Visible-Light-Mediated Aerobic Oxidative C(sp3)?C(sp3) Bond Cleavage of Morpholine Derivatives Using 4CzIPN as a Photocatalyst

Article abstract of DOI:10.1002/adsc.202100455

Herein, a metal-free strategy for the aerobic oxidative cleavage of the inert C(sp³)?C(sp³) bond was developed. Deconstruction of morpholine derivatives was conducted using visible light as an energy source and O₂ as an oxidant under mild conditions. This procedure demonstrated suitable selectivity and functional group tolerance. Moreover, a possible mechanism involving a radical process was proposed based on a series of mechanism exploration and control experiments. (Figure presented.).

Full text of DOI:10.1002/adsc.202100455

Title: Visible-Light-Mediated Aerobic Oxidative C(sp3)–C(sp3)
Bond Cleavage of Morpholine Derivatives using 4CzIPN as a
Photocatalyst
Authors: Chun-Lin Dong, Lan-Qian Huang, Zhi Guan, Chu-Sheng
Huang, and Yan-Hong He
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.202100455
Link to VoR: https://doi.org/10.1002/adsc.202100455

10.1002/adsc.202100455
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Visible-Light-Mediated Aerobic Oxidative C(sp3)–C(sp3) Bond
Cleavage of Morpholine Derivatives Using 4CzIPN as a
Photocatalyst
Chun-Lin Donga, Lan-Qian Huanga, Zhi Guana*, Chu-Sheng Huangb*, and Yan-Hong
Hea*
a
Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering,
Southwest University, Chongqing 400715, China
[Emails: guanzhi@swu.edu.cn (for Z. Guan); heyh@swu.edu.cn (for Y.-H. He)]
Guangxi Teachers Education University, Nanning 530001, China
b
[Email: huangcs@gxtc.edu.cn (for C.-S. Huang)]
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. Herein, a metal-free strategy for the aerobic
oxidative cleavage of the inert C(sp3)–C(sp3) bond was
Keywords: C–C bond cleavage; 4CzIPN; morpholine
developed. Deconstruction of morpholine derivatives was
conducted using visible light as an energy source and O2 as an
oxidant under mild conditions. This procedure demonstrated
suitable selectivity and functional group tolerance. Moreover,
a possible mechanism involving a radical process was
proposed based on a series of mechanism exploration and
control experiments.
derivatives; photocatalysis; radical
and cross-alkane metathesis[8] have been mostly used.
Notably, hazardous oxidants (O3,[9a] tert-butyl
hydroperoxide,[9b] NaIO4,[9c-9d] and Pb(OAc)4[9e]) or
relatively harsh reaction conditions (such as elevated
temperatures and high pressures)[10] are typically
needed for the oxidative cleavage of C–C bonds,
which limit the application of this strategy. Therefore,
exploring effective methods for the oxidative cleavage
of C–C bonds under mild conditions is highly required.
Morpholine moieties are widely used in drugs and
bioactive molecules owing to their advantageous
Introduction
As a means of selective deconstruction and
functionalization, the cleavage of C–C bonds is of
considerable significance in organic synthesis and
medicinal chemistry,[1] because it provides
a
the
complementary
strategy
for
activation/functionalization of C(sp3)–C(sp3) during
the construction of complex molecules.[2] However,
selective cleavage of the C–C bond under mild
conditions remains a huge challenge due to the
inherent characteristics, such as high bond dissociation
energy (~90 kcal/mol), non-polarity, and kinetic
inertness of this bond.[3] Therefore, the cleavage of C–
C bonds is commonly achieved by releasing the strain
in three- or four-membered rings; nevertheless,
relatively few studies have been reported on the
cleavage of C–C bonds in unstrained molecules,
specifically under mild and metal-free conditions. In
recent years, substantial efforts have been made to
develop methods for the cleavage of inert C–C
bonds;[4] among these methods, direct oxidative
addition,[5] β-carbon elimination,[6] retro-allylation,[7]
physicochemical,
biological,
and
metabolic
properties.[11] Among the top 200 pharmaceuticals by
retail sales in 2019, there are five drugs (namely,
Xarelto, Genvoya, Prezista, Kyprolis, and Alecensa)
containing morpholine moieties.[12] Considering the
importance of morpholine in the field of medicine,
studying the C–C cleavage of morpholine is of
considerable importance to the research of drug
metabolites. Additionally, multifunctional compounds
can be obtained by cleaving the C–C bond of
morpholine derivatives, which are highly valuable in
organic synthesis.
1
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10.1002/adsc.202100455
Advanced Synthesis & Catalysis
In 2008, Albini et al. discovered that
In our preliminary study, 4-phenylmorpholine (1a)
was selected as a model substrate. We initially
conducted the reaction using different photocatalysts
(1 mol%) in N,N-dimethylformamide (DMF) under
irradiation of 9 W blue light-emitting diodes (LEDs)
and an O2 atmosphere at room temperature for 24 h
[Supporting Information (SI), Table S1]. The reactions
performed using [Ir(dtbbpy)(ppy)2][PF6] and 4CzIPN
afforded the desired product 1b in acceptable yields
(59 and 61%, respectively). Considering the problem
of metal residues and the potential hazards of
transition metals,[16] we chose 4CzIPN as the
photocatalyst. Subsequently, we conducted a solvent
screening, and the results suggested that acetonitrile
(MeCN) was a more suitable solvent for this reaction
(SI, Table S2). To determine better reaction conditions,
photocatalyst loading, light source, and additives were
separately analyzed (SI, Tables S3–S6). Finally, 1b
was acquired in 75% yield under the following optimal
conditions (SI, Table S6, entry 3): substrate: 1a (0.3
mmol, 1.0 equiv.); photocatalyst: 4CzIPN (1 mol%);
additive: 2,6-lutidine (1.0 equiv.); solvent: MeCN;
irradiation source: 9 W blue LEDs; atmosphere: O2 (O2
balloon); and room temperature.
morpholinofluorophenyloxazolidinone irradiated with
ultraviolet (UV) light (310 nm) in N2-flushed water
yielded the corresponding ring-opening product in
only a small amount, as indicated by high-performance
liquid chromatography/mass spectrometry (Scheme
1(a)).[13] In 2012, Bruschi et al. reported the oxidative
cleavage of morpholine derivatives by O3; however,
the yield of the desired ring-opening product was only
17% (Scheme 1(b)).[14] In 2019, Beller et al. developed
a protocol for the aerobic cleavage of the C–C bond
using a Cu catalyst or Co–Mn catalyst (Scheme
1(c)).[15] Although oxidative cleavage of the
morpholine ring has been successfully achieved via
these methods, the application of these methods is
hindered by the low yield of products or the
requirement of harsh conditions, including high
temperatures and pressures. Considering the
importance of preparing drug metabolites or
potential metabolites via the selective cleavage of C–
C bonds in the later stage[16] and the strict restrictions
on the levels of residual heavy metals in the
pharmaceutical industry,[17] the establishment of
metal-free and mild strategies is necessary to realize
the oxidative cleavage of morpholine.
After determining the optimal conditions, we
studied a series of substituted morpholines to reveal
the substrate scope of the reaction (Schemes 2 and 3).
At first, the influence of the N-substituents of
morpholine on the reaction was investigated (Scheme
2). N-Phenylmorpholines with different substituents (-
Cl, -Br, -CN, and -COMe) on the phenyl moiety
performed well in the reaction, providing the desired
products 3b–10b in moderate yields. N-
Phenylmorpholine with a methyl group at the ortho
position of the N-phenyl moiety afforded 2b in a lower
yield than that of 11b acquired using N-
phenylmorpholine with a methyl group at the para
position; this might be due to steric hindrance.
However, when 4-(4-methoxyphenyl)morpholine (12a)
was used in our reaction system, 12b could only be
obtained in 20% yield, and most of the starting
material remained unchanged (conversion: 30%). The
carboxyl group was also tolerated in this reaction,
where 70% of the starting material was converted and
54% 13b was acquired. In this case, 2 mL MeCN was
used as a solvent to dissolve the substrate. Substrates
with disubstituted electron-withdrawing or electron-
donating groups on the N-phenyl moiety underwent
smooth oxidative cleavage (14b–16b). When 4-(3,5-
dichlorophenyl)morpholine (14a) was employed as a
substrate, the expected product 14b was achieved in
59% yield, and its corresponding hydrolysate (14c)
was obtained in 13% yield. To our delight, when the
N-groups on the morpholine moiety were changed to
biphenyl, pyridyl, and benzoheterocycles, the
corresponding products 17b–21b were acquired in
satisfactory yields.
Visible-light catalysis is a green and sustainable
method for constructing complex molecules under
mild conditions and has been extensively used for C–
C bond cleavage.[18] Inspired by related previous
studies and our continuous interest in visible-light
catalysis,[19] we proposed that photoredox catalysis
might be a mild and feasible method for the oxidative
cleavage of morpholine. Herein, we report a visible-
light-mediated C–C bond cleavage of morpholine
derivatives
for
the
synthesis
of
2-(N-
arylformamido)ethyl formates (Scheme 1(d)) using O2
as an oxidant and the organic dye 2,4,5,6-
tetrakis(carbazol-9-yl)-1,3-dicyanobenzene (4CzIPN)
as a photocatalyst; this strategy does not require the
use of transition metals and (over) stoichiometric
oxidants and has broad substrate applicability. This
reaction affords a mild approach for the aerobic
cleavage of the unstrained C(sp3)–C(sp3) bond.
Scheme 1. Oxidative cleavage of morpholine derivatives.
Scheme 2. Evaluation of the substrate scope by variation in
the N-substituents of morpholinea
Results and Discussion
2
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10.1002/adsc.202100455
Advanced Synthesis & Catalysis
Scheme 3. Substrate scope of ring-substituted morpholines
and tertiary aminesa
aUnless otherwise stated, the following conditions were
employed: a (0.3 mmol, 1.0 equiv.), 4CzIPN (1 mol%), and
2,6-lutidine (1 equiv.) in MeCN (1 mL) irradiated with 9 W
blue LEDs at room temperature under an O2 atmosphere (O2
balloon) for 24 h. Isolated yield.
aUnless otherwise stated, the following conditions were
used: a (0.3 mmol, 1.0 equiv.), 4CzIPN (1 mol%), and 2,6-
lutidine (1 equiv.) in MeCN (1 mL) irradiated with 9 W blue
LEDs at room temperature under an O2 atmosphere (O2
balloon) for 24 h. Isolated yield. b2 mL MeCN as the solvent.
cDMF as the solvent.
Additionally, 1b was easily hydrolyzed to N-
arylamino alcohol (1c) in excellent yield under basic
conditions (Scheme 4), which is a useful synthon in
organic synthesis.
Scheme 4. Hydrolysis of 1ba
Subsequently, the scope of substituted morpholines
was explored (Scheme 3). Ring-substituted
morpholines were also reactive in our reaction system
and yielded the desired products 22b–29b in 52–83%
yields. Note that the methyl group at the C3 position
of the morpholine ring exclusively led to the oxidative
cleavage of the unsubstituted C–C bond (22b),
whereas the methyl group at the C2 position resulted
in the selective cleavage of the C5–C6 bond vs. the
C2–C3 bond (3:2) (23b and 23b’, respectively). For
low-yield substrates, the lactams g and the alcohol
compounds c were detected as the main by-products
(SI, Scheme S3). In addition to morpholine derivatives,
aReaction conditions: to a solution of 1b (1.0 mmol) in
MeOH (4.1 mL), NaOH (5 mol/L) was added to achieve a
mixture with pH = 12.0, and then, the mixture was stirred at
55 °C (oil bath) for 12 h.
To gain some insight into this visible-light
photoredox catalysis, few control experiments were
performed (Table 1). Results revealed that both visible
light and the photocatalyst played an indispensable
role in the reaction because no product was detected
when the reaction was executed without one of them
(Table 1, entries 2 and 3). Moreover, when the reaction
was conducted under an Ar atmosphere instead of an
O2 atmosphere, only a trace amount of 1b was acquired
(Table 1, entry 4), indicating that O2 was required for
this reaction. When 2.0 equiv. of radical scavengers
(namely, 2,2,6,6-tetramethylpiperidinooxy (TEMPO)
and 2,6-di-tert-butyl-4-methylphenol (BHT) were
added to the reaction system, 1b was not obtained
(Scheme 5(a) and (b), respectively), suggesting that
the reaction might involve a radical process.
Subsequently, fluorescence quenching experiments,
cyclic voltammetry (CV), and light/dark experiments
were performed to further understand the reaction
1-phenylpiperidine (1d) underwent
a
similar
transformation and produced the oxidative product 1e
in 47% yield, which could not be achieved in Beller’s
study.[15] However, when the tertiary amine 2d was
employed in the reaction, most of the starting material
remained unchanged, and the dealkylated product 2f
was obtained in 19% yield possibly owing to the
hydrolysis of the imine ion intermediate formed during
photocatalysis.[20] To test the tolerance of this protocol
to N-alkyl groups, the reactions of N-benzyl and N-
cyclohexyl morpholines were conducted under the
standard conditions. Nevertheless, the cleavage
products of the C–N bond between the N and alkyl
groups were acquired instead of the cleavage product
of the C–C bond of the morpholine ring.[21]
3
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10.1002/adsc.202100455
Advanced Synthesis & Catalysis
mechanism. Fluorescence quenching experiments
showed that 1a effectively quenched the excited
photocatalyst 4CzIPN* (SI, Figures S1 and S2). The
oxidation potential of 1a (Eox = +1.030 V vs. saturated
calomel electrode (SCE) in MeCN) (SI, Figure S4)
measured by CV revealed that 1a could be oxidized by
4CzIPN* (Eox = +1.35 V vs. SCE in MeCN)[22] via a
single-electron transfer (SET) process. To evaluate the
role of 2,6-lutidine in the reaction, we also tested the
oxidation potential of 1a in the presence of 2,6-lutidine.
Results showed that in the presence of 2,6-lutidine, the
oxidation potential of 1a decreased to +0.991 V vs.
SCE in MeCN, implying that 1a could be easily
oxidized by 4CzIPN* (SI, Figure S4). Next, the
light/dark experiments indicated that the yield of the
reaction did not significantly increase under dark
conditions (SI, Figure S5), and the quantum yield (Φ)
experiments (Φ = 0.088; for details, see SI) further
proved that the reaction did not involve a radical chain
propagation process. Additionally, to explore the
source of the carbonyl O in the product, an 18O2
labeling experiment was conducted (Scheme 5(c)).
The model reaction was performed under an 18O2
atmosphere (18O2 balloon), and 18O was detected in the
resulting product by high-resolution mass
spectrometry (HRMS), suggesting that O2 was the
source of the carbonyl O.
Scheme 5. Mechanistic studies
Based on the above mentioned findings and
previous studies,[3d,23-27] a plausible mechanism was
proposed (Scheme 6). Initially, 4CzIPN absorbs
visible light and is converted to 4CzIPN*, which is
reduced by N-aryl morpholine (a) via a SET process to
produce the aminium radical cation I and 4CzIPN-. H-
abstraction occurs between I and superoxide anion
To verify whether the reaction included singlet
oxygen (1O2), we conducted some experiments.
Fluorescence quenching experiments of 4CzIPN* with
O2 and Ar were performed in MeCN (SI, Figure S3),
which showed that O2 efficiently quenched 4CzIPN*.
1
Next, when the O2 inhibitor β-carotene (2.0 equiv.)
•-
(O2 ) (generated by the SET process between 4CzIPN-
was introduced into the model reaction system, 1b was
and O2 during the photoredox cycle[24]) to provide an
iminium intermediate (IV).[25] IV loses a proton and is
transformed into an enamine (V). V reacts with
1O2 produced by sensitization with 4CzIPN* via
energy transfer (ET) to yield the dioxetane
intermediate VI.[23] VI readily decomposes to afford
the desired product b.[26] In some cases, a small part of
b is hydrolyzed into the by-product c.
not achieved (Scheme 5(d)), suggesting that the
1
1
reaction might involve O2. Considering that O2 can
be easily added to double bonds to form dioxetane,[23]
we speculate that the reaction may involve an enamine
intermediate. To detect the existence of the enamine
intermediate, the model reaction was executed under
standard conditions, and a small amount of reaction
mixture was withdrawn after 11 h for HRMS. The
enamine intermediate V was discovered by HRMS
(Scheme 5(e) and Figure S9).
In contrast, in the radical trapping experiments
(Scheme 5(b)), the radical intermediate II and HOO•
were detected by HRMS. Additionally, g was isolated
in small amounts from several reactions. Thus, we
hypothesize that a small amount of I may undergo
Table 1. Control experimentsa
•-
deprotonation in the presence of O2 . Subsequently, II
is captured by HOO• to generate a peroxide (III),
which is dehydrated to form g.[27]
Entry
Conditions
Yield (%) b
Scheme 6. Proposed mechanism
1
2
3
4
standard conditions
dark
Without photocatalyst
Ar instead of O2 atmosphere
75
not detected
not detected
trace
aUnless otherwise stated, the following conditions were
used: 1a (0.3 mmol, 1.0 equiv.), 4CzIPN (1 mol%), and 2,6-
lutidine (1 equiv.) in MeCN (1 mL) irradiated with 9 W blue
LEDs at room temperature under an O2 atmosphere (O2
balloon) for 24 h. bIsolated yield.
4
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10.1002/adsc.202100455
Advanced Synthesis & Catalysis
(s, 1H), 7.97 (s, 1H), 7.43 (t, J = 7.7 Hz, 2H), 7.33 (t, J = 7.4
Hz, 1H), 7.22 (d, J = 7.9 Hz, 2H), 4.34 (t, J = 5.6 Hz, 2H),
4.11 (t, J = 5.6 Hz, 2H); 13C NMR (151 MHz, Chloroform-
d): δ 162.7, 160.6, 140.7, 129.8, 127.3, 124.5, 60.6, 44.2.
2-(Phenylamino)ethan-1-ol
(1c):28
Rf
=
0.25
(Dichloromethane:Methanol = 50:1); 130.2 mg, 95% yield;
1
colorless liquid; H NMR (600 MHz, Dimethyl sulfoxide
(DMSO)-d6): δ 7.07–7.04 (m, 2H), 6.57 (d, J = 7.9 Hz, 2H),
6.51 (t, J = 7.2 Hz, 1H), 5.39 (t, J = 5.8 Hz, 1H), 4.66 (t, J =
5.5 Hz, 1H), 3.55 (q, J = 5.9 Hz, 2H), 3.08 (q, J = 5.9 Hz,
2H); 13C NMR (151 MHz, DMSO-d6): δ 149.4, 129.3, 116.1,
112.5, 60.2, 46.1.
2-(N-o-Tolylformamido)ethyl formate (2b):15a Rf = 0.25
(Petroleum ether:EtOAc = 2:1); 18.8 mg, 30% yield; light
1
yellow liquid; H NMR (600 MHz, Chloroform-d): δ 8.15
(s, 1H), 7.98 (s, 1H), 7.31–7.30 (m, 2H), 7.28–7.26 (m, 1H),
7.16 (d, J = 7.8 Hz, 1H), 4.30 (t, J = 5.6 Hz, 2H), 3.98 (t, J
= 5.3 Hz, 2H), 2.27 (s, 3H); 13C NMR (151 MHz,
Chloroform-d): δ 163.3, 160.5, 138.9, 135.8, 131.6, 128. 8,
128.8, 127.2, 60.6, 44.2, 17.7.
Conclusion
In summary, herein, we successfully developed a
mild method for the aerobic cleavage of unstrained
C(sp3)–C(sp3) bonds using visible light as an energy
source and O2 as an oxidant. The reaction avoids the
use of transition metals, elevated temperatures, high
pressures, and dangerous stoichiometric oxidants. This
procedure demonstrated the suitable tolerance of
functional groups, and 31 products were obtained with
yields of up to 83%; thus, this study provides an
alternative approach for the oxidative cleavage of
morpholine derivatives under mild conditions.
2-(N-(3-Chlorophenyl)formamido)ethyl formate (3b):15a
Rf = 0.25 (Petroleum ether:EtOAc = 3:1); 38.3 mg, 56%
yield; light yellow liquid; 1H NMR (600 MHz, Chloroform-
d): δ 8.41 (s, 1H), 7.99 (s, 1H), 7.37 (t, J = 8.0 Hz, 1H),
7.32–7.30 (m, 1H), 7.25–7.23 (m, 1H), 7.12–7.10 (m, 1H),
4.35 (t, J = 5.5 Hz, 2H), 4.09 (t, J = 5.6 Hz, 2H); 13C NMR
(151 MHz, Chloroform-d): δ 162.3, 160.5, 142.0, 135.5,
130.8, 127.4, 124.5, 122.3, 60.6, 44.3.
2-(N-(3-Bromophenyl)formamido)ethyl formate (4b):15a
Rf = 0.25 (Petroleum ether:EtOAc = 3:1); 49.4 mg, 61%
yield; yellow liquid; 1H NMR (600 MHz, Chloroform-d): δ
8.40 (s, 1H), 7.98 (s, 1H), 7.48–7.45 (m, 1H), 7.40–7.39 (m,
1H), 7.31 (t, J = 8.0 Hz, 1H), 7.17–7.15 (m, 1H), 4.35 (t, J
= 5.6 Hz, 2H), 4.09 (t, J = 5.6 Hz, 2H); 13C NMR (151 MHz,
Chloroform-d): δ 162.2, 160.4, 142.1, 131.1, 130.4, 127.4,
123.3, 122.8, 60.6, 44.3.
Experimental Section
General. Unless otherwise stated, all reagents were
purchased from commercial suppliers and used without
further purification. Reactions were monitored by thin-layer
chromatography (TLC) with Haiyang GF 254 silica gel
plates (Qingdao Haiyang chemical industry Co., Ltd.,
Qingdao, China) using UV light and vanillic aldehyde or
phosphomolybdic acid as visualizing agents. Flash column
chromatography was performed using 200–300 mesh silica
2-(N-(3-Cyanophenyl)formamido)ethyl formate (5b):15a
Rf = 0.25 (Petroleum ether:EtOAc = 2:1); 30.0 mg, 55%
yield; light yellow liquid; 1H NMR (600 MHz, Chloroform-
d): δ 8.45 (s, 1H), 7.99 (s, 1H), 7.64 (d, J = 7.8 Hz, 1H),
7.60–7.57 (m, 2H), 7.51 (d, J = 8.0 Hz, 1H), 4.38 (t, J = 5.5
Hz, 2H), 4.13 (t, J = 5.5 Hz, 2H); 13C NMR (151 MHz,
Chloroform-d): δ 162.0, 160.4, 141.9, 130.9, 130.6, 128.3,
127.2, 117.6, 114.2, 60.6, 44.5.
1
gel under high pressures. H nuclear magnetic resonance
(NMR) and 13C NMR spectra were recorded via 600 MHz
and 151 MHz NMR spectrometers, respectively. Chemical
shifts (δ) were expressed in ppm with tetramethylsilane as
an internal standard, and coupling constants (J) are reported
in Hz. High-resolution mass spectra were acquired using
electrospray ionization sources (quadrupole time-of-flight
mass spectrometer, Bruker Impact II, Bremen, Germany).
Melting points (m. p.) were evaluated using a melting point
apparatus (WPX-4, Yice instrument equipment Co., Ltd.,
Shanghai) and were uncorrected. Furthermore, 9 W blue
LEDs (Xinyuan Optoelectronics, LD-QP, rated power: 9 W,
frequency: 50/60 Hz) were procured from Taobao.
2-(N-(3-Acetylphenyl)formamido)ethyl formate (6b):15a
Rf = 0.25 (Petroleum ether:EtOAc = 1.5:1); 37.4 mg, 53%
yield; light yellow liquid; 1H NMR (600 MHz, Chloroform-
d): δ 8.44 (s, 1H), 7.97 (s, 1H), 7.90–7.89 (m, 1H), 7.82 (t,
J = 2.0 Hz, 1H), 7.57–7.54 (m, 1H), 7.44–7.42 (m, 1H), 4.35
(t, J = 5.5 Hz, 2H), 4.14 (t, J = 5.6 Hz, 2H), 2.63 (s, 3H); 13C
NMR (151 MHz, Chloroform-d): δ 196.8, 162.3, 160.5,
141.3, 138.7, 130.2, 128.5, 127.1, 123.5, 60.6, 44.2, 26.6.
2-(N-(4-Chlorophenyl)formamido)ethyl formate (7b):15a
Rf = 0.25 (Petroleum ether:EtOAc = 3:1); 41.8 mg, 61%
yield; light yellow liquid; 1H NMR (600 MHz, Chloroform-
d): δ 8.37 (s, 1H), 7.97 (s, 1H), 7.41–7.39 (m, 2H), 7.17–
7.15 (m, 2H), 4.34 (t, J = 5.6 Hz, 2H), 4.08 (t, J = 5.5 Hz,
2H); 13C NMR (151 MHz, Chloroform-d): δ 162.3, 160.5,
139.3, 133.1, 130.0, 125.7, 60.6, 44.4.
General experimental procedure for the synthesis of b.
A 10 mL round-bottom flask equipped with a stirring bar
was charged with a (0.3 mmol, 1.0 equiv.), 4CzIPN (1
mol%), 2,6-lutidine (1 equiv.), and MeCN (1 mL). The
mixture was stirred at room temperature under an O2
atmosphere (O2 balloon) and irradiated with 9 W blue LEDs
(415–494 nm, Xinyuan Optoelectronics; the distance
between light and the flask was approximately 4 cm) for 24
h. After completion of the reaction (detected by TLC),
MeCN was removed from the reaction mixture. The residue
was purified by flash chromatography on silica gel using
petroleum ether/ethyl acetate (EtOAc) as the eluent to
obtain b.
2-(N-(4-Bromophenyl)formamido)ethyl formate (8b):15a
Rf = 0.25 (Petroleum ether:EtOAc = 3:1); 47.5 mg, 58%
yield; yellow liquid; 1H NMR (600 MHz, Chloroform-d): δ
8.37 (s, 1H), 7.97 (s, 1H), 7.56 (d, J = 8.6 Hz, 2H), 7.11 (d,
J = 8.7 Hz, 2H), 4.34 (t, J = 5.6 Hz, 2H), 4.08 (t, J = 5.6 Hz,
2H); 13C NMR (151 MHz, Chloroform-d): δ 162.2, 160.4,
139.8, 133.0, 125.9, 120.8, 60.6, 44.3.
2-(N-Phenylformamido)ethyl formate (1b):15a Rf = 0.25
2-(N-(4-Cyanophenyl)formamido)ethyl formate (9b):15a
Rf = 0.25 (Petroleum ether:EtOAc = 3:1); 45.3 mg, 69%
(Petroleum ether:EtOAc = 3:1); 43.4 mg, 75% yield; light
1
yellow liquid; H NMR (600 MHz, Chloroform-d): δ 8.40
5
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10.1002/adsc.202100455
Advanced Synthesis & Catalysis
1
yield; light yellow solid; m. p.: 75–76 °C; H NMR (600
MHz, Chloroform-d): δ 8.54 (s, 1H), 7.97 (s, 1H), 7.74 (d, J
= 8.3 Hz, 2H), 7.35 (d, J = 8.3 Hz, 2H), 4.39 (t, J = 5.5 Hz,
2H), 4.15 (t, J = 5.5 Hz, 2H); 13C NMR (151 MHz,
Chloroform-d): δ 161.8, 160.4, 144.8, 133.9, 123.3, 117.9,
110.5, 60.6, 44.1.
2-(N-(3,4-Dimethylphenyl)formamido)ethyl
formate
(16b):15a Rf = 0.25 (Petroleum ether:EtOAc = 3:1); 35.3 mg,
53% yield; light yellow liquid; 1H NMR (600 MHz,
Chloroform-d): δ 8.34 (s, 1H), 7.98 (s, 1H), 7.16 (d, J = 8.0
Hz, 1H), 6.96–6.92 (m, 2H), 4.31 (t, J = 5.7 Hz, 2H), 4.06
(t, J = 5.7 Hz, 2H), 2.28 (m, 6H); 13C NMR (151 MHz,
Chloroform-d): δ 162.7, 160.5, 138.3, 138.3, 136.0, 130.8,
125.9, 122.1, 60.6, 44.2, 19.8, 19.2.
2-(N-(4-Acetylphenyl)formamido)ethyl
formate
(10b):15a Rf = 0.25 (Petroleum ether:EtOAc = 1.5:1); 39.9
mg, 57% yield; light yellow liquid; H NMR (600 MHz,
1
2-(N-([1,1'-Biphenyl]-4-yl)formamido)ethyl
formate
Chloroform-d): δ 8.55 (s, 1H), 8.04 (d, J = 8.3 Hz, 2H), 7.97
(s, 1H), 7.32 (d, J = 8.3 Hz, 2H), 4.38 (t, J = 5.6 Hz, 2H),
4.17 (t, J = 5.6 Hz, 2H), 2.62 (s, 3H); 13C NMR (151 MHz,
Chloroform-d): δ 196.6, 162.1, 160.4, 144.8, 135.4, 130.1,
122.8, 60.6, 43.9, 26.5.
(17b): Rf = 0.25 (Petroleum ether:EtOAc = 3:1); 51.5 mg,
64% yield; white solid; m. p.: 76–77 °C; 1H NMR (600 MHz,
Chloroform-d): δ 8.46 (s, 1H), 8.00 (s, 1H), 7.64 (d, J = 7.9
Hz, 2H), 7.59–7.57 (m, 2H), 7.46 (t, J = 7.7 Hz, 2H), 7.38
(t, J = 7.5 Hz, 1H), 7.28 (d, J = 8.2 Hz, 2H), 4.38 (t, J = 5.6
Hz, 2H), 4.14 (t, J = 5.6 Hz, 2H); 13C NMR (151 MHz,
Chloroform-d): δ 162.6, 160.6, 140.4, 139.8, 129.0, 128.5,
127.8, 127.0, 124.7, 60.7, 44.3; HRMS (ESI): m/z: calcd.
for C16H15NO3 (M+H)+: 270.1125; found: 270.1122.
4-(4-Acetylphenyl)morpholin-3-one (10 g): Rf = 0.25
(Petroleum ether:EtOAc = 1:1); 4.0 mg, 6% yield; white
solid; m. p.: 122–123 °C; 1H NMR (600 MHz, Chloroform-
d): δ 8.01 (d, J = 8.2 Hz, 2H), 7.50 (d, J = 8.2 Hz, 2H), 4.37
(s, 2H), 4.07–4.05 (m, 2H), 3.83–3.82 (m, 2H), 2.60 (s, 3H);
13C NMR (151 MHz, Chloroform-d): δ 197.0, 166.7, 145.4,
135.2, 129.4, 124.6, 68.6, 64.0, 49.1, 26.6; HRMS (ESI):
m/z: calcd. for C12H13NO3 (M+H)+: 220.0968; found:
220.0966.
2-(N-(Pyridin-2-yl)formamido)ethyl formate (18b):15a Rf
= 0.25 (Petroleum ether:EtOAc = 3:1); 33.2 mg, 57% yield;
1
light yellow liquid; H NMR (600 MHz, Chloroform-d): δ
9.12 (s, 1H), 8.43–8.42 (m, 1H), 7.99 (s, 1H), 7.76–7.74 (m,
1H), 7.17–7.14 (m, 2H), 4.42 (t, J = 5.8 Hz, 2H), 4.32 (t, J
= 5.8 Hz, 2H); 13C NMR (151 MHz, Chloroform-d): δ 162.2,
160.7, 153.2, 148.8, 138.6, 120.6, 112.7, 61.0, 40.7.
2-(N-p-Tolylformamido)ethyl formate (11b):15a Rf = 0.25
(Petroleum ether:EtOAc = 3:1); 42.2 mg, 68% yield; light
1
yellow liquid; H NMR (600 MHz, Chloroform-d): δ 8.35
2-(N-(Benzo[d]thiazol-2-yl)formamido)ethyl
formate
(s, 1H), 7.98 (s, 1H), 7.22 (d, J = 7.8 Hz, 2H), 7.09 (d, J =
8.3 Hz, 2H), 4.32 (t, J = 5.7 Hz, 2H), 4.07 (t, J = 5.7 Hz,
2H), 2.37 (s, 3H); 13C NMR (151 MHz, Chloroform-d): δ
162.7, 160.6, 138.1, 137.4, 130.4, 124.7, 60.6, 44.3, 20.9.
(19b): Rf = 0.25 (Petroleum ether:EtOAc = 4:1); 33.4 mg,
1
45% yield; white solid; m. p.: 104–105 °C; H NMR (600
MHz, Chloroform-d): δ 8.63 (s, 1H), 8.07 (s, 1H), 7.85–7.82
(m, 2H), 7.46 (t, J = 7.5 Hz, 1H), 7.34 (t, J = 7.3 Hz, 1H),
4.62 (t, J = 4.9 Hz, 2H), 4.45 (t, J = 5.0 Hz, 2H); 13C NMR
(151 MHz, Chloroform-d): δ 161.7, 160.3, 156.8, 147.8,
132.4, 126.3, 124.4, 121.7, 121.3, 61.0, 47.1; HRMS (ESI):
m/z: calcd. for C11H10N2O3S (M+Na)+: 273.0304; found:
273.0300.
2-(N-(4-Methoxyphenyl)formamido)ethyl
formate
(12b):15a Rf = 0.25 (Petroleum ether:EtOAc, 2:1); 13.4 mg,
20% yield; light yellow liquid; 1H NMR (600 MHz,
Chloroform-d): δ 8.30 (s, 1H), 7.99 (s, 1H), 7.13 (d, J = 8.4
Hz, 2H), 6.93 (d, J = 8.4 Hz, 2H), 4.32 (t, J = 5.6 Hz, 2H),
4.04 (t, J = 5.6 Hz, 2H), 3.83 (s, 3H); 13C NMR (151 MHz,
Chloroform-d): δ 162.8, 160.6, 158.9, 133.4, 126.7, 114.9,
60.6, 55.6, 44.5.
2-(N-(Dibenzo[b,d]furan-3-yl)formamido)ethyl formate
(20b): Rf = 0.25 (Petroleum ether:EtOAc = 3:1); 38.4 mg,
45% yield; yellow liquid; 1H NMR (600 MHz, Chloroform-
d): δ 8.50 (s, 1H), 7.99–7.95 (m, 3H), 7.59 (d, J = 8.3 Hz,
1H), 7.51–7.48 (m, 1H), 7.44 (d, J = 1.9 Hz, 1H), 7.40–7.37
(m, 1H), 7.20–7.19 (m, 1H), 4.40 (t, J = 5.6 Hz, 2H), 4.19
(t, J = 5.6 Hz, 2H); 13C NMR (151 MHz, Chloroform-d): δ
162.8, 160.5, 156.9, 156.5, 139.8, 127.7, 123.6, 123.3, 123.3,
121.5, 120.8, 119.5, 111.8, 108.3, 60.7, 44.8; HRMS (ESI):
m/z: calcd. for C16H13NO4 (M+H)+: 284.0917; found:
284.0913.
4-(N-(2-(Formyloxy)ethyl)formamido)benzoic
acid
(13b):15a Rf = 0.25 (Petroleum ether:EtOAc:CH3COOH =
50:50:1); 38.4 mg, 54% yield; white solid; m. p.: 122–
1
123 °C; H NMR (600 MHz, DMSO-d6): δ 12.96 (s, 1H),
8.62 (s, 1H), 8.13 (s, 1H), 7.97 (d, J = 8.5 Hz, 2H), 7.48 (d,
J = 8.7 Hz, 2H), 4.23 (t, J = 5.5 Hz, 2H), 4.12 (t, J = 5.5 Hz,
2H); 13C NMR (151 MHz, DMSO-d6): δ 167.1, 163.0, 162.2,
145.0, 131.2, 128.6, 122.6, 60.6, 43.0.
2-(N-(9-Phenyl-9H-carbazol-2-yl)formamido)ethyl
formate (21b): Rf = 0.25 (Petroleum ether:EtOAc = 2:1);
66.3 mg, 62% yield; light yellow liquid; 1H NMR (600 MHz,
Chloroform-d): δ 8.45 (s, 1H), 8.14 (t, J = 7.9 Hz, 2H), 7.92
(s, 1H), 7.64 (t, J = 7.8 Hz, 2H), 7.55–7.50 (m, 3H), 7.45–
7.39 (m, 2H), 7.33–7.31 (m, 1H), 7.19 (d, J = 1.9 Hz, 1H),
7.11 (dd, J = 8.2, 1.9 Hz, 1H), 4.35 (t, J = 5.6 Hz, 2H), 4.13
(t, J = 5.6 Hz, 2H); 13C NMR (151 MHz, Chloroform-d): δ
163.0, 160.5, 141.7, 141.4, 138.7, 137.1, 130.2, 128.1, 127.1,
126.5, 122.6, 122.6, 121.4, 120.6, 120.4, 116.9, 110.0, 106.3,
60.8, 44.9; HRMS (ESI): m/z: calcd. for C22H18N2O3
(M+H)+: 359.1390; found: 359.1387.
2-(N-(3,5-Dichlorophenyl)formamido)ethyl
formate
(14b):15a Rf = 0.25 (Petroleum ether:EtOAc = 5:1); 46.4 mg,
59% yield; light yellow liquid; 1H NMR (600 MHz,
Chloroform-d): δ 8.42 (s, 1H), 8.00 (s, 1H), 7.33–7.31 (m,
1H), 7.14 (s, 2H), 4.36 (t, J = 5.5 Hz, 2H), 4.07 (t, J = 5.5
Hz, 2H); 13C NMR (151 MHz, Chloroform-d): δ 161.8,
160.4, 142.8, 136.1, 127.3, 122.4, 60.5, 44.4.
N-(3,5-Dichlorophenyl)-N-(2-hydroxyethyl)formamide
(14c): Rf = 0.25 (Petroleum ether:EtOAc = 2:1); 9.1 mg,
1
13% yield; light yellow liquid; H NMR (600 MHz,
Chloroform-d): δ 8.45 (s, 1H), 7.32–7.31 (m, 1H), 7.20–
7.20 (m, 2H), 3.94 (t, J = 5.2 Hz, 2H), 3.85 (t, J = 5.3 Hz,
2H); 13C NMR (151 MHz, Chloroform-d): δ 162.7, 143.4,
136.0, 127.2, 122.6, 60.4, 48.9; HRMS (ESI): m/z: calcd.
for C9H9Cl2NO2 (M+H)+: 234.0083; found: 234.0081.
2-(N-Phenylformamido)propyl formate (22b):15a Rf =
0.25 (Petroleum ether:EtOAc = 3:1); 39.0 mg, 63% yield;
1
light yellow liquid; H NMR (600 MHz, Chloroform-d): δ
8.25 (s, 1H), 8.07 (s, 1H), 7.43 (t, J = 7.3 Hz, 2H), 7.41–
7.38 (m, 1H), 7.20 (d, J = 7.6 Hz, 2H), 4.87–4.83 (m, 1H),
4.32–4.29 (m, 1H), 4.24–4.20 (m, 1H), 1.26 (d, J = 6.9 Hz,
3H); 13C NMR (151 MHz, Chloroform-d): δ 163.2, 160.6,
138.5, 129.7, 128.6, 128.5, 64.3, 49.8, 15.6.
2-(N-(3,5-Dimethylphenyl)formamido)ethyl
formate
(15b):15a Rf = 0.25 (Petroleum ether:EtOAc, 5:1); 39.2 mg,
59% yield; light yellow liquid; 1H NMR (600 MHz,
Chloroform-d): δ 8.36 (s, 1H), 7.99 (s, 1H), 6.96 (s, 1H),
6.80 (s, 2H), 4.32 (t, J = 5.7 Hz, 2H), 4.07 (t, J = 5.7 Hz, 2H),
2.34 (s, 6H); 13C NMR (151 MHz, Chloroform-d): δ 162.7,
160.6, 140.5, 139.7, 129.0, 122.3, 60.6, 44.1, 21.3.
Mixture of 1-(N-phenylformamido)propan-2-yl formate
(23b)15a and 2-(N-phenylformamido)ethyl acetate
(23b’):15a Rf = 0.25 (Petroleum ether:EtOAc = 3:1); 50.0 mg,
81% yield; light yellow liquid; 1H NMR (600 MHz,
Chloroform-d): δ 8.39 (d, J = 7.1 Hz, 1.67H), 7.88 (s, 1H),
6
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10.1002/adsc.202100455
Advanced Synthesis & Catalysis
7.44–7.41 (m, 3.34H), 7.32–7.30 (m, 2H), 7.20 (t, J = 9.7
Hz, 3H), 5.27–5.24 (m, 1H), 4.26–4.24 (d, J = 5.8 Hz,
1.36H), 4.08–4.06 (m, 1.38H), 4.05–3.95 (m, 2H), 1.90 (s,
2H), 1.28 (d, J = 6.5 Hz, 3H); 13C NMR (151 MHz,
Chloroform-d): δ 170.7, 162.9, 162.6, 160.4, 141.1, 129.9,
129.8, 127.3, 127.2, 124.5, 124.4, 68.4, 61.4, 49.2, 44.4,
17.9, 17.9.
1-(N-(3,5-Dimethylphenyl)formamido)propan-2-yl
acetate (29b): Rf = 0.25 (Petroleum ether:EtOAc = 5:1);
1
45.9 mg, 61% yield; yellow liquid; H NMR (600 MHz,
Chloroform-d): δ 8.34 (s, 1H), 6.93 (s, 1H), 6.78 (s, 2H),
5.13–5.10 (m, 1H), 3.99–3.88 (m, 2H), 2.33 (s, 6H), 1.81 (s,
3H), 1.23 (d, J = 6.4 Hz, 3H); 13C NMR (151 MHz,
Chloroform-d): δ 170.3, 162.8, 141.1, 139.4, 128.6, 122.1,
68.8, 48.9, 21.2, 20.8, 17.8; HRMS (ESI): m/z: calcd. for
C14H19NO3 (M+Na)+: 272.1257; found: 272.1256.
2-(N-Phenylformamido)ethyl acetate (23b’):15a Rf = 0.25
(Petroleum ether:EtOAc = 3:1); 20.1 mg, 32% yield; light
1
yellow liquid; H NMR (600 MHz, Chloroform-d): δ 8.40
4-(N-Phenylformamido)butanoic acid (1e): Rf = 0.25
(Petroleum ether:EtOAc:CH3COOH = 100:100:1); 29.4 mg,
47% yield; light yellow liquid; 1H NMR (600 MHz,
Chloroform-d): δ 8.39 (s, 1H), 7.42 (t, J = 7.8 Hz, 2H), 7.31
(t, J = 7.6 Hz, 1H), 7.19 (d, J = 7.8 Hz, 2H), 3.89 (t, J = 7.3
Hz, 2H), 2.38 (t, J = 7.3 Hz, 2H), 1.91–1.86 (m, 2H); 13C
NMR (151 MHz, Chloroform-d): δ 177.4, 162.9, 140.5,
129.8, 127.2, 124.2, 44.2, 31.1, 22.8; HRMS (ESI): m/z:
calcd. for C11H13NO3 (M+Na)+: 230.0788; found: 230.0782.
(s, 1H), 7.42 (t, J = 7.9 Hz, 2H), 7.32 (t, J = 7.5 Hz, 1H),
7.21–7.20 (m, 2H), 4.25 (t, J = 5.6 Hz, 2H), 4.07 (t, J = 5.6
Hz, 2H), 1.90 (s, 3H); 13C NMR (151 MHz, Chloroform-d):
δ 170.7, 162.5, 141.0, 129.7, 127.1, 124.5, 61.4, 44.3, 20.6.
1-(N-Phenylformamido)propan-2-yl acetate (24b):15a Rf
= 0.25 (Petroleum ether:EtOAc = 3:1); 55.0 mg, 83% yield;
1
yellow liquid; H NMR (600 MHz, Chloroform-d): δ 8.38
(s, 1H), 7.42 (t, J = 6.8 Hz, 2H), 7.31–7.28 (m, 1H), 7.18 (d,
J = 7.8 Hz, 2H), 5.15–5.11 (m, 1H), 4.02–3.93 (m, 2H), 1.77
(s, 3H), 1.24–1.23 (m, 3H); 13C NMR (151 MHz,
Chloroform-d): δ 170.1, 162.6, 141.2, 129.6, 126.8, 124.2,
68.7, 48.7, 20.7, 17.7.
N-Butylaniline (2f):29 Rf = 0.25 (Petroleum ether); 8.3 mg,
19% yield; light yellow liquid; 1H NMR (600 MHz,
Chloroform-d): δ 7.17 (t, J = 7.8 Hz, 2H), 6.71 (d, J = 7.5
Hz, 1H), 6.64 (d, J = 7.8 Hz, 2H), 3.11 (t, J = 7.3 Hz, 2H),
1.61 (p, J = 7.3 Hz, 2H), 1.46–1.40 (m, 2H), 0.95 (t, J = 7.0
Hz, 3H); 13C NMR (151 MHz, Chloroform-d): δ 148.1,
129.3, 117.6, 113.1, 44.1, 31.6, 20.3, 13.9.
1-(N-(3-Acetylphenyl)formamido)propan-2-yl acetate
(25b): Rf = 0.25 (Petroleum ether:EtOAc = 3:1); 41.9 mg,
53% yield; light yellow liquid; 1H NMR (600 MHz,
Chloroform-d): δ 8.42 (s, 1H), 7.88 (d, J = 7.7 Hz, 1H), 7.83
(t, J = 2.0 Hz, 1H), 7.54 (t, J = 7.9 Hz, 1H), 7.41–7.39 (m,
1H), 5.16–5.11 (m, 1H), 4.06–3.95 (m, 2H), 2.64 (s, 3H),
1.81 (s, 3H), 1.25 (d, J = 6.4 Hz, 3H); 13C NMR (151 MHz,
Chloroform-d): δ 196.9, 170.2, 162.4, 141.9, 138.6, 130.0,
128.4, 126.8, 123.4, 68.6, 49.0, 26.7, 20.9, 17.8; HRMS
(ESI): m/z: calcd. for C14H17NO4 (M+Na)+: 286.1050;
found: 286.1048.
Acknowledgements
This work was financially supported by the National Natural
Science Foundation of China (Grant Nos. 21977084 and
22078268).
1-(N-(4-Acetylphenyl)formamido)propan-2-yl acetate
(26b): Rf = 0.25 (Petroleum ether:EtOAc = 3:1); 41.7 mg,
53% yield; light yellow liquid; 1H NMR (600 MHz,
Chloroform-d): δ 8.51 (s, 1H), 8.02 (d, J = 8.6 Hz, 2H), 7.29
(d, J = 10.1 Hz, 2H), 5.17–5.13 (m, 1H), 4.11–3.95 (m, 2H),
2.62 (s, 3H), 1.78 (s, 3H), 1.25 (d, J = 6.5 Hz, 3H); 13C NMR
(151 MHz, Chloroform-d): δ 196.6, 170.2, 162.2, 145.3,
135.1, 130.0, 122.8, 68.6, 48.5, 26.5, 20.9, 17.8; HRMS
(ESI): m/z: calcd. for C14H17NO4 (M+Na)+: 286.1050;
found: 286.1053.
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(27b): Rf = 0.25 (Petroleum ether:EtOAc = 4:1); 41.2 mg,
54% yield; light yellow liquid; 1H NMR (600 MHz,
Chloroform-d): δ 8.35 (s, 1H), 7.39 (d, J = 8.1 Hz, 2H), 7.14
(d, J = 8.3 Hz, 2H), 5.13–5.10 (m, 1H), 3.99–3.90 (m, 2H),
1.81 (s, 3H), 1.23 (d, J = 6.4 Hz, 3H); 13C NMR (151 MHz,
Chloroform-d): δ 170.2, 162.4, 139.9, 132.7, 129.8, 125.5,
68.7, 49.0, 20.9, 17.8; HRMS (ESI): m/z: calcd. for
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(27c): Rf = 0.25 (Petroleum ether:EtOAc = 2:1); 4.7 mg, 7%
yield; light yellow liquid; 1H NMR (600 MHz, Chloroform-
d): δ 8.39 (s, 1H), 7.40–7.39 (m, 2H), 7.21–7.19 (m, 2H),
4.09–4.03 (m, 1H), 3.90–3.86 (m, 1H), 3.73–3.70 (m, 1H),
1.20 (d, J = 6.3 Hz, 3H); 13C NMR (151 MHz, Chloroform-
d): δ 163.4, 140.2, 133.0, 129.9, 125.8, 66.5, 54.1, 21.3;
HRMS (ESI): m/z: calcd. for C10H12ClNO2 (M+H)+:
214.0629; found: 214.0626.
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1-(N-(4-Cyanophenyl)formamido)propan-2-yl acetate
(28b): Rf = 0.25 (Petroleum ether:EtOAc = 3:1); 38.1 mg,
52% yield; light yellow liquid; 1H NMR (600 MHz,
Chloroform-d): δ 8.50 (s, 1H), 7.74 (d, J = 8.6 Hz, 2H), 7.33
(d, J = 8.7 Hz, 2H), 5.18–5.12 (m, 1H), 4.11–4.08 (m, 1H),
3.96–3.92 (m, 1H), 1.79 (s, 3H), 1.25 (d, J = 6.5 Hz, 3H);
13C NMR (151 MHz, Chloroform-d): δ 170.1, 161.9, 145.3,
133.7, 123.3, 118.0, 110.1, 68.6, 48.6, 20.8, 17.8; HRMS
(ESI): m/z: calcd. for C13H14N2O3 (M+Na)+: 269.0897;
found: 269.0894.
7
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10.1002/adsc.202100455
Advanced Synthesis & Catalysis
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10.1002/adsc.202100455
Advanced Synthesis & Catalysis
FULL PAPER
Visible-Light-Mediated Aerobic Oxidative C(sp3)–
C(sp3) Bond Cleavage of Morpholine Derivatives
using 4CzIPN as a Photocatalyst
Adv. Synth. Catal. Year, Volume, Page–Page
Chun-Lin Donga, Lan-Qian Huanga, Zhi Guana*,
Chu-Sheng Huangb*, and Yan-Hong Hea*
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