Convergent, regiospecific synthesis of quinolines from o- aminophenylboronates

Article abstract of DOI:10.1021/ol8016726

(Chemical Equation Presented) A direct convergent two-component synthesis of quinolines from αβ-unsaturated ketones and o-aminophenylboronic acid derivatives is reported. The reaction is regiocomplementary to the traditional Skraup-Doebner-Von Miller synthesis and proceeds under basic rather than strongly acidic conditions. Quinolines substituted in the benzenoid ring can be accessed by using substituted o-aminophenylboronates prepared by direct palladium-catalyzed borylation of the corresponding o-bromoanilines.

Full text of DOI:10.1021/ol8016726

Article
pubs.acs.org/joc
One-Pot Phosphine-Catalyzed Syntheses of Quinolines
San Khong and Ohyun Kwon*
Department of Chemistry and Biochemistry, University of California, Los Angeles, 607 Charles E. Young Drive East, Los Angeles,
California 90095-1569, United States
S
* Supporting Information
ABSTRACT: In this study we developed an efficient one-pot
procedure for the preparation of 3-substituted and 3,4-
disubstituted quinolines from stable starting materials
(activated acetylenes reacting with o-tosylamidobenzaldehydes
and o-tosylamidophenones, respectively) under mild con-
ditions. The reaction appears to operate under a general base
catalysis mechanism, instigated by the β-phosphonium enoate
α-vinyl anion generated in situ through nucleophilic addition of PPh3 to the activated alkyne. Michael addition of the
deprotonated tosylamides to the activated alkynes and subsequent rapid aldol cyclization led to the formation of labile N-
tosyldihydroquinoline intermediates. Driven by aromatization, detosylation of the dihydroquinoline intermediates occurred
readily in the presence of dilute aqueous HCl to give the final quinoline products.
Scheme 1. Friedlander Quinoline Synthesis
INTRODUCTION
̈
■
The quinoline unit is found in a wide variety of pharmacolog-
ically and biologically active compounds.1 Not surprisingly,
quinoline derivatives continue to attract the attention of
medicinal chemists, and strategies for accessing new scaffolds of
quinoline derivatives are of great interest to synthetic chemists.
In recent years, many transition metal-catalyzed processes have
been developed for mild and efficient syntheses of quinolines.2
Notably, the number of conventional metal-free paths for
quinoline syntheses have also been growing.3 Several classical
methods for targeting the quinoline core, including the Skraup,
For the synthesis of 3-substituted quinolines in particular, in
2009 Verpoort reported a one-pot methodology to avoid self-
condensation of the aminobenzaldehyde by employing an
aminobenzyl alcohol as a precursor; they also prevented self-
condensation of the other coupling partner through late
introduction of the strong base.6 This approach, however,
requires an elevated temperature and a stoichiometric amount
of the strong base. More recently, Li reported an alternative
approach to 3-substituted quinolines by coupling alkynones
with aminobenzaldehyde in the presence of a catalytic amount
of Lewis acid as the activator.7 Despite the use of a mild Lewis
acid, this approach requires thermal assistance, long reaction
times, and the use of unstable aminobenzaldehydes. The
synthesis of 3-substituted quinolines is also generally difficult
when using other methods.4a,8 Herein, we report a simple and
efficient one-pot phosphine-catalyzed procedure for the
synthesis of 3-substituted quinolines under mild conditions
from stable starting materials.
Doebner−von Miller, Friedlander, Pfitzinger, Conrad−Lim-
̈
pach, and Combes syntheses,4a,b remain relevant today for the
preparation of quinoline-containing materials, ligands, and
pharmaceutical agents.4a Nevertheless, such reactions are often
performed under unfavorably harsh conditions, typically with
either a strong acid or base and thermal assistance.4a,b For
example, the Friedlander quinoline synthesis, a particularly
̈
powerful tool for generating quinoline core systems, is
performed at high temperature in the presence of either a
strong acid or base.4 In addition to unattractive reaction
conditions, the instability of the coupling partners in the
Friedlander quinoline synthesis further limits its synthetic
̈
potential.4,5 In particular, when the synthesis of 3-substituted
quinolines is attempted using Friedlander methodology (R2 =
̈
R3 = H), self-condensation of both aldehyde coupling partners
can lower the reaction efficiency and complicate the product’s
purification (Scheme 1).6 To prevent self-condensation of
We developed the title quinoline synthesis during an
expansion of our original double-Michael reaction.9,10 We
attempted to develop alternative modes of this tandem reaction
to generate a variety of heterocyclic scaffolds (Scheme 2). The
double-Michael reaction requires two pronucleophilic groups in
one of the starting materials to undergo the two successive
Michael additions. Replacing one pronucleophilic group with
aminobenzaldehydes in Friedlander methodology, several
̈
classical approaches, namely the Borsche, Pfitzinger, and
Niemantowski quinoline syntheses, have been developed
employing alternative starting materials.4 In a recent report,
for example, aminobenzaldehydes were generated in situ from
corresponding nitrobenzaldehydes and subsequently used in
Received: July 31, 2012
the Friedlander synthesis.5
̈
© XXXX American Chemical Society
A
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Scheme 2. 3-Substituted Quinoline Synthesis Versus Double-Michael Reaction
an electrophilic group would alter the nature of the reaction to
a cascade of nucleophilic additions (Michael addition followed
by an aldol reaction, or vice versa). The presence of an N-tosyl
group in the substrates not only activated the pronucleophile
but also completely inhibited the self-condensation normally
2a to oligomerize in the presence of the nucleophilic catalyst
PPh3, thereby explaining the poor reaction yield. Therefore, we
tested the slow addition (syringe pump, 2 h) of 2a to the
reaction mixture, but the yield was unchanged (entry 2). We
observed (1H NMR spectra) almost no oligomerization in a
mixture of 2a and 20 mol % PPh3 after several days. Increasing
the reaction time from 17 to 24 h barely increased the reaction
yield (entry 3), implying that a significantly longer time might
be required for the reaction to reach completion. Surprisingly,
the addition of a stoichiometric amount of PPh3 did not
accelerate the reaction; indeed, it completely shut down the
observed for Friedlander substrates. In fact, N-tosylated o-
̈
aminobenzaldehydes are bench-stable at room temperature for
months of storage without any deterioration. The activated
acetylenes are likewise very stable under storage and during the
reaction.
1
reaction and yielded no product (entry 4). H NMR spectra
RESULTS AND DISCUSSION
■
revealed the complete destruction of 2a within 5 min in the
presence of a stoichiometric amount of PPh3. When the
concentration of 1a was increased to 0.2 M or greater, the
reaction yield improved significantly (entries 1 and 5−7).
Among the solvents tested for the reaction, MeCN provided
the highest yield (entry 8); reactions performed in DMSO and
DCM (data not shown) provided product yields lower than
those obtained in THF and MeCN. The reactions of 1a in THF
at concentrations of 0.4 and 0.2 M resulted in the same yields
(entries 6 and 7). Because 1a is not soluble in MeCN at a
concentration of 0.4 M, we considered the optimal concen-
tration of 1a in MeCN to be 0.2 M. Decreasing the loading of
the catalyst PPh3 to 10 mol % improved the reaction yield by
4% (entry 10). The reaction yield decreased, however, after
decreasing the catalyst loading of 5 mol % (entry 11).
Increasing the number of equivalents of the activated acetylene
2a did not improve the reaction performance (entry 12).
Careful monitoring revealed that the reaction required only 4 h
to reach completion in MeCN (entry 13). Finally, decreasing
the amount of 2a to 1.5 equiv did not change the reaction yield
(entry 14), but it did drop dramatically to 14% when we used
1.2 equiv of 2a (entry 15).
The isolated dihydroquinoline adduct 3a was unstable and
readily decomposed at room temperature.3a Treating the
vinylogous hemiaminal with acetyl chloride and pyridine
resulted in the clean production of the stable quinoline 4a in
excellent yield (Scheme 3a). In this two-pot procedure,
decomposition of the unstable dihydroquinoline 3a during its
isolation resulted in a lower yield of the quinoline product 4a.
Such loss could be avoided through a one-pot procedure to
directly convert the unstable dihydroquinoline intermediate
into the corresponding quinoline. The ideal reagent for such a
procedure would necessarily contain a “chloride” to trap the
tosyl group in the form of the byproduct TsCl; in addition, it
should transform the OH group into a good leaving group.
Hydrogen chloride met these requirements; simply quenching
In a preliminary study of the reaction, we reacted 0.1 M of N-
tosyl-2-aminobenzaldehyde (1a) with 2.0 equiv of 3-butyn-2-
one (2a) in THF in the presence of 20 mol % PPh3 as the
catalyst. We stopped the reaction prior to completion, after 17
h, for a quick evaluation of its feasibility, identifying the
dihydroquinoline 3a as the product in 28% yield (Table 1, entry
1). We suspected that the long reaction time might have caused
a
Table 1. Optimization of Dihydroquinoline Synthesis
b
2a
PPh3
concentration
(M)
time
(h)
yield
(%)
entry (equiv) (mol %)
solvent
1
2
3
4
5
6
7
8
9
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.5
2.0
1.5
1.2
20
20
20
100
20
20
20
20
20
10
5
THF
0.1
0.1
0.1
0.1
0.05
0.2
0.4
0.2
0.4
0.2
0.2
0.2
0.2
0.2
0.2
17
28
28
32
0
c
THF
17
24
24
17
17
17
THF
THF
THF
25
67
68
71
THF
THF
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
17
d
d
N/A
N/A
10
11
12
13
14
15
17
17
17
4
75
49
47
76
76
14
5
10
10
10
4
4
a
Butynone 2a was added in one portion to a solution of 1a and PPh3
b
c
in the indicated solvent. Concentration of the aldehyde 1a. Addition
of butynone 2a over 2 h via syringe pump. Not available.
d
B
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Scheme 3. (a) Quinoline Formation from Dihydroquinoline, (b) One-Pot Phosphine-Catalyzed Synthesis of Quinoline
a
Table 2. One-Pot Phosphine-Catalyzed Syntheses of Substituted 3-Acetylquinolines
a
b
2a (1.5 equiv) was added in one portion to a solution of 1 (0.2 M) and PPh3 (10 mol %) in MeCN. Isolated yield.
the reaction with 1 M aqueous HCl provided the quinoline 4a
in 88% yield together with TsCl as a byproduct (Scheme 3b).
This higher yield for the isolated quinoline relative to that of
the isolated dihydroquinoline confirmed the loss of the latter
product through decomposition in the two-pot procedure.
Having optimized the one-pot procedure for the synthesis of
the 3-substituted quinoline, we further examined the scope of
this reaction for the synthesis of 3-acetylquinolines (Table 2).
Regardless of the electron-donating or -withdrawing ability of
the substituents on the aminobenzaldehyde, the reactions were
highly efficient, generating the desired quinolines in high yields.
Nevertheless, the nature of the substituents had a significant
impact on the rate of the reaction. The reaction of the
nonsubstituted N-tosyl-2-aminobenzaldehyde (1a) reached
completion within 4 h in 88% yield (entry 1). The
electronically similar N-tosyl-3-amino-2-naphthaldehyde (1b)
was converted into the quinoline 4b in a comparable yield of
89% after a similar reaction time of 5 h (entry 2). The presence
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a
Table 3. One-Pot Phosphine-Catalyzed Syntheses of 3-Substituted Quinolines
a
b
c
2 (1.5 equiv) was added in one portion to a solution of 1a (0.2 M) and PPh3 (10 mol %) in MeCN. Isolated yield. Diacetylene 2q (0.10 mmol)
was added to a solution of 1a (0.21 mmol, 0.21 M) and PPh3 (20 mol %) in MeCN.
D
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a
Table 4. One-Pot Phosphine-Catalyzed Syntheses of 3,4-Disubstituted Quinolines
a
b
2b (1.5 equiv) was added in one portion to a solution of 1 (0.2 M) and PPh3 (10 mol %) in MeCN. Isolated yield.
of electron-withdrawing groups significantly slowed the rates of
the reactions (entries 3−5), whereas electron-donating groups
accelerated them (entries 6 and 7). In general, the presence of a
substituent, regardless of its electronic nature, had a positive
impact on the yield of the reaction (entry 1 vs entries 2−7).
The successful syntheses of the 3-acetylquinolines in Table 2
encouraged us to expand the scope of the reaction to include
other 3-substituted quinolines (Table 3). In general, the
reaction was highly efficient for acetylenic ketones but much
less efficient for other activated alkynes (entries 1−10 vs entries
12 and 13). We obtained lower yields for the reactions
performed with methyl propiolate or an acetylenic sulfone, due
to formation of the corresponding simple Michael adducts with
the aldehyde functionality intact (entries 12 and 13). With
regard to the acetylenic ketone, the reactions of aryl acetylenyl
ketones were faster and provided higher yields than those of
alkyl acetylenyl ketones (entry 1 vs entries 2−9). The
electronic nature of the aryl group of the acetylenic ketone
greatly impacted the reaction rate and yield. With electron-
deficient aryl groups, the reactions required only a few minutes
to reach completion in excellent yields (entry 2 vs entries 3−8
and 11). In contrast, electron-rich aryl groups prolonged the
reaction and resulted in excellent but lower yields (entry 2 vs
entries 9 and 10). We also examined the versatility of the
reaction when using a multifunctional acetylenic ketone,
namely a bis(acetylenic ketone); here, the reaction proceeded
smoothly to form the bisquinoline product in good yield (entry
11).
3,4-disubstituted quinolines. The reactions afforded the desired
products, albeit in lower yields after longer reaction times
(Table 3, entry 2 vs Table 4). Longer reaction times were
expected because of the lower reactivity of ketones relative to
corresponding aldehydes. Among the selected o-aminophe-
nones, those with larger R groups required the longest reaction
times (entry 3 vs entries 1, 2 and 4), although the size of the R
group had only a minor impact on the reaction yield (entries
1−4).
MECHANISTIC DISCUSSION
■
Scheme 4 outlines three possible mechanistic scenarios.
Mechanism 1 involves a general base catalysis. Nucleophilic
addition of the free phosphine to the activated alkyne results in
the phosphonium allenolate A, which acts as a base to activate
the pronucleophile through deprotonation, resulting in a
subsequent general base-catalyzed Michael/aldol reaction.
Mechanism 2 is based on a nucleophilic phosphine catalysis,
in which the phosphine is consumed and regenerated along the
catalytic cycle; the ion pair B, which is also generated in
mechanism 1, is presumably associated in a sufficiently tight
manner to enforce the nucleophilic addition within the ion
pair.9 Mechanism 3 is also based on a nucleophilic phosphine
catalysis, where the aldol addition occurs immediately after the
formation of the phosphonium allenolate A; hence, the ion pair
B is not formed.
Because we isolated the Michael adduct together with the
quinoline product in the reaction of methyl propiolate (Table
3, entry 12),11 we speculate that mechanism 3 was most
unlikely to operate. As indicated in Table 5, the reaction
We further expanded the scope of the reaction to include
less-reactive o-aminophenones as partners for the syntheses of
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Scheme 4. Possible Mechanistic Schemes for Phosphine-Catalyzed Dihydroquinoline Formation
proceeded to form the quinoline product in the presence of a
catalytic amount of a non-nucleophilic base. This result
supports the operation of the general base catalysis mechanism
in this reaction.
In the hopes of seeing reaction intermediates that could help
to identify the true mechanistic pathway out of the three
possibilities discussed above, we used NMR spectroscopy to
monitor the reaction between 1a and 2a in the presence of 10
mol % PPh3 in CD3CN; unfortunately, no intermediates were
evident at any time during the course of the reaction. The H
1
NMR spectra of the reaction mixture revealed that the signal
for the NH unit of reactant 1a disappeared within 10 min
(Figure 1C). Apparently, the reaction was initiated rapidly in
MeCN with partial deprotonation of the NH group; fast proton
exchange made the NH proton undetectable, on the time scale
1
of H NMR spectroscopy, at 10.83 ppm (the presence of N-
F
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tosylaminobenzaldehyde 1a was verified through TLC analysis
during the reaction period). At the same time, two new signals,
corresponding to protons Ha and Hb of the dihydroquinoline
adduct, were growing (Figures 1C−F). Because of rapid proton
exchange, the proton of the OH group of the dihydroquinoline
product was also undetectable in the 1H NMR spectra recorded
throughout the course of the reaction. In general, only the
starting materials and the final dihydroquinoline products were
evident (i.e., no intermediates were observed) at any time
Table 5. Non-Nucleophilic Base Catalysis for
Dihydroquinoline Synthesis
a
entry
catalyst
K2CO3
yield (%)
1
b
during the reactions monitored using H NMR spectroscopy.
1
69
71
58
b
2
Cs2CO3
CONCLUSION
3
1 M aq NaOH
■
a
b
We have developed an efficient one-pot procedure for the
syntheses of 3-substituted and 3,4-disubstituted quinolines from
the reactions of activated acetylenes with N-tosyl-2-amino-
Isolated yield. Heterogeneous reaction mixture.
Figure 1. 1H NMR spectra revealing the formation of the dihydroquinoline 3a. (A, B) Control experiments performed without (A) 3-butyn-2-one
(2a) or (B) N-tosyl-2-aminobenzaldehyde (1a) in the reaction mixture; spectra recorded after 4 h. (C−F) Spectra of the reaction proper after (C)
10 min, (D) 1 h, (E) 3.5 h, and (F) 4 h.
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and then 3-butyn-2-one (2) (23.5 μL, 0.3 mmol) was added in one
portion. The mixture was stirred under argon at room temperature;
upon completion of the reaction (4.0−4.5 h), the mixture was
concentrated in vacuo and purified through flash column chromatog-
raphy (gradient EtOAc/Hex, 3:7 to 1L1) to furnish a slightly yellow
solid (52.1 mg, 76% yield): IR (film) νmax 3391, 3088, 3050, 3006,
2923, 1645, 1632, 1597, 1566, 1485, 1456, 1343, 1210, 1160, 1088,
1017, 1009 cm−1; 1H NMR (500 MHz, THF-d8) δ 7.81 (d, J = 8.1 Hz,
1H), 7.41−7.37 (m, 4H), 7.32 (s, 1H), 7.21 (t, J = 7.7 Hz, 1H), 7.15
(d, J = 8.2 Hz, 2H), 6.81 (d, J = 6.1 Hz, 1H), 5.85 (d, J = 6.1 Hz, 1H),
2.32 (s, 3H), 2.26 (s, 3H); 13C NMR (125 MHz, THF-d8) δ 194.2,
143.3, 137.0, 135.0, 134.2, 132.2, 130.0, 128.9, 128.8, 126.5, 125.6,
124.8, 124.6, 73.3, 24.1, 20.2; HRMS (ESI-TOF) m/z [M − OH]+
Calcd for C18H16NO3S 326.0851, found 326.0847.
benzaldehydes and N-tosyl-2-aminobenzophenones, respec-
tively. This approach provides a convenient and direct route
toward 3-substituted quinolines, which are challenging to
prepare using other methods. The reaction conditions are mild,
and many different substituents can be introduced without
compromising yields.
EXPERIMENTAL SECTION
■
General Information. All reactions were performed in dry
solvents under an Ar atmosphere and anhydrous conditions, unless
otherwise indicated. DCM, THF, and MeCN were freshly distilled
over CaH2 prior to use. Anhydrous DMSO was used as received from
a commercial source. All other reagents were used as received from
commercial sources. Reactions were monitored through thin layer
chromatography (TLC) on 0.25-mm SiliCycle silica gel plates and
visualized under UV light and with permanganate or 2,4-
dinitrophenylhydrazine (DNP) staining. Flash column chromatog-
raphy (FCC) was performed using SiliCycle Silica-P Flash silica gel
(60-Å pore size, 40−63 μm). IR spectra were recorded using a Jasco
FT-IR 4100 spectrometer. NMR spectra of the dihydroquinoline 3a
were obtained using Bruker Avance-500 instruments, calibrated to
1-(Quinolin-3-yl)ethanone (4a).16 30.1 mg, 88% yield; slightly
yellow solid: mp 98−99 °C; IR (film) νmax 3065, 3009, 2920, 1681,
1
1615, 1587, 1571, 1493, 1371 cm−1; H NMR (500 MHz, CDCl3) δ
9.42 (s, 1H), 8.69 (s, 1H), 8.15 (d, J = 8.5 Hz, 1H), 7.93 (d, J = 8.0
Hz, 1H), 7.83 (t, J = 7.5 Hz, 1H), 7.62 (t, J = 7.5 Hz, 1H), 2.73 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 196.5, 149.5, 149.0, 137.3,
131.9, 129.22, 129.19, 129.1, 127.5, 126.7, 26.7; HRMS (ESI-TOF) m/
z [M + H]+ Calcd for C11H10NO 172.0762, found 172.0762.
1-(Benzo[g]quinolin-3-yl)ethanone (4b). 39.5 mg, 89% yield;
bright yellow solid: mp 150−152 °C; IR (film) νmax 3046, 2998,
2922, 1676, 1612, 1532, 1352, 1215 cm−1; 1H NMR (500 MHz,
CDCl3) δ 9.47 (s, 1H), 8.84 (s, 1H), 8.70 (s, 1H), 8.51 (s, 1H), 8.10
(d, J = 8.5 Hz, 1H), 8.06 (d, J = 8.5 Hz, 1H), 7.62−7.55 (m, 2H), 2.76
(s, 3H); 13C NMR (125 MHz, CDCl3) δ 196.5, 149.5, 149.0, 137.3,
131.9, 129.22, 129.19, 129.1, 127.5, 126.7, 26.7; HRMS (ESI-TOF) m/
z [M + H]+ Calcd for C15H12NO 222.0919, found 222.0921.
1-[7-(Trifluoromethyl)quinolin-3-yl]ethanone (4c). 44.8 mg, 94%
yield; white crystalline solid: mp 126−127 °C; IR (film) νmax 3059,
3020, 2929, 1689, 1594, 1464, 1124 cm−1; 1H NMR (500 MHz,
CDCl3) δ 9.50 (s, 1H), 8.75 (s, 1H), 8.45 (s, 1H), 8.08 (d, J = 8.5 Hz,
1H), 7.80 (d, J = 8.5 Hz, 1H), 2.77 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 196.1, 150.4, 148.7, 136.8, 133.3 (q, J = 32.9 Hz), 130.5,
130.4, 128.3, 127.2 (q, J = 4.4 Hz), 123.5 (q, J = 271.0 Hz), 123.1 (q, J
= 4.5 Hz), 26.8; HRMS (ESI-TOF) m/z [M + H]+ Calcd for
C12H9F3NO 240.0636, found 240.0632.
1
residual THF-d8 as the internal reference (1.73 and 3.58 ppm for H
NMR spectra; 25.4 and 67.6 ppm for 13C NMR spectra). NMR spectra
of the quinolines 4 were recorded using Bruker Avance-500
instruments, calibrated to CD(H)Cl3 as the internal reference (7.26
1
1
and 77.0 ppm for H and 13C NMR spectra, respectively). H NMR
spectral data are reported in terms of chemical shift (δ, ppm),
multiplicity, coupling constant (Hz), and integration. 13C NMR
spectral data are reported in terms of chemical shift (δ, ppm) and
multiplicity, with the coupling constant (Hz) in the case of JCF
coupling. The following abbreviations indicate the multiplicities: s,
singlet; d, doublet; t, triplet; q, quartet; m, multiplet; br, broad. High
resolution mass spectra were recorded using a Waters LCT Premier
XE time-of-flight instrument controlled by MassLynx 4.1 software.
Samples were infused using direct loop injection from a Waters
Acquity UPLC into the multi-mode ionization source. The lock mass
standard for accurate mass determination was leucine enkephalin
(Sigma L9133).
1-(7-Fluoroquinolin-3-yl)ethanone (4d). 36.4 mg, 96%; white
solid: mp 116−118 °C; IR (film) νmax 3051, 2923, 1670, 1619, 1602,
1579, 1274, 1193 cm−1; 1H NMR (500 MHz, CDCl3) δ 9.42 (s, 1H),
8.70 (s, 1H), 7.95 (dd, J = 8.9, 5.1 Hz, 1H), 7.77 (dd, J = 9.8, 2.3 Hz,
1H), 7.42 (dt, J = 8.7, 2.5, 1H), 2.73 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 196.2, 164.5 (d, J = 254.8 Hz), 150.9 (d, J = 12.7 Hz), 150.2,
140.0, 131.5 (d, J = 10.5 Hz), 128.8, 123.8, 118.2 (d, J = 25.7 Hz),
113.3 (d, J = 20.7 Hz), 26.7; HRMS (ESI-TOF) m/z [M + H]+ Calcd
for C11H9FNO 190.0668, found 190.0670.
General Procedure for the Syntheses of Substrates 1. The N-
tosylbenzaldehydes 1a−g were prepared from the corresponding
anthranilic acids in three steps without purification of any
intermediates.12 The N-tosyl-o-aminophenones 1t and 1u were
prepared directly from the corresponding o-aminophenones through
a single tosylation step.13 The N-tosyl-o-aminophenones 1v and 1w
were prepared from the corresponding 2-aminobenzonitriles in two
steps, without purification of any intermediates.14
Syntheses of Substrates 2. The activated acetylene 2 were
prepared in two steps, without purification of any intermediates,
according to reported procedures.15
1-(6,7-Difluoroquinolin-3-yl)ethanone (4e). 39.5 mg, 95% yield;
white solid: mp 151−153 °C; IR (film) νmax 3061, 2923, 1682, 1595,
1
1505, 1475, 1347, 1253, 1234 cm−1; H NMR (500 MHz, CDCl3) δ
General Procedure for the Syntheses of Quinolines. o-
Aminobenzaldehyde (1, 0.2 mmol), PPh3 (5.3 mg, 10 mol %), and
MeCN (1 mL) were added sequentially to a flame-dried flask (10
mL); unless otherwise noted, the mixture was stirred until complete
dissolution occurred. The activated acetylene 2 (0.3 mmol) was added
in one portion, and then the mixture was stirred under Ar at room
temperature. Upon completion of the reaction, 1 M aqueous HCl (1
mL) was added, and then the mixture was stirred for 5 min before
saturated aqueous NaHCO3 (1 mL) was added to neutralize the
mixture. The mixture was poured into a separatory funnel along with
DCM (10 mL) and saturated aqueous NaHCO3 (10 mL). The
aqueous phase was separated and extracted with DCM (2 mL). The
combined organic phases were dried (Na2SO4) and concentrated in
vacuo; the residue was purified through flash column chromatography
[ethyl acetate (EtOAc)/hexanes (Hex), 3:7, unless specified
otherwise] to afford the desired quinoline product.
9.39 (s, 1H), 8.65 (s, 1H), 8.45 (s, 1H), 7.90 (dd, J = 7.7, 7.7 Hz, 1H),
7.68 (dd, J = 8.3, 8.3 Hz, 1H), 2.74 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 196.0, 153.7 (dd, J = 257.0, 17.8 Hz), 150.6 (dd, J = 257.0,
17.8 Hz), 147.1 (d, J = 11.2 Hz), 136.2, 129.3, 123.8 (d, J = 7.1 Hz),
115.9 (d, J = 17.2 Hz), 114.3 (d, J = 17.2 Hz), 26.7; HRMS (ESI-
TOF) m/z [M + H]+ Calcd for C11H8F2NO 208.0574, found
208.0584.
1-(6,7-Dimethoxyquinolin-3-yl)ethanone (4f).17 EtOAc/Hex, 1:1.
45.7 mg, 99% yield; white solid: mp 160−163 °C; IR (film) νmax 3008,
2960, 2925, 2831, 1667, 1597, 1504, 1438, 1427, 1228, 1144, 1003
cm−1; 1H NMR (500 MHz, CDCl3) δ 9.24 (s, 1H), 8.56 (s, 1H), 7.46
(s, 1H), 7.14 (s, 1H), 4.06 (s, 3H), 4.03 (s, 3H), 2.71 (s, 3H); 13C
NMR (125 MHz, CDCl3) δ 196.6, 154.4, 150.4, 147.4, 147.3, 135.0,
127.9, 122.4, 107.8, 106.0, 56.2, 56.0, 26.6; HRMS (ESI-TOF) m/z [M
+ H]+ Calcd for C13H14NO3 232.0974, found 232.0964.
1-(6-Methoxyquinolin-3-yl)ethanone (4g). 37.1 mg, 92% yield;
light-yellow solid: mp 122−124 °C; IR (film) νmax 2956, 2923, 2852,
1682, 1619, 1595, 1503, 1368, 1227, 1023 cm−1; 1H NMR (500 MHz,
CDCl3) δ 9.25 (s, 1H), 8.57 (s, 1H), 8.02 (d, J = 9.0 Hz, 1H), 7.45
1-(1-Tosyl-1,4-dihydroquinolin-3-yl)ethanone (3a). To a flame-
dried flask (10 mL) were sequentially added N-tosyl 2-amino-
benzaldehyde (1a) (0.2 mmol), PPh3 (5.3 mg, 10 mol %), and
MeCN (1 mL). The mixture was stirred until complete dissolution,
H
dx.doi.org/10.1021/jo3015825 | J. Org. Chem. XXXX, XXX, XXX−XXX

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(dd, J = 9.0, 2.5 Hz, 1H), 7.14 (d, J = 2.5 Hz, 1H), 3.93 (s, 3H), 2.71
(s, 3H); 13C NMR (125 MHz, CDCl3) δ 196.8, 158.3, 146.7, 146.0,
135.8, 130.6, 129.4, 127.9, 127.8, 124.8, 55.5, 26.8; HRMS (ESI-TOF)
m/z [M + H]+ Calcd for C12H12NO2 202.0868, found 202.0870.
Phenyl(quinolin-3-yl)methanone (4h).7 44.2 mg, 95% yield;
crystalline yellow solid: mp 73−75 °C; IR (film) νmax 3052, 1647,
129.2, 128.7, 127.9, 127.2, 126.4, 124.5; HRMS (ESI-TOF) m/z [M +
H]+ Calcd for C16H11N2O3 279.0770, found 279.0776.
3,4-Dimethoxyphenyl(quinolin-3-yl)methanone (4o). 54.6 mg,
93% yield; white solid: mp 93−95 °C; IR (film) νmax 3042, 2995,
2934, 1637, 1592, 1580, 1513, 1418, 1295, 1264, 1247, 1228, 1143,
1113, 1020 cm−1; 1H NMR (500 MHz, CDCl3) δ 9.28 (d, J = 1.3 Hz,
1H), 8.54 (d, J = 1.3 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.93 (d, J = 8.1
Hz, 1H), 7.85 (t, J = 8.2 Hz, 1H), 7.65 (t, J = 8.2 Hz, 1H), 7.55 (s,
1H), 7.42 (d, J = 8.1 Hz, 1H), 6.94 (d, J = 8.4 Hz, 1H), 3.99 (s, 3H),
3.97 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 196.1, 150.4, 148.7,
136.8, 131.9, 129.22, 129.19, 129.1, 127.5, 126.7, 26.7; HRMS (ESI-
TOF) m/z [M + H]+ Calcd for C18H16NO3 294.1130, found
294.1130.
1
1616, 1597, 1571, 1287, 1243 cm−1; H NMR (500 MHz, CDCl3) δ
9.33 (s, 1H), 8.56 (s, 1H), 8.20 (d, J = 8.0 Hz, 1H), 7.92 (d, J = 8.0
Hz, 1H), 7.88−7.86 (m, 3H), 7.69−7.63 (m, 2H), 7.58−7.48 (m, 2H);
13C NMR (125 MHz, CDCl3) δ 194.8, 150.3, 149.4, 138.7, 136.9,
133.0, 131.8, 129.97, 129.95, 129.4, 129.1, 128.6, 127.5, 126.5; HRMS
(ESI-TOF) m/z [M + H]+ Calcd for C16H12NO 234.0919, found
234.0915.
Quinolin-3-yl(thien-2-yl)methanone (4p).7 41.1 mg, 86% yield;
white solid: mp 89−91 °C; IR (film) νmax 3102, 3065, 1629, 1617,
1588, 1517, 1492, 1410, 1366, 1292, 1251, 1062 cm−1; 1H NMR (500
MHz, CDCl3) δ 9.33 (s, 1H), 8.64 (s, 1H), 8.18 (d, J = 8.9 Hz, 1H),
7.93 (d, J = 8.9 Hz, 1H), 7.84 (t, J = 7.2 Hz, 1H), 7.79 (d, J = 5.0 Hz,
1H), 7.70 (d, J = 5.0 Hz, 1H), 7.64 (t, J = 7.5 Hz, 1H), 7.21 (t, J = 5.0
Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 186.1, 149.5, 149.3, 143.1,
137.7, 135.01, 134.99, 131.7, 130.6, 129.4, 129.0, 128.3, 127.6, 126.6;
HRMS (ESI-TOF) m/z [M + H]+ Calcd for C14H10NOS 240.0483,
found 240.0494.
1,4-Phenylenebis(quinolin-3-ylmethanone) (4q). Synthesized
from o-aminobenzaldehyde 1 (57.8 mg, 0.21 mmol), PPh3 (5.3 mg,
20 mol %), and the activated bis-acetylene 2q (18.2 mg, 0.1 mmol) in
MeCN (1 mL); gradient EtOAc/Hex, from 3:7 to 1:1. 24.5 mg, 63%
yield; pale-yellow powder: mp 237−239 °C; IR (film) νmax 3023, 1641,
1614, 1595, 1571, 1366, 1290, 1246, 1122 cm−1; 1H NMR (500 MHz,
CDCl3) δ 9.38 (s, 2H), 8.61 (s, 2H), 8.22 (d, J = 8.2 Hz, 2H), 8.03 (s,
4H), 7.96 (d, J = 8.2 Hz, 2H), 7.89 (t, J = 8.2 Hz, 2H), 7.68 (t, J = 8.2
Hz, 2H); 13C NMR (125 MHz, CDCl3) δ 194.0, 150.0, 149.6, 140.4,
139.1, 132.2, 130.0, 129.5, 129.22, 129.18, 127.8, 126.5; HRMS (ESI-
TOF) m/z [M + H]+ Calcd for C26H17N2O2 389.1290, found
389.1291.
Naphth-1-yl(quinolin-3-yl)methanone (4i).7 56.3 mg, 99% yield;
pale-yellow oil: IR (film) νmax 3051, 1652, 1616, 1589, 1568, 1493,
1286, 1237, 1186 cm−1; 1H NMR (500 MHz, CDCl3) δ 9.43 (s, 1H),
8.54 (s, 1H), 8.21−8.19 (m, 2H), 8.08 (d, J = 8.2 Hz, 1H), 7.96 (d, J =
8.2 Hz, 1H), 7.87−7.84 (m, 2H), 7.66 (d, J = 7.1 Hz, 1H), 7.62−7.53
(m, 4H); 13C NMR (125 MHz, CDCl3) δ 196.3, 150.4, 149.7, 139.5,
135.2, 133.8, 132.0, 130.8, 130.7, 129.4, 129.3, 128.5, 128.4, 127.6,
127.5, 126.7, 126.6, 125.4, 124.3; HRMS (ESI-TOF) m/z [M + H]+
Calcd for C20H14NO 284.1075, found 284.1072.
2-Fluorophenyl(quinolin-3-yl)methanone (4j). 49.2 mg, 98% yield;
light-yellow solid: mp 84−86 °C; IR (film) νmax 3086, 1664, 1610,
1
1595, 1568, 1448, 1296, 1213 cm−1; H NMR (500 MHz, CDCl3) δ
9.33 (s, 1H), 8.54 (s, 1H), 8.16 (d, J = 8.8 Hz, 1H), 7.90 (d, J = 7.9
Hz, 1H), 7.84 (t, J = 7.8 Hz, 1H), 7.66 (d, J = 14.1 Hz, 1H), 7.62−7.59
(m, 2H), 7.33 (t, J = 7.9 Hz, 1H), 7.20 (t, J = 8.5 Hz, 1H); 13C NMR
(125 MHz, CDCl3) δ 191.7, 160.1 (d, J = 253.6 Hz), 149.7, 138.9,
133.9 (d, J = 8.4 Hz), 132.1, 130.9 (d, J = 2.7 Hz), 129.9, 129.4 (d, J =
10.1 Hz), 127.5, 126.6, 126.0 (d, J = 14.4 Hz), 124.6 (d, J = 3.8 Hz),
116.4 (d, J = 21.8 Hz); HRMS (ESI-TOF) m/z [M + H]+ Calcd for
C16H11FNO 252.0825, found 252.0829.
4-Bromophenyl(quinolin-3-yl)methanone (4k). 61.2 mg, 98%
yield; white crystalline solid: mp 115−117 °C; IR (film) νmax 3090,
3056, 1645, 1618, 1584, 1566, 1491, 1366, 1231, 1168, 1069 cm−1; 1H
NMR (500 MHz, CDCl3) δ 9.30 (s, 1H), 8.53 (s, 1H), 8.20 (d, J = 8.1
Hz, 1H), 7.92 (d, J = 8.1 Hz, 1H), 7.87 (t, J = 8.1 Hz, 1H), 7.74 (d, J =
8.5 Hz, 2H), 7.69 (d, J = 8.5 Hz, 2H), 7.65 (t, J = 8.1 Hz, 1H); 13C
NMR (125 MHz, CDCl3) δ 193.7, 150.0, 149.5, 138.6, 135.7, 131.94,
131.92, 131.4, 129.6, 129.5, 129.1, 128.2, 127.6, 126.4; HRMS (ESI-
TOF) m/z [M + H]+ Calcd for C16H11BrNO 312.0024, found
312.0013.
Methyl Quinoline-3-carboxylate (4r).18 22.7 mg, 61/% yield; white
crystalline solid: mp 69−70 °C; IR (film) νmax 3056, 2948, 2924, 2849,
1714, 1618, 1572, 1433, 1367, 1290, 1240, 1193, 1100 cm−1; 1H NMR
(500 MHz, CDCl3) δ 9.44 (s, 1H), 8.84 (s, 1H), 8.16 (d, J = 7.9 Hz,
1H), 7.93 (d, J = 7.9 Hz, 1H), 7.83 (t, J = 7.9 Hz, 1H), 7.62 (t, J = 7.9
Hz, 1H), 4.01 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 165.7, 149.9,
149.7, 138.7, 131.8, 129.4, 129.0, 127.3, 126.7, 122.9, 52.4; HRMS
(ESI-TOF) m/z [M + H]+ Calcd for C11H10NO2 188.0712, found
188.0709.
Quinolin-3-yl(tosyl)methanone (4s).19 17.0 mg, 30% yield; yellow
crystalline solid: mp 165−170 °C; IR (film) νmax 3068, 3056, 2925,
2851, 1616, 1593, 1585, 1497, 1312, 1304, 1290, 1153, 1140, 1091
3,4-Dichlorophenyl(quinolin-3-yl)methanone (4l). 58.4 mg, 97%
yield; light-yellow solid: mp 112−113 °C; IR (film) νmax 3076, 1637,
1
1617, 1577, 1385, 1293, 1238 cm−1; H NMR (500 MHz, CDCl3) δ
1
cm−1; H NMR (500 MHz, CDCl3) δ 9.25 (d, J = 1.7 Hz, 1H), 8.79
9.28 (d, J = 1.9 Hz, 1H), 8.52 (d, J = 1.9 Hz, 1H), 8.19 (d, J = 7.9 Hz,
1H), 7.95−7.92 (m, 2H), 7.87 (ddd, J = 8.5, 7.0, 1.3 Hz, 1H), 7.69−
7.61 (m, 3H); 13C NMR (125 MHz, CDCl3) δ 192.4, 149.8, 149.6,
138.7, 136.5, 133.4, 132.1, 131.6, 130.7, 129.5, 129.12, 129.10, 128.9,
127.8, 126.4; HRMS (ESI-TOF) m/z [M + H]+ Calcd for
C16H10Cl2NO 302.0139, found 302.0135.
3-(Quinoline-3-carbonyl)benzonitrile (4m). 49.5 mg, 96% yield;
off-white crystalline solid: mp 105−107 °C; IR (film) νmax 3067, 2227,
1653, 1616, 1596, 1567, 1291, 1179 cm−1; 1H NMR (500 MHz,
CDCl3) δ 9.30 (d, J = 2.7 Hz, 1H), 8.53 (d, J = 2.7 Hz, 1H), 8.21 (d, J
= 10.6 Hz, 1H), 8.14 (s, 1H), 8.09 (dt, J = 9.8, 1.9 Hz, 1H), 7.95−7.92
(m, 2H), 7.89 (t, J = 9.7 Hz, 1H), 7.69 (q, J = 10.1 Hz, 2H); 13C NMR
(125 MHz, CDCl3) δ 192.6, 149.74, 149.66, 138.9, 137.9, 135.8, 133.7,
133.2, 132.4, 129.6, 129.5, 129.2, 128.7, 127.9, 126.3, 117.6, 113.2;
HRMS (ESI-TOF) m/z [M + H]+ Calcd for C17H11N2O 259.0871,
found 259.0882.
3-Nitrophenyl(quinolin-3-yl)methanone (4n). 54.6 mg, 98% yield;
white solid: mp 138−140 °C; IR (film) νmax 3086, 1642, 1612, 1527,
1491, 1346, 1285 cm−1; 1H NMR (500 MHz, CDCl3) δ 9.31 (s, 1H),
8.69 (s, 1H), 8.56 (s, 1H), 8.50 (d, J = 8.5 Hz, 1H), 8.20 (t, J = 7.3 Hz,
2H), 7.94 (d, J = 8.5 Hz, 1H), 7.90 (t, J = 7.3 Hz, 1H), 7.77 (t, J = 7.3
Hz, 1H), 7.67 (t, J = 7.3 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ
192.4, 149.71, 149.70, 148.2, 138.9, 138.3, 135.3, 132.4, 129.9, 129.5,
(d, J = 1.8 Hz, 1H), 8.14 (d, J = 8.5 Hz, 1H), 7.95 (d, J = 8.5 Hz, 1H),
7.90 (d, J = 8.2 Hz, 2H), 7.86 (t, J = 8.4 Hz, 3H), 7.67 (t, J = 8.4 Hz,
1H), 7.32 (d, J = 8.3 Hz, 2H), 2.39 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 149.2, 147.0, 144.8, 137.9, 136.5, 135.0, 132.5, 130.1, 129.5,
129.1, 128.2, 127.8, 126.3, 21.5; HRMS (ESI-TOF) m/z [M + H]+
Calcd for C16H14NO2S 284.0745, found 284.0753.
4-Methylquinolin-3-yl(phenyl)methanone (4t).7 EtOAc/Hex, 1:5.
40.3 mg, 82% yield; yellow crystalline solid: mp 82−86 °C; IR (film)
νmax 3059, 3030, 2918, 1658, 1645, 1581, 1494, 1449, 1248, 1161
1
cm−1; H NMR (500 MHz, CDCl3) δ 8.82 (s, 1H), 8.17 (d, J = 8.3
Hz, 1H), 8.12 (d, J = 8.5 Hz, 1H), 7.85−7.78 (m, 3H), 7.68−7.61 (m,
2H), 7.49 (t, J = 7.8 Hz, 2H), 2.67 (s, 3H); 13C NMR (125 MHz,
CDCl3) δ 196.9, 148.5, 148.0, 143.5, 137.4, 133.8, 131.8, 130.3, 130.1,
130.0, 128.7, 127.5, 127.2, 124.3, 15.8; HRMS (ESI-TOF) m/z [M +
H]+ Calcd for C17H14NO 248.1075, found 248.1064.
Phenyl(4-phenylquinolin-3-yl)methanone (4u).7 EtOAc/Hex, 1:5.
44.6 mg, 72% yield; yellow crystalline solid: mp 108−110 °C; IR
1
(film) νmax 3062, 1654, 1570, 1486, 1324 cm−1; H NMR (500 MHz,
CDCl3) δ 9.00 (s, 1H), 8.24 (d, J = 8.5 Hz, 1H), 7.83−7.78 (m, 2H),
7.63−7.61 (m, 2H), 7.57−7.54 (m, 1H), 7.46−7.42 (m, 1H), 7.30−
7.25 (m, 7H); 13C NMR (125 MHz, CDCl3) δ 196.7, 148.8, 148.4,
146.9, 137.3, 134.8, 133.1, 131.7, 130.4, 130.0, 129.7, 129.6, 128.4,
I
dx.doi.org/10.1021/jo3015825 | J. Org. Chem. XXXX, XXX, XXX−XXX

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128.14, 128.12, 127.4, 126.7, 126.3; HRMS (ESI-TOF) m/z [M + H]+
Calcd for C22H16NO 310.1232, found 310.1230.
(j) Korivi, R. P.; Cheng, C.-H. J. Org. Chem. 2006, 71, 7079. For In,
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Org. Chem. 2008, 73, 4160. (l) Lekhok, K. C.; Prajapati, D.; Boruah, R.
C. Synlett. 2008, 655. (m) Sakai, N.; Annaka, K.; Konakahara, T. J. Org.
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Nicholas, K. M. J. Org. Chem. 2003, 68, 6427.
(3) Metal-free quinoline syntheses. (a) Ali, S.; Zhu, H.-T.; Xia, X.-F.;
Ji, K.-G.; Yang, Y.-F.; Song, X.-R.; Lian, Y.-M. Org. Lett. 2011, 13,
2598. (b) Peng, C.; Wang, Y.; Liu, L.; Wang, H.; Zhao, J.; Zhu, Q. Eur.
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J.; DeShong, P. Org. Lett. 2007, 9, 3209. (f) Zhao, Y.-L.; Zhang, W.;
Wang, S.; Liu, Q. J. Org. Chem. 2007, 72, 4985. (g) Zhang, Q.; Zhang,
Z. G.; Yan, Z. H.; Liu, Q.; Wang, T. Y. Org. Lett. 2007, 9, 3651.
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(4) Reviews on classical quinoline syntheses: (a) Kouznetsov, V. V.;
4-Cyclohexylquinolin-3-yl(phenyl)methanone (4v). 47.5 mg, 75%
yield; pale-yellow oil: IR (film) νmax 3066, 2927, 2853, 1665, 1577,
1498, 1448, 1282, 1241 cm−1; 1H NMR (500 MHz, CDCl3) δ 8.64 (s,
1H), 8.34 (br s, 1H), 8.16 (d, J = 8.4 Hz, 1H), 7.85 (d, J = 6.3 Hz,
2H), 7.75 (t, J = 7.1 Hz, 1H), 7.61 (q, J = 7.3 Hz, 2H), 7.46 (t, J = 7.3
Hz, 2H), 3.25 (br s, 1H), 1.97 (br s, 2H), 1.85−1.77 (m, 4H), 1.26 (br
s, 4H); 13C NMR (125 MHz, CDCl3) δ 198.2, 150.7, 148.7, 148.1,
137.6, 133.8, 132.0, 130.7, 130.1, 129.6, 128.9, 128.6, 126.7, 126.6,
32.0, 27.0, 25.7; HRMS (ESI-TOF) m/z [M + H]+ Calcd for
C22H22NO 316.1701, found 316.1699.
4-Cyclopropylquinolin-3-yl(phenyl)methanone (4w). 36.6 mg,
67% yield; pale-yellow oil: IR (film) νmax 3064, 3005, 2922, 1654,
1596, 1567, 1499, 1447, 1322, 1279, 1241, 1226, 1170 cm−1; 1H NMR
(500 MHz, CDCl3) δ 8.83 (s, 1H), 8.51 (d, J = 8.5 Hz, 1H), 8.17 (d, J
= 8.5 Hz, 1H), 7.85−7.79 (m, 3H), 7.68−7.66 (m, 1H), 7.65−7.59 (m,
1H), 7.59−7.46 (m, 2H), 2.11−2.08 (m, 1H), 0.95−0.93 (m, 2H),
0.59−0.57 (m, 2H); 13C NMR (125 MHz, CDCl3) δ 197.2, 148.9,
148.5, 147.4, 138.0, 133.4, 132.7, 130.3, 130.0, 129.6, 128.6, 128.3,
127.1, 125.5, 12.8, 8.2; HRMS (ESI-TOF) m/z [M + H]+ Calcd for
C19H16NO 274.1232, found 274.1230.
ASSOCIATED CONTENT
Men
́ ́
dez, L. Y. V.; Gomez, C. M. M. Curr. Org. Chem. 2005, 9, 141.
■
S
* Supporting Information
(b) Madapa, S.; Tusi, A.; Batra, S. Curr. Org. Chem. 2008, 12, 1116.
1
Copies of H and 13C NMR spectra. This material is available
Review on Friedlander quinoline synthesis: (c) Marco-Contelles, J.;
̈
Perez-Mayoral, E.; Samadi, A.; Carreiras, M.; do, C.; Soriano, E. Chem.
Rev. 2009, 109, 2652.
free of charge via the Internet at http://pubs.acs.org.
(5) Li, A.-H.; Beard, D. J.; Coate, H.; Honda, A.; Kadalbajoo, M.;
Kleinberg, A.; Laufer, R.; Mulvihill, K. M.; Nigro, A.; Rastogi, P.;
Sherman, D.; Siu, K. W.; Steinig, A. G.; Wang, T.; Werner, D.; Crew,
A. P.; Mulvihill, M. J. Synthesis 2010, 10, 1678 and references therein.
(6) Mierde, H. V.; Voort, P. V. D.; Verpoort, F. Tetrahedron Lett.
2009, 50, 201.
AUTHOR INFORMATION
Corresponding Author
*E-mail: ohyun@chem.ucla.edu.
Notes
■
The authors declare no competing financial interest.
(7) Li, H.; Xu, X.; Yang, J.; Xie, X.; Huang, H.; Li, Y. Tetrahedron Lett.
2011, 52, 530.
ACKNOWLEDGMENTS
■
(8) (a) Uhle, F. C.; Jacobs, W. A. J. Org. Chem. 1945, 10, 76.
(b) Monrad, R. N.; Madsen, R. Org. Biomol. Chem. 2011, 9, 610.
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2007, 129, 12928. (b) Sriramurthy, V.; Kwon, O. Org. Lett. 2010, 12,
1084.
Financial support was provided by the NIH (R01GM071779
and P41GM081282). This material is based upon work
supported by the National Science Foundation under Equip-
ment Grant No. CHE-1048804.
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