52,
C, 71.98 (71.96); H, 4.96 (4.97); N, 4.95 (4.94).
137.30, 129.06, 128.40, 127.90, 127.22, 126.12, 125.24,
120.80, 77.59, 60.68, 30.68, 14.29; IR (KBr): ν 3298, 2985,
2935, 1715, 1603, 1496, 1371, 1278, 1117, 798, 772, 710,
577 cm-1; ESI-MS [M+Na]+ calcd for C20H19NO3:
321.1365, found: 344.1257; Analytical Data. Found (calcd)
for: C20H19NO3 C, 74.76 (74.75); H, 5.95 (5.96); N, 4.37
(4.36).
1-(2-bromophenyl)-1-(quinolin-8-yl)ethan-1-ol
(3m):
Purified by column chromatography to provide a white
o
1
solid (18.9 mg, yield: 58%). mp 95-97 C. H NMR (400
MHz, CDCl3): δ 8.84 (s, 1H), 8.74 (dd, J = 4.3, 1.7 Hz, 1H),
8.19 (dd, J = 8.4, 1.7 Hz, 1H), 7.90 (dd, J = 8.0, 1.6 Hz,
1H), 7.74 (dd, J = 7.9, 1.7 Hz, 1H), 7.52 - 7.43 (m, 3H),
7.40 -7.32 (m, 2H), 7.09 (td, J = 7.6, 1.6 Hz, 1H), 2.17 (s, 1-(quinolin-8-yl)-1-(4-(trifluoromethoxy)phenyl)ethan-
3H); 13C NMR (101 MHz, CDCl3): δ 147.44, 146.44, 1-ol (3q): Purified by column chromatography to provide a
o
1
146.15, 142.23, 137.37, 135.16, 128.78, 128.52, 128.44, bronzing solid (28.9 mg, yield: 87%). mp 57-59 C. H
128.41, 127.19, 126.67, 126.03, 122.77, 120.53, 78.88, NMR (400 MHz, CDCl3): δ 8.70 (dd, J = 4.3, 1.9 Hz, 1H),
30.31; IR (KBr): ν 3227, 2924, 2854, 1596, 1461, 1430, 8.53 (s, 1H), 8.18 (dd, J = 8.3, 1.9 Hz, 1H), 7.76 (ddd, J =
1366, 1265, 1068, 1023, 926, 830, 794, 756, 648, 508 cm-1; 12.6, 7.7, 1.5 Hz, 2H), 7.59 – 7.52 (m, 1H), 7.47 – 7.41 (m,
ESI-MS [M+Na]+ calcd for C17H14BrNO: 327.0259, found: 2H), 7.36 (dd, J = 8.3, 4.3 Hz, 1H), 7.09 – 7.03 (m, 2H),
350.0149; Analytical Data. Found (calcd) for: C17H14BrNO 2.03 (s, 3H); 13C NMR (101 MHz, CDCl3): δ 148.63,
C, 62.23 (62.21); H, 4.29 (4.30); N, 4.27 (4.27).
147.86, 147.61, 147.59, 146.24, 142.71, 137.38, 129.16,
127.88, 127.34, 126.80, 126.13, 120.82,120.48 (d, J=255
Hz), 120.06, 77.47, 31.08; 19F NMR (376 MHz, CDCl3): δ
-57.80 (s, 3F); IR (KBr): ν 3246, 2985, 2932, 1597, 1500,
1259, 1174, 1098, 1053, 796, 713, 586 cm-1; ESI-MS
[M+Na]+ calcd for C18H14F3NO2: 333.0977, found:
1-(4-fluorophenyl)-1-(quinolin-8-yl)ethan-1-ol
Purified by column chromatography to provide a bronzing
(3n):
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201800943
Advanced Synthesis & Catalysis
356.0870; Analytical Data. Found (calcd) for: C18H14F3NO2 J = 7.3 Hz, 1H), 6.88 (d, J = 2.6 Hz, 1H), 3.84 (s, 3H), 1.92
C, 64.88 (64.86); H, 4.23 (4.23); N, 4.21 (4.20).
(s, 3H); 13C NMR (101 MHz, CDCl3): δ 156.97, 149.41,
145.20, 144.86, 142.62, 135.89, 130.29, 127.68, 126.21,
125.24, 120.99, 120.86, 104.09, 77.55, 55.47, 30.98; IR
(KBr): ν 3195, 2961, 2931, 1617, 1600, 1416, 1371, 1256,
1047, 1029, 843, 801, 700 cm-1; ESI-MS [M+Na]+ calcd
for C18H17NO2: 279.1259, found: 302.1156; Analytical
Data. Found (calcd) for: C18H17NO2 C, 77.43 (77.40); H,
6.14 (6.13); N, 5.02 (5.01).
1-(quinolin-8-yl)-1-(4-(trifluoromethyl) phenyl) ethan-1-
ol (3r): Purified by column chromatography to provide a
o
1
white solid (26.6 mg, yield: 84%). mp 117-119 C. H
NMR (400 MHz, CDCl3): δ 8.55 (dd, J = 4.4, 1.7 Hz, 1H),
8.36 (s, 1H), 8.04 (dd, J = 8.4, 1.7 Hz, 1H), 7.69 (dd, J =
12.2, 7.7 Hz, 2H), 7.46 (dd, J = 12.8, 8.0 Hz, 3H), 7.36 (d,
J = 8.2 Hz, 2H), 7.21 (dd, J = 8.3, 4.3 Hz, 1H), 1.93 (s, 3H);
13C NMR (101 MHz, CDCl3): δ 154.08, 147.90, 146.04, Methyl
8-(1-hydroxy-1-phenylethyl)quinoline-5-
142.27, 137.32, 129.06, 128.27 (d, J=32 Hz )127.98, carboxylate (4b): Purified by column chromatography to
127.23, 126.10, 125.55, 124.65 (d, J=4 Hz ), 124.26 (d, provide a white liquide (25.1 mg, yield: 82%). mp 35-37 oC.
J=270Hz), 120.82, 77.43, 30.80; 19F NMR (376 MHz, 1H NMR (400 MHz, CDCl3): δ 9.40 (dd, J = 8.8, 1.8 Hz,
CDCl3): δ -62.21 (s, 3F); IR (KBr): ν 3279, 2926, 1592, 1H), 8.73 (dd, J = 4.1, 1.9 Hz, 1H), 8.44 (s, 1H), 8.29 (d, J
1496, 1406, 1372, 1323, 1174, 1132, 1103, 1077, 1065, = 7.8 Hz, 1H), 7.80 (d, J = 7.8 Hz, 1H), 7.46 (dd, J = 8.8,
1052, 842, 833, 612 cm-1; ESI-MS [M+Na]+ calcd for 4.2 Hz, 1H), 7.41 – 7.37 (m, 2H), 7.23 (t, J = 7.7 Hz, 2H),
C18H14F3NO: 317.1027, found: 340.0923; Analytical Data. 7.16 (d, J = 7.0 Hz, 1H), 4.01 (s, 3H), 2.05 (s, 3H); 13C
Found (calcd) for: C18H14F3NO C, 68.16 (68.13); H, 4.45 NMR (101 MHz, CDCl3): δ 166.65, 149.30, 148.53, 147.81,
(4.45); N, 4.40 (4.41).
146.33, 135.63, 130.35, 127.81, 127.78, 126.36, 126.14,
125.21, 121.96, 77.74, 52.36, 31.02; IR (KBr): ν 3383,2927,
2853, 1718, 1504, 1435, 1367, 1277,1201, 1132, 1055,
1023, 762, 738, 701 cm-1; ESI-MS [M+Na]+ calcd for
C19H17NO3: 307.1208, found: 330.1107; Analytical Data.
Found (calcd) for: C19H17NO3 C, 74.27 (74.25); H, 5.57
(5.58); N, 4.55 (4.56).
1-(naphthalen-2-yl)-1-(quinolin-8-yl)ethan-1-ol
Purified by column chromatography to provide a white
(3s):
o
1
solid (26.9 mg, yield: 90%). mp 58-60 C. H NMR (400
MHz, CDCl3): δ 8.59 (s, 1H), 8.43 (d, J = 4.0 Hz, 1H), 7.86
(d, J = 8.3 Hz, 1H), 7.81 (s, 1H), 7.66 – 7.50 (m, 5H), 7.45
(d, J = 8.6 Hz, 1H), 7.36 (t, J = 7.7 Hz, 1H), 7.28 – 7.17 (m,
2H), 7.01 (dd, J = 8.3, 4.3 Hz, 1H), 2.00 (s, 3H); 13C NMR 1-(5-chloroquinolin-8-yl)-1-phenylethan-1-ol
(4c):
(101 MHz, CDCl3): δ 147.59, 147.17, 146.19, 142.90, Purified by column chromatography to provide a white
137.12, 132.90, 132.04, 128.91, 128.04, 127.59, 127.38, solid (24.6 mg, yield: 87%). mp 113-115 oC. 1H NMR (400
127.30, 127.24, 125.97, 125.64, 125.31, 124.43, 123.42, MHz, CDCl3): δ 8.64 (dd, J = 4.4, 1.8 Hz, 1H), 8.50 (dd, J
120.50, 77.83, 30.99; IR (KBr): ν 3320, 2924, 2855, 1598, = 8.6, 1.8 Hz, 1H), 8.07 (s, 1H), 7.61 – 7.51 (m, 2H), 7.36
1495, 1437, 1370, 1124, 1096, 905, 820, 792, 747, 673, – 7.30 (m, 3H), 7.17 – 7.12 (m, 2H), 7.09 – 7.04 (m, 1H),
479 cm-1; ESI-MS [M+Na]+ calcd for C21H17NO: 299.1310, 1.93 (s, 3H); 13C NMR (101 MHz, CDCl3): δ 149.44,
found: 322.1203; Analytical Data. Found (calcd) for: 148.32, 146.83, 142.67, 134.06, 130.82, 127.74, 127.17,
C21H17NO C, 84.27 (84.25); H, 5.72 (5.72); N, 4.67 (4.68).
126.94, 126.30, 126.03, 125.20, 121.39, 77.43, 31.03; IR
(KBr): ν 3317, 3063, 2985, 2932, 1570, 1492, 1448, 1355,
1290, 1160, 1067, 1035, 997, 940, 854, 797, 690, 612, 535
cm-1; ESI-MS [M+Na]+ calcd for C17H14ClNO: 283.0764,
found: 306.0660; Analytical Data. Found (calcd) for:
C17H14ClNO C, 71.98 (71.96); H, 4.96 (4.97); N, 4.94
(4.94).
1-(naphthalen-1-yl)-1-(quinolin-8-yl)ethan-1-ol
(3t):
Purified by column chromatography to provide a white
solid (16.1 mg, yield: 54%). mp 170-172 oC. 1H NMR (400
MHz, CDCl3): δ 9.31 (s, 1H), 8.89 (dd, J = 4.3, 1.9 Hz, 1H),
8.38 (d, J = 8.8 Hz, 1H), 8.26 (dd, J = 8.4, 1.9 Hz, 1H),
7.86 – 7.80 (m, 2H), 7.67 (ddd, J = 23.9, 7.7, 1.4 Hz, 2H),
7.50 – 7.42 (m, 2H), 7.35 (ddd, J = 8.1, 6.6, 1.2 Hz, 1H), 1-(benzo[f]quinolin-5-yl)-1-phenylethan-1-ol
(4d):
7.28 – 7.23 (m, 1H), 7.18 (ddd, J = 8.5, 6.7, 1.5 Hz, 1H), Purified by column chromatography to provide a white
7.07 (dd, J = 7.4, 1.5 Hz, 1H), 2.31 (s, 3H); 13C NMR (101 solid (26.9 mg, yield: 90%). mp 162-164 oC. 1H NMR (400
MHz, CDCl3): δ 147.48, 146.30, 144.34, 142.08, 137.55, MHz, CDCl3): δ 8.91 (dd, J = 8.5, 1.6 Hz, 1H), 8.68 (dd, J
135.03, 131.49, 129.08, 128.85, 128.81, 128.38, 127.97, = 4.4, 1.7 Hz, 1H), 8.56 – 8.50 (m, 1H), 8.37 (s, 1H), 8.06
126.99, 126.32, 124.86, 124.74, 124.50, 124.39, 120.60, (s, 1H), 7.97 (dd, J = 6.3, 3.1 Hz, 1H), 7.70 – 7.65 (m, 2H),
79.83,32.47; IR (KBr): ν 3194, 2924, 2854, 1597, 1497, 7.51 – 7.40 (m, 3H), 7.21 (t, J = 7.5 Hz, 2H), 7.13 (t, J =
1462, 1312, 1093, 1058, 831, 788, 690 cm-1; ESI-MS 7.2 Hz, 1H), 2.10 (s, 3H); 13C NMR (101 MHz, CDCl3): δ
[M+Na]+ calcd for C21H17NO: 299.1310, found: 322.1209; 149.82, 147.10, 146.94, 140.64, 131.65, 130.90, 129.23,
Analytical Data. Found (calcd) for: C21H17NO C, 84.28 128.44, 127.73, 127.67, 127.27, 126.42, 126.13, 125.19,
(84.25); H, 5.71 (5.72); N, 4.68 (4.68).
122.21, 120.89, 77.52, 31.07; IR (KBr): ν 3286, 2977, 2932,
1596, 1486, 1403, 1368, 1174, 1107, 1002, 903, 760, 699,
512 cm-1; ESI-MS [M+Na]+ calcd for C21H17NO: 299.1310,
found: 322.1208; Analytical Data. Found (calcd) for:
C21H17NO C, 84.28 (84.25); H, 5.72 (5.72); N, 4.69 (4.68).
1-(6-methoxyquinolin-8-yl)-1-phenylethan-1-ol
(4a):
Purified by column chromatography to provide a white
solid (19.5 mg, yield: 70%). mp 112-114 oC. 1H NMR (400
MHz, CDCl3): δ 8.47 – 8.41 (m, 2H), 7.93 (dd, J = 8.5, 1.7
Hz, 1H), 7.40 – 7.31 (m, 3H), 7.20 – 7.12 (m, 3H), 7.06 (t,
8
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10.1002/adsc.201800943
Advanced Synthesis & Catalysis
1-phenyl-1-(quinolin-8-yl)propan-1-ol (4e): Purified by
column chromatography to provide a white solid (11.3 mg,
yield: 43%). mp 99-101 oC. 1H NMR (400 MHz, CDCl3): δ
8.90 (s, 1H), 8.70 (dd, J = 4.3, 1.7 Hz, 1H), 8.14 (dd, J =
8.3, 1.8 Hz, 1H), 7.75 (dd, J = 10.8, 7.7 Hz, 2H), 7.56 (t, J
= 7.7 Hz, 1H), 7.47 (d, J = 7.5 Hz, 2H), 7.33 (dd, J = 8.3,
4.3 Hz, 1H), 7.28 – 7.19 (m, 2H), 7.13 (t, J = 7.2 Hz, 1H),
2.50 (dq, J = 14.3, 7.2 Hz, 1H), 2.27 (dq, J = 14.4, 7.3 Hz,
1H), 1.05 (t, J = 7.3 Hz, 3H); 13C NMR (101 MHz, CDCl3):
δ 148.51, 147.45, 146.76, 142.12, 137.33, 129.16, 127.64,
127.51, 127.34, 126.04, 125.99, 125.82, 120.56, 80.14,
35.29, 8.47; IR (KBr): ν 3379, 2926, 1612, 1496, 1406,
1372, 1323, 1174, 1132, 1102, 1076, 1065, 915,842, 832,
612 cm-1; ESI-MS [M+Na]+ calcd for C18H17NO: 263.1310,
found: 286.1201; Analytical Data. Found (calcd) for:
C18H17NO C, 82.14 (82.10); H, 6.50 (6.51); N, 5.33 (5.32).
Org.Biomol. Chem. 2007, 5, 873-888; f) P. Tian, H.-Q.
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1,3-diphenyl-1-(quinolin-8-yl)propan-1-ol (4f): Purified
by column chromatography to provide a colorless liquid
(12.5 mg, yield: 37%). 1H NMR (400 MHz, CDCl3): δ 9.02
(s, 1H), 8.59 (dd, J = 4.3, 1.7 Hz, 1H), 8.00 (dd, J = 8.3, 1.8
Hz, 1H), 7.69 (d, J = 7.3 Hz, 1H), 7.61 (d, J = 8.1 Hz, 1H),
7.45 (dd, J = 7.8, 6.0 Hz, 3H), 7.21 – 7.11 (m, 7H), 7.06 (dt,
J = 9.6, 4.5 Hz, 2H), 2.95 – 2.86 (m, 1H), 2.74 – 2.59 (m,
2H), 2.52 – 2.43 (m, 1H); 13C NMR (101 MHz, CDCl3): δ
148.10, 147.48, 146.60, 143.01, 142.01, 137.38, 129.15,
128.42, 128.31, 128.27, 127.66, 127.47, 126.17, 126.08,
125.77, 125.54, 120.63, 79.89, 44.71, 30.34; IR (KBr): ν
3289, 3058, 3026, 2930, 1602, 1494, 1447, 1370, 1056,
829, 795, 700 cm-1; ESI-MS [M+Na]+ calcd for C24H21NO:
339.1623, found: 362.1513; Analytical Data. Found (calcd)
for: C24H21NO C, 84.90 (84.92); H, 6.23 (6.24); N, 4.13
(4.13).
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phenyl(quinolin-8-yl)methanol (4h): Purified by column
chromatography to provide a white solid (19.9 mg, yield:
85%). mp 102-105 oC. 1H NMR (400 MHz, CDCl3): δ 8.87
- 8.80 (m, 1H), 8.22 – 8.14 (m, 1H), 7.73 (d, J = 8.0 Hz,
1H), 7.50 (d, J = 7.7 Hz, 2H), 7.47 – 7.38 (m, 3H), 7.33 (t,
J = 7.5 Hz, 2H), 7.25 – 7.21 (m, 1H), 6.95 (s, 1H), 6.41 (s,
1H); 13C NMR (101 MHz, CDCl3): δ 148.54, 146.51,
143.85, 140.17, 137.03, 128.80, 128.50, 128.13, 127.38,
127.05, 126.77, 126.32, 121.00, 76.42; IR (KBr): ν 3228,
1596, 1497, 1448, 1369, 1260, 1242, 1016, 890, 794, 729,
605 cm-1; ESI-MS [M+Na]+ calcd for C16H13NO: 235.0997,
found: 258.0892; Analytical Data. Found (calcd) for:
C16H13NO C, 81.70 (81.68); H, 5.56 (5.57); N, 5.96 (5.95).
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Acknowledgements
This work was supported by the National Natural Science
Founda-tion of China (grant No. 21572155 and 21372175), the
Natural Science Foundation of Tianjin (16JCYBJC19700).
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[19]Unpublished experiments: reaction of 1-(quinolin-8-
yl)ethan-1-one(0.1mmol) and arylboronic acids (2.5
eq.) in the presence of [Rh(COD)Cl]2 (5 mol%), K2CO3
(0.8 eq.), CuCN (1.5 eq.) under similar reaction
10
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10.1002/adsc.201800943
Advanced Synthesis & Catalysis
FULL PAPER
Formation of Tertiary Alcohol via Chelation-
Assisted Nickel(II)-Catalyzed Addition of
Arylboronic Acids to Unactivated 1-(Quinolin-8-
yl)ethan-1-one
Adv. Synth. Catal. Year, Volume, Page – Page
Shutao Wu,a Weijie Guo,b Tao Wang,c Qingxiao
Xie,d Jianhui Wang a* and Guiyan Liub*
11
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