Gold catalysis in the synthesis of azaindoles: Pyrrolo[2,3-b]pyridines and pyrrolo[2,3-b]pyrazines

Article abstract of DOI:10.3998/ark.5550190.0015.500

The synthesis of substituted 1-benzyl-1H-pyrrolo[2,3-b]pyridines and 5-benzyl-5H-pyrrolo- [2,3-b]pyrazines has been performed by cycloisomerization of the corresponding N-benzyl- 3-alkynyl-5-arylpyridin(or pyrazin)-2-yl amines with AuCl₃. Alkyn

Full text of DOI:10.3998/ark.5550190.0015.500

General Papers
ARKIVOC 2014 (iv) 350-361
Oxidation of alcohols to carbonyl compounds with molecular iodine
in the presence of potassium tert-butoxide
Qun-Li Luo,* Wen-Hui Nan, Yu Li, and Xiang Chen
Key Laboratory of Applied Chemistry of Chongqing Municipality, College of Chemistry and
Chemical Engineering, Southwest University, Chongqing 400715, China
E-mail: qlluo@swu.edu.cn
DOI: http://dx.doi.org/10.3998/ark.5550190.0015.500
Abstract
An efficient protocol for the oxidation of alcohols to carbonyl compounds with molecular iodine
and potassium tert-butoxide is described. Various primary and secondary alcohols were
converted to the corresponding aldehydes and ketones in high yields. The oxidation of 2-
phenylethanol produced an “abnormal” acetalic ketone. The readily availability of starting
materials, convenient synthetic procedure, operational simplicity, mild reaction conditions, and
high yields makes this protocol a competitive alternative in the synthesis of ynones and ketones
as well as aryl aldehydes.
Keywords: Molecular iodine, alcohol oxidation, aldehyde, ynone
Introduction
Carbonyl compounds are valuable intermediates in the manufacture of agrochemicals, dyes,
pharmaceuticals, and fine chemicals.1 Preparation of carbonyl compounds can be achieved
through the oxidation of alcohols using a variety of oxidants.2 Halogens and related reagents
have been attractive oxidants because they are widely available and fairly cheap. As an oxidant
of group VIIa, molecular iodine is distinguished by its low toxicity, operational simplicity and
mild oxidation strength compared to other halogens.3,4 As an environmentally benign oxidizing
agent, molecular iodine has been used in various organic reactions.5–9 It is known that secondary
alcohols are readily converted into ketones, while primary alcohols can be first oxidized into the
aldehydes and further into the carboxylic acids or their derivatives. Thus, the oxidation of
primary alcohols to the corresponding carbonyl compounds is not so easily controlled as that of
secondary alcohols. Accordingly, primary alcohols can be facilely oxidized to esters,10 amides,11
nitriles,12 and azolines13 by molecular iodine in basic solution, while there are only a few
examples that involve oxidizing primary alcohols to aldehydes with molecular iodine.14–18
Among them, Itoh and co-workers developed an iodine oxidation involving photoirradiation at
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room temperature,14 Miller and co-workers reported iodine oxidations in the presence of 2,2,6,6,-
tetramethyl-1-piperdinyloxyl (TEMPO),15 Konwar et al expanded the complex oxidation system
of DMSO/N2H4·H2O/I2/H2O/CH3CN under refluxing conditions and that of KI/I2/K2CO3/H2O at
90 °C,16, 17 and Lee et al performed the oxidation of benzyl alcohols with iodine and Li2CO3 in an
ionic liquid at 60 °C.18 These results demonstrate that molecular iodine struggles to oxidize
alcohols into aldehydes without the help of heating, photoirradiation or co-activators because of
its intrinsically low oxidizing strength.
The values of standard electrode potentials suggest that the hypohalogenite is a stronger
oxidant than the corresponding elemental halogen under standard conditions.19 Thus, the
oxidizing strength of molecular iodine can be promoted after it is transformed to hypoiodite. As
an oxidant with useful synthetic utility, tert-butyl hypoiodite can be in situ generated from the
very simple protocol,20 i.e. the reaction of molecular iodine with potassium tert-butoxide (t-
BuOK).21 The oxidation of secondary alcohols to ketones by tert-butyl hypoiodite, in situ
generated from t-BuOK and molecular iodine, has been reported for half a century,22 but there
are no related studies into the oxidation of primary alcohols to aldehydes, although it is
interesting but challenging because an aldehyde is theoretically inclined to undergo the
Tishchenko reaction23 in the presence of an alkoxide, and hence, oxidation products were more
likely to stay in the stage of esters rather than that of aldehydes under such conditions. In
addition, the oxidation of propargyl alcohols to ynones with molecular iodine has been
unreported. Following our research on the reactions promoted by molecular iodine,24 we fully
investigated the oxidation of alcohols to carbonyl compounds with molecular iodine in the
presence of t-BuOK, and disclosed that oxidizing alcohols to aldehydes and ynones could be
achieved with the combination of molecular iodine and t-BuOK. This simple protocol has been
elaborated to achieve the conversion of 1-arylmethanols to aryl aldehydes, avoiding further
transformation of the generated aldehydes to esters in the presence of alkoxides. Our
investigations exemplify the versatility of molecular iodine in organic reactions and enrich the
realm of halogen chemistry.
Results and Discussion
Initially, 1-naphthylmethanol, a primary alcohol that is easily converted to 1-naphthaldehyde,
was chosen as the substrate in the model reaction. The investigation began with solvent
screening experiments at a relatively low temperature (Table 1, Entries 1−5). Despite the
moderate yields, the transformations did work at −15 °C in various aprotic solvents, except for
acetonitrile. A possible explanation was that acetonitrile was incompatible with the reaction
system because of the relatively high acidity of its α-hydrogen. When the temperature was
increased to 10 °C, the yields grew by nearly 20% (Entries 3−5 vs 6 & 7), and no over-oxidation
products were detected by thin layer chromatography (TLC). Thus, the base screening
experiments were performed at 10 °C. Among the tested solvents, dichloromethane (DCM) gave
a sound performance (Entry 7). DCM is cheap, able to dissolve most organic chemicals,
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relatively easy to dry, and not particularly hygroscopic, and was therefore the solvent of choice
for the next investigations. The results of the base screening experiments (Entries 9−15) showed
that the conversions did not work with most other tested bases except carbonates, with which
single digit yields were obtained (Entries 12 & 13). In contrast, t-BuOK was significantly
superior (Entries 9−15 vs 7). When the amount of iodine was increased to double the
stoichiometry required, an excellent yield was obtained in a short time (Entry 8), which showed
that the conversion could be accelerated with excess oxidant.
Table 1. Reaction condition screening for the oxidation of 1-naphthylmethanol by molecular
iodinea
Entry Base Solvent Temperature Yieldb
Entry Base Solvent Temperature Yieldb
1
2
3
4
5
6
7
t-BuOK CH3CN −15 oC
0
9
Et3N CH2Cl2
10 DIPEA CH2Cl2
11 DBU CH2Cl2
10 oC
10 oC
10 oC
10 oC
10 oC
10 oC
10 oC
0
0
t-BuOK DMF
t-BuOK DMA
t-BuOK THF
−15 oC
−15 oC
−15 oC
26%
46%
45%
48%
64%
77%
90%
0
12 K2CO3 CH2Cl2
13 Na2CO3 CH2Cl2
5%
7%
0
t-BuOK Toluene −15 oC
t-BuOK Toluene
10 oC
10 oC
10 oC
14
15
K3PO4 CH2Cl2
KF CH2Cl2
t-BuOK CH2Cl2
0
8c t-BuOK CH2Cl2
a
Reaction conditions: 1-naphthylmethanol (1 mmol), iodine (1.2 mmol), base (2.5 mmol), and
solvent (5 mL), 24 h unless noted otherwise. C10H7 = 1-naphthyl.
b The product was isolated by chromatographic purification on silica column.
c 1-naphthylmethanol (1 mmol), iodine (2 mmol), base (4.2 mmol), and DCM (5 mL), 1.5 h.
To further assess the effect of reaction temperature on the yield, the oxidizations of another
substrate, 4-methoxybenzyl alcohol, to 4-methoxybenzaldehyde from −40 °C to 40 °C were
examined. As shown in Figure 1, the highest yield (91%) was obtained at 10 °C. When the
temperature was lower than 10 °C, the reaction was slow, while at higher temperatures, side
reactions did increase. Thus, 10 °C was further confirmed as the optimal temperature for the
oxidization of alcohols to carbonyl compounds.
Under the optimized conditions, the oxidizations of various alcohols to carbonyl compounds
were investigated. The results, summarized in Table 2, show that a wide range of alcohols, both
primary and secondary, were smoothly converted to carbonyl compounds giving the expected
aldehyde or ketone in mostly good to excellent yields. Several α-aryl primary and secondary
alcohols gave yields higher than 95% (Entries 2, 6, 12, 15). In general, the substrates containing
electron-donating substituted aryl groups were more active than those containing electron-
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withdrawing groups (Entries 3 vs 5−10; 13 vs 14). For sluggish substrates, increasing the
amounts of iodine and t-BuOK produced better results (Entries 6−10). Among the tested
substrates, 4-nitrobenzyl alcohol was the least active, with the yield being improved to 60% with
the use of a fivefold stoichiometric amount of iodine and a four fold stoichiometric amount of t-
BuOK (Entries 9 vs 10). For the active substrates, slightly decreasing the amount of t-BuOK was
favored (Entries 1 vs 2, 12). For those oxidations in which the desired aryl aldehydes were
inclined to undergo the Tishchenko reaction, decreasing the reaction temperature along with
increased amounts of iodine and t-BuOK was the better choice (Entries 7 & 8). Moreover,
cinnamyl alcohol (1i) was exclusively transformed into cinnamaldehyde (2i) in 82% yield in a
short time, and neither iodinated nor oxidized products of the carbon-carbon double bond were
identified,25 which implies that the C=C bond of allyl alcohols is not iodinated or oxidized by the
current protocol.
100
90
80
70
60
50
40
30
CHO
I , -BuOK, DCM
t
OH
20
10
0
2
temperature
O
O
-50
-40
-30
-20
-10
0
10
20
30
40
50
Temperature oC
Figure 1. Influence of temperature on the oxidation of 4-methoxybenzyl alcohol by molecular
iodine.a aReaction conditions: 4-methoxybenzyl alcohol (1 mmol), iodine (2 mmol), t-BuOK (4.2
mmol), and DCM (5 mL) at the indicated temperature. For the temperature at or below 0 oC, the
reaction time was 10 h, while for that above 0 oC, the reaction time was 6.5 h. Yield of the
isolated product after silica gel chromatography.
To our delight, a variety of substituted propargylic alcohols derived from aliphatic or aromatic
alkynes were compatible with the reaction conditions, and clean ynones were obtained in good to
excellent yields (Entries 13–17). The most common methods for the preparation of ynones
involve the metal-catalyzed couplings of acyl halides and terminal alkynes (or alkynyl metal) as
well as the Pd-catalyzed acyl or carbonylative Sonogashira reactions.26–28 In addition, there are a
few metal-free methodologies reporting the oxidation of propargylic alcohols with different
oxidation systems.29 However, the use of molecular iodine is unprecedented. Thus, the present
protocol provides a competitive alternative method for the synthesis of ynones because of its
efficiency and avoiding both metals and peroxides.
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Table 2. Substrate scope of the oxidation of alcohols to carbonyl compounds by iodinea
Entry
1
2c
R1
R2
H
Alcohol 1 Temperature Time Product 2
Yieldb
90%
>99%f
1-naphthyl
1-naphthyl
p-CH3OC6H4-
p-CH3C6H4-
m-BrC6H4-
o-BrC6H4-
p-ClC6H4-
o-ClC6H4-
p-NO2C6H4-
p-NO2C6H4-
10 oC
10 oC
10 oC
10 oC
10 oC
10 oC
−20 oC
−20 oC
10 oC
10 oC
10 oC
10 oC
10 oC
10 oC
10 oC
10 oC
10 oC
10 oC
−20 oC
1.5 h
1.5 h
6.5 h
7.5 h
8 h
1a
1a
1b
1c
1d
1e
1f
2a
2a
2b
2c
2d
2e
2f
H
3
H
91%
4
H
83%
5
H
85%
>99% f
6d
7d
8e
9
H
5 h
H
2.5 h
8 h
76%
H
85%
1g
1h
1h
1i
2g
2h
2h
2i
H
17 h
20 h
2 h
15%
10e
H
60%
11c C6H5CH=CH-
12c
phenyl
H
82%
>99% f
phenyl
1.5 h
5 h
1j
2j
13 2-phenylethynyl p-CF3C6H4-
14d 2-phenylethynyl p-CH3OC6H4-
15d 2-phenylethynyl thiophen-2-yl
16d
17d 2-phenylethynyl C6H5CH=CH-
18c
19d
20e
85%
1k
1l
2k
2l
6 h
98%
3 h
97%
1m
1n
1o
1p
1p
1q
2m
2n
2o
2p
2p
2q
1-hexynyl
p-CH3OC6H4-
4 h
88%
2.5 h
3 h
90%
60% g
phenyl
phenyl
ethyl
ethyl
4 h
81%
>99% f
-CH2CH2CH2CH2CH2-
−40 to −15 oC 3.5 h
a
Reaction conditions: alcohol (1 mmol), iodine (2 mmol), t-BuOK (4.2 mmol), and DCM (5
mL) unless noted otherwise.
b Yield of the isolated product after silica gel chromatography unless stated otherwise.
c The reactions were performed with iodine (2 mmol) and t-BuOK (3 mmol).
d The reactions were performed with iodine (3 mmol) and t-BuOK (5 mmol).
e The reactions were performed with iodine (5 mmol) and t-BuOK (8 mmol).
f The yield was determined by 1H NMR. The 1H NMR spectra indicated that the starting alcohol
was completely transformed and there were no detectable side products inside except of the
desired carbonyl compound.
g
A mixture containing 2-iodopropionophenone (2p’). The molar ratio of 2p to 2p’, determined
by 1H NMR, was approximately 1:2.
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Notably, the oxidation of a secondary alcohol containing β-sp3 hydrogen atoms possibly
suffered from the further α-iodination of the desired ketone (Entry 18). Nevertheless, this could
be avoided by decreasing the reaction temperature along with increased amounts of iodine and t-
BuOK (Entries 19 & 20). This protocol can, however, not be applied to the preparation of
aliphatic aldehydes, since active aldehydes are inclined to undergo the disproportionation
reactions in strongly basic solutions, by pathways such as the Tishchenko reaction and the
Cannizzaro reaction, whereas aliphatic aldehydes containing α-hydrogen atom(s) tend to
condense with each other in basic solutions. Consequently, when primary alcohols containing β-
hydrogen atom(s) were employed under the present protocol, the main reactions were the
disproportionation of the aldehydes generated in situ to the corresponding esters, i.e. the
Tishchenko reaction (Scheme 1). Increasing the steric hindrance of the β-alkyl substituted
primary alcohol (e.g., 1t) led to a small amount of the corresponding tert-butyl ester (2t’).
Interestingly, under the present protocol, 2-phenylethanol (1u) generated an acetal, 2,2-
diphenethoxy-1-phenylethanone (2u), in an acceptable yield of 42%. Better results were not
achieved despite of several optimization experiments. Other analogs of 1u containing electron-
donating or electron-withdrawing groups mainly gave oxidations similar to that of β-alkyl
substituted primary alcohols, and yielded the corresponding esters (results not shown because of
their similarity to 1r).
Scheme 1. Oxidation of primary alcohols containing β-hydrogen atom(s) with molecular iodine
and t-BuOK.a
aReaction conditions: alcohol (1 mmol), iodine (2 mmol), t-BuOK (4.2 mmol), and DCM (5 mL)
for the indicated time unless noted otherwise. Yield of the isolated product after silica gel
chromatography.
bAlcohol (1 mmol), iodine (3 mmol), t-BuOK (5 mmol), and DCM (5 mL) were employed.
cA mixture containing tert-butyl cyclohexanecarboxylate (2t’). The molar ratio of 2t to 2t’was
about 78:22, which was determined by 1H NMR.
dAlcohol (1 mmol), iodine (5 mmol), t-BuOK (7.5 mmol), and DCM (5 mL) were employed.
Compared to the existing methods, the present protocol has several advantages. First, the
reagents are widely available and much cheaper than those employed in many other oxidation
systems. This reaction system does not require synthetic co-activators or special reagents. The
required common reagents are only t-BuOK and I2, both commercially available in small
amounts or in bulk and are quite cheap. Second, both reagents employed in this system and the
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corresponding side products (t-BuOH and KI) have low toxicity and are environmentally
benign.4,5 Neither transition metal-containing reagents nor peroxides are required, which is often
problematic due to the disposal of metal waste, or due the risk of explosion from the latter. Third,
this protocol permitted the reactions to be set up easily. Neither unstable reagents nor special
equipment are needed as both t-BuOK and I2 are solid and stable towards air. Neither the reagent
storage and transfer nor the reaction installation required special conditions or techniques.
Conclusions
The oxidation of various primary and secondary alcohols with molecular iodine proceeded
smoothly in the presence of potassium tert-butoxide to afford the corresponding aldehydes and
ketones in high yields at 10 °C or below. This simple protocol provides a competitive alternative
method to synthesize ynones and ketones as well as aryl aldehydes from alcohols because of
several practical features, including operational simplicity, mild reaction conditions, direct
availability of starting materials, and high yields in a relatively short reaction time at easy-to-
control reaction temperatures. Under the protocol, 2-phenylethanol yielded an unexpected
product, 2,2-diphenethoxy-1-phenylethanone. These findings exemplify the versatility of
molecular iodine in organic reactions and enriches the realm of halogen chemistry.
Experimental Section
General. Commercially available reagents were used as received. Solvents for reactions were
dried with standard procedures and stored with Schlenk flasks over molecular sieves if not noted
1
otherwise. All solvents for chromatographic separations were distilled before use. H and 13C
NMR spectra were recorded on a Bruker av 300 spectrometer at 293 K and the chemical shifts
(δ) were internally referenced by the residual solvent signals relative to tetramethylsilane (CDCl3
at 7.26 ppm, and CD3OD at 3.31 ppm for 1H; CDCl3 at 77.00 ppm, and CD3OD at 49.00 ppm for
13C). Data are reported as (s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, b =
broad; coupling constant(s) in Hz; integration). High resolution mass spectra (HRMS) were
obtained by electrospray ionization at the Department of Analytical Chemistry, Chengdu
Institute of Biology, Chinese Academy of Sciences (CAS). All the known products were
confirmed by comparison with spectroscopic analysis of the authentic samples (see
Supplementary Material). The yields in Tables 1−2 and Scheme 1 refer to isolated yields of
compounds (average of two runs) unless noted otherwise.
Starting alcohols 1a–1j, 1p–1r, 1t and 1u, potassium tert-butoxide, and molecular iodine, are
commercially available. The other starting alcohols 1k–1o, and 1s, were prepared, and the
experimental details are described in Supplementary Material.
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General procedure for the oxidation of alcohols with molecular iodine and potassium tert-
butoxide. (Tables 1 and 2, Scheme 1). In a typical run, a reaction flask (25 mL) was charged
with an indicated amount of I2 (typically, 508 mg, 2 mmol) and potassium tert-butoxide
(typically, 470 mg, 4.2 mmol). The mixture was suspended in CH2Cl2 (5 mL) and stirred at 10 oC
for 30 min, then alcohol (1 mmol) was added. The mixture was continually stirred at an indicated
temperature (typically, at 10 °C) until the consumption of the alcohol (monitoring with TLC,
typically, for a few hours), then diluted with CH2Cl2 (10 mL) and washed with saturated aqueous
sodium thiosulfate (10 mL). The aqueous phase was extracted with CH2Cl2 (three portions of 10
mL each). The combined organic phase was washed with deionized water and saturated aqueous
NaCl, dried over anhydrous Na2SO4, and then filtered and concentrated. The crude product was
purified by column chromatography (silica, hexane or hexane/EtOAc mixture as eluent). The
yields are listed in Tables 1 and 2 as well as Scheme 1.
1-Naphthaldehyde (2a).30 A white amorphous solid (111 mg, 90% yield). 1H NMR (CDCl3, 300
MHz): δ 10.36 (s, 1H), 9.26 (d, J 8.5 Hz, 1H), 8.05 (d, J 8.2 Hz, 1H), 7.94 (d, J 6.9 Hz, 1H), 7.89
(d, J 8.2 Hz, 1H), 7.68 (t, J 7.2 Hz, 1H), 7.61−7.54 (m, 2H). 13C NMR (CDCl3, 75 MHz): δ
193.44, 136.61, 135.15, 133.54, 131.18, 130.33, 128.92, 128.34, 126.81, 124.73.
1
4-Methoxybenzaldehyde (2b).30 Colorless oil (> 99% yield). The yield was determined by H
NMR. 1H NMR (CDCl3, 300 MHz): δ 9.87 (s, 1H), 7.83 (d, J 8.6 Hz, 2H), 6.99 (d, J 8.7 Hz, 2H),
3.88 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ 190.85, 164.54, 131.95, 129.84, 114.24, 55.54.
1
4-Methylbenzaldehyde (2c).30 A colorless oil (100 mg, 83% yield). H NMR (CDCl3, 300
MHz): δ 9.96 (s, 1H), 7.77 (d, J 8.0 Hz, 2H), 7.31 (d, J 7.9 Hz, 2H), 2.44 (s, 3H). 13C NMR
(CDCl3, 75 MHz): δ 192.04, 145.55, 134.12, 129.83, 129.68, 21.87.
1
3-Bromobenzaldehyde (2d).30 A light yellow oil (157 mg, 85% yield). H NMR (CDCl3, 300
MHz): δ 9.95 (s, 1H), 7.99 (t, J 1.6 Hz, 1H), 7.81 (d, J 7.6 Hz, 1H), 7.70 (ddd, J 1.0 Hz, 1.8 Hz,
7.9 Hz, 1H), 7.42 (d, J 7.8 Hz, 1H). 13C NMR (CDCl3, 75 MHz): δ 190.64, 137.79, 137.14,
132.12, 130.50, 128.28, 123.19.
2-Bromobenzaldehyde (2e).30 A light yellow oil (> 99% yield). The yield was determined by 1H
NMR from the extraction of the reaction mixture. 1H NMR (CDCl3, 300 MHz): δ 10. 35 (s, 1H),
7.93−7.86 (m, 1H), 7.67−7.60 (m, 1H), 7.48−7.38 (m, 2H). 13C NMR (CDCl3, 75 MHz): δ
191.80, 135.28, 133.82, 133.40, 129.78, 127.85, 127.06.
1
4-Chlorobenzaldehyde (2f).30 A colorless oil (107 mg, 76% yield). H NMR (CDCl3, 300
MHz): δ 9.98 (s, 1H), 7.82 (d, J 8.4 Hz, 2H), 7.81 (d, J 8.4 Hz, 2H). 13C NMR (CDCl3, 75 MHz):
δ 190.71, 140.69, 134.51, 130.72, 129.24.
1
2-Chlorobenzaldehyde (2g).30 A colorless oil (119.5 mg, 85% yield). H NMR (CDCl3, 300
MHz): δ 10.43 (s, 1H), 7.78 (dd, J 1.6 Hz, 7.7 Hz, 1H), 7.41 (dt, J 1.6 Hz, 7.6 Hz, 1H),
13
7.44−7.39 (m, 1H), 7.35−7.224 (m, 2H). C NMR (CDCl3, 75 MHz): δ 189.25, 137.51, 134.83,
132.05, 130.26, 128.97, 126.98.
1
4-Nitrobenzaldehyde (2h).30 A slightly yellowish solid (91 mg, 60% yield). H NMR (CDCl3,
300 MHz): δ 10.16 (s, 1H), 8.40 (d, J 8.6 Hz, 2H), 8.08 (d, J 8.7 Hz, 2H). 13C NMR (CDCl3, 75
MHz): δ 190.26, 151.11, 140.03, 130.48, 124.31.
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1
Cinnamaldehyde (2i).31 A slightly yellowish oil (108.4 mg, 82% yield). H NMR (CDCl3, 300
MHz): δ 9.70 (d, J 7.7 Hz, 1H), 7.59−7.48 (m, 3H), 7.46−7.40 (m, 3H), 6.71 (dd, J 7.7 Hz, 16.0
Hz, 1H). 13C NMR (CDCl3, 75 MHz): δ 193.80, 152.88, 133.84, 131.22, 129.01, 128.42, 128.40.
1
Benzophenone (2j).30, 31 A white amorphous solid (180 mg, 99% yield). H NMR (CDCl3, 300
MHz): δ 7.80 (d, J 7.8 Hz, 4H), 7.58 (t, J 7.4 Hz, 2H), 7.47 (d, J 7.4 Hz, 4H). 13C NMR (CDCl3,
75 MHz): δ 196.63, 137.40, 133.32, 129.93, 128.15.
3-Phenyl-1-(4-(trifluoromethyl)phenyl)prop-2-yn-1-one (2k).28 A pale yellow solid (231 mg,
1
85% yield). H NMR (CDCl3, 300 MHz): δ 8.29 (d, J 8.1 Hz, 2H), 7.75 (d, J 8.4 Hz, 2H),
13
7.69−7.65 (t, 2H), 7.51−7.38 (m, 3H). C NMR (CDCl3, 75 MHz): δ 176.51, 139.23 (q, J 1.2
Hz), 134.97 (q, J 32.5 Hz), 133.10, 131.10, 129.67, 128.68, 125.56 (q, J 9.4 Hz), 123.45 (q, J
271.1 Hz), 119.51, 94.35, 86.46.
1-(4-Methoxyphenyl)-3-phenylprop-2-yn-1-one (2l).28, 30 A pale yellow solid (231.5 mg, 98%
yield). 1H NMR (CDCl3, 300 MHz): δ 8.19 (d, J 8.7 Hz, 2H), 7.68−7.65 (m, 2H), 7.50−7.38 (m,
3H), 6.98 (d, J 8.7 Hz, 2H), 3.89 (s, 3H). 13C NMR (CDCl3, 75 MHz): δ 176.62, 164.41, 132.89,
131.92, 130.55, 130.17, 128.59, 113.81, 92.27, 86.83, 55.54.
3-Phenyl-1-(thiophen-2-yl)prop-2-yn-1-one (2m).28, 30 A pale yellow solid (206 mg, 97%
1
yield). H NMR (CDCl3, 300 MHz): δ 8.01 (d, J 3.8 Hz, 1H), 7.73 (d, J 4.9 Hz, 1H), 7.66 (d, J
13
7.1 Hz, 2H), 7.49−7.39 (m, 3H), 7.19 (t, J 3.9Hz, 1H). C NMR (CDCl3, 75 MHz): δ 169.78,
144.86, 135.26, 133.00, 130.83, 128.66, 128.32, 119.86, 91.70, 86.41.
1
1-(4-Methoxyphenyl)hept-2-yn-1-one (2n).32 A slightly yellow liquid (190 mg, 88% yield). H
NMR (CDCl3, 300 MHz): δ 8.11 (d, J 9.0 Hz, 2H), 6.95 (d, J 9.0 Hz, 2H), 3.88 (s, 3H), 2.49 (t, J
7.0 Hz, 3H), 1.70−1.60 (m, 2H), 1.58−1.44 (m, 2H), 0.96 (t, J 7.4 Hz, 3H). 13C NMR (CDCl3, 75
MHz): δ 176.96, 164.21, 131.87, 130.28, 113.67, 95.92, 79.57, 55.52, 29.85, 22.05, 18.85, 13.51.
1
(E)-1,5-Diphenylpent-1-en-4-yn-3-one (2o).26 A slightly yellow solid (209 mg, 90% yield). H
NMR (CDCl3, 300 MHz): δ 7.92 (d, J 16.1 Hz, 1H), 7.67−7.59 (m, 4H), 7.48−7.40 (m, 6H), 6.87
(d, J 16.1 Hz, 1H). 13C NMR (CDCl3, 75 MHz): δ 178.17, 148.31, 133.92, 132.86, 131.12,
130.57, 129.00, 128.63, 128.59, 128.41, 120.06, 91.49, 86.49.
Propiophenone (2p).30 A colorless oil (109 mg, 81% yield). 1H NMR (CDCl3, 300 MHz): δ 7.97
(d, J 7.8 Hz, 4H), 7.56 (t, J 7.3 Hz, 2H), 7.46 (d, J 7.4 Hz, 4H), 3.01 (q, J 7.2 Hz, 2H), 1.23 (t, J
7.2 Hz, 3H). 13C NMR (CDCl3, 75 MHz): δ 200.81, 136.82, 132.83, 128.49, 127.90, 31.72, 8.17.
1
Cyclohexanone (2q).30 A colorless oil (> 99% yield). The yield was determined by H NMR
1
from the extraction of the reaction mixture. H NMR (CDCl3, 300 MHz): δ 2.32 (t, J 6.6 Hz,
2H), 1.90−1.80 (m, 4H), 1.75−1.67 (m, 2H).
1
3-Phenylpropyl 3-phenylpropanoate (2r).31 A colorless oil (196 mg, 73% yield). H NMR
(CDCl3, 300 MHz): δ 7.35−7.28 (m, 4H), 7.26−7.16 (m, 6H), 4.12 (t, J 6.5 Hz, 2H), 2.98 (t, J 7.8
Hz, 2H), 2.66 (t, J 7.7 Hz, 4H), 2.01−1.90 (m, 2H). 13C NMR (CDCl3, 75 MHz): δ 172.95,
141.17, 140.50, 128.50, 128.42, 128.39, 128.29, 126.27, 125.99, 63.80, 35.86, 32.12, 30.96,
30.16.
2-Benzamidoethyl 2-benzamidoacetate (2s). A white amorphous solid (111 mg, 68% yield). 1H
NMR (CD3OD, 300 MHz): δ 7.88−7.76 (m, 4H), 7.56−7.47 (m, 2H), 7.46−7.38 (m, 4H), 4.34 (t,
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J 5.4 Hz, 2H), 4.14 (s, 2H), 3.66 (t, J 5.4 Hz, 2H). 13C NMR (CD3OD, 75 MHz): δ 171.37,
170.51, 170.45, 135.38, 134.79, 132.95, 132.69, 129.57, 129.51, 128.37, 128.29, 64.66, 42.62,
40.00. HRMS (ESI) calcd for C18H18N2NaO4 (M++Na): 349.1159; found: 349.1160.
Cyclohexylmethyl cyclohexanecarboxylate (2t).31 A colorless oil (194 mg, 90% yield), which
1
was a mixture containing 2t and tert-butyl cyclohexanecarboxylate (2t’) according to the H
1
NMR spectrum. The molar ratio of 2t to 2t’ was approximately 78:22. 2t (70% yield). H NMR
(CDCl3, 300 MHz): δ 3.84 (d, J 6.4 Hz, 2H), 2.27 (tt, J 3.6, 11.2 Hz, 1H), 1.92−1.10 (m, 19H),
1.00−0.86 (m, 2H).13C NMR (CDCl3, 75 MHz): δ 176.19, 69.21, 43.27, 37.10, 29.60, 29.02,
26.32, 25.78, 25.64, 25.43.
1
2,2-Diphenethoxy-1-phenylethanone (2u). Light yellow oil (50.5 mg, 42% yield). H NMR
(CDCl3, 300 MHz): δ 8.01 (d, J 7.6 Hz, 2H), 7.54 (d, J 7.2 Hz, 1H), 7.38 (t, J 7.4Hz, 2H),
13
7.28−7.09 (m, 10H), 5.24 (s, 1H), 3.88−3.67 (m, 4H), 2.87 (t, J 6.8 Hz, 4H). C NMR (CDCl3,
75 MHz): δ 193.62, 138.38, 133.62, 133.43, 129.69, 128.95, 128.31, 128.28, 126.30, 102.49,
68.37, 36.16. HRMS (ESI) calcd for C24H24NaO3 (M++Na): 383.1618; found: 383.1617.
Acknowledgements
The authors thank the financial support from the National Natural Science Foundation of China
(No. 20971105) and the Fundamental Research Funds for the Central Universities
(XDJK2012B011).
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