Zn(OTf)2-promoted chemoselective esterification of hydroxyl group bearing carboxylic acids

Article abstract of DOI:10.1021/jo302502r

Selective esterification of aliphatic and aromatic carboxylic acids with various alcohols is studied using triphenylphosphine, I₂, and a catalytic amount of Zn(OTf)₂. Use of this catalyst allows the formation of esters at a faster rate with good to excellent yield by activating the in situ generated acyloxyphosphonium ion intermediate. During the esterification process, both their aromatic and aliphatic hydroxyl groups are fully preserved from transesterification. The results show that the bulkiness and the reactivity of this doubly activated intermediate III control the selectivity and the rate of the reaction, respectively. The method is also useful for direct amidation reactions.

Full text of DOI:10.1021/jo302502r

Article
pubs.acs.org/joc
Zn(OTf)2‑Promoted Chemoselective Esterification of Hydroxyl Group
Bearing Carboxylic Acids
Narsimha Mamidi and Debasis Manna*
Department of Chemistry, Indian Institute of Technology Guwahati, Assam 781039, India
S
* Supporting Information
ABSTRACT: Selective esterification of aliphatic and aromatic
carboxylic acids with various alcohols is studied using triphenylphos-
phine, I2, and a catalytic amount of Zn(OTf)2. Use of this catalyst
allows the formation of esters at a faster rate with good to excellent
yield by activating the in situ generated acyloxyphosphonium ion
intermediate. During the esterification process, both their aromatic
and aliphatic hydroxyl groups are fully preserved from trans-
esterification. The results show that the bulkiness and the reactivity
of this doubly activated intermediate III control the selectivity and
the rate of the reaction, respectively. The method is also useful for
direct amidation reactions.
Scheme 1. Model Reaction of Zn(OTf)2-Catalyzed
Esterification of Carboxylic Acids
INTRODUCTION
■
Esterification is one of the essential chemical reactions that
have been widely used in the chemical and pharmaceutical
industries.1 This basic chemical transformation has been already
accomplished by several chemical methods, but only a few
methods offer direct esterification, functional group tolerance,
and selective and mild reaction conditions.2 Hence, there is a
clear and unmet need for improved, regioselective, and
chemoselective esterification methods.3 The biologically active
ester derivatives like epicatechin gallate, epigallocatechin gallate,
caffeic acid, phenethyl ester, and others are good example of
such class of complex compounds. Chemoselective synthesis of
these compounds in fewer steps using regular esterification
reaction conditions are very difficult because of the requirement
of other functional group protection or the use of harsh
reaction condition and/or a large excess of reactants.4
There have been continuous efforts in recent years aimed at
developing mild reaction protocols for chemoselective ester-
ification with improved efficiency. Robles and co-workers
reported a mild and selective esterification reaction method
(Scheme 1)3c based on the Garegg−Samuelsson reaction
conditions.3a Recently, Zhang and co-workers reported the use
of hypervalent iodine reagent iodosodilactone as an efficient
coupling reagent for direct esterification/amidation with
triphenylphosphine and 4-dimethylaminopyridine.3d The mech-
anistic studies showed the generation of acyloxyphosphonium
ion as the key intermediate for the formation of ester/amide.
Earlier, Mukaiyama and co-workers reported that oxidative
activation of triphenylphosphine by di(2-pyridyl)disulfide
causes generation of acyloxyphosphonium ion intermediate
from carboxylic acids, followed by reaction with alcohols or
amines gives corresponding esters and amides.3b All these
methods use in situ activation of acid for direct esterification/
amidation. Although very attractive, the activation is not always
strong and/or selective enough for the complex substrates.
Therefore, the key feature for further development of mild and
selective esterification methods is that the acid should be
activated to more reactive species.
In this context, here we describe a significant improvement of
these methods that is mild, highly efficient, and chemoselective
using triphenylphosphine, I2, and a catalytic amount of
Zn(OTf)2 as an activator. Hypothetically, there could be a
possibility of the reaction proceeding via in situ generation of
the zinc-coordinated acyloxyphosphonium ion intermediate,
which might increase the electrophilicity well enough to
facilitate the intermolecular attack of the alcohol or amine at
a faster rate (within 3−5 h) to produce the corresponding
ester/amide with good to excellent yield. The reaction
Received: November 20, 2012
© XXXX American Chemical Society
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a
Table 1. Screening of Lewis Acids and Solvent System for the Esterification Reaction
c
entry
Lewis acid (mol %)
phosphine/I2
solvent
temp (°C)
time (h)
yield (%)
b
1
2
Zn(OTf)2; (1)
Zn(OTf)2; (2)
Zn(OTf)2; (5)
Zn(OTf)2; (5)
Zn(OTf)2; (5)
Zn(OTf)2; (5)
−
Zn(OTf)2; (5)
Zn(OTf)2; (5)
Zn(OTf)2; (5)
Zn(OTf)2; (5)
Zn(OAc)2; (5)
ZnCl2; (5)
Ph3P/I2
Ph3P/I2
Ph3P/I2
Ph3P/I2
Ph3P/I2
−
Ph3P/I2
Ph3P/I2
Ph3P/I2
Ph3P/I2
Ph3P/I2
Ph3P/I2
Ph3P/I2
Ph3P/I2
Ph3P/I2
Ph3P/I2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH2Cl2
THF
100
24
12
4
23
41
86
87
ND
ND
ND
26
20
13
10
10
8
80
60
80
rt
3
4
4
5
24
24
24
48
30
24
24
28
24
24
20
24
6
60
60
7
b
8
60
9
60
60
60
80
80
10
11
12
13
14
15
16
DMF
toluene
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
b
Zn(ClO4)2·6H2O; (5)
Cu(OTf)2; (5)
FeCl3; (5)
100
7
b
100
6
80
5
a
Performed with carboxylic acid (1.0 equiv), Ph3P (2.0 equiv), I2 (2.0 equiv), Lewis acid (1−5 mol %), and alcohol (1.1 equiv) in dry acetonitrile.
b
c
Reactions were performed under the sealed tube conditions. Isolated yield. ND: not detectable.
condition is functional group tolerant and useful for selective
esterification of primary over secondary alcohols. In addition,
this method also shows the use of several structurally complex
and biologically active alcohol and acid conversion to their
corresponding esters, which are proven as a difficult substrate
for direct esterification.
by either only Lewis acid or Robles’s protocol using Ph3P (1.5
equiv), I2 (1.5 equiv) and imidazole (3.3 equiv), showing the
viability of our method of esterification (Scheme 1).3c
Encouraged by this excellent result, we decided to optimize
the reaction conditions studying several Lewis acids, solvents,
and temperature (Table 1). The best result was obtained with 5
mol % of Zn(OTf)2 catalyst with CH3CN as solvent. However,
the use of lower amount of the catalyst resulted in poor yields
(Table 1, entries 1 and 2). The reaction was sluggish at lower
temperature (entry 5), and there was no significant improve-
ment of ester formation at higher temperature (entry 4).
Exclusion of either Ph3P/I2 or Zn(OTf)2 did not result in a
detectable amount of the desired ester (entries 6 and 7). In the
meantime, esterification of palmitic acid with ethanol in the
absence of Zn(OTf)2 resulted the desired ester with moderate
yield (50%). Thus, both Ph3P/I2 and Zn(OTf)2 are
indispensable for chemoselctive esterification of less reactive
3,4-dihydroxybenzoic acid. In addition, a set of solvents was
also studied, resulting lower yield than with CH3CN (entries
8−11). The catalytic amount of other nontoxic Lewis acids
such as Cu(OTf)2, FeCl3, InCl3, BF3·OEt2, and AlCl3 resulted
poor or no yield even at high temperature under similar
experimental conditions (Table 1, entries 15 and 16; results are
not shown for InCl3, BF3·OEt2, and AlCl3). We also observed
that, in the presence of the lower amount of Ph3P/I2 (less than
2.0 equiv), the activated intermediate can suffer the attack of a
second molecule of the acid to generate significant amounts of
anhydride and Ph3PO.3c Therefore, Ph3P/I2 (2.0 equiv) and
Zn(OTf)2 (5 mol %) in CH3CN solvent are the best reaction
conditions at 60 °C.
RESULT AND DISCUSSION
■
It is well documented that the Lewis acid catalyzed
esterification is very efficient due to the enhancement of
electrophilicity of carboxylic acids and anhydrides.7 Con-
sequently, considerable attention has been directed toward
the investigation of a wide variety of Lewis acids such as CoCl2,
InCl3, TiCl4, AgClO4, ZnCl2, CeCl3, Yb(OTf)3, HfCl4·(THF)2,
and others for their role is esterification.5 Recently, a catalytic
amount of Zn(OTf)2 was used for amide cleavage and
esterification of β-hydroxyethylamides.6a It was also used for
the microwave-irradiated esterification of simple acids and
alcohols.6b However, to the best of our knowledge, there is no
previous report of zinc-catalyzed chemoselective esterification/
amidation using Ph3P/I2. Although the chemoselective
esterifications of phenolic acids and alcohols have been
successfully achieved by a few methods, the reaction conditions
are either harsh or their purifications are troublesome,7 whereas
the reported Lewis acid catalyzed esterification for most of
these phenolic acids/alcohols are very slow and yields are poor
to moderate only.8
We hypothesized that the combination of in situ carboxylic
acid activation followed by the Lewis acid activation of this
activated ester intermediate would give us an otherwise
unattainable enhanced reactivity. Therefore, to check the
feasibility of the Lewis acid catalyzed esterification, caffeic
acid (1a) and cetyl alcohol (2a) were chosen as a substrate for
the model reaction, using Ph3P (2.0 equiv), I2 (2.0 equiv), a
catalytic amount of (5 mol %) Zn(OTf)2 in CH3CN solvent at
60 °C (Table 1, entry 3). To our delight, we obtained the ester
3aa with excellent yield of 86% (within 4 h) using this double
activation method. Interestingly, the ester 3aa was not obtained
We also determine the scope of this methodology for
esterification/amidation by analyzing the reactivity of various
acids, alcohols, and amines using these optimized reaction
conditions. We first tested the esterification of cinnamic acids
(1a−e) with primary (2a−c), secondary (2d), and tertiary
alcohol (2e). The esterification of caffeic acids with primary
alcohols produced the desired ester with good to excellent
yields (86−90%). The reaction with the secondary alcohol (2c)
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resulted moderate to good yields (70−75%) only but failed
with the hindered tertiary alcohol (Table 2).
that the presence of Zn(OTf)2 in the reaction medium
surmounts the direct effect of these functional groups on
esterification. The reactions with secondary alcohols were
sluggish, as expected. The esterification is also compatible and
selective with the presence of both terminal and internal
alkenes and alkynes, and no addition of I2 over these multiple
bonds was observed (Table 3, entries 3 and 7; Table 4, entries
1, 2 and 4). Other functional groups present in carboxylic acids
and alcohols such as carbonyl, nitro, bromo, and methoxy were
also unaffected under the adopted reaction condition.
Table 2. Esterification of Cinnamic Acids under Optimized
a
Reaction Conditions
b
time
(h)
yield
(%)
After studying the usefulness of our method of chemo-
selective esterification for various acids and alcohols, we
decided to establish the applicability of this method for the
synthesis of biologically active molecules/intermediates. The
esterfication of saturated fatty acids (palmitic acid and octanoic
acid), unsaturated fatty acid (oleic acid), (+)-menthol,
cholesterol, indole-3-propionic acid, quinoline-2-carboxylic
(Table 5, entries 1−9), and gallic acid (Table 3, entry 4)
resulted in a corresponding ester with moderate to excellent
yield, which is very important in the synthesis of complex
molecules. This could be due the mild reaction conditions,
avoiding possible decomposition or simultaneous reactions
with other functional groups within the same molecule. The
esterification yields were higher for primary alcohols compared
to secondary and tertiary alcohols, as expected. Significantly,
when chiral carboxylic acids and alcohols were used, retention
of the stereochemistry was also observed. The chiral ester 13
and 21 showed >99% ee as measured by HPLC (Figure S38−
S41, Supporting Information).
entry
acid
alcohol
product
1
1a: R1 = OH, R2= OH
1a: R1 = OH, R2= OH
1a: R1 = OH, R2= OH
1b: R1 = OH, R2= OMe
1b: R1 = OH, R2= OMe
1b: R1 = OH, R2= OMe
1c: R1 = OMe, R2 = OH
1c: R1 = OMe, R2 = OH
1c: R1 = OMe, R2 = OH
1c: R1 = OMe, R2 = OH
1d: R1 = OH, R2= H
1d: R1 = OH, R2= H
1d: R1 = OH, R2= H
1e: R1 = H, R2= OH
1e: R1 = H, R2= OH
1e: R1 = H, R2= OH
1e: R1 = H, R2= OH
2b
2d
2e
2a
2b
2d
2a
2b
2c
2d
2a
2b
2d
2a
2b
2c
2d
4
5
3ab
3ad
3ae
3ba
3bb
3bd
3ca
3cb
3cc
3cd
3da
3db
3dd
3ea
3eb
3ec
3ed
86
70
ND
86
86
73
86
86
90
73
90
90
73
90
90
90
75
2
3
12
4
4
5
4
6
5
7
4
8
4
9
3.5
5
10
11
12
13
14
15
16
17
3.5
3.5
5
3.5
3.5
3.5
5
a
Performed with carboxylic acid (1.0 equiv), Ph3P (2.0 equiv), I2 (2.0
To extend the use of this methodology beyond esterification,
we tested amidation reaction. The amidation of various
carboxylic acids with n-butylamine, benzylamine, (pyridin-2-
yl)methanamine, N′,N′-dimethylethane-1,2-diamine and piper-
idine under the optimized reaction condition of esterification
resulted the desired amide with good to excellent yields of 75−
98% (Table 6, entries 1−8). Therefore, this reaction condition
is a good alternative to the methods known for amidation. It is
worth noting that adopted reaction condition worked well for
several hetercylic substrates (Table 3, entries 6 and 10; Table 5
entries 5, 6, 8, and 9; Table 6, entries 4−8).
The results obtained in our study suggest that the reaction
between Ph3P and I2 yielded the triphenylphosphonium iodide
intermediate (I), and subsequent attack of carboxylic acid
generates the acyloxyphosphonium ion intermediate (II), in
accordance with the Garegg−Samuelsson reaction mechanis-
m,3a,10 whereas addition of Zn(OTf)2 to intermediate (II)
proposed the formation of zinc-coordinated active intermediate
(III) as reported earlier.6a This could enhance the electro-
philicity toward a carbonyl center of acyloxyphosponium ion
intermediate (III) and facilitate the nucleophilic attack of the
alcohol. This is the key step for selectivity of our esterification
reaction (Scheme 2). The generation of these proposed
intermediates in the reaction mixture was studied by 13C
NMR and 31P NMR spectroscopy as shown in the Figure 1 (for
full spectra, see Figures S1 and S2, Supporting Information).
The NMR spectra were collected after addition of each reagent
with a sufficient time gap.10a The observed changes in their
chemical shifts (as shown in Tables S1 and S2, Supporting
Information) indicate the formation of intermediate I10b and II.
The downfield shift of the 31P NMR signal (Δδ = 3.0 ppm) and
the 13C NMR signal for the CO group (Δδ = 0.5 ppm), after
addition of Zn(OTf)2 to the intermediate II, indicate the
formation of intermediate III. These spectral changes also
equiv), Zn(OTf)2 (5 mol %), and alcohol (1.1 equiv) in dry
acetonitrile. Isolated yield. ND: not detectable.
b
The chemoselectivity was established by performing
reactions between various hydroxyl group bearing aromatic
and aliphatic carboxylic acids and different types of alcohols
(Table 3, entries 1−18). The overall yields of these esters are
generally good, except for secondary alcohol and gallic acid.
Similar results were also obtained for the esterification aliphatic
acids with secondary benzylic alcohols (Table 3, entries 17 and
18). The α-hydroxycarboxylic acid (L-tartaric acid) also
produced an excellent yield of 98%.9a Treatment of unsym-
metrical diol using these optimized reaction conditions resulted
in exclusively regioselective esterification of primary alcohol
(Table 3, entry 11) in the presence of secondary alcohol,
showing the high selectivity of this method. Likewise, selective
esterification of aliphatic acid in the presence of aromatic acid
was also observed (Table 3, entry 12).
To investigate the compatibility of different protecting
groups under these reaction conditions, we performed
esterification with the protected acids/alcohols. It has already
been reported that the presence of acid-sensitive protecting
groups do not produce the desire ester with better yield due to
either deprotection or labile functional groups suffer
nucleophilic attack.9b However, we could not find any
deprotected/decomposed compound in the case of Ts-, Boc-,
Tr-, TBDPS-, TBDMS-, and acetonide- protecting groups of
acids/alcohols (Table 3, entries 9−11 and 13−16). The yields
of the esterification reactions of protected acids/alcohols were
also excellent (89−97%), showing a good selectivity for these
compounds.
We also investigated the role of electron-donating and
electron-withdrawing functional groups on the selective
esterification (Table 4, entries 1−5). The results clearly showed
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a
Table 3. Chemoselective Esterification of Carboxylic Acids and Alcohols under Optimized Reaction Conditions
a
Performed with carboxylic acid (1.0 equiv), Ph3P (2.0 equiv), I2 (2.0 equiv), Zn(OTf)2 (5 mol %), and alcohol (1.1 equiv) in dry acetonitrile.
Isolated yield. Ph3P (4.0 equiv), I2 (4.0 equiv), Zn(OTf)2 (10 mol %), and alcohol (2.2 equiv) in dry acetonitrile.
b
c
propose the coordination of zinc ion to the CO group of
I2 have been largely employed for the synthesis of iodoalkanes.
Therefore, the reaction mechanism rules out phenolic carbons
as substrate for SN2-type reactions, while the generation of the
nucleophilic species due to deprotection, a relatively weak base,
secures that carboxylate rather than phenolates are formed, in
the presence of stoichiometric amounts of reagents. This could
be the main reason behind the selectivity of esterification.
intermediate III.
Selectivity of esterification under this optimized reaction
conditions can be explained by the formation of much hindered
intermediate III. When this intermediate suffers attack by more
hindered secondary and tertiary alcohols, a bigger steric
repulsion between the ligands of phosphine and substituent
of the alcohols minimizes the probability of nucleophilic
addition.11 Under this optimized reaction condition, the
phenolic hydroxyl group present on either substrate would
not essentially take part in the reactions, even though Ph3P and
CONCLUSION
■
Therefore, we have developed a mild, safe, and highly
chemoselective esterification/amidation reaction method for
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a
Table 4. Substrate Scope of Esterification under Optimized Reaction Conditions
a
Performed with carboxylic acid (1.0 equiv), Ph3P (2.0 equiv), I2 (2.0 equiv), Zn(OTf)2 (5 mol %), and alcohol (1.1 equiv) in dry acetonitrile.
Isolated yield.
b
a
Table 5. Synthesis of Biologically Active Esters
a
Performed with carboxylic acid (1.0 equiv), Ph3P (2.0 equiv), I2 (2.0 equiv), Zn(OTf)2 (5 mol %), and alcohol (1.1 equiv) in dry acetonitrile.
Isolated yield.
b
aromatic and aliphatic carboxylic acids in the presence of
triphenylphosphine, I2, and zinc triflate. In particular, we have
demonstrated the utility of zinc ion assisted activation of
acyloxyphosphonium ion intermediate in the selective ester-
ification of hydroxyl group bearing carboxylic acids. In addition,
we have shown selective esterification of primary alcohols in the
presence of sterically hindered alcohols and selective
esterification of aliphatic carboxylic acid over aromatic
carboxylic acid, which may be of interest in the synthesis of
polyfunctionalized substrates. We believe this facile and
efficient protocol will serve as a useful alternative to the
existing esterification methods and will decrease the burden of
protecting groups in the synthesis of several complex
molecules, which constitutes an important objective in modern
organic chemistry.
EXPERIMENTAL SECTION
■
General Information. All reagents were purchased from different
commercial sources and used directly without further purification. Dry
solvents were obtained according to the reported procedures. Column
chromatography was performed using 60−120 mesh silica gel.
Reactions were monitored by thin-layer chromatography (TLC) on
1
silica gel 60 F254 (0.25 mm). H NMR, 13C NMR, and 31P NMR
spectra were recorded at 400, 100, and 162 MHz, respectively.
Coupling constants (J values) are reported in hertz, and chemical shifts
are reported in parts per million (ppm) downfield from
1
tetramethylsilane using residual chloroform (δ = 7.24 for H NMR,
δ = 77.23 for 13C NMR) as an internal standard. 31P NMR spectra
E
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a
Table 6. Amidation of Carboxylic Acids under Optimized Reaction Conditions
a
Performed with carboxylic acid (1.0 equiv), Ph3P (2.0 equiv), I2 (2.0 equiv), Zn(OTf)2 (5 mol %), and amine (1.1 equiv) in dry acetonitrile.
Isolated yield.
b
under reduced pressure. Column chromatography with silica gel and a
gradient solvent system of ethylacetate to hexane yielded the target
compound. Synthesized compounds were properly characterized by
NMR, HRMS (ESI), and melting points.
Scheme 2. Possible Reaction Mechanism for the Zn(OTf)2-
Mediated Esterification
Characterization of the Synthesized Compounds. (E)-
Hexadecyl 3-(3,4-dihydroxyphenyl)acrylate (3aa):.12a,b white solid
(97 mg, 86%); mp 105−107 °C (lit.12a mp 105−107 °C); H NMR
1
(400 MHz, DMSO-d6) δppm 7.48 (d, 1H, J = 16.0 Hz), 7.04 (s, 1H),
6.88 (d, 1H, J = 8.0 Hz), 6.80(d, 1H, J = 8.0 Hz), 6.19 (d, 1H, J = 16.0
Hz), 4.13 (t, 2H, J = 6.8 Hz), 1.69−1.59 (m, 2H), 1.25 (m, 26H), 0.87
(t, 3H, J = 6.8 Hz); 13C NMR (100 MHz, CDCl3 + DMSO-d6) δppm
166.7, 147.2, 144.6, 143.9, 125.1, 120.3, 114.8, 113.5, 113.4, 63.1, 30.7,
28.5, 28.1, 27.7, 24.8, 21.5, 13.1; HRMS (ESI) calcd for C25H41O4 [M
+ H]+ 405.3005, found 405.3006.
(E)-Octyl 3-(3,4-dihydroxyphenyl)acrylate (3ab):.12a,b white solid
(70 mg, 86%); mp 65−66 °C (lit.12a mp 64−66 °C); H NMR (400
1
MHz, CDCl3) δppm 7.54 (d, 1H, J = 16.0 Hz), 7.09 (s, 1H), 6.92 (d,
1H, J = 8.0 Hz), 6.85 (d, 1H, J = 8.0 Hz), 6.23 (d, 1H, J = 16.0 Hz),
4.16 (t, 2H, J = 6.8 Hz), 1.70−1.65 (m, 2H), 1.38−1.28 (br s, 10H),
0.79 (t, 3H, J = 6.8 Hz); 13C NMR (100 MHz, CDCl3 + DMSO-d6)
δppm 166.6, 147.1, 144.5, 143.9, 125.1, 120.4, 114.8, 113.5, 113.4, 63.1,
30.6, 28.1, 28.0, 27.6, 24.8, 21.4, 13.0; HRMS (ESI) calcd for
C17H25O4 [M + H]+ 293.1753, found 293.1757.
(E)-Isopropyl 3-(3,4-dihydroxyphenyl)acrylate (3ad):12c colorless
oil (43 mg, 70%); 1H NMR (400 MHz, CDCl3) δppm 7.54 (d, 1H, J =
16.0 Hz), 7.11 (s, 1H), 6.97 (d, 1H, J = 8.0 Hz), 6.81 (d, 1H, J = 8.0
Hz), 6.24 (d, 1H, J = 16.0 Hz), 5.13−5.02 (m, 1H), 1.36 (d, 6H, J =
6.0 Hz); 13C NMR (100 MHz, CDCl3 + DMSO-d6) δppm 166.0, 147.1,
144.5, 143.9, 125.1, 120.4, 114.8, 113.5, 113.4, 68.3, 22.5; HRMS
(ESI) calcd for C12H15O4 [M + H]+ 223.0970, found 223.0974.
(E)-Hexadecyl 3-(4-hydroxy-3-methoxyphenyl)acrylate (3ba):12a
were recorded in CDCl3 and calibrated to external standard 85%
H3PO4. Multiplicities are reported as follows: s (singlet), d (doublet), t
(triplet), m (multiplet), and br (broadened). Melting points were
determined using a melting point apparatus and are uncorrected. Mass
spectra were recorded using a Q-TOF mass spectrometry system, and
data were analyzed using the built-in software. Infrared (IR) spectra
were recorded in KBr using a FT-IR spectrophotometer from 4000 to
450 cm−1. Optical rotations were measured on a polarimeter at room
temperature. HPLC spectra were recorded by using a Chiralcel OD
column and n-hexane/2-propanol as the eluent.
General Procedure for the Zn(OTf)2-Catalyzed Esterification/
Amidation of Carboxylic Acids. To a stirring solution of I2 (2.0
equiv) and triphenylphosphine (2.0 equiv) in dry acetonitrile (10 mL)
was added carboxylic acid (1.0 equiv) under a N2 atmosphere, the
reaction mixture was stirred for 10 min, and then (5 mol %) of
Zn(OTf)2 was added. Stirring was continued for 30 min at 60 °C, and
then alcohol/amine (1.1 equiv) in dry acetonitrile was added. After
completion of the reaction (monitored by TLC), the mixture was
cooled to room temperature and the solvent was removed under
reduced pressure. The residue was dissolved in ethylacetate and
washed with saturated NaHCO3 followed by brine solution. The
organic layer was dried over anhydrous Na2SO4 and concentrated
white solid (93 mg, 86%); mp 65−66 °C (lit.12a mp 65−67 °C); H
1
NMR (400 MHz, CDCl3) δppm 7.56 (d, 1H, J = 16.0 Hz), 7.11 (s, 1H),
7.00 (d, 1H, J = 8.4 Hz), 6.81 (d, 1H, J = 8.4 Hz), 6.27 (d, 1H, J = 16.0
Hz), 5.73 (br s, 1H), 4.15 (t, 2H, J = 6.6 Hz), 3.89 (s, 3H), 1.68−1.65
(m, 2H), 1.27−1.23 (br s, 26H), 0.85 (t, 3H, J = 6.6 Hz); 13C NMR
(100 MHz, CDCl3) δppm 167.6, 148.7, 146.1, 144.6, 128.4, 121.9,
116.7, 113.3, 110.8, 64.8, 56.2, 32.1, 29.9, 29.6, 29.0, 26.2, 22.9, 14.3;
HRMS (ESI) calcd for C26H43O4 [M + H]+ 419.3161, found 419.3160.
(E)-Octyl 3-(4-hydroxy-3-methoxyphenyl)acrylate (3bb):12a color-
less oil (63 mg, 86%); 1H NMR (400 MHz, CDCl3) δppm 7.56 (d, 1H,
J = 16.0 Hz), 7.11 (s, 1H), 7.00 (d, 1H, J = 8.4 Hz), 6.81 (d, 1H, J =
8.4 Hz), 6.02 (d, 1H, J = 16.0 Hz), 5.73 (br s, 1H), 4.15 (t, 2H, J = 6.8
Hz), 3.89 (s, 3H), 1.70−1.63 (m, 2H), 1.36−1.23 (br s, 10H), 0.86 (t,
3H, J = 6.8 Hz); 13C NMR (100 MHz, CDCl3) δppm 167.7, 148.8,
F
dx.doi.org/10.1021/jo302502r | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
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Figure 1. Monitoring the progress of reaction by 31P NMR (A) and 13C NMR spectra (B) in CDCl3.
146.0, 144.6, 128.2, 121.9, 116.3, 113.3, 110.7, 64.8, 56.0, 31.9, 29.8,
29.3, 28.9, 26.1, 22.8, 14.2; HRMS (ESI) calcd for C18H27O4 [M + H]+
307.1909, found 307.1911.
(E)-Methyl 3-(3-hydroxy-4-methoxyphenyl)acrylate (3cc):12e col-
orless oil (48 mg, 90%); H NMR (400 MHz, CDCl3) δppm 7.60 (d,
1
1H, J = 16.0 Hz), 7.13 (s, 1H), 7.02 (d, 1H, J = 8.8 Hz), 6.83 (d, 1H, J
= 8.8 Hz), 6.29(d, 1H, J = 16.0 Hz), 5.85 (br s, 1H), 3.91 (s, 3H), 3.79
(s, 3H); 13C NMR (100 MHz, CDCl3) δppm 167.9, 148.8, 146.1, 144.9,
128.2, 122.0, 115.9, 113.2, 110.7, 56.2, 51.8; HRMS (ESI) calcd for
C11H13O4 [M + H]+ 209.0814, found 209.0812.
(E)-Isopropyl 3-(4-hydroxy-3-methoxyphenyl)acrylate (3bd):12d
1
colorless oil (45 mg, 73%); H NMR (400 MHz, CDCl3) δppm 7.49
(d, 1H, J = 16.0 Hz), 7.05 (s, 1H), 6.93 (d, 1H, J = 8.4 Hz), 6.75 (d,
1H, J = 8.4 Hz), 6.19 (d, 1H, J = 16.0 Hz), 5.78 (br s, 1H), 5.08−5.02
(m, 1H), 3.82 (s, 3H), 1.23 (d, 6H, J = 6.4 Hz); 13C NMR (100 MHz,
CDCl3) δppm 167.1, 148.7, 146.1, 144.4, 128.3, 121.8, 116.9, 113.3,
110.8, 67.8, 56.1, 22.1; HRMS (ESI) calcd for C13H17O4 [M + H]+
237.1127, found 237.1127.
(E)-Isopropyl 3-(3-hydroxy-4-methoxyphenyl)acrylate (3cd):12f
1
colorless oil (45 mg, 73%); H NMR (400 MHz, CDCl3) δppm 7.57
(d, 1H, J = 16.0 Hz), 7.13 (s, 1H), 7.02 (d, 1H, J = 8.0 Hz), 6.83 (d,
1H, J = 8.0 Hz), 6.27 (d, 1H, J = 16.0 Hz), 5.76 (br s, 1H), 5.15−5.10
(m, 1H), 3.92 (s, 3H), 1.30 (d, 6H, J = 5.6 Hz); 13C NMR (100 MHz,
CDCl3) δppm 167.0, 148.6, 146.1, 144.3, 128.4, 121.9, 117.0, 113.2,
110.7, 67.8, 56.2, 22.1; HRMS (ESI) calcd for C13H17O4 [M + H]+
237.1127, found 237.1127.
(E)-Hexadecyl 3-(3-hydroxy-4-methoxyphenyl)acrylate (3ca):12a
white solid (93 mg, 86%); mp 69−70 °C (lit.12a mp 69−70 °C); H
1
NMR (400 MHz, CDCl3) δppm 7.58 (d, 1H, J = 16.0 Hz), 7.04 (d, 1H,
J = 8.0 Hz), 7.00 (s, 1H), 6.88 (d, 1H, J = 8.0 Hz), 6.27 (d, 1H, J =
16.0 Hz), 6.04 (br s, 1H), 4.16 (t, 2H, J = 6.8 Hz), 3.89 (s, 3H), 1.69−
1.61 (m, 2H), 1.28−1.18 (m, 26H), 0.85 (t, 3H, J = 6.6 Hz); 13C
NMR (100 MHz, CDCl3) δppm 167.7, 148.2, 147.02, 144.9, 127.2,
123.2, 115.8, 115.0, 109.5, 64.8, 56.1, 32.1, 29.9, 29.5, 29.0, 26.2, 22.9,
14.3; HRMS (ESI) calcd for C26H43O4 [M + H]+ 419.3161, found
419.3162.
(E)-Hexadecyl 3-(4-hydroxyphenyl)acrylate (3da):12a white solid
(107 mg, 90%); mp 84−85 °C (lit.12a mp 84−85 °C); 1H NMR (400
MHz, CDCl3) δppm 7.61 (d, 1H, J = 16.0 Hz), 7.39 (d, 2H, J = 8.8 Hz),
6.84 (d, 2H, J = 8.8 Hz), 6.60 (br s, 1H), 6.27 (d, 1H, J = 16.0 Hz),
4.17 (t, 2H, J = 6.8 Hz), 1.69−1.65 (m, 2H), 1.31−1.23 (m, 26H),
0.85 (t, 3H, J = 6.6 Hz); 13C NMR (100 MHz, CDCl3) δppm 168.4,
158.4, 145.0, 130.2, 127.1, 116.1, 115.4, 65.1, 32.1, 29.9, 29.6, 29.5,
28.9, 26.2, 22.9, 14.2; HRMS (ESI) calcd for C25H41O3 [M + H]+
389.3056, found 389.3055.
(E)-Octyl 3-(3-hydroxy-4-methoxyphenyl)acrylate (3cb):12a color-
less oil (68 mg, 86%); 1H NMR (400 MHz, CDCl3) δppm 7.59 (d, 1H,
J = 16.0 Hz), 7.05 (d, 1H, J = 8.4 Hz), 7.00 (s, 1H), 6.89 (d, 1H, J =
8.4 Hz), 6.27 (d, 1H, J = 16.0 Hz), 5.93 (br s, 1H), 4.16 (t, 2H, J = 6.8
Hz), 3.90 (s, 3H), 1.69−1.64 (m, 2H), 1.36−1.23 (m, 10H), 0.86 (t,
3H, J = 5.6 Hz); 13C NMR (100 MHz, CDCl3) δppm 167.6, 148.2,
147.0, 144.8, 127.3, 123.2, 115.9, 114.9, 109.6, 64.8, 56.1, 32.0, 29.9,
29.3, 29.0, 26.2, 22.8, 14.3; HRMS (ESI) calcd for C18H27O4 [M + H]+
307.1909, found 307.1910.
(E)-Octyl 3-(4-hydroxyphenyl)acrylate (3db):12a yellow oil (76 mg,
1
90%); H NMR (400 MHz, CDCl3) δppm 7.61 (d, 1H, J = 16.0 Hz),
7.40 (d, 2H, J = 8.4 Hz), 7.16 (br, s, 1H), 6.86 (d, 2H, J = 8.4 Hz),
6.28 (d, 1H, J = 16.0 Hz), 4.18(t, 2H, J = 6.8 Hz), 1.71−1.64 (m, 2H),
1.37−1.23 (m, 10H), 0.86 (t, 3H, J = 6.8 Hz); 13C NMR (100 MHz,
CDCl3) δppm 168.7, 158.7, 145.4, 130.2, 126.8, 116.2, 115.0, 65.2, 31.9,
G
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29.9, 29.4, 29.3, 28.8, 26.1, 22.8, 14.2; HRMS (ESI) calcd for
C17H25O3 [M + H]+ 277.1804, found 277.1805.
Butyl 3-hydroxynaphthalene-2-carboxylate (8):13e yellow oil (59
mg, 90%); H NMR (400 MHz, CDCl3) δppm 10.43 (br, s, 1H), 8.30
1
(E)-Isopropyl 3-(4-hydroxyphenyl)acrylate (3dd):12g colorless oil
(46 mg, 73%); 1H NMR (400 MHz, CDCl3) δppm 7.59 (d, 1H, J = 16.0
Hz), 7.39 (d, 2H, J = 8.4 Hz), 6.83 (d, 2H, J = 8.8 Hz), 6.25 (d, 1H, J
= 16.0 Hz), 5.14−5.08 (m, 1H), 1.29 (d, 6H, J = 6.0 Hz); 13C NMR
(100 MHz, CDCl3) δppm 167.9, 158.6, 144.9, 130.2, 127.0, 116.2,
115.8, 68.3, 22.1; HRMS (ESI) calcd for C12H15O3 [M + H]+
207.1021, found 207.1025.
(s, 1H), 7.64 (d, 1H, J = 8.4 Hz), 7.51 (d, 1H, J = 8.4 Hz), 7.33 (t, 1H,
J = 7.6 Hz), 7.23 (s, 1H), 7.16 (t, 1H, J = 7.6 Hz), 4.27 (t, 2H, J = 6.6
Hz), 1.75−1.61 (m, 2H), 1.41−1.23 (m, 2H), 0.89 (t, 3H, J = 7.4 Hz);
13C NMR (100 MHz, CDCl3) δppm 170.0, 156.5, 137.9, 132.3, 129.5,
129.3, 127.1, 126.4, 123.9, 114.5, 111.7, 65.7, 30.7, 19.4, 13.9; HRMS
(ESI) calcd for C15H17O3 [M + H]+ 245.1178, found 245.1176.
2-(Pyridin-2-yl)ethyl 3-hydroxynaphthalene-2-carboxylate (9):
(E)-Hexadecyl 3-(3-hydroxyphenyl)acrylate (3ea):12a white solid
(107 mg, 90%); mp 83−85 °C (lit.12a mp 83−85 °C); 1H NMR (400
MHz, CDCl3) δppm 7.62 (d, 1H, J = 16.0 Hz), 7.23 (t, 1H, J = 7.8 Hz),
7.10 (d, 1H, J = 8.0 Hz), 7.02 (s, 1H), 6.87 (d, 1H, J = 8.0 Hz), 6.40
(d, 1H, J = 16.0 Hz), 4.20 (t, 2H, J = 6.8 Hz), 1.59−1.55 (m, 2H), 1.26
(br s, 26H), 0.88 (t, 3H, J = 6.6 Hz); 13C NMR (100 MHz, CDCl3)
δppm 167.9, 156.7, 145.1, 136.0, 130.2, 120.7, 118.4, 117.9, 114.9, 65.3,
32.1, 29.9, 29.8, 29.7, 29.6, 29.5, 28.9, 26.2, 25.9, 22.9, 14.3; HRMS
(ESI) calcd for C25H41O3 [M + H]+ 389.3056, found 389.3055.
(E)-Octyl 3-(3-hydroxyphenyl)acrylate (3eb):12a yellow oil (76 mg,
1
yellow solid (69 mg, 88%); mp 95−97 °C; H NMR (400 MHz,
CDCl3) δppm 10.42 (br, s, 1H), 8.57 (d, 1H, J = 0.8 Hz), 8.35 (s, 1H),
7.73 (d, 1H, J = 8.4 Hz), 7.65−7.61 (m, 2H), 7.45 (t, 1H, J = 7.4 Hz),
7.30−7.23 (m, 3H), 7.17 (t, 1H, J = 6.3 Hz), 4.79 (t, 2H. J = 6.6 Hz),
3.31 (t, 2H, J = 6.8 Hz); 13C NMR (100 MHz, CDCl3) δppm 169.7,
157.6, 156.3, 149.6, 137.9, 136.8, 132.5, 129.3, 129.2, 127.1, 126.3,
124.0, 123.7, 122.0, 114.4, 111.7, 64.8, 37.2; HRMS (ESI) calcd for
C18H16NO3 [M + H]+ 294.1130, found 294.1131.
3-Phenylprop-2-ynyl 3-hydroxynaphthalene-2-carboxylate (10):
gray solid (65 mg, 81%); mp 72−73 °C; 1H NMR (400 MHz, CDCl3)
δppm 10.27 (br, s, 1H), 8.58 (s, 1H), 7.82 (d, 1H, J = 8.4 Hz), 7.68 (d,
1H, J = 8.4 Hz), 7.52−7.48 (m, 3H), 7.36−7.31 (m, 5H), 5.25 (s, 2H);
13C NMR (100 MHz, CDCl3) δppm 169.4, 156.4, 138.2, 133.0, 132.2,
129.5, 129.2, 128.5, 127.2, 126.5, 124.2, 122.1, 113.9, 111.9, 87.6, 82.4,
54.1; HRMS (ESI) calcd for C20H15O3 [M + H]+ 303.1021, found
303.1023.
1
90%); H NMR (400 MHz, CDCl3) δppm 7.62 (d, 1H, J = 16.0 Hz),
7.24 (t, 1H, J = 8.0 Hz), 7.08 (d, 1H, J = 8.0 Hz),7.02 (s, 1H), 6.88 (d,
1H, J = 8.0 Hz), 6.41 (d, 1H, J = 16.0 Hz), 5.96 (br s, 1H), 4.20 (t, 2H,
J = 6.8 Hz), 1.61 (m, 2H), 1.79−1.66 (m, 10H), 0.87 (t, 3H, J = 6.8
Hz); 13C NMR (100 MHz, CDCl3) δppm 168.1, 156.7, 145.3, 135.9,
130.2, 120.7, 118.3, 117.9, 114.9, 65.3, 31.9, 29.4, 29.3, 28.8, 26.1, 22.8,
14.3; HRMS (ESI) calcd for C17H25O3 [M + 1]+ 277.1804, found
277.1806.
(2S,3S)-Dibutyl 2,3-dihydroxysuccinate (11):13f colorless oil (86
1
mg, 98%); H NMR (400 MHz, CDCl3) δppm 4.47 (s, 2H), 4.18 (m,
(E)-Methyl 3-(3-hydroxyphenyl)acrylate (3ec):12h yellow oil (49
4H), 3.43 (br s, 2H), 1.60 (m, 4H), 1.33 (m, 4H), 0.87 (t, 6H, J = 7.4
Hz); 13C NMR (100 MHz, CDCl3) δppm 171.8, 72.3, 66.3, 30.6, 19.1,
13.7; HRMS (ESI) calcd for C12H22O6Na+ [M + Na]+ 285.1314,
found 285.1313.
1
mg, 90%); H NMR (400 MHz, CDCl3) δppm 7.64 (d, 1H, J = 16.0
Hz), 7.24 (t, 1H, J = 8.0 Hz), 7.07 (d, 1H, J = 7.6 Hz), 7.04 (s, 1H),
6.90 (d, 1H, J = 8.0 Hz), 6.40 (d, 1H, J = 16 Hz), 3.82(s, 3H); 13C
NMR (100 MHz, CDCl3) δppm 168.3, 156.6, 145.5, 135.9, 130.3,
120.8, 118.0, 114.8, 52.2; HRMS (ESI) calcd for C10H11O3 [M + H]+
179.0708, found 179.0710.
4-(Methoxycarbonyl)phenyl 4-methylbenzenesulfonate (12):13g
1
yellow oil (31 mg, 89%); H NMR (400 MHz, CDCl3) δppm 7.90 (d,
2H, J = 8.8 Hz), 7.63 (d, 2H, J = 8.4 Hz), 7.24 (d, 2H, J = 8.0 Hz),
6.99 (d, 2H, J = 8.8 Hz), 3.83 (s, 3H), 2.37 (s, 3H); 13C NMR (100
MHz, CDCl3) δppm 166.2, 153.2, 145.9, 132.3, 131.5, 130.1, 129.1,
128.7, 122.5, 52.5, 21.9; HRMS (ESI) calcd for C15H15O5S [M + H]+
307.0640, found 307.0639.
(E)-Isopropyl 3-(3-hydroxyphenyl)acrylate (3ed):12i colorless oil
(47 mg, 75%); 1H NMR (400 MHz, CDCl3) δppm 7.58 (d,1H, J = 16.0
Hz), 7.21 (t, 1H, J = 8.0 Hz), 7.07 (d, 1H, J = 8.0 Hz), 6.97 (s, 1H),
6.84 (d, 1H, J = 8.0 Hz), 6.36 (d, 1H, J = 16.0 Hz), 5.15−5.08 (m,
1H), 1.30 (d, 6H, J = 6.0 Hz); 13C NMR (100 MHz, CDCl3) δppm
167.4, 156.6, 144.9, 136.0, 130.3, 120.7, 118.9, 117.8, 114.8, 68.5, 22.1;
HRMS (ESI) calcd for C12H15O3 [M + H]+ 207.1021, found 207.1022.
Ethyl 4-hydroxybenzoate (4):13a white solid (55 mg, 91%); mp
(S)-tert-Butyl Benzyl Pyrrolidine-1,2-dicarboxylate (13):13h yellow
oil (yield 63 mg, 89%; >99% ee); enantiomeric excess (ee) was
analyzed by chiral stationary phase HPLC using a Chiralcel OD
column (n-hexane/2-propanol = 98:2, flow rate 0.8 mL/min, λ = 227
nm), chiral compound peak was observed at tR = 23.187 min; for
racemic compound peaks were observed at tR = 17.178 min and tR =
116−118 °C (lit.13a mp 114−117 °C); H NMR (400 MHz, CDCl3)
1
δppm 7.92 (d, 2H, J = 8.4 Hz), 6.86 (d, 2H, J = 8.8 Hz), 4.85 (br s, 1H),
4.33 (q, 2H, J = 7.1 Hz), 1.36 (t, 3H, J = 7.2 Hz); 13C NMR (100
MHz, CDCl3) δppm 167.3, 160.6, 132.1, 122.7, 115.5, 61.2 14.5; HRMS
(ESI) calcd for C9H11O3 [M + H]+ 167.0708, found 167.0707.
2-(Ethoxycarbonyl)cyclopentyl 4-hydroxybenzoate (5):13b color-
less oil (69 mg, 69%); 1H NMR (400 MHz, CDCl3) δppm 7.46 (d, 2H,
J = 8.8 Hz), 6.81 (d, 2H, J = 8.4 Hz), 5.68−5.63 (m, 1H), 4.23−4.20
(q, 2H, J = 7.3 Hz), 3.27−3.25 (m, 1H), 2.17−2.00 (m, 2H), 1.96−
1.81 (m, 4H), 1.23 (t, 3H, J = 7.3 Hz); 13C NMR (100 MHz, CDCl3)
δppm 173.5, 167.3, 160.6, 131.1, 122.7, 115.5, 79.7, 61.2, 50.3, 33.2,
29.3, 23.1, 14.5; HRMS (ESI) calcd for C15H19O5 [M + H]+ 279.1232,
found 279.1234.
1
22.848 min; H NMR (400 MHz, CDCl3) δppm 7.41−7.25 (m, 5H),
5.27−5.07 (m, 2H), 4.27 (dd, 1H, J = 4.2 Hz), 3.59−3.31 (m, 2H),
2.27−2.15 (m, 2H), 1.99−1.83 (m, 2H), 1.34 (s, 9H); 13C NMR (100
MHz, CDCl3) δppm 172.8, 153.6, 135.5, 128.4, 128.3, 128.1, 127.9,
127.8, 79.6, 66.4, 59.0, 46.1, 30.7, 28.2, 23.4; HRMS (ESI) calcd for
C17H23NO4Na+ [M + Na]+ 328.1525, found 328.1528.
(S)-2-Hydroxy-2-((S)-2,2-dimethyl-1,3-dioxolane-4-yl)ethyl octa-
1
noate (14): yellow oil (97 mg, 97%); H NMR (400 MHz, CDCl3)
δppm 5.14−5.10 (m, 1H), 4.27−4.18 (m, 2H), 4.12−4.07 (m, 1H),
3.99−3.95 (m, 1H), 3.74−3.70 (m, 1H), 2.30 (t, 2H, J = 7.4 Hz),
1.60−1.53 (m, 2H), 1.37 (s, 3H), 1.29 (s, 3H), 1.25−1.20 (br s, 8H),
0.82 (t, 3H, J = 6.6 Hz); 13C NMR (100 MHz, CDCl3) δppm 173.5,
110.0, 74.6, 70.8, 65.7, 62.9, 34.3, 31.8, 29.2, 29.1, 26.3, 25.5, 25.1,
22.8, 14.2; HRMS (ESI) calcd for C15H28O5K+ [M + K]+ 327.1574,
found 327.1577.
Allyl 2-hydroxybenzoate (6):13c white solid (56 mg, 87%); mp
101−102 °C (lit.13 mp 100−102 °C); H NMR (400 MHz, CDCl3)
1
δppm 10.73 (s, 1H), 7.86 (d, 1H, J = 8.0 Hz), 7.44 (t, 1H, J = 8.0 Hz),
6.96 (d, 1H, J = 8.4 Hz), 6.86 (t, 1H, J = 7.8 Hz), 6.01 (m, 1H), 5.42
(dd, 1H, J = 17.2, 1.6 Hz), 5.30 (dd, 1H, J = 17.2, 1.6 Hz), 4.83 (dd,
2H, J = 5.6, 1.2 Hz); 13C NMR (100 MHz, CDCl3) δppm 170.0, 162.0,
136.0, 131.8, 130.1, 119.4, 119.1, 117.8, 112.6, 66.0; ; HRMS (ESI)
calcd for C10H11O3 [M + H]+: 179.0708, found 179.0706.
Benzyl 3,4,5-trihydroxybenzoate (7):13d white solid (50 mg, 65%);
mp 89−90 °C (lit.13d mp 90−90.5 °C); 1H NMR (400 MHz, CDCl3)
δppm 7.41−7.32 (m, 7H), 5.14 (s, 2H); 13C NMR (100 MHz, CDCl3)
δppm 166.4, 149.3, 137.7, 136.7, 136.1, 129.1, 128.8, 128.5, 128.3, 126.2,
110.0, 67.1; HRMS (ESI) calcd for C14H13O5 [M + H]+: 261.0763,
found 261.0765.
2-(5-((Benzyloxy)carbonyl)pentyloxy)benzoic acid (15): yellow
1
solid (71 mg, 96%); mp 82−83 °C; H NMR (400 MHz, CDCl3)
δppm 10.83 (s, 1H), 7.82 (d, 1H, J = 8.0 Hz), 7.45 (t, 1H, J = 7.0 Hz),
7.38−7.32 (m, 5H), 6.98 (d, 1H, J = 8.4 Hz), 6.87 (d, 1H, J = 7.0 Hz),
5.12 (s, 2H), 4.33 (t, 2H, J = 6.4 Hz), 2.40 (t, 2H, J = 7.4 Hz), 1.83−
1.78 (m, 2H), 1.76−1.72 (m, 2H), 1.52−1.4 (m, 2H); 13NMR (100
MHz, CDCl3) δppm 173.3, 170.2, 156.6, 135.9, 135.7, 129.8, 128.6,
128.3, 128.2, 119.1, 117.6, 112.5, 66.2, 65.1, 34.1, 29.7, 28.3, 25.5, 24.5;
IR cm−1: 3083, 2985, 1731, 1698, 1614, 1524, 1416; HRMS (ESI)
calcd for C20H23O5 [M + H]+ 343.1545, found 343.1543.
H
dx.doi.org/10.1021/jo302502r | J. Org. Chem. XXXX, XXX, XXX−XXX

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((4S,5S)-5-((Benzyloxy)methyl)-2,2-dimethyl-1,3-dioxolan-4-yl)-
methyl 4-methylbenzoate (16): colorless oil (129 mg, 95%); 1H
NMR (400 MHz, CDCl3) δppm 7.91 (d, 2H, J = 8.0 Hz), 7.40−7.35
(m, 2H), 7.32−7.18 (m, 5H), 4.58 (s, 2H), 4.52 (dd, 1H, J = 3.6 Hz),
4.36 (dd, 1H, J = 5.2 Hz), 4.22−4.18 (m, 1H), 4.16−4.12 (m, 1H),
3.69−3.61 (m, 2H), 2.60 (s, 3H), 1.44 (s, 6H); 13C NMR (100 MHz,
CDCl3) δppm 167.3, 140.6, 137.9, 132.3, 131.8, 130.8, 129.3, 128.6,
127.9, 127.8, 125.9, 110.1, 76.9, 76.8, 73.8, 70.5, 64.4, 27.2, 21.9;
HRMS (ESI) calcd for C22H26O5Na+ [M + Na]+ 393.1678, found
393.1678.
4-[tert-Butyldimethylsilyl)oxy]butyl 3-hydroxynapthalene-2-car-
boxylate (17): light yellow solid (96 mg, 97%); mp 118−120 °C;
1H NMR (400 MHz, CDCl3) δppm 8.57 (s, 1H), 7.93 (d, 1H, J = 8.4
Hz), 7.78 (d, 1H, J = 8.4 Hz), 7.55 (t, 2H, J = 7.6 Hz), 7.43 (s, 2H),
4.96−4.90 (m, 2H), 2.67−2.57 (m, 2H), 1.86−1.78 (m, 2H), 1.47−
1.39 (m, 2H), 0.89 (s, 9H), 0.05 (s, 6H); 13C NMR (100 MHz,
CDCl3) δppm 170.4, 160.5, 149.4, 138.8, 136.8, 129.8, 129.2, 127.2,
125.6, 115.7, 110.4, 63.3, 56.1, 29.5, 28.7, 26.7, 26.3, 26.2, 18.6, 15.1;
HRMS (ESI) calcd for C21H31O4Si [M + H]+ 375.1992, found
375.1991.
7.56−7.46 (m, 2H), 5.58−5.53 (m, 1H), 4.15 (q, 2H, J = 7.2 Hz),
2.97−2.92 (m, 1H), 2.18−2.09 (m, 2H), 1.58−1.78 (m, 4H), 1.23 (t,
3H, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3) δppm 174.1, 165.4,
131.8, 131.2, 129.4, 128.2, 79.4, 60.9, 50.7, 32.8, 29.0, 23.7, 14.3;
HRMS (ESI) calcd for C15H17BrO4Na+ [M + Na]+ 363.0208, found
363.0208.
3-Phenylprop-2-ynyl 4-methylbenzoate (25): white solid (87 mg,
95%); mp 80−82 °C; 1H NMR (400 MHz, CDCl3) δppm 7.90 (d, 2H, J
= 8.0 Hz), 7.39−7.36 (m, 2H), 7.31 (t, 2H, J = 7.4 Hz), 7.22−7.20 (m,
1H), 7.17−7.13 (m, 2H), 5.03 (s, 2H), 2.54 (s, 3H); 13C NMR (100
MHz, CDCl3) δppm 166.9, 140.7, 132.5, 132.1, 131.9, 131.0, 129.1,
128.9, 128.5, 125.9, 122.4, 86.6, 83.4, 53.2, 21.9; HRMS (ESI) calcd
for C17H14O2Na+ [M + Na]+ 273.0891, found 273.0891.
(E)-Octyl 3-(4-methoxyphenyl)acrylate (26):14c yellow oil (76 mg,
1
93%); H NMR (400 MHz, CDCl3) δppm 7.63 (d, 1H, J = 16.0 Hz),
7.46 (d, 2H, J = 8.4 Hz), 6.89 (d, 2H, J = 8.4 Hz), 6.31 (d, 1H, J = 16.0
Hz), 4.18 (t, 2H, J = 6.6 Hz), 3.81 (s, 3H), 1.72−1.65 (m, 2H), 1.28
(br s, 10H), 0.88 (t, 3H, J = 5.8 Hz); 13C NMR (100 MHz, CDCl3)
δppm 167.4, 161.4, 144.2, 129.7, 127.2, 115.8, 114.3, 64.5, 55.3, 31.9,
29.3, 29.2, 29.1, 28.9, 28.8, 26.0, 22.7, 14.1; HRMS (ESI) calcd for
C18H26O3 [M + H]+ 291.1960, found 291.1961.
2,2,10,10-Tetramethyl-5-(phenoxymethyl)-3,3,9,9-tetraphenyl-
Ethyl palmitate (27):15a clear oil (55 mg, 98%); H NMR (400
1
4,8-dioxa-3,9-disilaundecan-6-yl octanoate (18): clear viscous oil
1
(208 mg, 75%); H NMR (400 MHz, CDCl3) δppm 7.65−7.62 (m,
MHz, CDCl3) δppm 4.05 (q, 2H, J = 7.0 Hz), 2.21 (t, 2H, J = 7.6 Hz),
1.56−1.51 (m, 2H), 1.21−1.15 (br s, 27H), 0.81 (t, 3H, J = 6.6 Hz);
13NMR (100 MHz, CDCl3) δppm 174.0, 60.2, 34.5 32.1, 29.9, 29.8,
29.6, 29.5, 29.4, 29.3, 25.2, 22.9, 14.4, 14.2; HRMS (ESI) calcd for
C18H37O2 [M + H]+ 285.2794, found 285.2790.
10H), 7.42−7.30 (m, 10H), 7.28−7.23 (m, 5H), 5.34−5.30 (m, 1H),
4.58 (dd, 2H, J = 11.6, 11.6 Hz), 3.88−3.81 (m, 2H), 3.78−3.74 (m,
1H), 2.21 (t, 2H, J = 7.4 Hz), 1.60−1.53 (m, 2H), 1.25 (br s, 10H),
1.02 (s, 18H), 0.86 (t, 3H, J = 6.4 Hz); 13C NMR (100 MHz, CDCl3)
δppm 173.3, 138.7, 135.8, 135.7, 133.6, 129.9, 128.4, 127.7, 78.4, 73.4,
63.2, 62.3, 34.5, 31.8, 29.9, 29.3, 29.1, 27.0, 25.1, 22.8, 19.4, 14.3;
HRMS (ESI) calcd for C51H66O5Si2Na+ [M + Na]+ 837.4346, found
837.4347.
Isopropyl palmitate (28):15b clear oil (45 mg, 77%); 1H NMR (400
MHz, CDCl3) δppm 5.00−4.94 (m, 1H), 2.22 (t, 2H, J = 7.4 Hz),
1.59−1.55 (m, 2H), 1.25−1.22 (br s, 24H), 1.19 (d, 6H, J = 6.4 Hz),
0.84 (t, 3H, J = 6.6 Hz); 13C NMR (100 MHz, CDCl3) δppm 172.7,
66.7, 34.2, 31.5, 29.3, 29.1, 29.0, 28.9, 28.7, 24.6, 22.3, 21.4, 13.7;
HRMS (ESI) calcd for C19H39O2 [M + H]+ 299.2950, found 299.2955.
3-(Trityloxy)propyl 3-nitrobenzoate (19): white solid (137 mg,
98%); mp 85−87 °C; 1H NMR (400 MHz, CDCl3) δppm 8.64 (s, 1H),
8.23 (d, 1H, J = 8.0 Hz), 8.16 (d, 1H, J = 7.6 Hz), 7.42−7.34 (m, 6H),
7.21−7.09 (m, 10H), 4.45 (t, 2H, J = 6.2 Hz), 3.22 (t, 2H, J = 5.8 Hz),
2.00 (m, 2H); 13C NMR (100 MHz, CDCl3) δppm 164.4, 148.2, 147.0,
144.5, 144.1, 135.3, 132.1, 129.6, 128.8, 128.7, 128.0, 127.9, 127.8,
127.3, 127.2, 127.0, 126.9, 124.5, 86.7, 63.3, 59.7, 29.3; HRMS (ESI)
calcd for C29H25NO5Na+ [M + Na]+ 490.1630, found 490.1633.
tert-Butyl octanoate (29):15c clear liquid (40 mg, 20%); H NMR
1
(400 MHz, CDCl3) δppm 2.50 (t, 2H, J = 7.3 Hz), 1.76−1.66 (m, 2H),
1.37−1.24 (br s, 8H), 0.98 (s, 9H), 0.85 (t, 3H, J = 6.0 Hz); 13C NMR
(100 MHz, CDCl3) δppm 172.0, 74.8, 63.9, 34.0, 31.6, 29.1, 28.9, 28.3,
25.0, 22.6, 19.1, 14.0; HR-MS m/z calcd. for C12H24O2[M + H]+
201.1855, found 201.1850.
Benzhydryl acetate (20):13i yellow oil (115 mg, 61%); H NMR
1
(Z)-3,4,5-Trimethoxybenzyl octadec-8-enoate (30): yellow oil (80
mg, 98%); 1H NMR (400 MHz, CDCl3) δppm 6.51 (s, 2H), 5.26−5.25
(m, 2H), 4.96 (s, 2H), 3.78 (s, 6H), 3.75 (s, 3H), 2.30−2.26 (m, 2H),
1.93−1.92 (m, 4H), 1.57−1.55 (m, 2H), 1.22−1.18 (br s, 20H), 0.80
(t, 3H, J = 6.4 Hz); 13C NMR (100 MHz, CDCl3) δppm 173.7, 153.4,
131.8, 130.1, 129.8, 105.5, 66.4, 60.9, 56.2, 34.4, 32.0, 31.0, 29.8, 29.6,
29.4, 29.3, 27.3, 25.1, 22.8, 14.2; HRMS (ESI) calcd for C28H46O5Na+
[M + Na]+ 485.3243, found 485.3245.
(400 MHz, CDCl3) δppm 7.20 (t, 4H, J = 7.2 Hz), 7.15 (d, 4H, J = 7.2
Hz), 7.10 (t, 2H, J = 7.0 Hz), 6.77 (s, 1H), 1.96 (s, 3H); 13NMR (100
MHz, CDCl3) δppm 169.9, 140.3, 128.5, 127.9, 127.1, 76.9, 21.2;
HRMS (ESI) calcd for C15H14O2Na+ [M + Na]+: 249.0891, found
249.0889.
(R)-1-Phenylethyl 2-phenylacetate (21):13j yellow oil (yield 55 mg,
70%; >99% ee); enantiomeric excess (ee) was analyzed by chiral
stationary phase HPLC using a Chiralcel OD column (n-hexane/2-
propanol = 97:3, flow rate 0.8 mL/min, λ = 254 nm), chiral compound
peak observed at tR = 7.231 min; for racemic compound peaks
(1S,2R,5S)-2-Isopropyl-5-methylcyclohexyl nicotinate (31):15d
1
yellow oil (78 mg,73%); H NMR (400 MHz, CDCl3) δppm 9.24 (s,
1H), 8.77 (d, 1H, J = 4.8 Hz), 8.31 (d, 1H, J = 8.0 Hz), 7.40 (t, 1H, J =
6.4 Hz), 5.00−4.94 (m, 1H), 2.27−2.11 (m, 1H), 2.00−1.89 (m, 2H),
1.77−1.73 (m, 2H), 1.65−1.55 (m, 2H), 1.19−1.10 (m, 2H), 0.95 (d,
6H, J = 10.0 Hz), 0.81−0.79 (m, 3H); 13C NMR (100 MHz, CDCl3)
δppm 164.6, 153.0, 150.7, 137.0, 126.6, 123.2, 75.4, 47.1, 40.8, 34.1,
26.4, 23.5, 21.9, 20.6, 16.4; HRMS (ESI) calcd for C16H24NO2 [M +
H]+ 262.1807, found 262.1805.
1
observed at tR = 7.189 min and tR = 7.975 min; H NMR (400 MHz,
CDCl3) δppm 7.32−7.22 (m, 10H), 5.88 (q, 1H, J = 6.6 Hz), 3.62 (s,
2H), 1.50 (d, 3H, J = 6.6 Hz); 13NMR (100 MHz, CDCl3) δppm 170.8,
141.6, 134.1, 129.3, 128.6, 128.5, 127.9, 127.1, 126.1, 72.8, 41.7, 22.2;
HRMS (ESI) calcd for C16H17O2 [M + H]+ 241.1229, found 241.1227.
3-Phenylprop-2-ynyl benzoate (22):14a yellow oil (93 mg, 96%);
1H NMR (400 MHz, CDCl3) δppm 8.10 (d, 2H, J = 8.4 Hz), 7.54 (t,
2H, J = 7.8 Hz), 7.48−7.52 (m, 4H), 7.32−7.26 (m, 2H), 5.14 (s, 2H);
13C NMR (100 MHz, CDCl3) δppm 165.9, 133.3, 132.0, 129.9, 129.7,
128.8, 128.5, 128.4, 122.3, 86.7, 83.2, 53.3; HRMS (ESI) calcd for
C16H12O2Na+ [M + Na]+ 259.0735, found 259.0735.
Butyl quinoline-2-carboxylate (32):15e yellow oil (64 mg, 96%);
1H NMR (400 MHz, CDCl3) δppm 8.24 (d, 1H, J = 8.8 Hz), 8.20 (d,
1H, J = 8.8 Hz), 8.07 (d, 1H, J = 8.8 Hz), 7.77 (d, 1H, J = 8.4 Hz),
7.69 (t, 1H, J = 7.7 Hz), 7.54 (t, 1H, J = 7.6 Hz), 4.42 (t, 2H, J = 6.8
Hz), 1.81−1.72 (m, 2H), 1.47−1.35 (m, 2H), 0.91 (t, 3H, J = 7.4 Hz);
13C NMR (100 MHz, CDCl3) δppm 165.2, 148.1, 147.4, 137.0, 130.5,
3-Phenylprop-2-ynyl 4-nitrobenzoate (23):14b creamy solid (82
mg, 98%); mp 61−62 °C (lit.13j mp 60−62 °C); 1H NMR (400 MHz,
CDCl3) δppm 8.17 (d, 2H, J = 8.8 Hz), 8.14 (d, 2H, J = 8.8 Hz), 7.36
(d, 2H, J = 7.6 Hz), 7.21 (t, 3H, J = 7.6 Hz), 5.10 (s, 2H); 13C NMR
(100 MHz, CDCl3) δppm 164.2, 150.8, 135.1, 132.1, 131.1, 129.1,
128.5, 123.7, 122.0, 87.4, 82.5, 54.3; HRMS (ESI) calcd for
C16H11NO4 Na+ [M + Na]+ 304.0586, found 304.0587.
130.0, 129.0, 128.3, 127.3, 120.8, 65.8, 30.6, 19.0, 13.6; HRMS (ESI)
calcd for C14H16NO2 [M + H]+ 230.1181, found 230.1185.
(3S,8S,9S,10R,13R,14S,17R)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-
Tetradecahydro-10,13-dimethyl-17-((R)-6-methylheptan-2-yl)-1H-
cyclopenta[a]phenanthren-3yl 2-naphthoate (33):15f crystalline
1
white solid (113 mg, 72%); mp 143−145 °C; H NMR (400 MHz,
2-(Ethoxycarbonyl)cyclopentyl 4-bromobenzoate (24): clear oil
CDCl3) δppm 8.60 (s, 1H), 8.06 (d, 1H, J = 8.4 Hz), 7.94 (d, 2H, J =
8.0 Hz), 7.86 (d, 1H, J = 8.4 Hz), 7.54 (t, 2H, J = 9.4 Hz), 5.51−5.43
(65 mg, 76%); 1H NMR (400 MHz, CDCl3) δppm 7.86−7.79 (m, 2H),
I
dx.doi.org/10.1021/jo302502r | J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Article
(m, 1H), 4.94−4.92 (m, 1H), 2.52 (d, 2H, J = 8.0 Hz), 2.03−1.74 (m,
4H), 1.57−1.42 (m, 4H), 1.34−1.11 (m, 18H), 1.08 (s, 3H), 0.92 (d,
3H, J = 6.4 Hz), 0.87 (d, 6H, J = 6.4 Hz), 0.69 (s, 3H); 13C NMR (100
MHz, CDCl3) δppm 166.4, 139.9, 135.7, 132.8, 131.1, 129.6, 128.3,
128.0, 126.8, 125.6, 123.1, 75.0, 56.9, 56.4, 50.3, 42.6, 40.0, 39.8, 38.5,
37.3, 36.9, 36.4, 36.1, 35.2, 32.1, 28.5, 28.2, 24.9, 24.5, 24.1, 23.1, 22.8,
21.3, 19.6, 19.0, 12.1; HRMS (ESI) calcd for C38H52O2 [M]+
540.3967, found 540.3967.
CDCl3) δppm 168.9, 154.1, 146.7, 137.5, 130.4, 129.8, 128.5, 128.0,
127.9, 120.0, 57.2, 49.9, 32.6, 31.0; HRMS (ESI) calcd for C14H18N3O
[M + H]+ 244.1450, found 244.1453.
(4-Hydroxyphenyl)(piperidin-1-yl)methanone (42):16g crystalline
1
white solid (56 mg, 75%); mp 215−216 °C; H NMR (400 MHz,
CDCl3) δppm 8.25 (d, 2H, J = 8.4 Hz), 7.92 (d, 2H, J = 8.4 Hz), 4.75
(br s, 1H), 4.42 (br s, 2H), 3.45 (br s, 2H), 1.90−1.23 (m, 6H); 13C
NMR (100 MHz, CDCl3) δppm 169.5, 158.3, 128.3, 126.4, 114.6, 47.5,
33.3, 28.9, 25.5, 24.0; HRMS (ESI) calcd for C12H15NO2 [M + H]+
206.1181, found 206.1180.
Hexadecyl 3-(1H-indol-3-yl)propanoate (34): crystalline white
1
solid (106 mg, 97%); mp 80−82 °C; H NMR (400 MHz, CDCl3)
(4-Nitrophenyl)(piperidin-1-yl)methanone (43):16h crystalline yel-
low solid (55 mg, 78%); mp 121−122 °C (lit.16g mp 120.9−122.3 °C);
1H NMR (400 MHz, CDCl3) δppm 8.27 (d, 2H, J = 8.0 Hz), 7.56 (d,
2H, J = 8.0 Hz), 3.73 (br s, 2H), 3.23 (br s, 2H), 1.72−1.54 (m, 4H),
1.40−1.05 (m, 2H); 13C NMR (100 MHz, CDCl3) δppm 167.0, 147.5,
142.3, 127.3, 123.2, 47.9, 42.4, 33.3, 25.8, 23.8; HRMS (ESI) calcd for
C12H15N2O3 [M + H]+ 235.1083, found 235.1086.
δppm 8.02 (br s, 1H), 7.61 (d, 1H, J = 8.0 Hz), 7.35 (d, 1H, J = 8.0 Hz),
7.19 (t, 1H, J = 7.4 Hz), 7.12 (t, 1H, J = 7.4 Hz), 7.01 (s, 1H), 4.06 (t,
2H, J = 6.8 Hz), 3.10 (t, 2H, J = 7.4 Hz), 2.72 (t, 2H, J = 7.8), 1.60−
1.53 (m, 4H), 1.29−1.22 (br s, 24H), 0.88 (t, 3H, J = 6.6 Hz); 13C
NMR (100 MHz, CDCl3) δppm 173.8, 136.5, 127.3, 122.0, 121.6,
119.3, 118.8, 114.9, 111.3, 63.0, 35.2, 32.9, 32.1, 29.9, 29.7, 29.6, 29.5,
29.4, 28.8, 26.1, 25.9, 22.9, 20.9, 14.3; HRMS (ESI) calcd for
C27H43NO2Na+ [M + Na]+ 436.3191, found 436.3190.
Isopropyl 3-(1H-indol-3-yl)propanoate (35): colorless oil (49 mg,
80%); 1H NMR (400 MHz, CDCl3) δppm 8.03 (br s, 1H), 7.60 (d, 1H,
J = 8.0 Hz), 7.30 (d, 1H, J = 8.0 Hz), 7.15 (t, 1H, J = 7.4 Hz), 7.10 (t,
1H, J = 7.4 Hz), 6.94 (s, 1H), 5.04−4.98 (m, 1H), 3.08 (t, 2H, J = 7.8
Hz), 2.67 (t, 2H, J = 7.8 Hz), 1.20 (d, 6H, J = 6.4 Hz); 13C NMR (100
MHz, CDCl3) δppm 173.3, 136.4, 127.3, 122.0, 121.6, 119.3, 118.8,
114.9, 111.3, 67.8, 35.5, 21.9, 20.8; HRMS (ESI) calcd for C14H18NO2
[M + H]+ 232.1338, found 232.1339.
ASSOCIATED CONTENT
■
S
* Supporting Information
1
HRMS and H and 13C NMR spectra for all new compounds.
This information is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Tel: 03 61258 2325. Fax: 03 61258 2349. E-mail: dmanna@
iitg.ernet.in.
■
N-Butyl-4-hydroxybenzamide (36):16a clear oil (60 mg, 85%); H
1
NMR (400 MHz, CDCl3) δppm 7.54 (d, 2H, J = 8.8 Hz), 6.79 (d, 2H, J
= 8.8 Hz), 6.42 (br s, 1H), 3.32 (q, 2H, J = 7.0 Hz), 1.53−1.45 (m,
2H), 1.32−1.24 (m, 2H), 0.83 (t, 3H, J = 7.2 Hz); 13C NMR (100
MHz, CDCl3) δppm 168.5, 160.7, 128.9, 125.5, 115.8, 40.1, 31.8,
20.3,13.9; HRMS (ESI) calcd for C11H16NO2 [M + H]+ 194.1181,
found 194.1179.
Notes
The authors declare no competing financial interest.
N-Butyl-3-methylbenzamide (37):16b yellow oil (66 mg, 94%); H
1
ACKNOWLEDGMENTS
■
NMR (400 MHz, CDCl3) δppm 7.27 (d, 2H, J = 7.2 Hz), 7.17−7.11(m,
2H), 6.16 (br s, 1H), 3.34 (q, 2H, J = 7.0 Hz), 2.38 (s, 3H), 1.55−1.50
(m, 2H), 1.38−1.33 (m, 2H), 0.93 (t, 3H, J = 7.4 Hz); 13C NMR (100
MHz, CDCl3) δppm 170.3, 136.9, 135.8, 130.9, 129.6, 126.7, 125.7,
39.6, 31.7, 20.2, 19.7, 13.8; HRMS (ESI) calcd for C12H18NO [M +
H]+ 192.1388, found 192.1388.
We gratefully acknowledge DBT (BT/PR13309/GBD/27/
244/2009) and CSIR (02-0090/12/EMR-II), Government of
India, for financial support.
REFERENCES
■
N-Butyl-4-nitrobenzamide (38):16c white solid (65 mg, 98%); mp
(1) (a) Carey, J. S.; Laffan, D.; Thomson, C.; Williams, M. T. Org.
Biomol. Chem. 2006, 4, 2337−2347. (b) Dugger, R. W.; Ragan, J. A.;
Ripin, D. H. B. Org. Process Res. Dev. 2005, 9, 253−258.
139−140 °C (lit.16b mp 135−140 °C); H NMR (400 MHz, CDCl3)
1
δppm 8.24 (d, 2H, J = 8.8 Hz), 7.90 (d, 2H, J = 8.4 Hz), 6.38 (br s, 1H),
3.44 (q, 2H, J = 6.6 Hz), 1.63−1.56 (m, 2H), 1.42−1.34 (m, 2H), 0.93
(t, 3H, J = 7.2 Hz); 13C NMR (100 MHz, CDCl3) δppm 165.8, 149.5,
140.6, 128.3, 123.7, 40.3, 31.6, 20.2, 13.8; HRMS (ESI) calcd for
C11H15N2O3 [M + H]+: 223.1083, found 223.1080.
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(4) (a) Sancho, R.; Lucena, C.; Macho, A.; Calzado, M. A.; Blanco-
Molina, M.; Minassi, A.; Appendino, G.; Munoz, E. Eur. J. Immunol.
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2763−2767. (d) Natarajan, K.; Singh, S.; Burke, T. R.; Grunberger, D.;
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Naturwissenschaften 1989, 76, 426−427. (f) Orita, A.; Tanahashi, C.;
Kakuda, A.; Otera, J. J. Org. Chem. 2001, 66, 8926−8934. (g) Ishihara,
2-Phenyl-N-((pyridin-2-yl)methyl)acetamide (39):16d brown color
solid (79 mg, 95%); mp 105−106 °C (lit.16c mp 105−106 °C); H
1
NMR (400 MHz, CDCl3) δppm 8.46 (d, 1H, J = 4.8 Hz), 7.62 (t, 1H, J
= 7.8 Hz), 7.37−7.27 (m, 5H), 7.20 (d, 1H, J = 7.6 Hz), 7.16 (t, 1H, J
= 6.2 Hz), 6.76 (br s, 1H), 4.52 (d, 2H, J = 4.8 Hz), 3.65 (s, 2H); 13C
NMR (100 MHz, CDCl3) δppm 171.2, 156.7, 148.7, 136.6, 135.0,
129.2, 128.6, 126.9, 122.1, 121.6, 44.5, 43.3; HRMS (ESI) calcd for
C14H15N2O [M + H]+ 227.1184, found 227.1188.
N-Benzylquinoline-2-carboxamide (40):16e crystalline yellow solid
(72 mg, 95%); mp 122−123 °C (lit.16d mp 123−124 °C); H NMR
1
(400 MHz, CDCl3) δppm 8.63 (br s, 1H), 8.35 (d, 1H, J = 8.4 Hz), 8.30
(d, 1H, J = 8.4 Hz), 8.01 (d, 1H, J = 8.4 Hz), 7.86 (d, 1H, J = 8.4 Hz),
7.3 (t, 1H, 7.8 Hz), 7.60 (t, 1H, J = 7.6 Hz), 7.41 (d, 2H, J = 7.2 Hz),
7.36 (t, 2H, J = 7.4 Hz), 7.30 (d, 1H, J = 7.2 Hz), 4.74 (d, 2H, J = 6.0
Hz); 13C NMR (100 MHz, CDCl3) δppm 164.5, 149.7, 146.5, 138.4,
137.5, 130.1, 129.7, 129.3, 128.7, 127.8, 127.5, 119.0, 43.6; HRMS
(ESI) calcd for C17H15N2O [M + H]+ 263.1184, found 263.1186.
N-(2-(Dimethylamino)ethyl)quinoline-2-carboxamide (41):16f
colorless solid (69 mg, 98%); mp 88−89 °C (lit.16c mp 87−89 °C);
1H NMR (400 MHz, CDCl3) δppm 8.26 (d, 1H, J = 8.4 Hz), 8.09 (d,
1H, J = 8.4 Hz), 7.86 (d, 1H, J = 8.0 Hz), 7.76 (t, 1H, J = 7.6 Hz), 7.74
(d, 1H, J = 7.6 Hz), 7.61 (t, 1H, J = 7.6 Hz), 6.54 (br s, 1H), 4.24−
4.18 (m, 2H), 3.56−3.48 (m, 2H), 2.05 (s, 6H); 13C NMR (100 MHz,
J
dx.doi.org/10.1021/jo302502r | J. Org. Chem. XXXX, XXX, XXX−XXX

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NOTE ADDED AFTER ASAP PUBLICATION
■
The version published February 6, 2013 contained bond angle
errors in the toc/abstract graphic, Tables 3 and 4, and
Supporting Information; the correct versions reposted February
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