BODIPY catalyzed amide synthesis promoted by BHT and air under visible light

Article abstract of DOI:10.1039/c6ob00736h

A novel and efficient protocol for the synthesis of amides is reported which employs a BODIPY catalyzed oxidative amidation reaction between aromatic aldehydes and amines under visible light. Compared with the known Ru or Ir molecular catalysts and other organic dyes, the BODIPY catalyst showed higher reactivity toward this reaction. Mechanistic studies reveal that dioxygen could be activated through an ET and a SET pathway, forming active peroxides in situ, which are vital for the key step of the reaction, i.e. the oxidation of hemiaminal to amide. The broad substrate scope and mild reaction conditions make this reaction practically useful and environmentally friendly for the synthesis of amide compounds.

Full text of DOI:10.1039/c6ob00736h

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Organic & Biomolecular Chemistry
PAPER
BODIPY Catalyzed Amide Synthesis Promoted by BHT and Air
under Visible Light
Xiao-Fei Wang,a Shu-Sheng Yu,a Chao Wang,a Dong Xuea*and Jianliang Xiaoa, b
Received 00th January 20xx,
Accepted 00th January 20xx
A novel and efficient protocol for the synthesis of amides is reported which employs a BODIPY catalyzed oxidative
amidation reaction between aromatic aldehydes and amines under visible light. Compared with the known Ru or Ir
molecular catalysts and other organic dyes, the BODIPY catalyst showed a higher reactivity toward this reaction.
Mechanistic studies reveal that dioxygen could be activated through an ET and a SET pathway, forming the active
peroxides in situ, which are vital for the key step of the reaction, i.e. the oxidation of hemiaminal to amide. The broad
substrate scope and mild reaction conditions make this reaction practically useful and environmental friendly for the
synthesis of amide compounds.
DOI: 10.1039/x0xx00000x
www.rsc.org/
a.Visible-Light-Mediated Decarboxylation/Oxidative Amidation of a-Keto Acids with Amines
Introduction
O
O
Cat.
Cat.
The amide bond is not only the structural backbone of
protein and peptides,1 but also prevalent in natural products,
pharmaceuticals, agrochemicals, materials and polymers.2 The
most used amide forming transformation is the coupling
reaction of amines with acylating agents, such as acyl
chlorides,3 or with carboxylic acids in the presence of coupling
agents.4From the view point of green chemistry, this protocol
generates a copious amount of byproducts and chemical
wastes and so needs to be improved or replaced.5 Thus,
“Amide formation avoiding poor atom economy reagents” is a
big challenge and highly important in organic chemistry.6
Another strategy for amide bond synthesis is the use of
catalytic methods.7 Synthetic reactions catalyzed by boronic
acids,8 N-heterocyclic carbenes,9 and transition-metals10−12
have shown potential applications in amide formation. In 2014,
Lei13 and Leow14 reported elegant oxidative amidation of α-
Keto acids and aromatic aldehydes with amines, providing a
greener catalytic process for amide formation by photoredox
catalysis (Scheme1).15-18 Preliminary mechanistic studies reveal
R3
OH
+
H
R3
N
N
[Ru(phen)3]Cl2
DMSO, O2, 32 oC
R1
R1
R2
O
R2
b. Phenazinium Salt-Catalyzed Aerobic Oxidative Amidation
O
Et
O
Cat.
EtOSO3
N
R3
Cat.
H
R3
H
N
N
R1
+
R1
THF (inhib.-free)
r.t., air
R2
R2
N
c. This work
Ph
Cat..
O
O
R3
Cat.
N
H
R3
Br
Br
H
N
R1
N
N
R1
+
R2
B
Dioxane, r.t., air
R2
F
F
Scheme 1 Oxidative Amidation of Aromatic acids and Aldehydes.
which are traditionally used as chemo sensors, labelling
reagents, fluorescent switches and laser dyes. 19,20 Recently,
the
tandem
oxidation/[3+2]
cycloaddition,21
cross-
dehydrogenative-coupling reaction22 and photo-oxidation23
catalyzed by BODIPY derivatives has been reported,providing
new example of promising metal-free photocatalysts with high
stability and easy-to-modify structures, which would allow for
easy optimization of their photocatalytic properties.24 These
BODIPY derivatives show strong absorption of visible light and
long-lived excited triplet state, activating O2 under visible light
irradiation. However, the application of these catalysts in
amide synthesis has not been reported. In continuing our work
on photoredox catalysis driven by visible light,25 herein we
report a BODIPY-catalyzed aerobic oxidative amidation of
aromatic aldehydes with low catalytic loading. Compared with
the known Ru or Ir molecular catalysts and other organic dyes,
the BODIPY catalyst showed higher reactivity toward this
reaction. The broad substrate scope and mild reaction
conditions make this reaction practically useful and
environmental friendly for the synthesis of amide compounds.
that O2 activation under visible light irradiation might be the
13
key step, and the photocatalysts Ru(bpy)3Cl2
phenazinium salts14 are vital for the reaction rate. The search
for new metal-free photocatalysts with low cost, low toxicity
and high efficiency for different organic reactions is a worthy
endeavor in this area of research.
and
BODIPY derivatives are a class of privileged organic dyes,
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investigated. We screened three light sources, 24 W
Household bulbs, 3 W Blue LEDs and 3 W Green LEDs.
Although BODIPY P2 shows strong absorption in much red-
shifted region of 523 nm (Figure 1), 3 W Blue LEDs gave the
highest yield (Table 1, entries 11, 17-18). The reason may be
that the energy of blue light is higher than green light.
Results and discussion
Our initial investigation focused on the direct oxidative
amidation of 4-bromobenzaldehyde (1a, 1 eq.) with pyrrolidine
(
2a, 3 equiv.) in the presence of 2 mol% of a photosensitizer
under the irradiation of 3 W Blue LEDs in MeCN. As seen from
Table 1, among the 15 photocatalysts that we had tested, nine
of the readily available ones gave poor yields (Table 1,
entries1-15). In contrast, the BODIPY derivatives P1-P6 gave
better results (Table 1, entries 10-15), with the catalyst P2
furnishing the highest yield of 60% after 12h at room
temperature (Table1, entry 11).26 Light source was then
Table 1 Optimization of reaction conditions a
Entry
Cat.
Additive
Solvent
MeCN
MeCN
MeCN
MeCN
Yieldb
37%
46%
42%
44%
1
2
3
4
Ru(bpy)3Cl2
-
-
-
-
Ru(phen)3Cl2
Ru(phen)3(PF6)2
Ir(dtbpy)(ppy)2PF6
Phenazine
5
-
MeCN
41%
Ethosulfate
6
7
Nile Red
-
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
H2O
29%
26%
22%
16%
27%
60%
48%
47%
54%
56%
9%
Rhodamine B
-
8
Alizarin Red S
-
9
Methylene Blue
-
10
11
12
13
14
15
16c
17d
18e
19
20
21
22
23
24
25
26
27f
28
P1
P2
P3
P4
P5
P6
P2
P2
P2
P2
P2
P2
P2
P2
P2
P2
no
P2
no
-
-
-
-
-
-
Figure 1 a) UV-Vis absorption spectra of BODIPY P2. c = 1.0 ×10-5 M in MeCN, 25
oC. b) Fluorescence spectra of BODIPY P2 at increasing concentration of 2a (0, 0.2
mmol, 0.4 mmol, 0.6 mmol, 0.8 mmol, 1.0 mmol, 1.2 mmol) upon excitation at
438 nm. c = 1.0 × 10-3 M in MeCN, 25 oC. The inset represents the Stern-Volmer
plot of BODIPY P2 vs. the concentration 2a.
-
-
-
50%
37%
11%
30%
65%
72%
85%
92%
91%
0
-
-
DMSO
THF
-
-
In addition, we found that the BODIPY P2 show strong
fluorescence with a maximal peak at 558 nm in MeCN (Figure 1,
b). The progressive addition of pyrrolidine 2a quenched the
fluorescence upon excitation of P2 with a quenching constant
K = 14.6 M-1 in MeCN. These results suggested that the
interaction of photoexcited BODIPY P2 with 2a was strong.
Next, solvents were screened and dioxane was found to be the
best solvent for this reaction, affording the product in 72%
yield (Table 1, entries 17-20). In an effort to probe whether or
not radicals were involved in the reaction, the effect of radical
inhibitors such as BHT (3, 5-di-tert-butyl-4-hydroxytoluene)
and BHEB (2,6-di-tert-butyl-4-ethylphenol) were investigated
(Table 1, entries 21-25). To our surprise, when two equivalents
of BHT or BHEB were added to the reaction mixture, the yield
was significantly improved to about 90% (Table 1, entries 22,
23). The Leow group14 showed that inhibitor-free solvents give
the best results foroxidative amidation reactions. Clearly, this
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
Dioxane
BHT (1 eq.)
BHT (2 eq.)
BHEB (2 eq.)
BHT (2 eq.)
no
0
no
0
R'
P4:
R' = OCH3
P1: R = Cl
Br
N
Br
R
R
P5: R' = CF3
P6:
P2:
R = Br
R = I
N
N
N
P3:
B
R' = Br
B
F
F
F
F
a: aldehyde 1a (0.2 mmol, 1 eq.), pyrrolidine 2a (3 equiv.), catalyst (2 mol%),
irradiation with a 3 W Blue LEDs under air at room temperature for 12 h. b: Yield
determined by 1H NMR, 1,3,5-trimethoxylbenzene as internal standard. c: under
argon. d: 24 W Household bulb. e: 3 W Green LEDs. f: No light.
2 | J. Name., 2012, 00, 1-3
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is different from our findings. It is reasonable to suspect that
the BHT-OOH comes from the reaction of BHT with oxygen
activated by the photocatalyst under the irradiation of the 3 W
Blue LEDs. Careful study showedthat BHT peroxide, BHT-OOH,
could be isolated underthe identical reaction conditionsin the
absence of the substrates.The BHT-OOH compound showed
higher reactivity than H2O2, and could serve as an oxidant for
the reported oxidative amidation of aldehydes (vide infra).26
Notably, the photocatalyst, oxygen and visible light are all
essential for the amidation reaction (Table 1, entries 16, 27-28).
In the absence of any of these components, no reaction
occurred.
Ph
O
O
P2 (2 mol %)
3 W Blue LEDs
P2
Br
N
+
H
Br
N
H
R1
R1
Dioxane, BHT
Air, r.t.,
N
N
B
F
F
1
2a
3
O
O
N
O
O
N
N
N
Br
Cl
F
3a, 90%
3b, 72%
3c, 75%
3d, 70%c
O
N
O
N
O
N
O
N
Scheme 3 Amidation of Aromatic Aldehydes with Amines.
a4-Formylbenzonitrile 1f (0.2 mmol, 1 equiv.), amine (3 equiv), P2 (2 mol%), BHT (2
equiv.), under air, dioxane (2 mL), Blue LEDs irradiation at room
3
W
O2N
NC
F3C
O2N
MeO2C
temperature.Isolated yield.b Amine (4 equiv.) and additional P2 (2 mol%) was added
3e, 75%
3f, 95%
3g, 85%
3h, 83%
during reaction.
O
N
O
N
O
N
O
N
Br
pyrrolidine afforded the mono-amidation product 3t albeit
with low yield. However, aliphatic aldehydes could not give the
desired amide products under the optimized reaction
conditions.
Me
MeO
3i, 75%c
3j, 74%c
3k, 78%
3l, 86%
O
N
O
H
O
N
O
N
O
N
S
N
To further demonstrate the utility of this new protocol for
amides synthesis, we run two direct oxidative amidation
reactions of 4-bromobenzaldehyde with pyrrolidine (2a, 3
equiv.) under the irradiation of solar light outside the
laboratory in the presence of 2 mol% P2, one at 0.2 mmol and
the other at gram scale (Scheme 4). After 6 and 48 hours, the
desired products were isolated in 90% and 68% yield,
respectively. Compared with the reaction irradiated with 3 W
LEDs, the solar light was more effective in promoting the
reaction, showing the potential of application of this
photocatalyst in “greener” organic synthesis.
3m, 80%
3o, 35%
3p, 72%b
3n, 89%
O
N
O
O
O
N
N
N
N
N
N
Me
3q, 92%b
3r, 79%b
3s, 71%
3t, 59%
Scheme 2 Amidation of Aromatic Aldehydes with Pyrrolidine.
aAldehydes 1 (0.2 mmol, 1 equiv.), pyrrolidine2a (3 equiv.), P2 (2 mol%), BHT (2
equiv.), under air, dioxane (2 mL), 3 W Blue LEDs irradiation at room temperature
for 12 h. Isolated yield.b Reaction for 16 h.c Reaction for 24 h.
With the optimized reaction conditions in hand, a wide
range of aromatic aldehydes (1a-t) were investigated to
illustrate the reaction efficiency and scope in the presence of
the photosensitizer P2 under an air atmosphere (Scheme 2).
Generally, the desired amides (3a-t) were obtained in good to
excellent yields via this BODIPY catalyzed oxidative amidation
reaction under visible light. The aromatic aldehydes bearing
electron-withdrawing or donating groups all underwent the
amidation smoothly to give the desired amides in good
toexcellent yields (3a-3l, 70%-95%). A wide range of useful
functional groups attached to the aromatic aldehydes, such as
CN, COOMe, Br, Cl, F, CF3 and NO2, were tolerated under the
reaction conditions and are available for further
functionalization. Furthermore, polycyclic and heterocyclic
aromatic aldehydes also gave the desired products in 59-92%
Scheme 4 Oxidative Amidation Using Solar Light Irradiation.
Next, various amines were examined to explore the
generality of the reaction conditions. Six- and seven-
membered ring amines reacted with 4-formylbenzonitrile 1f
smoothly to give the corresponding amides in good yields
(Scheme 3). Isoindoline and subsitituted six-memberred ring
amines are also good substrates, affording the desired amides
in 68%-96% yields. However, the reaction of 1f with
benzylamine and N-methylbenzylamine could not give the
desired products (3fk, 3fl) under the optimized reaction
(
3m-3s). In addition, the reaction of isophthalaldehyde with
conditions, which ascribe to the easy generation of imines of
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these two amines under the reaction conditions. In addition,
the primary amines and aromatic amines could not give the
desired amide products under the optimized reaction
conditions.
O
O
Air, Dioxane, 12 h
N
H
H
+
H2O2
+
1)
2)
N
(2 equiv)
H
Br
Br
Br
Br
3a
, 76% yield
1a
2a
In order to understand the effect of BHT on this reaction,
the following studies were conducted. As showed in Scheme 5,
when a solution of BHT in dioxane was irradiated under
identical reaction conditions for 6 hours, a BHT hydroperoxide,
BHT-OOH, was isolated with 95% yield. For the analogues of
BHT, the corresponding hydroperoxide were also obtained
with high isolated yields. These BHT-OOH compounds showed
higher reactivity than H2O2 toward the oxidative amidation of
4-bromobenzaldehyde with pyrrolidine, affording the desired
product with high yields27 (Scheme 6). In addition, the BHT-
OOH compound could promote the reaction between
pentane-2, 4-dioneand aniline under solvent-free condition,
affording amide 4a in 63% yield (Scheme 6).28 These results
demonstrate that BHT-OOH can be easily formed in situ and
most likely contributes to the amidation reaction, and it could
be used as an easy-to-handle oxidant in oxidation reactions.
O
O
N
O
Air, Dioxane, 2 h
+
+
N
H
1a
2a
3a
, 87% yield
OOH
(2 equiv)
O
N
O
O
Air, Dioxane, 2 h
Air, Dioxane, 2 h
+
+
+
H
H
3)
4)
N
H
2a
Br
Br
Br
Br
1a
3a, 83% yield
OOH
(2 equiv)
O
O
N
O
+
N
H
2a
1a
3a
, 84% yield
tBu
OOH
(2 equiv)
O
NH2
H
N
O
O
Air, Neat, 12 h
5)
+
+
O
4a, 12 h, 63%
OOH
(2 equiv)
Scheme 6 The BHT-OOH Compound Promoted Oxidative Amidation
Leow group14, which showed that when H2O2 was used as the
oxidant, photocatalyst displayed no accelerating effect on the
oxidative amidation under visible light irradiation. In the
current study, H2O2 was detected in the reaction of 4-
bromobenzaldehyde with pyrrolidine under visible light
irradiation after 4 hours using P2 as photocatalyst (see ESI,
Figure S4). These results suggest that the BHT-OOH compound
or H2O2, which are generated in situ from O2, are the real
oxidants for this oxidative reaction.
Scheme 5 The Reaction of BHT derivatives with oxygen.
To gain insight into the amidation mechanism, control
experiments were performed. First, we conducted the radical
chain probe experiment (scheme 7). When the reaction was
irradiated with visible light, the reaction went well. However,
the reaction stopped after the light was switched off. And the
reaction worked again, when the light was turned on. The
experiment of on-off switching of visible light suggested that
the reaction is not a radical chain reaction. Then, the effect of
photocatalyst was studied (the results are shown in the ESI).
When H2O2 (1 equiv.) was added to the reaction of 4-
bromobenzaldehyde (1a) with pyrrolidine (2a) in the absence
of photocatalyst and visible light, the product 3a was obtained
only in 29% yield after 4 hours. However, when both the
photocatalyst P2 (2 mol%) and H2O2 (1 equiv.) were added
under the optimized reaction conditions, the product yield
increased to 61% under visible light irradiation after 4 hours,
suggesting that the amidation with H2O2 as oxidant was also
promoted by light and photosensitizer P2 (see ESI, Table S4).
These results are different from the findings reported by the
Scheme 7 The Experiment of On-Off Switching of Visible Light
Based on our experiments26 and the literature reports,22, 24
a
reaction mechanism for this oxidative amidation is suggested
as shown in Scheme 8. Firstly, P2 is converted into a high-
energy excited singlet 1[P2]*] under visible light irradiation,
which undergoes intersystem crossing (ISC) to produce a
triplet 3[P2]*24. Secondly, dioxygen is activated through two
possible pathways. One is an energy transfer (ET) pathway
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from 3[P2]* to O2, regenerating the ground state P2 while (Scheme 8).26 These results support the proposal that the two
producing the singlet oxygen (1O2). The latter then reacts with possible pathways may operate in parallel in this reaction.
BHT, generating the hydroperoxide radical ·OOH and the BHT
radical
BHT-OOH (Scheme 8).26 Subsequently, the BHT-OOH
compound oxidizes the α-hydroxy amine to afford the amide
A, which combine to give rise to the BHT hydroperoxide
Conclusions
B
In summary, we have developed a novel protocol of amide
synthesis, which involves the aerobic oxidative amidation of
aromatic aldehydes with amines under the photoredox
catalysis of a BODIPY. Experiments suggest that dioxygen could
be activated through an ET and a SET pathway, forming the
active oxidants in situ. The mild reaction conditions, broad
substrate scope and air as oxidant make the protocol
practically useful and environmentally friendly for the
synthesis of compounds containing the amide motifs.
Experimental
General Information
Scheme 8 Proposed Mechanism for the Aerobic Oxidative Amidation.
All commercial reagents were used without further
purification unless specified. Analytical thin layer
chromatography (TLC) was performed on precoated silica gel
60 F254 plates and visualization on TLC was achieved by UV
light (254 nm). Flash column chromatography was undertaken
on silica gel (400 mesh) using a proper eluent. 1H and 13C NMR
spectra were recorded on Bruker Avance 400 spectrometer in
CDCl3 using tetramethylsilane (TMS) as the internal standard.
All spectra are referenced to CDCl3 residual CHCl3 peak (1H
NMR = 7.26 ppm; 13C NMR = 77.1 ppm). All chemical shifts are
quoted in parts per million (ppm), measured from the center
of the signal except in the case of multiplets of more than one
proton, which are quoted as a range. Splitting patterns are
abbreviated as follows: s = singlet, d = doublet, t = triplet, q =
quartet, m = multiplet, and br = broad and combinations
thereof. HRMS (ESI) were performed on a Fourier Transform
Ion Cyclotron Resonance Mass Spectrometer. Melting points
(MP) were determined uncorrected. IR spectra were recorded
in KBr disks with a microscopic melting point X-5 spectrometer.
Fluorescence measurements were conducted on a F-7000
Hitachi fluorescence spectrometer.
product and BHT-OH. On the other hand, dioxygen can also be
activated through a single electron transfer (SET) pathway to
·-
form the superoxide radical O2 from the radical anion [P2]·-,
which is generated by SET from the amine to the excited state
3[P2]*. Then, the active species O2·- produces H2O2 by reacting
with the amine radical cation presumably via H-atom
abstraction, which oxidizes
B
to afford the amide.
O
H
O
O
N
DMPO
N
+
N
H
Scavenger:DMPO (4 equiv)
P2 (2 mol %), Blue LEDs
Air, Dioxane, 12 h
Br
Br
3a, 27%b
1a
2a
O
OH
P2 (2 mol %)
Scavenger for 1O2
DABCO: 0%b
TEMP: 16%b
Scavenger (2 equiv)
3 W Blue LEDs
Air, Dioxane, 6 h
OOH
N
N
O
O
N
DABCO
H
+
N
Scavenger: DABCO (4 equiv)
P2 (2 mol %), Blue LEDs
Air, Dioxane, 12 h
H
Br
Br
General Experimental Procedure for Preparation of
Photosensitizers
1a
2a
3a, 26%b
Scheme 9 The Capture of Reaction Intermediates.
aP2 (2 mol %), 4-bromobenzaldehyde 1a (1 eq., 0.2 mmol), pyrrolidine2a (3 eq.),
scavenger (4 equiv.) under air, 3 W Blue LEDs, dioxane (2 mL). bYield determined by 1
NMR, 1,3,5-trimethoxylbenzene as internal standard. DMPO 5,5-dimethyl-1-
1,4-Diazabicyclo[2.2.2]octane, TEMP 2,2,6,6-
5,5-Difluoro-1,3,7,9-tetramethyl-10-phenyl-5H-dipyrrolo[1,2-
c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide (I).29 Trifluoroacetic
acid (25 μL, 0.33 mmol) in dry CH2Cl2 (1.5 mL) was added
dropwise to a solution of benzaldehyde (0.27 mL, 2.5 mmol)
and 2,4-dimethyl-1H-pyrrole (0.64 mL, 6.25 mmol) in dry
CH2Cl2 (125 mL) at room temperature. The reaction mixture
was stirred for 3 hours at room temperature, 2, 3-Dichloro-5,
6-dicyano-1, 4-benzoquinone (0.56 g, 2.5 mmol) was added
under ice bath cooling and the mixture was stirred for 10 min.
After stirring for an additional 1 hour at room temperature,
NEt3 (5 mL, 36 mmol) was added, followed by slow addition of
H
=
pyrroline-N-oxide,DABCO
tetramethylpiperidine.
=
=
The formation of the superoxide is supported by the
·-
observation that when an O2 scavenger, 5, 5-dimethyl-1-
pyrroline-N-oxide (DMPO), was added to reaction mixture
under the optimized reaction conditions, the yield of desired
product decreased to 27% (Scheme 9).26 Similarly, when an1O2
scavenger, 1, 4-diazabicyclo [2.2.2] octane (DABCO), was
added to the reaction mixture under the optimized reaction
conditions, the yield of desired product decreased to 26%
BF3ꢀEt2O (5 mL, 40.5 mmol). After 2 hours of stirring at room
temperature, the reaction mixture was washed with saturated
aqueous Na2CO3 solution (3 × 50 mL), dried over Na2SO4, and
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concentrated on a rotary evaporator. The brown, oily residue (m, 3 H), 7.27-7.25 (m, 2 H), 2.67 (s, 6 H), 1.40 (s, 6 H) ppm; 13
C
was purified by column chromatography on silica. The product NMR (100 MHz, CDCl3): δC 156.8, 145.3, 141.3, 134.7, 131.3,
fraction showing greenish fluorescence was dried to yield a 129.5, 129.4, 127.7, 85.7, 16.9, 16.0 ppm.
red-brown solid.
2,8-Dihalogen-5,5-difluoro-1,3,7,9-tetramethyl-10-phenyl-5H- tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-
dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide(P1- ium-5-uide
P4): Red solid; 30% yield; 1H NMR (400 MHz,
2,8-Dibromo-5,5-difluoro-10-(4-methoxyphenyl)-1,3,7,9-
(
P6).30 A mixture of the 1,3,7,9-tetramethyl-BODIPY (0.5 mmol, CDCl3): δH 7.14 (d, J = 8.5 Hz, 2 H), 7.03 (d, J = 8.5 Hz, 2 H), 3.89
1 equiv.) and NXS (2.0 mmol, 4 equiv.,NXS = NCS or NBS or NIS) (s, 3 H), 2.58 (s, 6 H), 1.42 (s, 6 H) ppm; 13C NMR (100 MHz,
in CH2Cl2 (20 mL) was stirred overnight at room temperature. CDCl3): δC 160.5, 153.7, 142.3, 140.6, 130.8, 129.1, 126.3,
After completion of the reaction, the solvent was concentrated 114.8, 111.7, 55.4, 13.9, 13.7 ppm.
under reduced pressure. The crude product was further 2,8-Dibromo-5,5-difluoro-1,3,7,9-tetramethyl-10-(4-
purified
using column chromatography (petroleum (trifluoromethyl)phenyl)-5H-dipyrrolo[1,2-c:2',1'-
P5): Red solid; 35% yield;
ether/dichloromethane = 20:1) to afford the corresponding f][1,3,2]diazaborinin-4-ium-5-uide
(
photosensitizers P1 to P6.
1H NMR (400 MHz, CDCl3): δH 7.82 (d, J = 8.0 Hz, 2 H), 7.44 (d, J
= 8.0 Hz, 2 H), 2.60 (s, 6 H), 1.34 (s, 6 H) ppm; 13C NMR (100
MHz, CDCl3): δC 154.8, 140.3, 139.8, 138.3, 132.1 (q, JC-F = 32.8
Hz, 1 C), 130.0, 128.7, 126.4 (q, JC-F = 3.5 Hz, 1 C), 123.7 (q, JC-F
General Experimental Procedure for the Synthesis of Oxidation
Amidation Compounds
A sealed tube was equipped with a magnetic stir bar and was = 271 Hz, 1 C), 112.3, 13.9, 13.8 ppm.
charged with P2 (2 mg, 2 mol%), BHT (88 mg, 0.4 mmol, 2 2,8-Dibromo-10-(4-bromophenyl)-5,5-difluoro-1,3,7,9-
equiv.), aldehydes (0.2 mmol, 1 equiv.), amines (0.6 mmol, 3 tetramethyl-5H-dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-
equiv.) and dioxane (2 mL) under air at room temperature. The ium-5-uide
reaction tube was placed at a distance of 5 cm from 3 W Blue CDCl3): δH 7.68 (d, J = 8.4 Hz, 2 H), 7.15 (d, J = 8.4 Hz, 2 H), 2.61
LEDs and stirred for 12 hours (for substrates 1a 1b 1c 1e 1f
(s, 6 H), 1.41 (s, 6 H) ppm; 13C NMR (100 MHz, CDCl3): δC 154.4,
2j), 16 hours (for 140.4, 133.3, 132.8, 130.2, 129.6, 123.9, 112.1, 112.0, 14.0,
2c), 24 hours (for substrates 1d 1i 1j 2b 13.7 ppm.
(
P6): Red solid; 43% yield; 1H NMR (400 MHz,
,
,
,
,
,
1g
,
1h
,
1k
,
1l
,
1m
1q
,
1n
, 1o, 1s, 1t, 2f, 2g, 2i,
substrates 1p
,
,
1r
,
,
,
,
,
2e), 36 hours (for substrate 2d) or 48 hours (for substrate 2h). (4-bromophenyl)(pyrrolidin-1-yl)methanone
(
3a)14: White
Thin layer chromatography (TLC) was used to monitor the solid; 45.5 mg; 90% yield; mp: 78-80 oC; 1H NMR (400 MHz,
progress of the reaction. After the reaction was completed, CDCl3): δH 7.50 (d, J = 8.4 Hz, 2 H), 7.37 (d, J = 8.4 Hz, 2 H), 3.60
the reaction mixture was quenched with saturated aqueous (t, J = 6.8 Hz, 2 H), 3.38 (t, J = 6.6 Hz, 2 H), 1.97-1.90 (m, 2 H),
Na2SO3 solution (20 mL) and extracted with EA (3 × 10 mL). The 1.88-1.82 (m, 2 H) ppm; 13C NMR (100 MHz, CDCl3): δC 167.5,
organic phase was dried over Na2SO4, and concentrated on a 135.0, 130.4, 127.8, 123.1, 48.6, 45.3, 25.4, 23.4 ppm; IR (KBr):
rotary evaporator. The crude product was further purified by 2961, 1607, 1439, 1006, 841, 747 cm-1; HRMS (m/z, ESI) Calcd.
column chromatography (petroleum ether/ ethyl acetate = 3:1) for C11H13BrNO+ [M+H]+: 254.0175, found: 254.0174.
to give the desired products.
(4-chlorophenyl)(pyrrolidin-1-yl)methanone
(
3b): Yellow solid;
o
30.2 mg; 72% yield; mp: 67-69 C; H NMR (400 MHz, CDCl3):
1
5,5-Difluoro-1,3,7,9-tetramethyl-10-phenyl-5H-dipyrrolo[1,2-
c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide(I): Red-brown solid; δH 7.46 (d, J = 8.4 Hz, 2 H), 7.36 (d, J = 8.4 Hz, 2 H), 3.62 (t, J =
1
78% yield; H NMR (400 MHz, CDCl3): δH 7.40-7.39 (m, 3 H), 6.8 Hz, 2 H), 3.40 (t, J = 6.6 Hz, 2 H), 1.99-1.90 (m, 2 H), 1.89-
7.20-7.18 (m, 2 H), 5.90 (s, 2 H), 2.48 (s, 6 H), 1.29 (s, 6 H) ppm; 1.84 (m, 2 H) ppm; 13C NMR (100 MHz, CDCl3): δC 168.6, 135.8,
13C NMR (100 MHz, CDCl3): δC 155.4, 143.2, 141.8, 135.0, 131.4, 135.5, 128.7, 128.5, 49.6, 46.3, 26.4, 24.4 ppm;IR (KBr):2973,
129.1, 128.9, 128.0, 121.2, 14.6, 14.3 ppm.
1625, 1421, 1088, 850, 756 cm-1; HRMS (m/z, ESI) Calcd. for
C11H12ClNNaO+ [M+Na]+: 232.0499, found: 232.0496.
2,8-Dichloro-5,5-difluoro-1,3,7,9-tetramethyl-10-phenyl-5H-
dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide
(
P1): (4-fluorophenyl)(pyrrolidin-1-yl)methanone
(
3c): Yellow solid;
Red solid; 60% yield; H NMR (400 MHz, CDCl3): δH 7.53-7.51 29.8 mg; 77% yield; mp: 79-82 C; H NMR (400 MHz, CDCl3):
(m, 3 H), 7.27-7.24 (m, 2 H), 2.59 (s, 6 H), 1.36 (s, 6 H) ppm; 13
δH 7.55-7.51 (m, 2 H), 7.09-7.05 (m, 2 H), 3.63 (t, J = 6.8 Hz, 2
NMR (100 MHz, CDCl3): δC 152.5, 142.4, 138.0, 134.2, 129.7, H), 3.42 (t, J = 6.6 Hz, 2 H), 1.99-1.92 (m, 2 H), 1.91-1.84 (m, 2
1
o
1
C
129.5, 129.4, 127.8, 122.6, 12.4, 11.9 ppm.
H) ppm; 13C NMR (100 MHz, CDCl3): δC 168.7, 163.5 (d, JC-F
=
2,8-Dibromo-5,5-difluoro-1,3,7,9-tetramethyl-10-phenyl-5H-
248 Hz, 1 C), 133.3 (d, JC-F = 3.2 Hz, 1 C), 129.4 (d, JC-F = 8.5 Hz,
dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide
1
(
P2): 1 C), 115.3 (d, JC-F = 21.7 Hz, 1 C), 49.7, 46.3, 26.5, 24.4 ppm; IR
Red solid; 83% yield; H NMR (400 MHz, CDCl3): δH 7.54-7.52 (KBr): 2955, 1636, 1427, 1215, 850, 756 cm-1; HRMS (m/z, ESI)
(m, 3 H), 7.26-7.24 (m, 2 H), 2.61 (s, 6 H), 1.36 (s, 6 H) ppm; 13
C
Calcd. for C11H13FNO+ [M+H]+: 194.0976, found: 194.0970.
3d)27: Yellow oil; 24.5 mg;
NMR (100 MHz, CDCl3): δC 154.0, 142.1, 140.7, 134.4, 130.4, phenyl(pyrrolidin-1-yl)methanone
(
1
129.6, 129.5, 127.8, 111.8, 13.7, 13.6 ppm; IR (KBr): 1533, 70% yield; H NMR (400 MHz, CDCl3): δH 7.51-7.49 (m, 2 H),
1459, 1348, 1180, 992, 720, 529 cm-1; HRMS (m/z, ESI) Calcd. 7.39-7.37 (m, 3 H), 3.63 (t, J = 6.8 Hz, 2 H), 3.41 (t, J = 6.6 Hz, 2
for C19H18BBr2F2N2+ [M+H]+: 480.9892, found: 480.9897.
H), 1.98-1.91 (m, 2 H), 1.89-1.82 (m, 2 H) ppm; 13C NMR (100
MHz, CDCl3): δC 169.7, 137.3, 129.7, 128.2, 127.1, 49.6, 46.1,
(
P3): 26.4, 24.5 ppm; IR (KBr): 2960, 1622, 1421, 718 cm-1; HRMS
5,5-Difluoro-2,8-diiodo-1,3,7,9-tetramethyl-10-phenyl-5H-
dipyrrolo[1,2-c:2',1'-f][1,3,2]diazaborinin-4-ium-5-uide
1
Red solid; 69% yield; H NMR (400 MHz, CDCl3): δH 7.55-7.53
6 | J. Name., 2012, 00, 1-3
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(m/z, ESI) Calcd. for C11H13NNaO+ [M+Na]+: 198.0889, found: 6.6 Hz, 2 H), 2.02-1.95 (m, 2 H), 1.94-1.88 (m, 2 H) ppm; 13C
198.0885.
NMR (A100 MHz, CDCl3): δC 166.9, 147.9, 138.7, 133.3, 129.6,
(4-nitrophenyl)(pyrrolidin-1-yl)methanone
(
3e): Light yellow 124.6, 122.3, 49.6, 46.5, 26.4, 24.4 ppm; IR (KBr): 2958, 1613,
solid; 33.5 mg; 75% yield; mp: 77-79 oC; 1H NMR (400 MHz, 1530, 1442, 1351, 824, 723 cm-1; HRMS (m/z, ESI) Calcd. for
CDCl3): δH 8.24 (d, J = 8.6 Hz, 2 H), 7.66 (d, J = 8.6 Hz, 2 H), 3.64 C11H13N2O3+ [M+H]+: 221.0921, found: 221.0918.
(t, J = 6.8 Hz, 2 H), 3.36 (t, J = 6.6 Hz, 2 H), 2.02-1.94 (m, 2 H), (3-bromophenyl)(pyrrolidin-1-yl)methanone (3l): Yellow oil;
1
1.93-1.87 (m, 2 H) ppm; 13C NMR (100 MHz, CDCl3): δC 167.3, 43.5 mg; 86% yield; H NMR (400 MHz, CDCl3): δH 7.64 (t, J =
148.4, 143.2, 128.1, 123.7, 49.4, 46.4, 26.4, 24.4 ppm; IR (KBr): 1.6 Hz, 1 H), 7.54-7.51 (m, 1 H), 7.43-7.41(m, 1 H), 7.26 (t, J =
2958, 1621, 1521, 1430, 1351, 862, 721 cm-1; HRMS (m/z, ESI) 7.8 Hz, 1 H), 3.62 (t, J = 6.8 Hz, 2 H), 3.41 (t, J = 6.6 Hz, 2 H),
Calcd. for C11H13N2O3+ [M+H]+: 221.0920, found: 221.0918.
1.97-1.92 (m, 2 H), 1.90-1.86 (m, 2 H) ppm; 13C NMR (100 MHz,
4-(pyrrolidine-1-carbonyl)benzonitrile 3f): Yellow oil; 38.3 mg; CDCl3): δC 168.0, 139.1, 132.8, 130.2, 129.9, 125.6, 122.4, 49.6,
(
95% yield; 1H NMR (400 MHz, CDCl3): δH 7.68 (d, J = 8.4 Hz, 2 H), 46.3, 26.4, 24.4 ppm; IR (KBr): 2958, 1625, 1430, 803, 747 cm-1;
7.59 (d, J = 8.4 Hz, 2 H), 3.62 (t, J = 6.8 Hz, 2 H), 3.34 (t, J = 6.6 HRMS (m/z, ESI) Calcd. for C11H13BrNO+ [M+H]+: 254.0175,
Hz, 2 H), 1.99-1.92 (m, 2 H), 1.91-1.83 (m, 2 H) ppm; 13C NMR found: 254.0174.
(100 MHz, CDCl3): δC 167.6, 141.4, 132.2, 127.8, 118.2, 113.5, naphthalen-2-yl(pyrrolidin-1-yl)methanone (3m): Yellow oil;
49.4, 46.3, 26.4, 24.3 ppm; IR (KBr): 2967, 2225, 1604, 1445, 36.2 mg; 80% yield; 1H NMR (400 MHz, CDCl3): δH 8.00 (s, 1 H),
862, 762 cm-1; HRMS (m/z, ESI) Calcd. for C12H13N2O+ [M+H]+: 7.86-7.83 (m, 3 H), 7.62-7.60 (m, 1 H), 7.53-7.48 (m, 2 H), 3.69
201.1022, found: 201.1019.
(t, J = 6.9 Hz, 2 H), 3.47 (t, J = 6.6 Hz, 2 H), 2.00-1.94 (m, 2 H),
3g): 1.89-1.83 (m, 2 H) ppm; 13C NMR (100 MHz, CDCl3): δC 169.7,
pyrrolidin-1-yl(4-(trifluoromethyl)phenyl)methanone
(
o
1
Yellow solid; 41.4 mg; 85% yield; mp: 75-77 C; H NMR (400 134.5, 133.8, 132.6, 128.5, 128.1, 127.8, 127.0, 126.9, 126.5,
MHz, CDCl3): δH 7.66 (d, J = 8.2 Hz, 2 H), 7.61 (d, J = 8.2 Hz, 2 H), 124.4, 49.7, 46.3, 26.4, 24.5 ppm; IR (KBr): 2970, 1607, 1421,
3.64 (t, J = 6.8 Hz, 2 H), 3.38 (t, J = 6.6 Hz, 2 H), 2.00-1.94 (m, 2 871, 765 cm-1; HRMS (m/z, ESI) Calcd. for C15H15NNaO+
H), 1.92-1.87 (m, 2 H) ppm; 13C NMR (100 MHz, CDCl3): δC168.2, [M+Na]+: 248.1046, found: 248.1046.
140.7, 131.6 (q, JC-F = 32.2 Hz, 1 C), 127.5, 125.4 (q, JC-F = 3.6 Hz, pyren-1-yl(pyrrolidin-1-yl)methanone (3n): Yellow oil; 53.3 mg;
1
1 C), 123.8 (q, JC-F = 271 Hz, 1 C), 49.5, 46.3, 26.4, 24.4 ppm; IR 89% yield; H NMR (400 MHz, CDCl3): δH 8.21-7.97 (m, 9 H),
(KBr): 2958, 1610, 1448, 1324, 1130, 853 cm-1; HRMS (m/z, ESI) 3.89 (t, J = 7.0 Hz, 2 H), 3.12 (t, J = 6.8 Hz, 2 H), 2.07-2.00 (m, 2
Calcd. for C12H12F3NNaO+ [M+Na]+: 266.0763, found: 266.0762. H), 1.85-1.79 (m, 2 H) ppm; 13C NMR (100 MHz, CDCl3): δC169.6,
methyl 4-(pyrrolidine-1-carbonyl)benzoate (3h): Yellow solid; 132.6, 131.6, 131.1, 130.7, 128.6, 128.0, 127.1, 126.9, 126.2,
o
1
38.8 mg; 83% yield; mp: 96-98 C; H NMR (400 MHz, CDCl3): 125.6, 125.4, 124.7, 124.6, 124.5, 124.1, 123.7, 48.6, 45.8, 26.0,
δH 8.04 (d, J = 8.3 Hz, 2 H), 7.54 (d, J = 8.3 Hz, 2 H), 3.90 (s, 3 H), 24.6 ppm; IR (KBr): 2960, 1621, 1418, 844, 718 cm-1; HRMS
3.62 (t, J = 6.8 Hz, 2 H), 3.35 (t, J = 6.6 Hz, 2 H), 1.97-1.91 (m, 2 (m/z, ESI) Calcd. for C21H18NO+ [M+H]+: 300.1383, found:
H), 1.89-1.82 (m, 2 H) ppm; 13C NMR (100 MHz, CDCl3): δC 300.1381.
168.7, 166.4, 141.4, 131.1, 129.6, 127.0, 52.3, 49.4, 46.2, 26.4, pyrrolidin-1-yl(thiophen-2-yl)methanone (3o): Yellow solid;
o
1
24.4 ppm; IR (KBr): 2955, 1716, 1621, 1421, 1280, 1103, 736 26.1 mg; 72% yield; mp: 57-59 C; H NMR (400 MHz, CDCl3):
+
cm-1; HRMS (m/z, ESI) Calcd. for C13H16NO3 [M+H]+: 234.1125, δH 7.50 (d, J = 3.6 Hz, 1 H), 7.45 (d, J = 5.0 Hz, 1 H), 7.06-7.04
found: 234.1121.
(m, 1 H), 3.75 (t, J = 6.0 Hz, 2 H), 3.65 (t, J = 6.4 Hz, 2 H), 2.00-
3i): Yellow solid; 28.5 mg; 1.90 (m, 4 H) ppm; 13C NMR (100 MHz, CDCl3): δC 161.8, 139.6,
pyrrolidin-1-yl(p-tolyl)methanone
(
75% yield; mp: 73-75 oC; 1H NMR (400 MHz, CDCl3): δH 7.42 (d, 129.5, 129.4, 127.1, 48.9, 47.3, 26.7, 24.1 ppm; IR (KBr): 2955,
J = 8.0 Hz, 2 H), 7.18 (d, J = 8.0 Hz, 2 H), 3.63 (t, J = 6.8 Hz, 2 H), 1583, 1433, 829, 741 cm-1; HRMS (m/z, ESI) Calcd. for
3.43 (t, J = 6.6 Hz, 2 H), 2.36 (s, 3 H), 1.98-1.91 (m, 2 H), 1.88- C9H11NNaOS+ [M+Na]+: 204.0453, found: 204.0452.
1.82 (m, 2 H) ppm; 13C NMR (100 MHz, CDCl3): δC 169.8, 139.9, pyridin-4-yl(pyrrolidin-1-yl)methanone
(3p): Yellow oil; 32.4
134.3, 128.8, 127.2, 49.7, 46.2, 26.4, 24.5, 21.4 ppm; IR (KBr): mg; 92% yield; 1H NMR (400 MHz, CDCl3): δH 8.64 (s, 2 H), 7.34-
2967, 1607, 1421, 839, 750 cm-1; HRMS (m/z, ESI) Calcd: for 7.33 (m, 2 H), 3.59 (t, J = 6.6 Hz, 2 H), 3.32 (t, J = 6.5 Hz, 2 H),
C12H16NO+ [M+H]+: 190.1226, found: 190.1224.
1.94-1.89 (m, 2 H), 1.87-1.84 (m, 2 H) ppm; 13C NMR (100 MHz,
(4-methoxyphenyl)(pyrrolidin-1-yl)methanone
o
(
3j): Yellow oil; CDCl3): δC 167.1, 150.1, 144.5, 121.2, 49.2, 46.2, 26.3, 24.3
1
30.4 mg; 74% yield; mp: 71-73 C; H NMR (400 MHz, CDCl3): ppm; IR (KBr): 2957, 1624, 1442, 835, 659 cm-1; HRMS (m/z, ESI)
δH 7.51 (d, J = 8.8 Hz, 2 H), 6.89 (d, J = 8.8 Hz, 2 H), 3.82 (s, 3 H), Calcd. for C10H12N2O+ [M+H]+: 177.1022, found: 177.1022.
3.62 (t, J = 6.8 Hz, 2 H), 3.47 (t, J = 6.6 Hz, 2 H), 1.97-1.91 (m, 2 pyridin-2-yl(pyrrolidin-1-yl)methanone (3q): Yellow oil; 27.8
H), 1.89-1.84 (m, 2 H) ppm; 13C NMR (100 MHz, CDCl3): δC mg; 79% yield; 1H NMR (400 MHz, CDCl3): δH 8.56 (d, J = 4.7 Hz,
169.4, 160.8, 129.4, 129.2, 113.4, 55.3, 49.8, 46.3, 26.5, 24.5 1 H), 7.81-7.74 (m, 2 H), 7.33-7.30 (m, 1 H), 3.71 (t, J = 6.3 Hz, 2
ppm; IR (KBr): 2964, 1613, 1424, 1254, 1174, 1024, 847, 762 H), 3.66 (t, J = 6.8 Hz, 2 H), 1.93-1.88 (m, 4 H) ppm; 13C NMR
+
cm-1; HRMS (m/z, ESI) Calcd. for C12H16NO2 [M+H]+: 206.1176, (100 MHz, CDCl3): δC 166.5, 154.6, 148.0, 136.8, 124.6, 123.8,
found: 206.1173.
49.1, 46.8, 26.6, 24.0 ppm; IR (KBr): 2961, 1627, 1448, 812, 753
3k): Yellow solid; cm-1; HRMS (m/z, ESI) Calcd. for C10H12N2NaO+ [M+Na]+:
(3-nitrophenyl)(pyrrolidin-1-yl)methanone
o
34.5 mg; 78% yield; mp: 61-63 C; H NMR (400 MHz, CDCl3): 199.0841, found: 199.0842.
(
1
δH 8.37 (t, J = 1.7 Hz, 1 H), 8.27-8.25 (m, 1 H), 7.86 (d, J = 7.6 Hz, (1-methyl-1H-indol-2-yl)(pyrrolidin-1-yl)methanone
(3r):
1
1 H), 7.60 (t, J = 8.0 Hz, 1 H), 3.66 (t, J = 6.8 Hz, 2 H), 3.43 (t, J = Yellow oil; 32.4 mg; 71% yield; H NMR (400 MHz, CDCl3): δH
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7.63 (d, J = 8.0 Hz, 1 H), 7.36 (d, J = 8.2 Hz, 1 H), 7.32-7.28 (m, 1 4-(4-methylpiperidine-1-carbonyl)benzonitrile
(
3fe): Yellow
H), 7.16-7.12 (m, 1 H), 6.75 (s, 1 H), 3.93 (s, 3 H), 3.72-3.67 (m, solid; 39.2 mg; 86% yield; mp: 83-85 oC; 1H NMR (400 MHz,
4 H), 2.00-1.92 (m, 4 H) ppm; 13C NMR (100 MHz, CDCl3): δC CDCl3): δH 7.68 (d, J = 7.6 Hz, 2 H), 7.46 (d, J = 7.6 Hz, 2 H), 4.63
162.4, 138.0, 132.8, 126.3, 123.5, 121.6, 120.1, 109.9, 104.6, (d, J = 11.4 Hz, 1 H), 3.53 (d, J = 11.7 Hz, 1 H), 3.00 (t, J = 11.8
49.7, 46.2, 31.5, 26.4, 24.3 ppm; IR (KBr): 2958, 1616, 1524, Hz, 1 H), 2.78 (t, J = 11.8 Hz, 1 H), 1.78-1.58 (m, 5 H), 0.96 (d, J
1462, 1342, 744 cm-1; HRMS (m/z, ESI) Calcd. for C14H17N2O+ = 6.5 Hz, 3 H) ppm; 13C NMR (100 MHz, CDCl3): δC 168.0, 140.8,
[M+H]+: 229.1335, found: 229.1334.
132.3, 127.4, 118.1, 113.1, 47.9, 42.5, 34.6, 33.6, 31.8, 30.9,
pyrrolidin-1-yl(quinolin-2-yl)methanone
(
3s): Yellow oil; 27.1 29.6, 22.6, 21.5, 14.0 ppm; IR (KBr): 2923, 2225, 1630, 1457,
mg; 59% yield; 1H NMR (400 MHz, CDCl3): δH 8.23 (d, J = 8.4 Hz, 1271, 1109, 853, 756 cm-1; HRMS (m/z, ESI) Calcd. for
1 H), 8.08 (d, J = 8.4 Hz, 1 H), 7.90 (d, J = 8.4 Hz, 1 H), 7.83 (d, J C14H17N2O+ [M+H]+: 229.1335, found: 229.1342.
= 8.0 Hz, 1 H), 7.73 (t, J = 7.4 Hz, 1 H), 7.58 (t, J = 7.4 Hz, 1 H), 4-(4-benzylpiperidine-1-carbonyl)benzonitrile (3ff): Yellow oil;
1
3.86 (t, J = 6.0 Hz, 2 H), 3.73 (t, J = 6.2 Hz, 2 H), 1.97-1.91 (m, 4 55.7 mg; 90% yield; H NMR (400 MHz, CDCl3): δH 7.65 (d, J =
H) ppm; 13C NMR (100 MHz, CDCl3): δC166.5, 154.2, 146.5, 8.1 Hz, 2 H), 7.44 (d, J = 7.6 Hz, 2 H), 7.23 (d, J = 7.0 Hz, 2 H),
136.8, 129.8, 129.7, 128.2, 127.6, 127.5, 120.7, 49.2, 46.9, 26.6, 7.17-7.14 (m, 1 H), 7.08 (d, J = 7.4 Hz, 2 H), 4.63 (d, J = 11.3 Hz,
24.0 ppm; IR (KBr): 2964, 1627, 1410, 844, 771 cm-1; HRMS 1 H), 3.52 (d, J = 11.8 Hz, 1 H), 2.92 (t, J = 12.2 Hz, 1 H), 2.69 (t,
(m/z, ESI) Calcd. for C14H15N2O+ [M+H]+: 227.1178, found: J = 11.5 Hz, 1 H), 2.53 (t, J = 6.8 Hz, 2 H), 1.80-1.76 (m, 2 H),
227.1179.
1.57 (d, J = 11.4 Hz, 1 H), 1.27-1.21 (m, 1 H), 1.11-1.09 (m, 1 H)
3t): Yellow oil; 14.2 ppm; 13C NMR (100 MHz, CDCl3): δC 168.1, 140.7, 139.6, 132.3,
3-(pyrrolidine-1-carbonyl)benzaldehyde
(
mg; 35% yield; 1H NMR (400 MHz, CDCl3): δH 10.04 (s, 1 H), 129.0, 128.3, 127.5, 126.1, 118.1, 113.2, 47.8, 42.8, 42.4, 38.1,
8.04 (s, 1 H), 7.93 (d, J = 7.5 Hz, 1 H), 7.80 (d, J = 7.5 Hz, 1 H), 32.5, 31.6 ppm; IR (KBr): 2918, 2228, 1627, 1448, 1283, 844,
7.59 (t, J = 7.6 Hz, 1 H), 3.67 (t, J = 6.7 Hz, 2 H), 3.44 (t, J = 6.5 700 cm-1; HRMS (m/z, ESI) Calcd. for C20H21N2O+ [M+H]+:
Hz, 2 H), 2.00-1.96 (m, 2 H), 1.94-1.89 (m, 2 H) ppm; 13C NMR 305.1648, found: 305.1649.
(100 MHz, CDCl3): δC 191.5, 168.2, 138.2, 136.3, 133.0, 130.8, ethyl
1-(4-cyanobenzoyl)piperidine-3-carboxylate
(3fg):
1
129.2, 128.3, 49.6, 46.4, 26.4, 24.4 ppm; IR (KBr): 2923, 1698, Yellow oil; 44.6 mg; 78% yield; H NMR (400 MHz, CDCl3): δH
1621, 1450, 1191, 812, 741 cm-1; HRMS (m/z, ESI) Calcd. for 7.69 (d, J = 8.1 Hz, 2 H), 7.48 (d, J = 7.2 Hz, 2 H), 4.15 (br, s, 2 H),
C12H14NO2+ [M+H]+: 204.1019, found: 204.1020.
4-(piperidine-1-carbonyl)benzonitrile
3.59-3.46 (m, 1 H), 3.34-3.08 (m, 2 H), 2.59-2.43(m, 1 H), 2.10-
3fb)31: Yellow solid; 2.08 (m, 1 H), 1.75 (s, 2 H), 1.61-1.45 (m, 1 H), 1.24 (s, 3 H),
(
41.1 mg; 96% yield; mp: 86-88 C; H NMR (400 MHz, CDCl3): 0.86-0.82 (m, 1 H) ppm; 13C NMR (100 MHz, CDCl3): δC 172.7,
δH 7.68 (d, J = 8.1 Hz, 2 H), 7.47 (d, J = 8.1 Hz, 2 H), 3.69 (br, s, 2 172.3, 168.3, 140.2, 132.3, 127.5, 118.0, 113.3, 60.7, 48.8, 47.8,
H), 3.26 (br, s, 2 H), 1.67 (br, s, 4 H), 1.50 (br, s, 2 H) ppm; 13C 43.9, 42.3, 41.4, 40.8, 27.1, 24.7, 23.5, 14.0 ppm; IR (KBr): 2926,
NMR (100 MHz, CDCl3): δC 168.2, 140.9, 132.4, 127.5, 118.2, 2228, 1724, 1639, 1436, 1274, 1182, 1091, 1026, 853, 765 cm-1;
o
1
113.2, 48.6, 43.2, 26.5, 25.5, 24.4 ppm; IR (KBr): 2931, 2228, HRMS (m/z, ESI) Calcd. for C16H19N2O3 [M+H]+: 287.1390,
1627, 1448, 1271, 853 cm-1; HRMS (m/z, ESI) Calcd. for found: 287.1391.
+
C13H15N2O+ [M+H]+: 215.1178, found: 215.1177.
4-(4-methylpiperazine-1-carbonyl)benzonitrile
(3fh): Yellow
4-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzonitrile
3fc): White solid; 46.1 mg; 88% yield; mp: 147-149 oC; 1H NMR CDCl3): δH 7.71 (d, J = 8.4 Hz, 2 H), 7.50 (d, J = 8.4 Hz, 2 H), 3.81
solid; 31.2 mg; 68% yield; mp: 91-93 oC; 1H NMR (400 MHz,
(
(400 MHz, CDCl3): δH 7.74-7.72 (m, 2 H), 7.56-7.55 (m, 2 H), (br, s, 2 H), 3.38 (br, s, 2 H), 2.51 (br, s, 2 H), 2.35-2.33 (m, 5 H)
7.26-7.16 (m, 3.7 H, major), 6.91 (br, s, 0.4 H, minor), 4.89 (br, ppm; 13C NMR (100 MHz, CDCl3): δC168.2, 140.1, 132.4, 127.8,
s, 1.1 H, major), 4.51 (br, s, 0.8 H, minor), 4.00 (br, s, 0.8 H, 118.1, 113.6, 55.1, 54.6, 47.5, 45.9, 42.1 ppm; IR (KBr): 2923,
minor), 3.58 (br, s, 1.1 H, major), 3.00-2.87 (m, 2 H) ppm; 13C 2222, 1633, 1442, 1289, 1003, 841 cm-1; HRMS (m/z, ESI) Calcd.
NMR (100 MHz, CDCl3): δC 168.9 (major), 168.4 (minor), 140.5, for C13H16N3O+ [M+H]+: 230.1287, found: 230.1290.
134.5, 133.4, 132.5 (major), 132.2 (minor), 129.2 (minor), 4-(isoindoline-2-carbonyl)benzonitrile (3fi): Light yellow solid;
128.7 (major), 127.9 (minor), 127.6 (major), 127.3, 126.9 46.2 mg; 93% yield; mp: 169-171 oC; 1H NMR (400 MHz, CDCl3):
(major), 126.6 (minor), 125.8, 118.1, 113.7, 49.7 (minor), 45.2 δH 7.75 (d, J = 7.9 Hz, 2 H), 7.67 (d, J = 7.6 Hz, 2 H), 7.35-7.26
(major), 44.8 (major), 40.7 (minor), 29.5 (major), 28.1 (minor) (m, 3 H), 7.17-7.15 (m, 1 H), 5.01 (s, 2 H), 4.72 (s, 2 H) ppm; 13
C
ppm; IR (KBr): 2919, 2225, 1627, 1445, 1259, 847, 756 cm-1; NMR (100 MHz, CDCl3): δC 168.2, 140.7, 135.8, 132.4, 128.0,
HRMS (m/z, ESI) Calcd. for C17H15N2O+ [M+H]+: 263.1178, 127.7, 127.5, 122.9, 122.4, 118.0, 113.8, 54.7, 52.5 ppm; IR
found: 263.1177.
(KBr): 2912, 2225, 1615, 1424, 847, 759 cm-1; HRMS (m/z, ESI)
4-(morpholine-4-carbonyl)benzonitrile
(
3fd
)
27c: White solid; Calcd. for C16H12N2NaO+ [M+Na]+: 271.0841, found: 271.0840.
36.3 mg; 84% yield; mp: 129-131 oC; 1H NMR (400 MHz, CDCl3): 4-(azepane-1-carbonyl)benzonitrile
(3fj): Yellow solid; 42.9 mg;
δH 7.70 (d, J = 8.1 Hz, 2 H), 7.49 (d, J = 8.1 Hz, 2 H), 3.76 (br, s, 4 94% yield; mp: 87-88 oC; 1H NMR (400 MHz, CDCl3): δH 7.67 (d,
H), 3.60 (br, s, 2 H), 3.36 (br, s, 2 H) ppm; 13C NMR (100 MHz, J = 7.8 Hz, 2 H), 7.44 (d, J = 7.9 Hz, 2 H), 3.65 (t, J = 5.2 Hz, 2 H),
CDCl3): δC 168.3, 139.6, 132.5, 127.8, 118.0, 113.7, 66.7, 48.0, 3.28 (t, J = 5.0 Hz, 2 H), 1.81-1.80 (m, 2 H), 1.69-1.57 (m, 6 H)
42.5 ppm; IR (KBr): 2928, 2222, 1619, 1439, 1280, 1112, 1009, ppm; 13C NMR (100 MHz, CDCl3): δC 169.4 (major), 162.8
+
847 cm-1; HRMS (m/z, ESI) Calcd. for C12H13N2O2 [M+H]+: (minor), 141.6, 132.3, 127.1, 118.1, 112.8, 49.5 (major), 47.6
217.0971, found: 217.0970.
(minor), 46.3 (major), 43.3 (minor), 30.1 (minor), 29.3 (major),
27.8 (minor), 27.6 (major), 27.0 (major), 26.8 (minor), 26.7
8 | J. Name., 2012, 00, 1-3
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ARTICLE
3
4
C. A. G. N. Montalbetti and V. Falque, Tetrahedron 2005, 61,
10827.
(minor), 26.3 (major) ppm; IR (KBr): 2926, 2228, 1630, 1427,
1280, 862 cm-1; HRMS (m/z, ESI+) Calcd. for C14H17N2O+ [M+H]+:
229.1335, found: 229.1334.
(a) J. S. Davies, J. Howe and M. Le Breton, J. Chem. Soc.,
Perkin Trans. 1995, , 2335; (b) F. Albericio, J. M. Bofill, A. El-
Faham and S. A. Kates, J. Org. Chem. 1998, 63, 9678; (c) R. T.
Pon, S. Yu and Y. S. Sanghvi, Bioconjugate Chem. 1999, 10
2
N-phenylacetamide (
4a)28: White solid; 42.5 mg; 63% yield;
o
1
mp: 99-101 C; H NMR (400 MHz, CDCl3): δH7.86 (br, s, 1 H);
7.50 (d, J = 7.9 Hz, 2 H), 7.29 (t, J = 7.6 Hz, 2 H), 7.09 (t, J = 7.4
Hz, 1 H), 2.14 (s, 1 H) ppm; 13C NMR (APT, 100 MHz, CDCl3): δC
168.7, 138.0, 128.9, 124.2, 120.0, 24.4 ppm.
,
1051; (d) S.-Y.Han and Y.-A.Kim, Tetrahedron 2004, 60, 2447;
(e) J. Hachmann and M. Lebl, Biopolymers 2006, 84, 340; (f)
E. Valeur and M. Bradley, Chem. Soc. Rev. 2009, 38, 606.
For reviews, see: (a) J. M.Humphrey and A. R. Chamberlin,
Chem. Rev. 1997, 97, 2243; (b) F. Albericio, Curr. Opin. Chem.
5
6
2,6-di-tert-butyl-4-hydroperoxy-4-methylcyclohexa-2,5-
dienone (
BHT-OOH): White solid; 95% yield; 1H NMR (400 MHz,
Biol. 2004, 8, 211.
D. J. C. Constable, P. J. Dunn, J. D. Hayler, G. R. Humphrey, J.
J. L. Leazer, R. J. Linderman, K. Lorenz, J. Manley, B. A.
Pearlman, A. Wells, A. Zaks and T. Y. Zhang, Green Chem.
2007, 9, 411.
H. Lundberg, F. Tinnis, N. Selander and H. Adolfsson, Chem.
Soc. Rev. 2014, 43, 2714.
(a) K. Ishihara, M. Kubota, H. Kurihara and H. Yamamoto, J.
Org. Chem. 1996, 61, 4560; (b) T. Marcelli, Angew. Chem. Int.
Ed. 2010, 49, 6840; (c) R. M. Al-Zoubi, O. Marion and D. G.
Hall, Angew. Chem. Int. Ed. 2008, 47, 2876; (d) H. Charville,
D. Jackson, G. Hodges and A. Whiting, Chem. Comm. 2010,
46, 1813.
CDCl3): δH 7.81(br, s, 1 H), 6.56 (s, 2 H), 1.36 (s, 3 H), 1.23 (s, 18
H) ppm; 13C NMR (100 MHz, CDCl3): δC 186.2, 148.8, 140.0,
78.8, 34.8, 29.4, 23.9 ppm; HRMS (m/z, ESI) Calcd. for
C15H24NaO3+ [M+Na]+: 275.1617, found: 275.1615.
7
8
2,6-di-tert-butyl-4-ethyl-4-hydroperoxycyclohexa-2,5-
dienone
MHz, CDCl3): δH 8.22 (br, s, 1 H), 6.50 (s, 2 H), 1.67 (q, J = 14.6
Hz, 7.3 Hz, 2 H), 1.22 (s, 18 H), 0.72 (t, J = 8.1 Hz, 3 H) ppm; 13
(
BHEB-OOH): White solid; 96% yield; 1H NMR (400
C
NMR (100 MHz, CDCl3): δC 186.6, 149.9, 139.4, 82.6, 34.9, 29.5,
+
29.4, 7.9 ppm; HRMS (m/z, ESI) Calcd. for C16H27O3 [M+H]+:
9
(a) J. W. Bode and S. S. Sohn, J. Am. Chem. Soc. 2007, 129,
267.1954, found: 267.1948.
13798; (b) H. U. Vora and T. Rovis, J. Am. Chem. Soc. 2007,
129, 13796; (c) S. De Sarkar and A. Studer, Org. Lett. 2010,
12, 1992.
2,4,6-tri-tert-butyl-4-hydroperoxycyclohexa-2,5-dienone
1
TBP-OOH): White solid; 92% yield; H NMR (400 MHz, CDCl3):
(
δH 7.73 (br, s, 1 H), 6.71 (s, 2 H), 1.25 (s, 18 H), 0.96 (s, 9 H)
ppm; 13C NMR (100 MHz, CDCl3): δC 186.4, 150.2, 139.6, 85.9,
40.4, 35.2, 29.5, 26.0 ppm; HRMS (m/z, ESI) Calcd. for
C18H31O3+ [M+Na]+: 295.2267, found: 295.2266.
10 (a) C. Gunanathan, Y. Ben-David and D. Milstein, Science
2007, 317, 790; (b) L. U. Nordstrøm, H. Vogt and R. Madsen,
J. Am. Chem. Soc. 2008, 130, 17672; (c) S. H.Hong, J. Org.
Chem. 2010, 75, 3002; (d) D. Srimani, E. Balaraman, P. Hu, Y.
Ben-David and D. Milstein, Adv. Synth. Catal. 2013, 355, 2525;
2,6-di-tert-butyl-4-hydroxy-4-methylcyclohexa-2,5-dienone
BHT-OH): White solid; 1H NMR (400 MHz, CDCl3): δH 6.55 (s, 2
(e) D.Cho, K. C. Ko and J. Y. Lee, Organometallics, 2013, 32
4571.
11 B. Kang, Z. Fu and S. H.Hong, J. Am. Chem. Soc. 2013, 135
11704.
12 (a) C. Gunanathan and D. Milstein, Science 2013, 341
,
,
,
(
H), 1.84 (br, s, 1 H), 1.41 (s, 3 H), 1.21 (s, 18 H) ppm; 13C NMR
(100 MHz, CDCl3): δC 186.1, 145.4, 143.2, 67.4, 34.5, 29.4, 28.0
+
ppm; HRMS (m/z, ESI) Calcd. for C15H24NaO2 [M+Na]+:
1229712; (b) C.Chen and S. H.Hong, Org. Biomol. Chem.
2011, , 20.
259.1668, found: 259.1670.
9
13 J. Liu, Q. Liu, H. Yi, C. Qin, R. Bai, X. Qi, Y. Lan and A. Lei,
Angew. Chem. Int. Ed. 2014, 53, 502.
14 D. Leow, Org. Lett. 2014, 16, 5812.
Acknowledgements
15 For reviews, see: (a) J. J. Douglas, J. D. Nguyen, K. P. Cole, C.
and R. J. Stephenson, Aldrichimica Acta 2014, 47, 15; (b) D. P.
Hari and B. König, Angew. Chem. Int. Ed. 2013, 52, 4734; (c)
Y.-Q. Zou, J.-R. Chen and W.-J. Xiao, Angew. Chem. Int. Ed.
2013, 52, 11701; (d) C. K. Prier, D. A. Rankic and D. W. C.
MacMillan, Chem. Rev. 2013, 113, 5322; (e) T. P. Yoon, ACS
The work was supported by the National Natural Science
Foundation of China (21372148), Natural Science Foundation
of Shaanxi Province (2015JM2049), Changjiang Scholars and
Innovative Research Team in University (IRT-14R33), 111
projects (B14041) and the Changjiang Scholar Programme.
Catal. 2013,
48, 9785; (g) T. P. Yoon, M. A. Ischay and J. Du, Nat. Chem.
2010, , 527; (h) J. M. R. Narayanam and C. R. J. Stephenson,
3, 895; (f) K. Zeitler, Angew. Chem. Int. Ed. 2009,
2
Notes and references
Chem. Soc. Rev. 2011, 40, 102.
16 For selected works from the MacMillan group, see: (a) A.
Noble, S. J. McCarver and D. W. C. MacMillan, J. Am. Chem.
Soc. 2015, 137, 624; (b) J. Jin and D. W. C. MacMillan, Angew.
Chem. Int. Ed. 2014, 54, 1565; (c) Z. Zuo, D. Ahneman, L. Chu,
J. Terrett, A. G. Doyle and D. W. C. MacMillan, Science 2014,
345, 437; (d) M. T. Pirnot, D. A. Rankic, D. B. C. Martin and D.
W. C. MacMillan, Science 2013, 339, 1593; (e) D. A. Nicewicz,
and D. W. C. MacMillan, Science 2008, 322, 77.
17 For selected works from the Yoon group, see: (a) J. Du, K. L.
Skubi, D. M. Schultz and T. P. Yoon, Science 2014, 344, 392;
(b) A. E. Hurtley, Z. Lu and T. P. Yoon, Angew. Chem. Int. Ed.
2014, 53, 8991; (c) D. M. Schultz and T. P. Yoon, Science
2014, 343, 6174; (d) T. R. Blum, Y. Zhu, S. A. Nordeen and T.
P. Yoon, Angew. Chem. Int. Ed. 2014, 53, 11056.
1
(a) T. Wiel and M. Bodanszky, the World of Peptides: A Brief
History of Peptide Chemistry, Springer: Berlin, 1991; (b) M.
Castanho, N. Santos, Peptide Drug Discovery and
Development, Wiley-VCH Verlag GmbH
Weinheim, 2011.
& Co. KGaA,
2
(a) A. K. Ghose, V. N. Viswanadhan and J. J. Wendoloski, J.
Comb. Chem. 1999, , 55; (b)S. D. Roughley and A. M. Jordan,
1
J. Med. Chem. 2011, 54, 3451; (c) J. A. DiPaolo, T. Huang, M.
Balazs, J. Barbosa, K. H. Barck, B. J. Bravo, R. A. D. Carano, J.
Darrow, D. R. Davies, L. E. De Forge, L. Diehl, R. Ferrando, S.
L. Gallion, A. M. Giannetti, P. Gribling, V. Hurez, S. G.
Hymowitz, R. Jones, J. E. Kropf, W. P. Lee, P. M. Maciejewski,
S. A. Mitchell, H. Rong, B. L. Staker, J. A. Whitney, S. Yeh, W.
B. Young, C. Yu, J. Zhang, K. Reif and K. S. Currie, Nat. Chem.
Biol. 2011,7,41.
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Journal Name
18 For selected works from the Stephenson group, see: (a) J. W.
Beatty and C. R. J. Stephenson, J. Am. Chem. Soc. 2014, 136
10270; (b) J. D. Nguyen, E. M. D'Amato, J. M. R. Narayanam,
and C. R. J. Stephenson, Nat. Chem. 2012, , 854.
,
4
19 For reviews, see: G. Ulrich, R. Ziesseland A. Harriman,
Angew. Chem. Int. Ed. 2008, 47, 1184.
20 (a) C. Trieflinger, K. Rurack and M. Daub, Angew. Chem. Int.
Ed. 2005, 44, 2288; (b) K. Tanaka, T. Miura, N. Umezawa, Y.
Urano, K. Kikuchi, T. Higuchi and T. Nagano, J. Am. Chem.
Soc. 2001,123, 2530.
21 (a) L.Huang, J. Zhao, Chem. Commun. 2013, 49, 3751; (b) S.
Guo, H. Zhang, L. Huang, Z. Guo, G. Xiong, J. Zhao, Chem.
Commun.2013, 49, 8689;(c) S. Guo, R.-J. Tao, J. Zhao, RSC
Adv.2014,
22 (a) X.-Z. Wang, Q.-Y. Meng, J.-J. Zhong, X.-W. Gao, T. Lei, L.-M.
Zhao, Z.-J. Li, B. Chen, L.-Z. Wu, Chem. Comm. 2015, 51
11256; (b) L.Huang, J. Zhao, RSC Adv. 2013, , 23377.
23 (a) W. Li, L. Li, H. Xiao, R. Qi, Y. Huang, Z. Xie, X. Jing, H. Zhang,
RSC Adv. 2013, , 13417; (b) L. Huang, J. Zhao, S. Guo, C.-S.
4, 36131.
,
3
3
Zhang, J. Ma, J. Org. Chem. 2013, 78, 5627; (c) C. Zhang, J.
Zhao, S. Wu, Z. Wang, W. Wu, J. Ma, S. Guo, L. Huang, J. Am.
Chem. Soc. 2013, 135, 10566; (d) W. Li, W. Zhang, X. Dong, L.
Yan, R. Qi, W. Wang, Z. Xie, X. Jing, J. Mater. Chem. 2012, 22
17445; (e) W. Li, Z. Xie and X. Jing, Catal. Commun. 2011, 16
,
,
94; (f) L. Huang, X. Cui, B. Therrien, J. Zhao, Chem. Eur. J.
2013, 19, 17472.
24 For review, see: J. Zhao, K. Xu, W. Yang, Z. Wang, F. Zhong,
Chem. Soc. Rev. 2015, 44, 8904.
25 (a) Y.-X.Liu, D. Xue, J.-D. Wang, C.-J. Zhao, Q.-Z. Zou, C. Wang
and J. Xiao, Synlett. 2013, 24, 507; (b) J.-D. Wang, Y.-X. Liu, D.
Xue, C. Wang and J. Xiao, Synlett. 2014, 25, 2013; (c) D. Xue,
Z.-H. Jia, C.-J. Zhao, Y.-Y. Zhang, C. Wang and J. Xiao, Chem.
Eur. J. 2014, 20, 2960.
26 For details, please see ESI.
27 For oxidative amidation using TBHP or H2O2, see: (a) K.
Ekoue-Kovi and C. Wolf, Org. Lett. 2007, 9, 3429; (b) R. Tank,
U. Pathak, M. Vimal, S. Bhattacharyya and L. K. Pandey,
Green Chem. 2011, 13, 3350; (c) X. Liu and K. F. Jensen,
Green Chem. 2012, 14, 1471.
28 X. Sun, M. Wang, P. Li, X. Zhang and L. Wang, Green Chem.
2013, 15, 3289.
29 (a) L. Jiao, C. Yu, J. Li, Z. Wang, M. Wu, E. Hao, J. Org. Chem.
2009, 74, 7525;(b) A. B. Nepomnyashchii, M. Bröring, J.
Ahrens, A. J. Bard, J. Am. Chem. Soc. 2011, 133, 8633; (c) A.
Coskun, E. U. Akkaya, J. Am. Chem. Soc. 2005, 127, 10464.
30 (a) C.Bonnier, D. D.Machin, O.Abdi, B. D. Koivisto, Org. Bio.
Chem. 2013, 11, 3756; (b) L. Wang, J.-W. Wang, A.-J. Cui, X.-X.
Cai, Y. Wan, Q. Chen, M.-Y. He, W. Zhang, RSC Adv. 2013, 3,
9219; (c) W. Wu, J. Zhao, H. Guo, J. Sun, S. Ji, Z. Wang, Chem.
Eur. J. 2012, 18, 1961.
31 G.-L.Li, K. K.-Y.Kung, M.-K. Wong, Chem. Comm. 2012, 48
4112.
,
10 | J. Name., 2012, 00, 1-3
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